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PATHOLOGY
A Color Atlas

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THE HEART,1
CONGENITAL HEART DISEASE, 2 Cardiovascular shunts and septal defects, 2 Conotruncal anomalies, 4 Cardiovascular obstructions, 6 VALVULAR LESIONS, 9 Rheumatic heart disease, 9 Infective endocarditis, 11 Other valvular lesions, 13 MYOCARDIAL DISEASES, 14 Myocarditis, 14 Cardiomyopathy, 17 CORONARY ARTERY DISEASES, 20 Coronary atherosclerosis, 20 Myocardial infarction, 22 Complications of myocardial infarction, 22 PERICARDIAL DISEASES, 25 CARDIAC TUMORS, 27

Chronic obstructive pulmonary disease, 60 PNEUMOCONIOSES, 62 IDIOPATHIC INTERSTITIAL LUNG DISEASES, 66 PULMONARY NEOPLASMS, 68

THE HEMATOPOIETIC AND LYMPHOID SYSTEM, 72
ANEMIAS, 74 Bone marrow changes, 74 Peripheral blood smears, 74 Tissue changes in anemia, 77 LEUKEMIAS, 78 Acute leukemias, 78 Chronic leukemias, 80 PLASMA CELL DYSCRASIAS, 82 REACTIVE LYMPHADENOPATHIES, 84 HODGKIN DISEASE, 87 Histopathologic subtypes of Hodgkin disease, 87 NON-HODGKIN LYMPHOMA, 89 OTHER HEMATOPOIETIC PROLIFERATIONS IN LYMPH NODES, 95 NEOPLASMS INVOLVING THE SPLEEN, 96 DISEASES OF THE THYMUS, 98

BLOOD VESSELS, 30
ARTERIOSCLEROSIS, 32 ANEURYSMS, 35 VASCULITIS, 36 Immune-mediated vasculitis, 38

UPPER RESPIRATORY TRACT, 40
INFLAMMATORY LESIONS, 42 BENIGN TUMORS AND RELATED CONDITIONS, 44 MALIGNANT TUMORS, 45

UPPER DIGESTIVE TRACT, loo
DEVELOPMENTAL ANOMALIES, 102 INFLAMMATORY LESIONS, 103 ORGAN-SPECIFIC LESIONS, 105 Dental cysts, 105 Oral and salivary gland lesions, 108 Esophageal lesions, 110 TUMORS, 112 Oral tumors, 112 Salivary gland tumors, 112 Esophageal tumors, 118

LUNGS, 48
DEVELOPMENTAL ANOMALIES, 50 PERINATAL LUNG DISEASES, 52 PULMONARY INFECTIONS, 54 PULMONARY CIRCULATORY DISORDERS, 57 Pulmonary emboli, 57 Pulmonary hypertension, 58 IMMUNE-MEDIATED LUNG DISEASES, 58 CHRONIC INFECTIONS AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (CORD), 60 Bronchiectasis, 60

GASTROINTESTINAL TRACT, 120
DEVELOPMENTAL DISORDERS, 122 CIRCULATORY DISTURBANCES, 124 OBSTRUCTIONS AND DILATATIONS OF INTESTINAL LUMEN, 125

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ORGAN-SPECIFIC DISEASES, 126 Gastritis and peptic ulcer, 126 Small intestinal diseases that cause malabsorption, 129 Inflammation of the appendix and the large intestine, 130 Inflammatory bowel disease (IBD), 132 TUMORS, 134 Gastric tumors, 134 Tumors of the small intestine, 136 Tumors of the appendix, 136 Intestinal polyps, 136 Carcinoma of the large intestine, 139 Anal tumors and related lesions, 140

DISEASES OF THE THYROID GLAND, 185 Thyroid hyperplasia, 185 Thyroiditis, 186 Benign thyroid tumors, 188 Malignant thyroid tumors, 190 DISEASES OF THE PARATHYROID GLANDS, 195 DISEASES OF THE ADRENAL CORTEX, 198 Adrenocortical insufficiency, 198 Adrenocortical hyperplasia and hyperfunction, 199 Adrenocortical tumors, 201 DISEASES OFTHE ADRENAL MEDULLA, 203

HEPATOBILIARY TRACT, 142
HEREDITARY METABOLIC DISEASES, 144 CIRCULATORY DISORDERS, 146 INFECTIOUS HEPATITIS, 147 Viral hepatitis, 147 Hepatitis caused by pathogens other than hepatitis viruses, 149 Biliary infections, 150 DRUG-INDUCED LIVER DISEASES, 152 ALCOHOLIC LIVER DISEASES, 153 AUTOIMMUNE LIVER DISEASES, 155 BILIARY OBSTRUCTION, 156 CIRRHOSIS, 158 TUMOR-LIKE CONDITIONS AND TUMORS, 159 Tumor-like conditions, 159 Epithelial tumors, 161 Mesenchymal tumors, 163 Metastatic tumors, 163 DISEASES OF THE GALLBLADDER, 164

KIDNEY AND URINARY TRACT, 208
DEVELOPMENTAL AND GENETIC DISORDERS, 210 Agenesis, malposition, exstrophy, and related defects, 210 Polycystic kidney disease, 212 Hereditary glomerular and tubular diseases, 213 VASCULAR DISORDERS, 216 IMMUNE-MEDIATED GLOMERULAR DISEASES, 217 Membranoproliferative glomerulonephritis, 219 Membranous glomerulonephritis, 220 IgA nephropathy and Henoch-Schonlein purpura, 222 Postinfectious glomerulonephritis, 223 Crescentic glomerulonephritis, 224 Systemic lupus erythematosus (SLE), 225 TUBULOINTERSTITIAL DISEASES, 227 LOWER URINARY TRACT INFECTIONS, 232 TUMORS, 234 Tumors of the kidney and renal pelvis, 234 Tumors of the urinary bladder, 235

MALE REPRODUCTIVE SYSTEM, 238
GENETIC AND DEVELOPMENTAL DISORDERS, 240 INFECTIONS, 241 TUMORS OF THE TESTIS, 242 Germ cell tumors, 242 Sex cord stromal tumors, 246 Mixed germ cell stromal tumors, 247 Tumors of rete testis, epididymis, and tunica vaginalis testis, 248 TUMORS AND TUMOR-LIKE LESIONS OF THE PROSTATE, 248 Benign prostatic hyperplasia, 248 Carcinoma of the prostate, 250

PANCREAS, 166
DEVELOPMENTAL AND GENETIC DISORDERS, 168 PANCREATITIS, 169 TUMORS OF THE EXOCRINE PANCREAS, 172 Benign tumors and tumors of borderline malignancy, 172 Carcinoma of the pancreas, 174 TUMORS OFTHE ENDOCRINE PANCREAS, 176 DIABETES MELLITUS, 177

ENDOCRINE GLANDS, 180
DISEASES OF THE PITUITARY GLAND, 182 Hypopituitarism, 182 Reactive changes, 183 Tumors, 183

FEMALE REPRODUCTIVE SYSTEM, 256
DEVELOPMENTAL DISORDERS, 258 INFECTIONS, 260

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HORMONALLY INDUCED CHANGES, 261 TUMORS OF THE VULVA, 263 TUMORS OF THE VAGINA, 265 TUMORS OF THE CERVIX, 266 TUMORS OF THE UTERUS, 268 Endometrial adenocarcinoma, 268 Endometrial stromal tumor,s 270 Tumors of the myometrium, 271 TUMORS OF THE OVARY, 273 Serous tumors, 273 Mucinous tumors, 275 Endometrioid carcinoma, 277 Clear cell carcinoma, 278 Transitional cell tumors, 278 Sex cord stromal tumors, 278 Germ cell tumors, 282 Unclassified and metastatic tumors of the ovary, 284 DISORDERS OF THE PLACENTA, 287 Abnormal implantation and separation of the placenta and rupture of membranes, 289 Infections, 289 Gestational trophoblastic disease, 290

SOFT TISSUE, 334
FIBROBLASTIC LESIONS, 336 Benign fibroblastic tumors and tumor-like lesions, 336 Fibromatoses, 337 FIBROHISTIOCYTIC TUMORS, 338 LIPOMATOUS TUMORS, 339 VASCULAR TUMORS, 341 PERIVASCULAR TUMORS, 343 SMOOTH MUSCLE CELL TUMORS, 344 TUMORS OF STRIATED MUSCLE, 345 NEURAL TUMORS, 347 Benign neural tumors, 347 Malignant neural tumors, 348 CARTILAGE AND BONE-FORMING TUMORS, 349 MISCELLANEOUS SOFT-TISSUE TUMORS, 350

BONES AND JOINTS, 354
DEVELOPMENTAL AND GENETIC DISORDERS, 356 METABOLIC AND DEGENERATIVE DISEASES, 357 Metabolic bone diseases, 357 Hyperparathyroidism, 359 Paget disease of bone, 359 Crystal-induced arthritis, 360 Osteonecrosis, 361 Degenerative joint disease, 361 I NFLAMMATORY DISEASES, 363 Infections of bones and joints, 363 Noninfectious arthropathies, 364 NEOPLASMS, 367 Benign bone-forming tumors, 367 Malignant bone-forming tumors, 369 Fibrous lesions of bone, 377 Giant cell tumor of bone, 378 Marrow tumors, 379 Vascular tumors, 380 Miscellaneous tumors and tumor-like conditions, 380 Tumors and tumor-like lesions of joints, 383

BREAST, 294
FIBROCYSTIC CHANGE, 296 TUMORS, 298 Fibroadenoma, 298 Adenoma, 298 Phyllodes tumor, 299 Intraductal papilloma, 300 Atypical hyperplasia, 301 Noninvasive carcinoma, 302 Invasive breast carcinoma, 303 Variants of invasive carcinoma 306 I mmunohistochemistry of breast carcinoma, 308

SKIN, 310
HEREDITARY SKIN DISEASES, 312 INFECTIONS, 312 Bacterial infections, 313 Fungal infections, 314 Viral infections, 314 INFLAMMATORY DERMATOSES, 316 I mmune-mediated dermatoses, 316 Granulomatous diseases, 319 Idiopathic skin disease, 321 NEOPLASMS AND RELATED DISORDERS, 323 Pigmentary lesions, 323 Epidermal tumors, 328 Adnexal tumors, 331 Mesenchymal tumors, 333

SKELETAL MUSCLES, 384
CONGENITAL MYOPATHIES, 386 MUSCULAR DYSTROPHIES, 386 I NFLAMMATORY MYOPATHIES, 389 GENETIC-METABOLIC MYOPATHIES, 392 Carbohydrate storage diseases, 392 Lipid storage myopathies, 393 Mitochondrial myopathies, 394 DENERVATION-RELATED MUSCLE DISEASES, 395

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NERVOUS SYSTEM, 398
DEVELOPMENTAL AND GENETIC DISORDERS, 400 PERINATAL BRAIN LESIONS, 401 TRAUMA OFTHE BRAIN AND THE SPINAL CORD, 403 CIRCULATORY DISTURBANCES, 405 Intracranial hemorrhages, 405 Cerebral ischemia, 408 INFECTIONS, 409 METABOLIC AND TOXIC DISEASES, 413 Inborn errors of metabolism, 414 DEMYELINATING DISEASES, 416 DEGENERATIVE DISEASES OF THE CENTRAL NERVOUS SYSTEM, 417 NEOPLASMS, 420 Astrocytic tumors, 422 Oligodendroglioma, 422 Ependymoma, 422 Neuronal, mixed neuronal-glial, and neuroendocrine neoplasms, 424 Pineal tumors, 424 Meningioma, 425 Vascular neoplasms, 425 Malformative and nonneoplastic mass lesions, 426 DISEASES OF PERIPHERAL NERVES, 426 Peripheral neuropathies, 426 Hereditary neuropathies, 428 Ischemic neuropathies, 430 Inflammatory neuropathies, 430 Neoplasms of peripheral nerves, 432

THE EYE AND OCULAR ADNEXA, 434
INFLAMMATION OFTHE EYE AND OCULAR ADNEXA, 436 EYE CHANGES IN SYSTEMIC DISEASES, 437 SPECIFIC OCULAR DISORDERS, 438 Glaucoma, 438 Diseases of the cornea, 440 Retinal degenerative diseases, 441 Cataracts, 442 TUMORS, 443 Melanoma, 443 Retinoblastoma, 445 Medulloepithelioma, 446

EAR, 448
INFLAMMATORY LESIONS OF THE EXTERNAL AND MIDDLE EAR, 450 PATHOLOGIC CHANGES OFTHE INNER EAR, 453 NEOPLASMS, 455 Tumors of the outer ear, 455 Tumors of the middle ear, 455 Tumors of the inner ear, 455

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PATHOLOGY
A

Color Atlas

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Patent ductal artery (ductus arteriosus) 6. atrioventricular.CONGENITAL HEART DISEASE Congenital heart disease encompasses disorders of the cardiovascular system that result from faulty embryogenesis and are present at birth. Ventricular septal defects involve the membranous part of the septum in 75% to 80% of cases seen at operation or autopsy (Fig.Total anomalous pulmonary venous connection 13. Defects of the muscular part of the septum account for only 10% to 20% of cases at operation or autopsy.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Most of them are small and close spontaneously.Ventricular septal defect (VSD) 2.Tricuspid atresia 11. Atrioventricular septal defect 10. shunts that result from faulty embryogenesis involve defects at the level of the atrial.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 1-1). Cardiac and vascular shunts. 1-3). Upper panel shows various levels of intracardiac shunts. Aortic stenosis 7. ventricular. Tetralogy of Fallot (including pulmonary atresia) 5. Pulmonary stenosis 4. even though they actually represent the most common form of VSD. Atrial septal defects occur at the oval fossa in 85% of cases and are known as fossa or secundum atrial septal defects (Fig. Diagram I-I. 1-2). or aortopulmonary septa (Diagram 1-1). Persistent fetal structures include a patent oval foramen and a patent ductal artery (Fig. The most common cardiac malformations in descending order of frequency are 1. In contrast. Inlet defects that involve the inlet septum beneath the septal tricuspid leaflet account for 5% of all VSD.Aortic atresia (hypoplastic left ventricular syndrome) 12. Lower panel shows various levels of shunts involving the great arteries. Complete transposition of the great arteries 9. Atrial septal defect 3. 66417308 : ¸Ÿ±U 24 ¥°Q .Persistent truncal artery (truncus arteriosus) Cardiovascular Shunts and Septa! Defects Shunts result either from patency of normal fetal structures that fail to close postnatally or from incomplete formation of one or more septa during cardiac embryogenesis. Outlet defects located beneath the right and left cusps of both semilunar valves account for 5% to 10% of all VSD. Coarctation of the aorta 8. ventriculoarterial.

1-3. in adult with plexogenic pulmonary hypertension. 66417308 : ¸Ÿ±U 24 ¥°Q . Muscular defect. Ventricular septal defects (*). I -I. connecting the aorta with the pulmonary artery. Atrial septal defect. as seen in an adult (*). Patent ductal artery (*). Outlet defect.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . A. D.3 Fig. 1-2. Membranous defect. fossa (secundum) type. Muscular defect that has undergone spontaneous closure (arrows). B.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . C. Fig. A B C D Fig.

a VSD. 1-4). accounting for 8% to 10% of all congenital heart defects. an overriding aorta. It comprises subpulmonary stenosis. 1-7) accounts for 5%.Conotruncal Anomalies Conotruncal anomalies are related to abnormal development of ventricular outflow tracts (Diagram 1-2). and right ventricular hypertrophy (Fig. 1-6) accounts for 1% of all congenital heart defects and complete transposition ofgreat vessels (Fig. Diagram 1-2. 1-5). The persistent truncal artery (Fig. Conotruncal anomalies. 66417308 : ¸Ÿ±U 24 ¥°Q . in some cases one or both arteries arise from the contralateral ventricle. Clinically these defects are associated with right-to-left shunts and peripheral cyanosis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Many patients have a VSD of the membranous or outlet type. Most are associated with an overriding great artery. as well as valvular or subvalvular pulmonary stenosis. Tetralogy of Fallot is the most common conotruncal anomaly. Pulmonary atresia with a VSD is considered the most severe form of tetralogy of Fallot (Fig.

66417308 : ¸Ÿ±U 24 ¥°Q . and ductal origin of the left pulmonary artery (arrow). B. A. B. Hypoplastic pulmonary trunk and enlarged ascending aorta (anterior view). Ventricular septal defect. Pulmonary atresia with ventricular septal defect. Displaced outlet septum (*) with pulmonary stenosis (probe). hypertrophied right ventricle). and an overriding aorta (opened. A B Fig.A B Fig. a ventricular septal defect (arrow probe).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 1-4.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Tetralogy of Fallot. I-S. overriding aorta. Atretic cordlike pulmonary trunk (arrow) and dilated ascending aorta (anterior view). A.

Anterior view. subvalvular. 66417308 : ¸Ÿ±U 24 ¥°Q . prolapse of the conjoined cusp.. bicuspid semilunar valves). 1-7. Long axis view showing ventriculoarterial discordance.g. causing aortic stenosis (Fig. or great vessels (e. B. Complete transposition of great arteries.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . A B Fig. 1-8).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The overriding truncal artery gives rise to ascending aorta and both pulmonary arteries (opened right ventricle). coarctation of aorta) (Diagram 1-3).. Congenital hypoplasia or nodular thickening of a unicommissural valve. Pure regurgitation occurs in 20% of patients and is the result of annular dilatation. or supravalvular. or infective endocarditis. hypoplastic ventricle).. In approximately 80% of patients bicuspid valves undergo calcification. A. Persistent truncal artery is located over a ventricular septa) defect (*).Cardiovascular Obstructions Cardiovascular obstructions can occur congenitally at the level of cardiac chambers (e. 1-9).g. valves (e. may cause critical aortic stenosis in the neonate (Fig. Aortic stenosis may be valvular. Fig. Such abnormal valves usually remain asymptomatic until late in adult life.g. Bicuspid aortic valves occur in 1% to 2% of the general population. 1-6. or less commonly a bicuspid valve.

7 Diagram 1-3. 1-8. A. Valvular and arterial stenosis. Upper panel shows aortic stenosis. Regurgitation resulting from healed infective endocarditis with cusp perforation. B. Congenitally bicuspid aortic valves (surgical specimens). The valve is calcified and stenotic. Regurgitation resulting from cuspid prolapse and annular dilatation. . C. A B C 66417308 : ¸Ÿ±U 24 ¥°Q . Lower panel shows pulmonary stenosis and aortic coarctation.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº Fig.

C. Pulmonary stenosis. A B C Fig. A. 1-10.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . represent mild stenosis of a unicommissural valve in a young adult (opened and closed positions). B. 1-9. and C.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Congenital aortic stenosis. A. Critical stenosis of a unicommissural valve in an infant.A B C Fig. Pronounced right ventricular hypertrophy (four-chamber view). Dome-shaped acommissural valve. Poststenotic dilatation of the pulmonary trunk (anterior view). B. 66417308 : ¸Ÿ±U 24 ¥°Q .

or age-related degeneration accompanied by calcifications. It is associated with a V-shaped invagination of the aorta. subvalvular. Rheumatic Heart Disease Rheumatic fever is an immune-mediated systemic inflammatory disease related to sensitization of the body to beta hemolytic group A streptococci. Isolated pulmonary stenosis is associated with a dome-shaped acommissural valve in approximately 45%.9 Pulmonary stenosis. Even though rheumatic heart disease may involve all parts of the heart and is thus a pancarditis. Rheumatic carditis in an active phase. unicommissural valve in 15%. In the granulomatous stage. like its left-sided counterpart. which have caterpillar (arrow) or owl's eye-shaped nuclei (curved arrow). A. It is associated with a patent ductal artery in 50%.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and only rarely in the valves. Aschoff bodies heal by scarring. I-I I. Fig. a biscuspid aortic valve in 50%. and a hypoplastic annulus in 5% of patients (Fig. just opposite the ductal artery. may be valvular. a bicuspid valve in 10%. subaortic stenosis in 25%. which is reached three to four weeks after the infection. Coarctation of the aorta. VALVULAR LESIONS Cardiac valves may be congenitally deformed or they may undergo secondary changes due to infections. It often is associated with other cardiac anomalies. a dysplastic tricuspid pulmonary valve in 25%. a membranous VSD in 30%. these bodies consist of macrophages. B. They most often are found in the myocardium and the subendocardial connective tissue. Coarctation of the aorta is the most common form of congenital vascular obstruction (Fig. An active rheumatic fever causes typical lesions.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Rheumatic carditis is less common today than it was in the preantibiotic era. lymphocytes. giant cells (Aschoff cells). 1-11). and occasional neutrophils. 1-10). A B Fig. endocarditis accounts for most important pathologic changes and most of the morbidity. with a typical indentation of the aortic wall (arrow) opposite the ductal arterial ligament (*). and mitral valve anomalies in 25% of cases. the most pathognomonic of which are the Aschoff bodies (Fig 1-12). Aschoff body composed of macrophages and lymphocytes is found in the interstitial plane of the myocardium. 66417308 : ¸Ÿ±U 24 ¥°Q . I-12. At higher magnification one can see that the Aschoff body is composed of macrophages. or supravalvular. hemodynamic stress.

66417308 : ¸Ÿ±U 24 ¥°Q . Histologically the vegetations are composed of fibrin covering the valve. thickening of the cusps. Within 6 to 8 weeks the valves contain relatively thick-walled blood vessels. B. Resolution of this inflammation results in scarring. Clinically chronic valvular changes present as stenosis or insufficiency. which may persist indefinitely. Histologically the lesion is composed of fibrin covering a valve that is infiltrated with mononuclear inflammatory cells. The deformed valves tend to calcify and become infected. which are normally avascular. Mitral valves (Fig. The valves. Acute rheumatic endocarditis. 1-15) are involved more often than the valves of the right heart.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . which are focally infiltrated with lymphocytes. Acute endocarditis presents with small translucent vegetations. Deposits of fibrin and underlying inflammation may extend onto the left atrial parietal endocardium and less often onto the chordae tendineae or papillary muscles. B C A Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 1-13). A. Higher magnification of the vegetation and the inflamed value. 1-14) and aortic valves (Fig. C. thickened. and obliteration of valve commisures. 1-13. The chordae tendineae become shortened. and fused to each other.Rheumatic valvulitis presents in the form of verrucous endocarditis characterized by the formation of tiny translucent nodules on the atrial side of atrioventricular valves and on the ventricular surfaces of semilunar valves (Fig. become vascularized soon after the onset of inflammation.

The valve is covered with large. Infective Endocarditis Inflammation may involve the valves or mural endocardium. infective endocarditis is classified as either valvular or mural. friable vegetations and are composed of fibrin. Valvular infection is more common and clinically more important. It most often is caused by gram-positive bacteria such as Streptococcus pneumoniae and Staphylococcus aureus. The infected valves are covered with luscious. I-17. and inflammatory cells (Figs. Stenotic orifice seen from the left atrium. A. Fig. 1-14. Chronic rheumatic endocarditis of aortic valve.II A B Fig. Fig. I-15. 1-16.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Acute bacterial endocarditis. Chronic rheumatic endocarditis of mitral valve. View from the opened left heart. irregular vegetations (arrow). Acute bacterial endocarditis. 1-16 and 1-17). Accordingly.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . bacterial colonies. The valves are deformed fused and the orifice is stenosed. B. friable. 66417308 : ¸Ÿ±U 24 ¥°Q . The vegetation consists of fibrin and bacteria. Fig.

1-21). Infective endocarditis of immunosuppressed persons may be caused by uncommon bacteria and even fungi (Fig. Potential Complications of Infective Endocarditis Direct Damage to Heart Perforation of valve cusps and/or leaflet causing insufficiency Valve ring or myocardial abscess and fistula formation Suppurative and obliterative pericarditis Dehiscence of prosthetic valves. intravenous drug abuse. 1-21. Acute bacterial endocarditis superimposed on chronic rheumatic endocarditis. 1-18 and 1-19). and insertion of prosthetic valves also are associated with an increased risk for infective endocarditis. Sepsis. Acute bacterial endocarditis superimposed on chronic healing endocarditis. conduits.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .Infective endocarditis affects valves of the left heart more often than those of the right heart. which may cause extensive local destructive lesions (Fig. other viscera Ischemia in distribution of ileofemoral or other major arteries Circulating Immune Complexes Focal or diffuse glomerulonephritis Fig. 1-20. 1-19. Fungal hyphae can be demonstrated in the vegetation by Gomori methenamine-silver stain. spleen. Fig. Factors that predispose to infection include congenitally deformed valves and preexisting valvular lesions such as those caused by rheumatic fever (Figs. kidneys. 66417308 : ¸Ÿ±U 24 ¥°Q . 1-20). myocardium. Fungal endocarditis. The arrow points to a microabscess formed in the central part of the vegetation. Infective endocarditis with extensive destruction of the valve. Fig. 1-18. Valvular deformities and thickened chordae tendineae are evidence of the chronic process.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Other complications of infective endocarditis are listed in Table 1-1. Fig. and patch components Late valve fibrosis causing stenosis (accompanied by insufficiency) Septic Embolization with Abscess Formation Cerebral abscess Osteomyelitis Mycotic aneurysm Lung abscess Sepsis Infectious Arteritis with Thrombotic Occlusion Infarcts—brain. cardiovascular surgery.

Floppy mitral valve. chordae lengthen. 66417308 : ¸Ÿ±U 24 ¥°Q . In floppy valve syndrome the valve cusps expand. 1-25). Carcinoid heart syndrome. typically occurs in terminally ill. Fig. Degenerative calcific aortic stenosis represents an agerelated lesion that typically is found in the elderly. or atherosclerosis. The valves are deformed by nodular calcifications within the cusps (Fig. 1-22). Small vegetations typically are found along the line of closure on otherwise normal valves (Fig. Chordae tendineae are variably thickened and focally fused. The greatest redundancy and gelatinous change are noted in the posterior leaflet (to the right). The valve appears irregularly thickened and deformed. elastin-free connective tissue (Fig. It is characterized by fibrotic changes in the endocardium of the right ventricle. Fig." The right upper portion of the valve is relatively spared and appears translucent. 1-25. 1-24. which is the most common cause of this disease in the elderly (Fig. Greatly thickened tricuspid valve and chordae show a whitish "onlay. and one or both cusps " billow " or prolapse into the atrium during systole (Fig. Fig. 1-27). 1-22. The tricuspid and pulmonary valves have focal or diffuse plaques of glycosaminoglycan-rich. Carcinoid heart disease is a complication of intestinal carcinoids metastatic to the liver. 1-24). but there also is localized thickening along the free margin of the anterior mitral leaflet. syphilis. The left ventricle also is involved in one third of patients examined at autopsy. but the changes are mild and cause no clinically significant hemodynamic abnormalities. emaciated patients who have cancer or other chronic diseases.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .13 Other Valvular Lesions Nonbacterial thrombotic endocarditis. Histologically the vegetations are composed of fibrin attached to a normal valve. The line of closure is covered with fine uniform vegetations. Nonbacterial thrombotic endocarditis. Histologically such vegetations resemble bland fibrin thrombi (Fig. 1-26).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Floppy mitral valves are common but they rarely cause clinically significant changes unless they are associated with myxomatous transformation. which is also known as marantic endocarditis. Aortic insufficiency may result from the dilatation of the aortic valve annulus caused by a variety of diseases such as rheumatic fever. 1-23. Nonbacterial thrombotic endocarditis. 1-23). Fig.

or (3) idiopathic (Table 1-2).A B Fig. eosinophilic.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Causes of Myocarditis MYOCARDIAL DISEASES The most important myocardial diseases are myocarditis and cardiomyopathies.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Myocarditis Inflammations of the myocardium are classified as (1) infectious. or giant cell (Fig. Histologically it is classified descriptively according to the predominant cell type infiltrating the myocardium or the pattern of reaction. Pathogens rarely 66417308 : ¸Ÿ±U 24 ¥°Q . most prominently on the posterior side. stenotic valve. fibrocalcific. Aortic insufficiency due to dilatation of the aortic root. B. Close-up view. A B Fig. 1-28). B. (2) immune-mediated. focal or diffuse. The calcific nodules are most prominent inside the cusps (arrow). A. such as lymphocytic. Focal endocardial thickening below the aortic valve is indicative of regurgitation. The commissures are focally fused. Similar case with more prominent calcification. most consistent with healed aortitis. 1-27. Degenerative calcific aortic stenosis. Superior view of tricuspid. I -26. Pathologically myocarditis is classified as acute or chronic. The aorta has a thickened wall and its luminal surface is covered with fibrous plaques and focal ulcerative calcific changes.

Some of the giant cells in the same heart were derived from muscle cells. Giant cell myocarditis with multinucleated giant cells positive for muscle-specific a-actin monoclonal antibody staining. 1-28. A. The "punched-out" lesions of myocyte necrosis are best defined by lack of positive staining (arrows) with monoclonal antibody to muscle-specific a-actin. D. Active myocarditis of the predominantly lymphocytic type. The cytolysis is associated with an infiltrate of activated immune cells in a child with suspected viral myocarditis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . F. B.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Ventricular myocardium with active myocarditis and myocytolysis (arrows). C. Ventricular myocardium with myocarditis and clusters of cells immunoreactively identified as macrophages. Microscopic appearances of myocarditis. E. Ventricular myocardium with influenza A-related myocarditis in a young child. 66417308 : ¸Ÿ±U 24 ¥°Q .15 A B C D E F Fig. Giant cell myocarditis with multinucleated giant cell and neighboring macrophages stained brown with an antibody CD68. Although this multinucleated cell is immunonegative. whereas others expressed macrophage markers. Isolated myocytes are surrounded by the infiltrate in a background of what appears to be edema. others in this case were immunopositive with the same antibody.

Focal. 3b—diffuse moderate or severe. moderate (grade 2). in which the myocytes typically contain Trypanosoma cruzi (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Cardiac transplant rejection. Transplant rejection is accompanied by an immunemediated myocarditis (Fig. Fig. Idiopathic myocarditis is the most common type of myocardial inflammation identified at autopsy. Fig. 1-29. Myocardial abscess. or granulomatous inflammation (Fig. 1-31).if ever are identified by routine histologic examination of the myocardium with a few exceptions such as Chagas disease. which hematogenously reaches the myocardium (Fig. 2—focal moderate. or 4—severe (Figs. 1-32 and 1-33). 1-29). Necrosis of cardiac myocytes is more prominent than the inflammatory infiltrate. It may present histologically as lymphocytic. Myocardial cell necrosis with myophagocytosis in a patient with diphtherial pharyngitis is by inference classified as diphtherial. Diphtherial myocarditis. 1-30. 1-32). Myocytes contain Trypanosoma cruzi. Chagas disease. 66417308 : ¸Ÿ±U 24 ¥°Q . The type of rejection may be classified by endocardial biopsy as: la—focal mild. 1-32. 1-30).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 3a—multifocal moderate. the cardiac lesions actually are caused by a toxin released by C. eosinophilic. lb— diffuse mild. Fig. Myocardial abscess caused by sepsis rarely contains identifiable bacteria (Fig. Fig. Myocardium contains aggregates of neutrophils. 1-34). giant cell. 1-31. diphtheriae.

nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 1-35.I7 Fig. Multifocal. Both the primary and the secondary categories have three possible functional states: (1) dilated. There is replacement fibrosis in the myocardium. Dilated cardiomyopathy. and many other diseases. 1-33. Cardiomyopathies are divided into two groups: primary (idiopathic. Thrombi tend to form in the dilated ventricle and there typically is functional mitral insufficiency. moderate (grade 3a). p. Cardiac transplant rejection. The interstitium contains infiltrates of lymphocyte and eosinophils. The dilated heart shows foci of scarring ( "replacement fibrosis" ) (Fig. 1-36). chronic anemia. and (3) restrictive. Dilated cardiomyopathy. in which it is accompanied by hypertrophy of all four cardiac chambers (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . 1-34. Fig. constrictive (Diagram 1-4. There is a mural thrombus in the left ventricle. due to unknown causes) and secondary (due to known causes). (2) hypertrophic. congestive. Cardiomyopathy Cardiomyopathies are diseases characterized by cardiac dysfunction in which the main abnormality lies in the working myocardium. 1-35). Typically it is found in the end stages of ischemic heart disease and in hypertensive heart disease. 18). Fig. Eosinophilic myocarditis. Ventricles and atria are dilated. Fig. alcoholic cardiomyopathy. Dilated cardiomyopathy (systolic disorder) is found in patients with hemochromatosis. 1-36. hyperdynamic.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . sarcoidosis.

Cor pulmonale causes right ventricular hypertrophy. myocardium (e. The most common cause of left ventricular hypertrophy is arterial hypertension... often accompanied by interstitial fibrosis. endomyocardial fibrosis). and in infants of diabetic mothers (Figs.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . so the ventricles can be of normal size (as in pericarditis) or markedly thickened (as in amyloidosis) (Figs.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. Specific and less specific causes of dilated. congenital cardiomyopathies such as those related to mutations of gene for beta-myosin heavy chain.. Congenital hypertrophic cardiomyopathy with asymmetric septa) hypertrophy. 1-37. and restrictive cardiomyopathy. cardiac amyloidosis). 66417308 : ¸Ÿ±U 24 ¥°Q . In all these diseases there is marked hypertrophy of the cardiac myocytes.g. glycogen storage disease. Restrictive cardiomyopathy (diastolic and systolic disorder) may be caused by pathologic processes involving the endocardium (e. constrictive pericarditis). 1-37 and 1-38). Hypertrophic cardiomyopathy (diastolic disorder) is found in patients with Friedreich ataxia. These diseases typically impede the diastolic filling of the cardiac chambers and reduce systolic ejection of blood. or pericardium (e. The pathologic changes depend on the process that has caused the disturbance. hypertrophic. 1-39 and 1-40).g.g.Diagram 1-4.

1-40.I9 Fig. Histologically the cardiac myocytes are hypertrophied and show branching and disarray. The ventricular myocardium appears thickened but pale. Fig. Amyloidosis. 66417308 : ¸Ÿ±U 24 ¥°Q . A B Fig. There also is considerable interstitial fibrosis. 1-38.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Amyloidosis of the heart. Electron microscopy shows pericellular amyloid fibers. A.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 1-39. The cardiac myocytes are surrounded by hyalinized material. B. Congenital hypertrophic cardiomyopathy.

so the artery appeared normal on angiography. Eccentric plaque causing narrowing of the coronary artery. Some lesions are composed only of fibrous tissue and are calcified. they have an atheromatous. Concentric plaque causing narrowing of the coronary artery. 1-46). estimated to be over 70 percent. 1-41. Rupture of atheroma also may cause microemboli and fibrin thrombi in the distal small branches of the coronary artery system (Fig. which was stained by Sudan red. Coronary Atherosclerosis Atherosclerotic plaques of coronary arteries have the same morphologic features as plaques in other sites. or chronic ischemic heart disease.CORONARY ARTERY DISEASES Atherosclerosis of coronary arteries is clinically the most important heart disease. which clinically presents as angina pectoris.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Coronary thrombi may be lysed through the action of fibrinolytic enzymes.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . estimated to be over 95 percent. 1-43). Narrowing or occlusion of coronary arteries typically causes myocardial ischemia. 1-42. The presence of multiple vascular channels inside a coronary artery indicates recanalization (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . myocardial infarction. Soft lipid-rich atherosclerotic plaques tend to rupture and provoke thrombus formation in the lumen of the coronary (Fig. had a core of lipid separated from the lumen by a white fibrous cap. Plaques may be eccentric (Fig. 1-45). Fig. 1-42) or may concentrically narrow the lumen of the coronaries (Fig. Consequences and potential outcomes of coronary atherosclerotic plaque rupture are outlined in Diagram 1-5. 1-44). Fig. The plaque projects outward rather than inward. cholesterol-rich core surrounded by a fibrous cap (Fig. Coronary artery with a fibrolipid plaque. 1-41). Fig. that is. 1-43. In cross section the plaque.

·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 66417308 : ¸Ÿ±U 24 ¥°Q . Potential outcomes of coronary plaque rupture.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Microemboli in small intramyocardial vessels. Diagram 1-5. collagen is blue and the thrombus is red. Fig. This small artery is occluded by a mass composed of platelets (blue). The lumen of the coronary artery has been subdivided into several channels by fibrous strands. Coronary artery recanalization. In this picro-Mallory trichome—stained slide. Fig.21 Fig. which provoked the intraluminal thrombosis. 1-45. and cholesterol (clefts). There is a small tissue in the plaque. 1-44. red cells (yellow). 1-46. Coronary thrombus.

Myocardial Infarction Myocardial infarction represents the major consequence of coronary artery occlusion. which form three to six weeks thereafter. Myocardial infarcts can be localized or diffuse. On gross examination the infarcted myocardium initially is redder than the surviving adjacent tissue at 12 hours after occlusion of the coronary and then becomes paler. occurs during the first 10 days and typically is accompanied by hematopericardium (Figs. lose their cross-striations. Fig. transmural or subendocardial (Figs. 1-52). Macrophages appear three to five days after the onset of ischemia and a fully established granulation tissue develops over a few days. 1-47). Transmural myocardial infarct. 1-49. The subendocardial pale areas correspond to the infarct. The myocardial cells become hypereosinophilic. 1-47 to 1-49). The pattern of infarction is best appreciated at autopsy by staining slices of cross-sectioned heart enzyme histochemically to demonstrate dehydrogenase activity. Contraction band necrosis in which the cytoplasm of myocardial cells contains densely eosinophilic bands also may be seen but it is more typical of reperfusion injury (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The transverse section of ventricles was stained to demonstrate succinic dehydrogenase activity. External cardiac rupture. By clinical history this infarct was six days old. Myocardial infarct. which extends across the areas supplied by at least three coronary arteries. Complications of Myocardial Infarction The outcome of myocardial infarction depends on many variables and includes a spectrum of clinical pictures from sudden death to complete recovery. Rupture of the septum can cause an acute left-to-right shunt and the rupture of papillary muscle Fig. it frequently is fatal. The infarcted area is invaded by neutrophils two to three days after the coronary occlusion (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . 1-51). 1-48. 1-47. Infarcted areas appear pale 12 hours after the onset of necrosis due to loss of enzyme activity in necrotic cells (Figs. Fig. 1-53 and 1-54). The yellow necrotic area is surrounded by a hemorrhagic red rim. and show coalescence of myofibrils (Fig. Histologic changes indicative of myocardial infarction appear approximately 6 to 12 hours after occlusion but the definite signs of necrosis can be identified only after 24 hours. The pale areas involving the anterior and septal wall of the left ventricle represent the infarct caused by occlusion of the anterior branch of the left coronary artery. Granulation tissue gives rise to fibrotic scars. by day 3 it is yellow (Fig. Subendocardial infarct. a complication of transmural infarcts.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 1-50). The tissue was stained to demonstrate succinic dehydrogenase activity. Normal myocardium is blue. 1-48 and 1-49).

Contraction band necrosis. Fig. 1-53.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Pericardium is filled with blood as a complication of cardiac rupture. The cytoplasm of myocytes contains deeply eosinophilic bands. Adjacent surviving cells appear pale and vacuolated. Rupture of a transmural infarct. In this three-day-old infarct the necrotic myocardial cells are surrounded by neutrophils. 1-50. Myocardial infarct. Myocardial infarct 24 hours after occlusion of the coronary artery. Fig. 1-52. Hematopericardium.23 Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . The necrotic myocytes have deeply eosinophilic amorphous cytoplasm. 1-54. I-5I.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. Fig.

(Courtesy of Dr. Papillary muscle rupture. Rupture of the interventricular septum. Ventricular aneurysms form at the site of large scars replacing infarcted myocardium of the left ventricle (Fig. Mural thrombus overlying a massive myocardial infarct. Lausanne. 1-55.may cause acute mitral insufficiency (Figs.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Ventricular aneurysm. Fig. 1-56. 1-55 and 1-56). The bulging aneurysm has a thin fibrotic wall. Fig. 1-58. 66417308 : ¸Ÿ±U 24 ¥°Q . 1-57.1-57). Switzerland. 1-58).) Fig. Fig. Fred Bosman. Mural thrombi form over the infarcted areas (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Hydropericardium is a common complication of congestive heart failure and generalized edema. There is granulation tissue under the layer of fibrin. as well as by adverse external influences such as -y-radiation. (2) hematopericardium. 66417308 : ¸Ÿ±U 24 ¥°Q . (3) fibrinohemorrhagic or fibrinopurulent pericarditis. i mmune-mediated.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and metabolic diseases. 1-60. The pericardium often is involved. Hematopericardium is a complication of heart rupture. Pericardial diseases present in several pathologic forms: (1) serous effusion. Fibrinous pericarditis. The surface of the epicardium is covered with fibrin. The surface of the heart is covered with a layer of fibrin. Pericarditis also is a common complication of myocardial infarction.25 PERICARDIAL DISEASES The pericardium may be affected by a variety of infectious. which can be accompanied by calcifications or adhesive mediastinitis (Figs. Fig. together with myocardium in myocarditis of viral origin or in any form of pancarditis such as rheumatic fever. or (4) constrictive fibrosing pericarditis. 1-59 to 1-64). 1-59. Causes of Pericarditis TYPE Infectious Viral Pyogenic Tuberculous Fungal I mmune-mediated Rheumatic fever Sarcoidosis Systemic lupus erythematosus Dressler syndrome Idiopathic Irradiation Surgery Metabolic Uremic CAUSE Coxsackievirus B Staphylococcus aureus Mycobacterium tuberculosis Histoplasma capsulatum — — — Myocardial infarction Radiotherapy Open heart surgery Chronic renal failure Fig. Fibrinous pericarditis. all of which can cause pericarditis and pericardial fibrosis or both (Table 1-3).

The heart is encased in a thick layer of white fibrous tissue. Constrictive pericarditis. 1-6 I. Fibrinohemorrhagic pericarditis. 1-62. Fig. 1-64.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and multinucleated giant cells. 1-63. Tuberculous pericarditis. The inflammatory infiltrate is composed of macrophages.26 Fig. lymphocytes. Fig. The layer on the surface of the epicardium consists of fibrin and granulation tissue. Fibrinohemorrhagic pericarditis. Fig. The heart is covered with blood-tinged fibrin. 66417308 : ¸Ÿ±U 24 ¥°Q .

The tumor may occlude the mitral orifice as a "ball valve. within the cardiac chambers. The most common tumor is myxoma (Fig. A. 1-67). 1-65. or invading the myocardium (Fig. Less often they occur in the right atrium or attached to the valves. A B C D Fig. Metastases to the heart are more common than primary tumors. Rhabdomyomas are cardiac tumors of infancy and childhood (Fig. located in the left atrium. The external surface is smooth and the tumor appears lobulated and myxomatous.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ ." B. Typically myxomas are benign tumors. The tumor is composed of elongated cells surround by myxomatous matrix that stains pink. 1-65). They may be found on the epicardial surface. There also are thin-walled blood vessels. Primary tumors of the pericardium are histologically classified as benign or malignant mesotheliomas or hemangiosarcomas (Fig. High-power view of stellate and elongated (lepidic) cells and hemosiderin laden macrophages.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .27 CARDIAC TUMORS Primary tumors of the heart are rare. D. Cardiac myxoma in the left atrium. 66417308 : ¸Ÿ±U 24 ¥°Q . C. 1-66). 1-68).

B. Fig. Fig. The tumor presents as a myocardial mass. The tumor is composed of glycogen-rich cells that have clear cytoplasm.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 1-66. Hemangiosarcoma of the pericardium.A B Fig. A.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Metastatic melanoma of the epicardium. 1-67. 1-68. Rhabdomyoma. 66417308 : ¸Ÿ±U 24 ¥°Q . This hemorrhagic tumor was found encasing the heart.

nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The pathology of cardiovascular prostheses. Hutchins GM: The changed spectrum of purulent pericarditis. Silver MD: Cardiac pathology. Edwards WD et al: Surgical pathology of the pulmonary valve. Mod Pathol 4:70-74. Mayo Clin Prot 64:1352-1360. 1997. II. Davies MJ: Coronary artery remodeling and the assessment of stenosis by pathologists. A look at the last five years. Olson LJ. An 86 year autopsy experience in 200 patients. Curr Opin Cardiol 12:146-152. 1993. 1977. Pardo-Mindan FJ. 1997. Hum Pathol 5:127-38. Am J Clin Pathol 100:671-680. Virmani R: Cardiac rhabdomyoma. 1987. 1993. Winters GL: The challenge of endomyocardial biopsy interpretation in assessing allograft rejection. Virmani R: Primary sarcomas of the heart.485 consecutive autopsies. 1991. Chest 81:166-169. 1982. Burke AP. Bulkley BH. Semin Diagn Pathol 9:238-48. Contreras-Mejuto F. Chan AC: Tumors of the heart. 1974. 1989. Edwards JE: Clinical and pathologic features of metastatic neoplasms of the pericardium. Aretz HT: Myocarditis. Virmani R: Cardiac myxoma. Maron BJ: Hypertrophic cardiomyopathies. Dickens P. A 20-year experience with a review of 12. Cancer 69:387-395. 1999. 1998.1992.29 Further Reading Adenle AD. Histopathology 34:93-98. de Alava E: Pathology of heart transplant through endomyocardial biopsy.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Burke AP. Altrichter PM. Arch Pathol Lab Med 117:1027-31. Am J Med 63:666-673. 1992. Lazano MD. Davies MJ: Review: the investigation of sudden cardiac death. Cowan D. Histopathology 33:497-500. Lam KY. A clinicopathologic study. Lancet 350:127-133. Hum Pathol 18:619-624. 66417308 : ¸Ÿ±U 24 ¥°Q . A study of 116 cases spanning 15 years. A clinicopathologic study. Burke AP. The Dallas criteria. Klacsmann PG.

66417308 : ¸Ÿ±U 24 ¥°Q .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

and after radiotherapy (Fig. in arterioles it causes hyaline arteriolosclerosis. 2-I. 2-6).g. progressive systemic sclerosis (scleroderma). 66417308 : ¸Ÿ±U 24 ¥°Q . Arterioles have narrow lumen due to layers of fibrous tissue. Hypertensive arteriosclerosis may be divided clinically and to some extent pathologically into chronic (benign) and accelerated (malignant) types. Hyperplastic arteriolosclerosis is characterized by narrowing of the lumen of arterioles due to the concentric proliferation of smooth muscle cells in the vessel wall (Fig. A. and fibroblasts (Fig. Included under this term are four pathologic entities: (1) arteriosclerosis. It often is prominent in the spleen.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .. Hyaline arteriolosclerosis. It has little or no clinical significance. A A B B Fig. 2-4).ARTERIOSCLEROSIS Arteriosclerosis is an inclusive generic term that is used to describe thickening and hardening of arteries. Malignant hypertension is characterized by hyperplastic arteriolar changes that often are accompanied by fibrinoid necrosis of the vessel wall (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . or thickening of the wall of arterioles. elastic tissue. Splenic arterioles in an elderly nondiabetic man. Arteriolosclerosis. 2-2). 2-1). (2) hypertensive arteriosclerosis. It typically is found in malignant hypertension. A. Chronic (benign) hypertension affects all arteries and arterioles. B. (3) Monckeberg medial calcific sclerosis. occurs in two forms: hyaline arteriolosclerosis (arteriolar hyalinosis) and hyperplastic (proliferative) arteriosclerosis. 2-2. B. In hyaline arteriolosclerosis the wall of arterioles appears thickened by homogeneously glassy pink material ( " hyaline" ) (Fig. smooth muscle cells. The lumen of the arteriole is narrowed due to concentric proliferation of smooth muscle cells in the vessel wall ("onionskin lesion"). and (4) atherosclerosis. Fig. 2-3). in muscular arteries it causes thickening of the media due to increased amounts of collagen. Hyperplastic arteriolosclerosis. 2-5). Monckeberg medial calcific sclerosis is an age-related degenerative process in which the media of large and mediumsized muscular arteries undergoes calcification (Fig. Thickened arterioles in kidney of a diabetic man appear homogeneously pink. In the large elastic arteries it causes changes indistinguishable from those of atherosclerosis. postmenopausal ovaries) and aging. chronic transplant rejection. It may accompany hypertension or diabetes and is a common feature of involutional atrophy (e.

2-S. 2-4. 2-6. 2-3. B.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The arterial wall is thickened and contains increased amounts of collagen and elastic tissue. Systemic sclerosis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fibrinoid necrosis. The vessels show hyperplastic changes and narrowing of the lumen. Fig. A B Fig. A. Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . The wall of the arteriole is infiltrated with fibrin and appears magenta red. Monckeberg medial calcific sclerosis. Immunofluorescence microscopy shows deposits of fibrin in the vessel wall. Media of this elastic artery shows a discrete area of calcification. Hypertensive change in muscular arteries.33 Fig.

Severe atherosclerosis of aorta. Ulcerated atheromas are seen in the aorta above the renal arteries. Fig. Atherosclerosis. 2-9. Atherosclerotic aneurysm.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Atheroma. 2-I I. Fig. Fig. Fatty streaks in the aorta of an adolescent boy. 2-8.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . It contains yellow. The intima contains fat-laden foam cells that stain with oil red O. 2-12. 2-7. whereas the lower aneurysm contains thrombi. 66417308 : ¸Ÿ±U 24 ¥°Q . porridge-like material. Fatty streak. Fig.Fig. Fig. Atheroma consists of amorphous cellular debris and cholesterol crystals walled off by fibrous tissue. 2-10.

predisposes to the formation of dissecting aneurysms of the aorta (Fig. Fig. Fig. and 2-11). Atherosclerotic aneurysms most often are located in the abdominal aorta. The earliest changes. 2-16. They typically occur in the thoracic aorta (Fig. Syphilitic aneurysms are a consequence of infection with Treponema pallidum. 2-I5. Atheromatous plaques. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 2-7 and 2-8). 2-14.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Atherosclerosis of the splenic artery leads to formation of cirsoid aneurysms (Fig. 2-13). 2-10. The calcified blood vessels appear serpentine. The blood has filled the space formed by the forcible separation of intima and media of the aorta. An aneurysm is a dilatation of the aorta or any other major artery. especially if it is combined with hypertension. These changes lead to diffuse intimal thickening followed by eccentric intimal thickening and ultimately to formation of fibrous plaques. 2-17). Dissecting aneurysm of the thoracic aorta. Atherosclerosis. 2-14). Berry aneurysm of the circle of Willis (arrow). the typical lesions of atherosclerosis. Layers of the aortic wall are loose and have been separated by blood. consist of an irreversibly altered softened central area filled with cholesterol crystals and cell debris ( "atheroma") surrounded by collagenous fibrous tissue (Figs. which are considered to be reversible. 2-12). Berry aneurysms are related to a defect in the muscle layer of cerebral arteries (Fig. are fatty dots and fatty streaks of the intima (Figs. 2-9. Cirsoid aneurysm of splenic artery. Dissecting aneurysm of the aorta. 66417308 : ¸Ÿ±U 24 ¥°Q . Weakening of the arterial wall may lead to aneurysm formation. Fig. 2-15).35 ANEURYSMS Atherosclerosis is a multifactorial disease involving primarily the aorta and its major branches. 2-13. Hypertension combined with cystic medial necrosis may lead to the formation of dissecting aneurysms even in the absence of atherosclerosis (Fig. often complicated by thrombosis (Fig. 2-16).

weakening of vessel wall. Injury of these small nutrient vessels of the aorta results in scarring of media. postcapillary venules. Intima has a "tree-bark" appearance. 2-22).e. A B VASCULITIS Vasculitis. through extension of infection from the perivascular tissue) or from inside (i. B. A. or inflammation of blood vessels. Aortic lesions typical of tertiary syphilis are caused by a tendency of Treponema pallidum to cause inflammation of vasa vasorum of the aorta (Fig. The aortic arch is dilated. and aneurysm formation (see Fig. or fungi during sepsis or by means of infected thromboemboli is a common cause of infectious vasculitis. Rickettsia have a predilection for the endothelial cells of capillaries.. 2-17.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Viruses are considered to cause granulomatous vasculitis of the central nervous system (Fig 2-19). arterioles. Hematogenous dissemination of viruses. Granulomatous giant cell vasculitis of cerebral arteries. bacteria. 66417308 : ¸Ÿ±U 24 ¥°Q . This patient had a herpes zoster virus infection. 2-20 and 2-21). Fungal vasculitis. Infection-induced vasculitis is an inflammation caused by invasion of the vessel wall by pathogens. Fungal meningitis can spread to the cerebral vessels (Fig. Histoplasma capsulatum has invaded the meningeal arteries. Fig.Fig. Fig. 2-18. 2-19.. may be caused by infections or may be immune mediated (Table 2-1). Pathogens can gain entry into the vessel wall from outside (i. 2-18). 2-17). Syphilitic aneurysm. Fungal vasculitis is a common complication of pneumonia caused by Aspergillus or Rhizopus in which these fungi invade the pulmonary arteries and veins from outside.e. and to a lesser extent small arteries (Figs. from the blood).

37 Types of Vasculitis Categorized on the Basis of Proposed Pathogenic Mechanisms Direct Infection of Vessels Bacterial vasculitis (such as neisserial) Mycobacterial vasculitis (such as tuberculous) Spirochetal vasculitis (such as syphilitic) Rickettsia) vasculitis (such as Rocky Mountain spotted fever) Fungal vasculitis (such as aspergillosis) Viral vasculitis (such as herpes zoster) Behcet disease Some drug-induced vasculitides (e.g. 2-21. Rocky Mountain spotted fever. Syphilitic aortitis.. B. Immunofluorescence microscopy performed on this skin biopsy specimen demonstrates dotlike Rickettsia ricketsii in the wall of small dermal vessels. Treponema . Fig. 2-22.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº pallidum infection caused infiltrate around vasa vasorum composed of lymphocytes and plasma cells. Infection with Rickettsia ricketsii causes segmental necrosis. 2-20. A. sulfonamide-induced vasculitis) Direct antibody attack-mediated vasculitis Goodpasture syndrome (anti-collagen IV) Kawasaki disease (possibly mediated by antiendothelial antibodies) Antineutrophil cytoplasmic autoantibody-mediated vasculitis Wegener granulomatosis Microscopic polyangiitis (microscopic polyarteritis) Churg-Strauss syndrome Some drug-induced vasculitides (such as thiouracil-induced vasculitis) Cell-mediated vasculitis Allograft cellular vascular rejection Unknown Giant cell (temporal arteritis) Takayasu arteritis Polyarteritis nodosa Behcet disease I mmunologic Injury Immune complex-mediated vasculitis Henoch-Schonlein purpura Cryoglobulinemic vasculitis Lupus vasculitis Rheumatoid vasculitis Serum sickness vasculitis Infection-induced immune-complex vasculitis Viral (such as hepatitis B and C) Bacterial (such as group A streptococci) Paraneoplastic vasculitis Fig. inflammation. and thrombosis in small blood vessels. Rocky Mountain spotted fever. A B 66417308 : ¸Ÿ±U 24 ¥°Q . The media of the aorta shows focal loss of elastic fibers and scarring caused by ischemia. Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

Diagram 2-I.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 2-23. (2) medium-sized vessel vasculitis. There is pronounced thickening and immense prominence of all coronary arteries due to a combination of ectasia and intimal thickening. The infiltrate typically contains multinucleated giant cells. 2-24. Vasculitis clinical syndromes. 2-23).Immune-mediated Vasculitis Vasculitis may be caused by antibody-mediated and cellmediated mechanisms elicited by a variety of antigens. Takayasu arteritis. 66417308 : ¸Ÿ±U 24 ¥°Q . Takayasu arteritis involves the aorta and its major branches. Right lateral view of the heart of an infant who died of Kawasaki disease. (Modified from Jennette JC et al: Arthritis Rheum 37:187. The infiltrate contains multinucleated giant cells. Kawasaki disease. causing necrosis and disruption of the media (Fig. For practical reasons it is best to classify vasculitides in three groups according to the type of blood vessel involved: (1) large vessel vasculitis.) Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. as well as adventitial fibrosis. Destruction of the media of the aorta is a consequence of a granulomatous inflammation. and (3) small vessel vasculitis (Diagram 2-1). 1994. Histologically it presents as a granulomatous inflammation. The causative antigens cannot be identified in many cases and the exact pathogenesis of many lesions is only partially understood.

1995. causing segmental mural necrosis and acute inflammation. Chandler AB. capillaries. Dermal venules show signs of leukocytoclastic vasculitis. Circulation 92:1355-1374. Polyarteritis nodosa. 1994. Such lesions predispose to thrombosis. Destruction of the vessel wall often leads to formation of microaneurysms (Fig. Henoch-Schonlein purpura ( HSP) and drug-induced vasculitis are examples of small vessel vasculitis. 2-25). 1997. 2-28. 2-26). Ross R: Rous-Whipple Award Lecture. 2-27). vascular ectasia. American Heart Association. Fig. Ledford DK: Immunologic aspects of vasculitis and cardiovascular disease. Falk RJ. Kawasaki disease often involves coronary arteries. Further Reading Jennette JC. Arthritis Rheum 37:187-201. Fig. von Segesser LK: Aortic dissection. Small dermal vessels are infiltrated with IgA as demonstrated by immunofluorescence microscopy in this slide stained with antibodies to IgA. and arterioles (Fig. JAMA 278:1962-1971. A small subcutaneous artery shows focal fibrinoid necrosis and transmural inflammation extending into the perivascular tissue. Lancet 349:1461-1464.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 1993. Polyarteritis nodosa is a necrotizing inflammation of medium-sized or small arteries (Fig. 2-24). Henoch-Schinlein purpura. Dinsmore RE et al: A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. 2-28). 2-27. Am J Pathol 143:987-1002. 1995. A report of the Committee on Vascular Lesions of the Council on Atherosclerosis. Pretre R. 1983.39 Fig. Klima T. Stary HC. A defense mechanism gone awry. Atherosclerosis. Small vessel vasculitis. Spjut HJ. The pancreatic artery forms an aneurysm that is filled with a thrombus. 2-25. 1994.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and aneurysm formation (Fig. Parums DV: The arteritides. Andrassy K et al: Nomenclature of systemic vasculitides: proposal of an international consensus conference. Coelho A et al: The morphology of ascending aortic aneurysms. Polyarteritis nodosa. typically involving postcapillary venules. Hum Pathol 14:810-817. 2-26. 1997. Lie JT: Histopathologic specificity of systemic vasculitis. Rheum Dis Clin NAm 21:883-909. In HSP this leukocytoclastic vasculitis typically is associated with a deposition of immunoglobulin A (IgA) in the wall of small vessels (Fig. Histopathology 25:1-20. 66417308 : ¸Ÿ±U 24 ¥°Q . Fig.

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sinusitis. pharyngitis. and dilated vessels (Fig. A. Fred. 3-3). Slides stained with Warthin-Starry stain show numerous intracellular coccobacilli corresponding to Klebsiella rhinoscleromatis. Chronic inflammation may result in the formation of nasal polyps. CT scan of paranasal sinus in 43-year-old man with rhinoscleroma. Rhinoscleroma. Occasionally the stroma of nasal polyps may contain atypical stromal cells with dysplastic or bizarre nuclei. C. 3-4). Texas.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . or by foreign material. Histologically nasal polyps represent edematous mucosa infiltrated with inflammatory cells. Granulation tissue is seen in the nasal cavity. Uncommon infections such as nasal infection caused byKlebsiella rhinoscleromatis (Fig. These pathologic processes can be caused by infectious agents.) B. Houston. 3-2) produce more distinct tissue changes. M.I NFLAMMATORY LESIONS Inflammation of the upper respiratory tract may present as isolated rhinitis. The pathologic findings in such conditions are banal and nondiagnostic. and by bacteria or allergies.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . which usually presents as " hay fever " or rhinorrhea ( " runny nose " ). or laryngitis. 3-1. For example. B A C D Fig. D. Myospherulosis is a form of inflammation related to packing of nasal cavities with gauze that contains petroleum jelly (Fig. Right nasal cavity and posterior wall of left maxillary sinus are involved. (Courtesy of Dr. chronic laryngitis may be seen in professional speakers or singers (Fig. Inflammation may be caused by chronic strain or irritation. and it is i mportant not to mistake them for malignancy. Such changes usually are found in polyps with ulcerated surface epithelium. 66417308 : ¸Ÿ±U 24 ¥°Q . Allergy is a common cause of rhinitis. which can be recognized in biopsy specimens. Nasal biopsy showing numerous foamy histiocytes (Mikulicz cells). especially eosinophils and plasma cells. 3-1) or Rhinosporidium seeberi (Fig. 3-5). most often by common respiratory viruses. or as a combined upper respiratory tract inflammation.

is surrounded by chronic inflammatory cells and fibrous tissue. 3-5. The central sac. 3-2. 66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 3-3. Rhinosporidiosis. 3-4. Fig. Myospherulosis.43 A B sporidium seeberi. Slovenia. (Courtesy of Dr. Fig. A. Ljubljana. As seen through the laryngoscope. The edematous stroma contains scattered bizarre cells between the dilated blood vessels. The inflamed nasal mucosa contains round sporangia of RhinoSporangium filled with spores and surrounded by multinucleated giant cells. B. Fig. V. Kambic.) Fig. containing a multinucleated foreign body giant cell and a cluster of sporelike bodies representing altered erythrocytes.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . the lesion appears as thickening of vocal cords. Chronic laryngitis. Nasal polyp.

Laryngeal papillomas are lined by nonkeratinizing squamous epithelium. Papillomas most often originate from nasal or laryngeal epithelium. They also may be located inside the wall of each organ or may cause focal thickening. There is no reliable way to histologically predict recurrence. A. 3-9). Nonepithelial tumors are less common. Schneiderian papilloma. Juvenile nasopharyngeal angiofibroma is a benign mesenchymal tumor restricted to adolescent boys and young men (Fig. Nasal papillomas. 3-6). Oak Park. These papillomas are lined by basaloid cells that occasionally show squamous differentiation. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 3-7. which may spare isolated mucin-containing respiratory cells as "microcysts " (Fig. which often contains hyaline material that should not be confused with amyloid (Fig. These lesions represent edema of connective tissue. which are also known as schneiderian papillomas.BENIGN TUMORS AND RELATED CONDITIONS Benign tumors of the upper respiratory tract are mostly of epithelial origin and present as papillomas or nodules projecting into the lumen. which occurs in 30 percent to 60 percent of surgically treated patients. The tumor involves the nasal cavity extending onto the septum and lateral wall. Sirota. IL. Proliferation of monotonous. 3-6.) A B Fig. Histologically these tumors are composed of gaping. 3-8). Exophytic and endophytic papillomas together account for 95 percent of all nasal lesions (Fig. Vocal cord nodules and solitary laryngeal polyps of adults are common nonneoplastic tumefactions related to strain and abuse of voice (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . R. and masses such as amyloidoma. bland. 3-11). Multiple papillomas are usually found in preschool children. and (3) oncocytic (cylindrical cells). (2) endophytic (inverted). (Courtesy of Dr. 66417308 : ¸Ÿ±U 24 ¥°Q . are of three histologic types: (1) exophytic (fungiform). irregular vessels surrounded by fibrous stroma (Fig. cysts. The tumor is exophytic but focally it shows features of an inverted papilloma. Schneiderian papilloma. 3-7). 3-10). These lesions typically contain human papilloma virus type 6 and 11. which cannot be distinguished with certainty without biopsy from nonneoplastic nodules inflammatory lesions. B. basaloid cells with a few clear spaces ("microcysts") representing mutinous cell remnants.

Nasopharyngeal carcinoma accounts for 85 percent of all malignant tumors of this site. It may show typical features of neuroblastoma of other sites such as fibrillary stroma. typically present as mass lesions or nonbleeding ulcers. The polypoid mass consists of edematous. Juvenile nasopharyngeal angiofibroma. Nasal tumors. 3-12). Olfactory neuroblastoma is a rare but important nasal tumor. 3-9. hyalinized stroma covered by an intact epithelium. The irregularly shaped. Ljubljana. dilated. Fig. Juvenile nasopharyngeal angiofibroma. Fig. Bilateral polypoid nodules of vocal cords. V. 3-I I.) Fig. it may present as a poorly differentiated small cell tumor (Fig. thin-walled vessels are surrounded by fibroblastic cells. 3-13).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and also paradoxically with antibodies to keratin. which may require radical surgery such as nasal amputation (Fig. Vocal cord nodule ("singer's node"). 3-8. (Courtesy of Dr. Kambic. As viewed through the nasal speculum. Three histologic subtypes are 66417308 : ¸Ÿ±U 24 ¥°Q . alternatively. 3-10.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .45 Fig. the mass filling the nasal cavity shows prominent surface vascularity. Histologically these tumors show prominent keratinizations and tend to invade the underlying tissues. MALIGNANT TUMORS Malignant tumors of the upper respiratory tract are mostly of epithelial origin and histologically represent squamous cell carcinomas. Both variants stain with antibodies to neurofila:nents and S-100 protein. Slovenia. which are usually found in elderly men.

66417308 : ¸Ÿ±U 24 ¥°Q . 3-13.A B Fig. Invasive squamous cell carcinoma of the nasal vestibule encroaching on the hyaline cartilage of the septum. WHO Histologic Classification of Nasopharyngeal Carcinoma Squamous cell carcinoma Keratinization or intercellular bridges or both Nonkeratinizing carcinoma Defined cell borders. B. A. prominent nucleoli. Squamous cell carcinoma of the nasal vestibule. The tumor is composed of small cells surrounded focally by fibrillar stroma. lymphoid stroma Fig. large polygonal cells or spindle-shaped cells.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . B. 3-14. A. Nests of tumor cells beneath the epithelium. Olfactory neuroblaStoma. Nasopharyngeal carcinoma. A B Fig. The friable exophytic and invasive tumor. The tumor is composed of polygonal cells with vesicular nuclei enclosed in a sea of lymphocytes.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . pavement like pattern Undifferentiated carcinoma Syncytial growth. 3-12.

Tumor cells are surrounded by lymphocytes. Invasive carcinomas show variable degrees of keratinization (Figs. A clinicopathologic and immunohistochemical study of 14 cases. 1999. and "Triton" tumors. 3-16. 1976.. Gale Net al: Criteria for grading in the Ljubljana classification of epithelial hyperplastic laryngeal lesions. Mills SE: Sinonasal malignant melanoma.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Cancer 70:1089-1101. 3-16 and 3-17). A clinicopathologic and immunophenotypic study of 120 cases. Laryngectomy specimen showirig recurrent carcinoma of the right vocal cord. Am J Clin Pathol 96:689-697. Franquemont DW. 1992. Heffner DK. 1996. Vertical section through a supraglottic squamous carcinoma. A clinicopathologic study of 67 cases. Such lesions are often aneuploid even though they show some degree of "surface maturation" into keratinized squamous cells. 3-14).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Devaney K. Fig. Michaels L: Benign mucosal tumors of the nose and paranasal sinuses. which occurs as a large polygonal cell tumor or as a spindleshaped cell tumor. Histopathology 34:226-233. Slavin RG: Nasal polyps and sinusitis. which accounts for the fact that these tumors previously were called lymphoepitheliomas. 1991. Lloreta-Trull J. 66417308 : ¸Ÿ±U 24 ¥°Q . Hyams VJ: Hemangiopericytoma-like intranasal tumors. Keratinizing intraepithelial dysplasia of larynx. Mod Pathol 9:658663. 1995. Troncoso Petal: Neuroendocrine tumors of the nasal cavity. Abbondanzo SL: Olfactory neuroblastoma and other round cell lesions of the sinonasal region. Vertical section through a carcinoma localized to the true vocal cord. A B Carcinoma of the larynx is a squamous cell carcinoma in 95 percent of patients. 1996. JAMA 278:1849-1854.47 Fig. Squamous cell carcinoma of the larynx. Fig. A. accounts for 60 percent to 80 percent of all tumors (Fig. Compagno J. Cancer 75:1281-1291. False cord and ventricle are free of tumor. 3-I5. Helliwell TR: "Risky" epithelium of the larynx-a practical diagnosis? Histopathology 34:262-265. 1992. Wenig BM: Non-Hodgkin's lymphoma of the sinonasal tract. An ultrastructural and morphometric study of 24 cases. 1999. Gnepp DR: Sinonasal fibrosarcomas. 3-15). A study by members of the Working Group on Epithelial Hyperplastic Laryngeal Lesions of the European Society of Pathology. A clinicopathologic study of 23 cases. The undifferentiated carcinoma. The true cord is involved. Ultrastruct Pathol 16:165-175. recognized (Table 3-1). Sem Ding Pathol 13:113-117. Further Reading Abbondanzo SL. Cardesa A. Wenig BM. It may begin as squamous cell dysplasia or carcinoma in situ (Fig. malignant schwannomas. 3-17. Mackay B. Am J Clin Pathol 66:672-683. Helquist H. 1997. B.

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abnormalities in size. producing a solitary midline cyst lined by bronchial epithelium (Figs. 4-4 and 4-5).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Tracheoesophageal fistulas. is considered to be an acquired abnormality that is caused by recurrent pulmonary inflammation and scarring (Fig. which is mentioned here for the sake of completeness and differential diagnosis. A B C D E Diagram 4-I. The most important of these anomalies are congenital cystic adenomatoid malformation and extralobar bronchopulmonary sequestration or accessory lobe (Figs. This resected cyst has a rugged internal surface. 66417308 : ¸Ÿ±U 24 ¥°Q .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . abnormal connections with other structures. Bronchogenic cyst. 4-2. causing only minor dysphagia. The most important of these conjoined anomalies is tracheoesophageal fistula ( Diagram 4-1). Bronchogenic cyst develops from an accessory fetal lung bud that becomes isolated from the rest of the tracheobronchial tree. Type C malformations account for 85 percent of all cases. Bronchial anomalies include abnormal branching patterns. So-called intralobar sequestration. and cartilage plate abnormalities. 4-I. which may be associated with abnormal or incomplete development of trachea or tracheal agenesis. 4-6). Fig. This posterior midline subpleural cyst was compressing the esophagus. Pulmonary anomalies range from minor variations in the lobar configuration to major developmental defects such as unilateral pulmonary agenesis or hypoplasia (Fig. Anomalies limited to parts of a lung may remain asymptomatic until adult life. Bronchogenic cyst. 4-1 and 4-2). Fig. 4-3). It is therefore not surprising that developmental anomalies involving one system are accompanied by abnormalities in the other.DEVELOPMENTAL ANOMALIES The respiratory system develops as a derivative of the primitive foregut. Pulmonary hypoplasia has been identified in 10 percent to 15 percent of all neonatal autopsies and in 50 percent of neonates who have other significant congenital anomalies.

.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . which is composed of abnormal bronchiolar structures. The interstitium is fibrosed and contains inflammatory cells. A B 66417308 : ¸Ÿ±U 24 ¥°Q . Histologically. 4-3. A B Fig. B. B. consists of a large cyst with several smaller cysts in the background. Intralobar sequestration. 4-4. 4-5. The wall of the cyst is lined by pseudostratified or tall columnar epithelium resembling the lining of proximal bronchioli or small bronchi. Fig. Congenital cystic adenomatoid malformation.51 Fig. The lung is composed of cystic bronchi and air spaces.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº Fig. the mass consists of bronchi and air spaces lined by cuboidal cells. 4-6. Pulmonary hypoplasia in a neonate. The mass consists of markedly dilated bronchi filled with mucus and surrounded by fibrous tissue. A. A. Congenital cystic adenomatoid malformation. This mass.

whereas the alveolar ducts are dilated and lined by fibrin-rich hyaline membranes (Fig. (2) subacute fibro - proliferative phase. and dilatation of lymphatics are common. (3) intrapartum infection with microorganisms in the birth canal. Aspiration of infected amniotic fluid by the fetus accounts for 20 percent to 40 percent of early-onset neonatal sepsis and pneumonia. Histologically pulmonary alveoli are collapsed and atelectatic. Oxygen therapy and mechanical ventilation cause additional changes that cannot be separated from those caused by the disease itself. 66417308 : ¸Ÿ±U 24 ¥°Q . Fig. 4-8. Clinically it presents as neonatal respiratory distress syndrome or hyaline membrane disease.PERINATAL LUNG DISEASES Failure of the lungs to fully expand and remain expanded is a common complication of pulmonary immaturity encountered in neonates who are born preterm. 4-7). 4-9). Severe hyaline membrane disease that is treated aggressively may result in development of chronic lung changes known as bronchopulmonary dysplasia (Fig. begins 48 to 72 hours after birth and is associated with proliferation of bronchiolar reserve cells. Neonatal respiratory distress syndrome. The atelectatic parenchyma appears dark red in contrast to the paler areas of normally aerated lung (right upper corner). A. Histologically it can be divided sequentially into three overlapping phases: (1) early reparative phase. dilatation of bronchioles proximal to atelectatic parenchyma. B. 4-8). Neonatal pneumonia typically is a complication of: (1) transplacental spread of maternal infection. or pulmonary interstitial emphysema. and (3) chronic fibroproliferative phase. Alveoli are collapsed and the alveolar ducts and respiratory bronchioli are dilated and lined by hyaline membranes. which is characterized by the presence of air in the connective tissue planes of the lungs. 4-10). Pulmonary interstitial air. i.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The lungs show patchy atelectasis (Fig. and interstitial fibrosis (Fig. is yet another complication of treatment of hyaline membrane disease with ventilatory support (Fig. ongoing peribronchial fibrosis and luminal obliteration (bronchiolitis obliterans). Resorption of hyaline membranes. 4-12). or (4) postnatal airborne infection.. Hyaline membranes are brown due to staining with meconium.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . A B Fig. Most neonatal pneumonias are acquired during labor and delivery. cleanup by macrophages. Secondary changes such as intraalveolar hemorrhage. The lungs of such neonates contain amniotic fluid with squamous and inflammatory cells (Fig. 4-11). Neonatal atelectasis.e. The process is dominated by organization of hyaline membranes by granulation tissue. 4-7. (2) intrauterine ascending amniotic fluid infection.

53 Fig. The alveoli contain nucleated squamous cells and scattered inflammatory cells. 4-9. B. Bronchopulmonary dysplasia. The lungs are consolidated except for a few cystic and slit-like spaces. A. 4-I I. 4-10. Amniotic fluid aspiration with early pneumonia. Pulmonary interstitial air. 66417308 : ¸Ÿ±U 24 ¥°Q .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The alveoli are partially obliterated by ingrown granulation tissue.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Bronchopulmonary dysplasia. Fig. 4-I2. Lungs are in part consolidated and in part cystic. A B Fig. Air-filled spaces extending the interlobular septa are seen through the pleura. Fig.

(2) topologically. Similar changes can be caused by fungi such as Histoplasma capsulatum. as intraalveolar or interstitial and characterized by a neutrophilic. in which the exudate of neutrophils and fibrin. 4-17) and suppuration resulting in abscess formation (Fig. as lobar or lobular. Pulmonary tuberculosis presents with a spectrum of changes. usually heals spontaneously by undergoing fibrosis and calcification (Fig. Lobar pneumonia in the stage of gray hepatization. 4-13.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . These infiltrates are initially composed of neutrophils and are predominantly inside the alveoli (Fig. 4-16). The alveolar walls are of normal thickness and do not contain red blood cells. bacterial. one-sided or bilateral. In lobar pneumonia entire lobes of one or both lungs are involved (Fig. imparts a gray color to the lungs. depending on the gross distribution. Histologically all tuberculous lesions contain granulomas (Fig. Fig. In severe cases the abundant fibrin cannot be removed and it stimulates the ingrowth of granulation tissue into the alveoli (organizing pneumonia) (Fig. The alveoli are filled with neutrophils. Bronchopneumonia presents in the form of more circumscribed infiltrates (Fig. can be classified (1) etiologically. consolidation of parenchyma (tuberculous pneumonia). depending on the distribution of the inflammatory cells. 4-13). or pulmonary infection. Primary tuberculosis. 4-14. in which the lungs appear red due to congestion. 4-21). lymphocytic or mixed inflammatory infiltrate. combined with reduced blood flow through the compressed capillaries. Pneumonia caused by Staphylococcus aureus may result in massive tissue breakdown (Fig. as viral. 66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . which is characterized by a solitary parenchymal nodule and hilar lymph node involvement. focal or diffuse. (2) gray hepatization. 4-15). Secondary tuberculosis results in widespread dissemination of mycobacteria and the formation of multiple small nodules (miliary tuberculosis). Fig. Without treatment. or extensive destructive lung lesions (cavitary tuberculosis) (Fig. consolidation of the lungs progresses through several phases known as: (1) red hepatization. The lungs appear only focally consolidated. Bronchopneumonia. Bacterial infection presents as lobar or lobular pneumonia (also known as bronchopneumonia). Fig. The entire lung appears consolidated and the parenchyma is bulging on cross section. and (3) resolution phase. in which the exudate is removed and the air spaces become patent again. Lobar pneumonia. 4-20). 4-19). 4-15. (3) histologically. 4-14). and so forth.PULMONARY INFECTIONS Pneumonia. The infiltrates are peribronchial and appear distinct from the surrounding parenchyma. fungal. 4-18).

D. Philadelphia. PA. Organizing pneumonia. Pulmonary tuberculosis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº Fig. The exudate is accompanied by necrosis of alveolar septa. The primary lesion appears as a sharply demarcated subpleural nodule. (Courtesy of Cathy Looby. From Woods CL. Necrotizing pneumonia. Lung abscess. Fig. 4-16. 4-19. and multinucleated giant cells arranged around a central area of caseating necrosis. The parenchyma and hilar lymph nodes contain numerous. . 4-18. Gutierrez Y: Diagnostic pathology of infectious diseases. Lea & Febiger. epithelioid macrophages. Fig. The bluish material represents bacterial colonies. Fig. 4-21. which is being organized by inflammatory cells and an ingrowth of fibroblasts. The large subpleural abscess contains brownish-yellow pus. 1993. 4-20. 4-17. Pulmonary tuberculosis.55 Fig. M. Philadelphia. The alveoli contain abundant fibrin. Secondary pulmonary tuberculosis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . often confluent tubercles. Fig..) 66417308 : ¸Ÿ±U 24 ¥°Q . The surrounding parenchyma appears consolidated and contains scattered smaller whitish-yellow abscesses. Granulomas of tuberculosis consist of lymphocytes.

A. In most instances the causative virus is not visible except in some infections that are caused by herpes simplex virus 1 ( HSV. Fig. presents histologically with an acellular intraalveolar exudate (Fig 4-22). The alveolar septa are widened. 4-24. The alveoli contain well-developed fibrin-rich hyaline membranes and some edema fluid. an opportunistic fungal infection that occurs in immunocompromised persons. 66417308 : ¸Ÿ±U 24 ¥°Q . fibrin-rich hyaline membranes. The alveoli contain edema fluid. Viral pneumonia. which is usually accompanied by a predominantly interstitial mononuclear cell infiltrate (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Alveolar cell injury caused by viruses such as influenza or adenovirus produce histologically nonspecific changes. and are accompanied by enlargement of the infected cells (Fig. Typical intranuclear inclusions are seen in desquamated pneumocytes.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . which appear enlarged. Pneumocystis carinii cysts are seen in silver-impregnated cytologic smear prepared . Viral pneumonia caused by the cytomegalovirus (CMV). Pneumocystis carinii pneumonia. Fungal cysts can be seen in slides impregnated with silver according to Gomori. 4-23. 4-24).Pneumocystis carinii pneumonia. A B Fig.1) or cytomegalovirus (CMV). 4-23). The alveoli contain proteinaceous acellular floccular material. from bronchial brushings. CMV inclusions appear as basophilic (blue) material in the nucleus and the cytoplasm. Such changes are indistinguishable from other forms of diffuse alveolar damage ( DAD). 4-22. Fig. and a few scattered mononuclear cells. Viral infections cause alveolar cell injury. B.

Pulmonary Emboli Pulmonary thromboembolism is one of the leading causes of death. 4-25). as they do in other organs with dual circulation (Fig.57 PULMONARY CIRCULATORY DISORDERS Blood flow through the lungs depends on proper cardiac function. Fig. Pulmonary emboli may involve the main pulmonary artery. episodes of dyspnea and hemoptysis. red blood cells.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . intraalveolar hemorrhage. and desquamated cells. although it often is clinically unrecognized. Pulmonary infarct. Circulatory collapse that occurs in shock and multiple organ failure often is clinically associated with adult respiratory distress syndrome (ARDS). or recanalized.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. The septa are necrotic and the alveoli contain blood. the thromboemboli become lysed. Clinically they may cause sudden death. Histologically. 4-27). organized. show signs of diffuse alveolar damage accompanied by focal atelectasis. Lungs . the alveoli of the infarcted area have necrotic septa and are filled with blood (Fig 4-28). Saddle emboli of the main pulmonary artery and the emboli occluding the major branches of the pulmonary artery usually cause sudden death (Fig. Air spaces contain hyaline membranes. 66417308 : ¸Ÿ±U 24 ¥°Q . Thromboemboli that lodge in peripheral pulmonary arteries cause infarcts. Acute left heart failure results in passive pulmonary congestion and intraalveolar hemorrhage. 4-27. Chronic heart failure results in brown induration of the lungs. Fig. Fig. 4-26). 4-25. On gross examination pulmonary infarcts appear red. or small intrparenchymal vessels. and hyaline membrane formation (Fig. 4-26. Infarct is triangular and hemorrhagic. its major branches. but only in patients whose pulmonary circulation is compromised by heart failure or atherosclerotic obstruction of the nutrient pulmonary circulation through the bronchial arteries. The main branches of the pulmonary artery are occluded with thromboemboli. In patients who survive. or only minor discomfort and thoracic pain. Diffuse alveolar damage. Pulmonary infarct. Pulmonary thromboembolism. 4-28.

Sjogren syndrome. and suberosis. eosinophilic pneumonia. bagassosis. 4-33). C.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . hypersensitivity pneumonia. or chronic thromboembolism of the pulmonary vascular system.Pulmonary Hypertension Pulmonary hypertension can be classified as primary or secondary. 4-31). Concentric intimal proliferation (grade 2). I MMUNE-MEDIATED LUNG DISEASES The lungs are exposed to numerous potential allergens inhaled daily and are thus a common site for a variety of i mmune-mediated diseases.) 66417308 : ¸Ÿ±U 24 ¥°Q . The most important in this group of diseases are asthma. 4-34). sarcoidosis. which show hyperplasia of mucussecreting cells. C. The lungs also may be affected by systemic autoi mmune diseases such as systemic lupus erythematosus. A B C D E F Fig. Many drugs may induce the same syndrome. and signs of chronic inflammation (Fig. 4-30). hypertrophy and hyperplasia of smooth muscle cells. or filarial worms. Concentric laminar intimal fibroelastosis (grade 3). Asthma is a disorder characterized by increased responsiveness of the airways to various stimuli as manifested by episodes of wheezing and increased resistance to expiratory air flow. which can be graded on a scale from 1 to 6 according to the Heath-Edwards classification (Fig. Congenital heart disease with left-to-right shunting of blood also causes pulmonary hypertension. and systemic sclerosis (scleroderma). Foreign antigens usually induce a cellmediated reaction in the form of granulomas (Fig. Medial hypertrophy and muscularization of an arteriole (grade I). Fibrinoid degeneration (grade 6). The causes of primary or idiopathic hypertension are not known. F. The principal pathologic changes occur in the bronchi and bronchioli. Eosinophilic pneumonia often is found in such cases by lung biopsy (Fig. D. Hypersensitivity pneumonia (extrinsic allergic alveolitis) can be induced by a number of allergens or drugs (Fig. Plexiform lesion (grade 4). and E. and Wegener granulomatosis. such as visceral larva migrans syndrome related to infestation with nematodes. Ultimately the disease may progress to diffuse pulmonary fibrosis. A. Clinically it may present under several conditions such as farmer's lung. (A. Elastica–van Gieson stain. 4-29. Plexogenic pulmonary arteriopathy.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . mushroom worker 's lung disease. 4-29). 4-32). Necrotizing arteritis (grade 6). The mucus inthelumen o f thebronchi may contain CharcotLeyden crystals derived from the granules of eosinophils and Curshman spirals. cestodes. Secondary pulmonary hypertension is a consequence of left heart failure. B. Other immune-mediated diseases such as Goodpasture syndrome and Churg-Strauss syndrome are less common. In advanced cases buds of organizing fibrovascular tissue (Masson bodies) fill the respiratory bronchioli and alveolar ducts (Fig. E. Pulmonary infiltration and eosinophilia (PIE) is a syndrome that could have many causes. Focal cellular infiltrates composed of lymphocytes and a few plasma cells are less common. mitral valve lesions.

Allergic drug reaction. C. 4-31. Inflammatory cells are present in variable amounts and often are not prominent. Fig. Fig. B. 4-34. Asthma. The air spaces contain loosely structured granulomas with multinucleated giant cells. Eosinophilic pneumonia. Charcot-Leyden crystals. which are also found in the alveolar spaces. Hypersensitivity pneumonia. Fig. Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 4-33. a thick basement membrane. 66417308 : ¸Ÿ±U 24 ¥°Q .59 B C A Fig. Hypersensitivity pneumonia. The bronchiole has a hy erplastic epithelium. The alveoli and thickened septa are infiltrated by eosinophils and lymphocytes. A. The alveolar septa are thickened and infiltrated with mononuclear cells. 4-30. The lumen contains mucus. Curshman spiral.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . In later stages of the disease the airways are obliterated by fibroblastic granulation tissue. 4-32. and prominent smooth muscle cells in its wall.

The lung lesions may present as pale infarcts or bulky necrotic nodules (Fig 4-35). People who are exposed to chronic irritants such as cigarette smoke also suffer from chronic pulmonary infections. 4-35. Panacinar (panlobular) emphysema typically is encountered in persons with a i -antitrypsin deficiency.. A. AIDS or cancer therapy). and panacinar (panlobular) emphysema. CHRONIC INFECTIONS AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) Chronic and recurrent pulmonary infections typically occur in persons who have congenitally reduced pulmonary defense (e.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . (4) inhalation of toxic gases. and surrounded by peribronchial fibrosis. which often are unrelated to emphysema. These changes contribute to a variegated ( " geographic map-like" ) appearance of tissues in histologic sections. Histologic features include vasculitis accompanied by thrombosis and pulmonary infarcts. It may occur in several clinical settings such as: (1) damage of bronchi by an infection in early life. and (5) in a localized form distal to a tumor or other lesions causing bronchial obstruction. purulent bronchitis and pulmonary insufficiency are the leading cause of death (Figs. without evidence of fibrosis.g. Kartagener syndrome.g. and granulomas often superimposed on a background of nonspecific chronic inflammation. 4-39). Chronic Obstructive Pulmonary Disease COPD is a clinical diagnosis that includes two closely related entities that typically cause dyspnea and other respiratory problems in chronic cigarette smokers: chronic bronchitis and emphysema. inflammation. as found under normal circumstances (Reid index). 4-41). The enlarged bronchial mucous glands occupy more than 40 percent of the thickness of the wall. The involved bronchi and bronchioli are markedly dilated. The lung parenchyma contains two nodules showing central necrosis. Other forms of emphysema such as paraseptal or irregular emphysema (usually associated with scarring) are less important clinically. and necrosis. In cystic fibrosis. 4-36 and 4-37). The section shows areas of vasculitis. filled with mucous or mucopurulent plugs. are a common cause of lung rupture and spontaneous pneumothorax (Fig. Emphysema is a permanent loss of pulmonary parenchyma that leads to an enlargement of air space distal to the terminal bronchioles. Similar air-filled bullae. B. Wegener granulomatosis is an immune-mediated disease that involves the upper and lower respiratory tracts and kidneys. It occurs in two main forms: centriacinar (centrilobular) emphysema. a common cause of bronchiectasis. 4-38). Centriacinar emphysema most often is found in cigarette smokers and typically shows centriacinar deposition of black pigment (anthracosis). (3) allergy to molds. Bronchiectasis Bronchiectasis is an irreversible dilatation of bronchi accompanied by an infection of the bronchial wall and obliteration of distal airways. immotile cilia syndrome. which involves the entire acinus ( "cotton candy lung" ) (Fig. All forms of emphysema can give rise to pulmonary subpleural bullae. (2) recurrent infections in patients with congenital disorders such as cystic fibrosis. The bronchi typically have thickened walls. Chronic bronchitis is defined clinically as chronic lung disease presenting as cough with expectoration and lasting at least three months during two consecutive years. The bronchi show histologic signs of chronic inflammation and contain mucus admixed with pus (Fig. or agammaglobulinemia. which involves the respiratory bronchioles and destroys the alveolar septa around it (Fig. 4-40). 66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .. Wegener granulomatosis.A B Fig. agammaglobulinemia) or acquired immunodeficiency (e.

4-39. Subpleural bullae. Also note the pigmentation inside the cystic central spaces. 4-41. Fig. Fig. 4-37. Fig. The bronchiole is filled with an exudate composed of neutrophils.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig.61 Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Panacinar emphysema. Cystic fibrosis. 66417308 : ¸Ÿ±U 24 ¥°Q . Chronic bronchitis. 4-40. Note that the large air spaces are surrounded by a normal alveolar network. 4-38. Centriacinar emphysema. The wall of the bronchus is thickened and inflamed. 4-36. The entire pulmonary parenchyma has a delicate cotton candy—like texture. Fig. This lung from a 20-year-old man shows diffuse bronchiectasis. Cystic fibrosis.

This lung of a slate worker shows perivascular inflammation and fibrosis. Reddish-brown macules composed of hemosiderin-laden macrophages gradually develop in the lungs (Fig. silicatosis. Numerous nonfibrous ferruginous bodies that have round or irregularly shaped black cores also are present. The most important pneumoconioses are silicosis. A. Larger nodules seen on radiographic examination of the lungs of coal workers with rheumatoid arthritis (Caplan lesion) show central necrosis surrounded by palisading macrophages that are reminiscent of subcutaneous rheumatoid nodules (Fig. coal workers' pneumoconiosis. and progressive massive fibrosis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and nodules (secondary dust foci). which represent carbon particles containing fibrotic patches of damaged alveolar septa.PNEUMOCONIOSES The term pneumoconiosis was coined by the German pathologist Friedrich Zenker in 1866 for all diseases of the lung parenchyma that are attributable to the inhalation of inorganic mineral dust. The lung of a coal worker shows anthracosilicotic lesions more prominent in the upper lobes. Coal workers ' pneumoconiosis is a fibrosing lung disease of coal workers. The lungs show grossly visible black pigmentation (Fig. iron and steel workers. 66417308 : ¸Ÿ±U 24 ¥°Q . 4-45). accelerated silicosis. Typical histologic findings include macules (primary dust foci). silicotic nodules. also known as alpha quartz. and berylliosis. The disease becomes evident within days or weeks after exposure. 4-47). 4-48). Typical lesions. Polarization microscopy reveals birefringent particulate matter that appears granular. and those who work in iron mines. 4-44). Black pigment is evidence of anthracosis. or lancetshaped. are found in the latter two entities (Fig. Hard metal disease sporadically develops in workers who are employed in industries in which synthetic hard metals are produced or are used in cuttings and fabrication of metal parts. 4-42). platy. 4-43. hard metal disease. Siderosis applies to the deposition of iron oxide in the lungs. Fig. The monocular cell infiltrate at the periphery represents a response to nonquartz silicate particles. Inhalation of silicates such as talc or kaolin produces peribronchial and perivascular aggregates of macrophages that are heavily laden with dust and associated with fibrosis (Fig. such as acute silicosis. B Fig. Silicosis is an inflammatory and fibrotic lung disease that is caused by the inhalation of silica crystals. Silica crystals can be seen in these lesions by polarization microscopy. The silicates not evident in this slide could be seen by polarization microscopy. Progressive massive fibrosis. Several clinical and pathologic forms of silicosis are known. It is composed of concentrically layered whorled collagen bands. 4-43). Silicatosis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Silicates account for one third of all known mineral species and are ubiquitous. A Silicatosis is caused by inhalation of particulate nonfibrous silicate minerals in the absence of silica dust.5 to 3 mm in diameter (Fig. 4-42. Silicosis. B. chronic silicosis. Histologically the lungs show variable degrees of fibrosis accompanied by infiltrates composed of macrophages and giant cells (Fig. 4-46). Multinucleated giant cells are especially prominent in talcosis. which represent larger stellate anthracotic connective tissue scars measuring 0. as is seen in welders. asbestosis.

A B Fig. Fig. lamellar concentric fibrosis. A.63 Fig. Fig. 4-46. The lungs show increased black pigmentation. 4-48. The lungs of this iron ore miner contain aggregates of hemosiderin-laden macrophages. 4-45.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Macule consists of fibrous tissue impregnated with carbon particles. Fig. 4-47. Coal workers' pneumoconiosis. The nodule has a variegated appearance and contains zones of necrosis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Variable degrees of fibrosis may be found. Caplan lesion in coal workers' pneumoconiosis. Siderosis. Hard metal disease. 66417308 : ¸Ÿ±U 24 ¥°Q . Coal workers' pneumoconiosis. 4-44. Nodule represents a stellate heavily pigmented scar. B. The lung parenchyma contains aggregates of macrophages and multinucleated giant cells. and anthracosis.

a malignant tumor of serosal surfaces (Fig. 4-50. 4-49 and Fig.Berylliosis is a granulomatous lung disease that develops after exposure to aerosolized beryllium particles. Diagram 4-2. Commercial and noncommercial asbestos. 66417308 : ¸Ÿ±U 24 ¥°Q . 4-54). and in space exploration programs. or mixed including both epithelial and sarcomatous elements (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Histologically mesotheliomas may be classified as epithelial. In addition to pulmonary fibrosis. 4-53). sarcomatous. Histologically the disease is indistinguishable from sarcoidosis and presents in the form of noncaseating pulmonary granulomas (Fig. The lung contains numerous noncaseating granulomas composed of epithelioid macrophages and giant cells. Sarcoidosis. 4-50). for the production of atomic energy.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The incidence of bronchial carcinoma also is increased after chronic exposure to asbestos. Fig. Asbestosis is a fibrotic lung disease consequent to longterm exposure to all types of asbestos (Diagram 4-2). 4-52). Fig. Asbestos bodies found in or adjacent to the walls of fibrotic res- piratory bronchioles are the hallmark of this disease (Fig. Noncaseating granulomas are found in the peribronchiolar parencyma. 4-49. 451). exposure to asbestos leads to the formation of fibrous plaques on visceral or parietal pleura (Fig. The most serious consequence of asbestos exposure is mesothelioma. Beryllium has been used for the production of lamps. Berylliosis.

White plaques cover the parietal pleura. Fibrosarcomatous mesothelioma is composed of spindle shaped cells. Fig. A. Asbestosis. 4-53. Malignant mesothelioma. Asbestos body. B.65 A B Fig. 4-51.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Air spaces contain beaded iron-encrusted brown asbestos bodies. 4-52. This epithelial variant shows a glandulopapillary growth pattern. This pleural tumor has invaded the pericardial cavity encasing the heart. 66417308 : ¸Ÿ±U 24 ¥°Q . B. Fig. Malignant mesothelioma. A.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . A B Fig. Asbestosis. 4-54.

I DIOPATHIC INTERSTITIAL LUNG DISEASES
Lungs may be affected by a number of chronic diseases of unknown etiology, which show common and overlapping clinical features but nevertheless have distinctive histologic characteristics. Dyspnea and deterioration of pulmonary function is invariably related to a loss of pulmonary parenchyma and pulmonary fibrosis. The most important of these diseases are listed in Table 4-1. Idiopathic organizing pneumonia, which is also known as bronchiolitis obliterans with organizing pneumonia (BOOP), is a restrictive lung disease that begins with symptoms that are suggestive of viral pneumonitis. The symptoms fail to resolve and the lung parenchyma undergoes patchy consolidation (Fig. 4-55). Microscopic sections show numerous fibroblastic polypoid protrusions (Masson bodies) obliterating the respiratory bronchioles, the alveolar ducts, and even the alveoli. The epithelium of terminal bronchioles proliferates, covering the surface of Masson bodies and lining the restructured air spaces. These findings are, however, non-

specific and also can be found in other forms of chronic pneumonia. Chronic idiopathic pulmonary fibrosis begins insidiously and progresses to end-stage lung disease over a variable period. The lungs are firm and fibrotic and the normal areas alternate with foci of scarring (Fig. 4-56). Microscopic features include prominent fibrosis replacing focally the normal lung parenchyma. The remaining air spaces are abnormal, dilated, and often lined by cuboidal cells (Fig. 4-57). Most cases of so-called usual interstitial pneumonia (UIP) show this histologic pattern. Some cases, however, are classified as desquamative interstitial pneumonia (DIP). In this variant the thick-walled alveoli are filled with numerous macrophages (Fig. 4-58). Pulmonary alveolar proteinosis is a disease of unknown etiology. It presents as progressive dyspnea and respiratory insufficiency. Parts of the lungs become consolidated due to the accumulation of lipid-rich proteinaceous material in the alveoli (Fig. 4-59).

A

B

C

Fig. 4-55. Bronchiolitis obliterans. A, The obliterated bronchioli surrounded with consolidated parenchyma impart a micronodular pattern to the cross section of the lung parenchyma. B, Masson bodies obliterate the lumen of bronchioli. C, Masson bodies in the alveolar ducts appear as oval shaped structures composed of fibroblasts and collagen.

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Clinicopathologic forms of pulmonary fibrosis Form (alternative name) Acute interstitial pneumonia (Hamman-Rich syndrome) Idiopathic organizing pneumonia (BOOP, COP) Usual interstitial pneumonia Desquamative interstitial pneumonia Nonspecific interstitial pneumonia (CIP) Duration Weeks Weeks to months Years Years Months Histologic appearance Uniform Uniform Heterogeneous Uniform Uniform Distribution Diffuse Patchy Patchy Diffuse Patchy

BOOP, bronchiolitis obliterans—organizing pneumonia; CIP, cellular.interstitial pneumonia; COP, cryptogenic organizing pneumonitis.

Fig. 4-56. Idiopathic pulmonary fibrosis. Cross section of the lung shows fibrosis with microcystic dilatation of air spaces.

Fig. 4-57. Idiopathic pulmonary fibrosis. The lung parenchyma has a simplified structure because of a loss of alveoli, which have been replaced by fibrous tissue.

Fig. 4-58. Desquamative interstitial pneumonia. The alveoli have thick walls and are filled with numerous macrophages.

Fig. 4-59. Pulmonary alveolar proteinosis. The alveoli are filled with granular, eosinophilic, lipid-rich, proteinaceous material.

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PULMONARY NEOPLASMS
Tumors of the lungs can be classified as central (hilar) or peripheral. Several microscopic categories are recognized (Table 4-2). Hilar tumors originate from the epithelium of the main bronchi (Fig. 4-60). Histologically they present as squamous cell, small (oat) cell, large cell carcinoma, or adenocarcinoma (Figs. 4-61 and 4-62). Peripheral subpleural tumors, which often arise in anthracotic fibrous scars, have his -

tologic features of adenocarcinoma (Fig. 4-63). Bronchioloalveolar carcinoma is a form of peripheral adenocarcinoma that grows along the alveolar septa, filling the alveoli and causing pneumonia-like consolidation of the lung parenchyma (Figs. 4-64 and 4-65). Carcinoids are low-grade malignant tumors of endocrine cells (Figs. 4-66 and 4-67). Other primary malignant tumors are less common.

Fig. 4-60. Hilar squamous cell carcinoma. The tumor originates from the main bronchus. Fig. 4-61. Squamous cell carcinoma of the bronchus. A focus of carcinoma (left) is seen adjacent to an area of squamous metaplasia.

A

B

Fig. 4-62. Small cell carcinoma. A, The tumor is composed of small blue cells that have elongated or round nuclei, depending on the plane of sectioning. The tumor contains areas of necrosis (right upper corner). B, Neuroendocrine granules can be seen by electron microscopy.

Fig. 4-63. Peripheral adenocarcinoma. The tumor contains areas of black discoloration, which suggest that it originated in an anthracotic scar.

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Fig. 4-64. Bronchioloalveolar carcinoma. The tumor infiltrates the parenchyma and produces lesions that resemble pneumonia. Fig. 4-65. Bronchioloalveolar carcinoma. The cuboidal mucussecreting tumor cells grow along the alveolar septa. Lung neoplasms
I. Epithelial tumors A. Benign tumors I. Papillomas 2. Adenomas a. Pleomorphic adenoma b. Monomorphic adenoma B. Dysplasia/carcinoma in situ C. Malignant tumors I. Squamous cell carcinoma (epidermoid carcinoma) 2. Small cell carcinoma a. Oat cell carcinoma b. Intermediate cell type c. Combined oat cell carcinoma 3. Adenocarcinomas a. Acinar adenocarcinoma b. Papillary adenocarcinoma c. Bronchioloalveolar carcinoma d. Solid carcinoma with mucus formation 4. Large cell carcinoma variants a. Giant cell carcinoma b. Clear cell carcinoma 5. Adenosquamous carcinoma 6. Carcinoid tumor 7. Bronchial gland carcinoma 8. Others II. Soft tissue tumors primary in the lung III. Pleural tumors A. Benign mesothelioma B. Malignant mesothelioma IV. Miscellaneous tumors A. Benign tumors B. Malignant tumors I. Carcinosarcoma 2. Pulmonary blastoma 3. Malignant melanoma 4. Malignant lymphoma 5. Others V. Unclassified tumors VI. Tumor-like lesions Modified from Colby TV, Koss MN, Travis WD: Tumors of the lower respiratory tract. Atlas of tumor pathology, series 3, fasc. 13, Washington, D.C., 1995, Armed Forces Institute of Pathology; and the World Health Organization Histological Typing of Lung Tumors, Am J Clin Pothol 77:I23126, 1982.

Fig. 4-66. Bronchial carcinoid. The tumor presented as a small nodule in the wall of the bronchus.

Fig. 4-67. Carcinoid tumor. The tumor is composed of uniform cells that have round nuclei.

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Sarcomas of the lung present as bulky solid masses (Fig. 4-68). Histologically they resemble sarcomas of soft tissues. Pulmonary blastoma is an organ-specific malignant tumor composed of cuboidal epithelial cells that form branching ducts surrounded by mesenchymal stroma that resemble fetal lungs (Fig. 4-69). Benign tumors and tumor-like conditions present as coin lesions on radiographic examination. Pulmonary hamartomas are composed of cartilage, bronchial epithelium, and

smooth muscle cells. On gross examination hamartomas appear as clefted cartilaginous nodules (Fig. 4-70). Sclerosing hemangioma, also called papillary pneumocytoma, is a benign tumor of controversial histogenesis (Fig. 4-71). Inflammatory pseudotumor is an inflammatory lesion that may resemble tumors (Fig. 4-72). Metastatic tumors appear on radiographic examination as sharply demarcated multiple round nodules ( " cannonball" lesions). Equivalent autopsy findings are typical (Fig. 4-73).

Fig. 4-68. Sarcoma of the lung. The tumor forms a bulky mass.

Fig. 4-69. Pulmonary blastoma. The tumor is composed of branching epithelium-lined ducts surrounded by spindle-shaped stromal cells.

A

B

Fig. 4-70. Pulmonary hamartoma. A, The nodule has a prominently clefted appearance on cross section. B, It is composed of cartilage and cleft-like spaces lined by cuboidal cells.

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Fig. 4-71. Sclerosing hemangioma. Vascular papillae are lined by cuboidal cells. -

Fig. 4-72. Inflammatory pseudotumor. The lesion is composed of a variety of cell types. Plasma cells and fibrosis predominate.

Fig. 4-73. Metastatic carcinoma. The parenchyma contains several round nodules.

Further Reading
Bjornsson J, Edwards WD: Primary pulmonary hypertension. A histopathologic study of 80 cases. Mayo Clin Proc 60:16-25, 1985. Blumenfeld W. McCook 0, Grississ JM: Detection of antibodies to Pneumocystic carinii in bronchoalveolar lavage fluid by immunoreactivity to Pneumocystis carinii within alveoli, granulomas, and disseminated sites. Mod Pathol 5:107-113, 1992. Colby TV: Bronchiolitis: pathologic considerations. Am J Clin Pathol 109:101-109, 1998. Dunnill MS: Pulmonary fibrosis. Histopathology 16:321-329, 1990. Hagan JL, Hardy JD: Lung abscess revisited. A survey of 184 cases. Ann Surg 197:755-762, 1983.

Hasleton PS, Roberts TE: Review: adult respiratory distress syndrome —an update. Histopathology 34:285-294, 1999. Jeffery PK: Structural and inflammatory changes in COPD: a comparison with asthma. Thorax 53:129-136, 1998. Marchevsky A, Rosen MJ, Chrystal G, Kleinerman J: Pulmonary complications of the acquired immunodeficiency syndrome. A clinicopathologic study of 70 cases. Hum Pathol 16:659-670, 1985. Mark EJ, Ramirez JF: Peripheral small-cell carcinoma of the lung resembling carcinoid tumor. A clinical and pathologic study of 14 cases. Arch Pathol Lab Med 109:263-269, 1985. Porter HJ: Pulmonary hypoplasia-size is not everything. Virchow Arch 432:3-6, 1998. Takemura T and others: Pulmonary vascular involvement in sarcoidosis. A report of 40 autopsy cases. Hum Pathol 23:1216-23, 1992. Travis WD, Gal AA, Colby TV et al: Reproducibility of neuroendocrine lung tumor classification. Hum Pathol 29:272-279, 1998. Travis WD, Rush W, Flieder DB et al: Survivial analysis of 200 pulmonary neuroendocrine tumors with clarification of criteria for atypical carcinoids and its separation from typical carcinoid. Am J SurgPathol22:934-944, 1998. Uner AL, Rozum-Slota B, Katzenstein AA: Bronchiolitis obliteransorganizing pneumonia (BOOP)-like variant of Wegener's granulomatosis. A clinicopathologic study of 16 cases. Am J Surg Pathol 20:794-801, 1996. Winn WC Jr, Myerowitz RL: The pathology of the Legionella pneumonias. A review of 74 cases and the literature. Hum Pathol 12:40142, 1981. Yousem SA, Lohr RH, Colby TV: Idiopathic bronchiolitis obliterans organizing pneumonia/cryptogenic organizing pneumonia with unfavorable outcome: pathologic predictors. Mod Pathol 10:864-871, 1997.ganizing pneumonia/cryptogenic organizing pneumonia with unfavorable outcome: pathologic predictors. Mod Pathol 10:864-871, 1997.

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ANEMIAS
Anemia is a reduction in the hemoglobin concentration in the blood, which decreases its oxygen-carrying capacity. The pathologic changes related to anemias can be seen primarily in the bone marrow, which is the site of red blood cell (RBC) production; the circulating blood; and the spleen, which is the primary site of RBC destruction. Pathophysiologically anemias can be classified into those attributable to (1) impaired production of erythrocytes; (2) inherited quantitative and structural abnormalities of hemoglobin synthesis; (3) increased rate of erythrocyte destruction, that is, hemolytic anemias; and (4) acute blood loss. On the basis of RBC morphology, anemias are classified as (1) microcytic, (2) normocytic, or (3) macrocytic (Table 5-1).

Morphologic Classification of Anemias Microcytic hypochromic anemias Iron deficiency Chronic disease Thalassemia Sideroblastic anemia Normocytic normochromic anemias Aplastic anemia Chronic disease Myelophthisic conditions Hemolytic anemia Macrocytic anemias Vitamin B12 deficiency Folic acid deficiency Chronic liver disease Myelodysplastic syndrome

Bone Marrow Changes
Hematopoietic cells constitute 40 percent of normal bone marrow (Fig. 5-1). Hemolytic anemia results in compensatory erythroid hyperplasia (Fig. 5-2). In aplastic anemia the bone marrow is acellular and contains few or no hematopoietic cells (Fig. 5-3). Anemia can result from the replacement of the normal hematopoietic cells as a result of sarcoidosis or other inflammatory conditions and tumors (Fig. 5-4). Specific causes of anemia such as parvovirus B19 occasionally may be identified by bone marrow biopsy (Fig. 5-5). Many other forms of anemia are characterized by specific bone marrow findings. For example, pernicious anemia shows megaloblastic changes (Fig. 5-6).

Peripheral Blood Smears
Peripheral blood smears are important for assessing anemia. Morphology of red blood cells may be used to classify anemias into general categories (e.g., microcytic versus macrocytic) or to obtain specific information about the nature of the underlying defect, as in spherocytosis,.elliptocytosis, pyropoikilocytosis, or acanthocytosis (Figs. 5-7 to 5-9).

Fig. 5-I. Normal bone marrow of an adult. Hematopoietic cells account for approximately 40 percent of marrow's cellularity.

Fig. 5-2. Erythroid hyperplasia. Markedly hypercellular bone marrow from a patient with hemolytic anemia contains an increased number of erythroid precursors. Megakaryocytes and granulocyte at all stages of maturation are present.

Fig. 5-3. Aplastic anemia. There is a marked reduction in hematopoietic cells with expansion of fat cells.

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Elliptocytosis and pyropoikilocytosis. elliptocytes constitute more than 25 percent of all cells in peripheral blood smears. Sarcoidosis. 5-6. Elliptocytes also are seen in iron deficiency anemia and various myeloproliferative and/or myelodysplastic disorders. Pyropoikilocytosis may be hereditary. Spherical RBCs may be seen in peripheral blood smears of patients who have hereditary spherocytosis or immune hemolytic anemia. clostridial sepsis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . A B Fig. Fig.75 Fig. Spherocytosis. Fig. 5-7. 66417308 : ¸Ÿ±U 24 ¥°Q . In hereditary elliptocytosis. Fig. and snake venom poisoning. 5-8. The bone marrow smear shows a reduced number of erythroid precursors. Pernicious anemia. Bone marrow aspirate smear contains megaloblastic red cell precursors and giant metamyelocytes. Parvovirus BI9—induced erythroid hypoplasia. or after RBC transfusion. A. The bone marrow contains several confluent noncaseating granulomas. but similar morphology of RBCs can be seen in severe burns. 5-5.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 5-4. A giant proerythroblast with a prominent intranuclear inclusion is seen in the middle of the field. B.

Fig. Reticulocytes contain red. Thalassemia minor. 66417308 : ¸Ÿ±U 24 ¥°Q . McLeod phenotype. Thalassemia." B. Acanthocytes.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Sickle cell anemia. 5-10. delicate.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The peripheral blood smear contains numerous target cells. 5-12. Neutral red–brilliant green shows Heinz bodies inclusions. Hemolytic anemia with Heinz bodies. but also in abetalipoproteinemia. that is. Thalassemia major. and several other conditions. The peripheral blood smear of this patient with low glucose-6phosphate dehydrogenase activity treated with dapsone contains numerous "bite cells. A B Fig. 5-1 I. The red blood cells vary in size and shape and are often deformed. sickle-shaped. A. granular deposits of ribonucleic acid. or RBCs with numerous irregular surface spikes. are seen in peripheral blood smears of patients with severe liver disease. 5-9. A. Acanthocytosis.Fig. A B Fig. B.

Myelofibrosis. The fibrous scars in these abnormally small spleens often are i mpregnated with iron and calcium salts and thus appear black (Fig. Replacement of blood cell precursors in the marrow by fibrous tissue is seen in anemia of myelofibrosis (Fig. In sickle cell anemia prolonged pooling of red blood cells and obstruction of the blood flow may cause infarcts. Extramedullary hematopoiesis. Erythroid and myeloid cells in various stages of maturation and megakaryocytes are seen in the liver and spleen. 5-15). 66417308 : ¸Ÿ±U 24 ¥°Q . Tissue Changes in Anemia Anemias produce a variety of tissue changes. Fig. 5-16. 5-17). 5-14). which ultimately lead to fibrotic shrinkage of the spleen ( " autosplenectomy " ) (Fig. Spleen is markedly enlarged. 5-15.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 5-14. Fig. Fig. It may be as - sociated with extramedullary hematopoiesis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Some tissue changes such as atrophic gastritis in pernicious anemia reflect the causes of anemia. which vary depending on the severity and duration of the disease and its pathogenesis. Spleen shows prominent congestion of the red pulp sinuses. Intrasplenic hemolysis of hereditary spherocytosis is accompanied by splenomegaly (Fig. The cut surface is homogeneously red. 5-13). 5-13. usually in the spleen and the liver (Fig. Hereditary spherocytosis. Fig. Hereditary spherocytosis. 5-10 to 5-12). 5-18). The hematopoietic bone marrow has been replaced with fibroblastic tissue. Histologically such enlarged spleens have dilated sinuses filled with blood (Fig. 5-16).77 Certain forms of hemolytic anemia such as sickle cell anemia or thalassemia also have typical morphologic features (Figs.

·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . LEUKEMIAS Leukemias are neoplastic diseases of hematopoietic cells presenting primarily with changes in the blood and bone marrow. which are impregnated with iron and calcium salts and therefore appear black. Fig. based on the degree of maturation of the major cell population. 66417308 : ¸Ÿ±U 24 ¥°Q . Within each cytologic type. minimally differentiated (AML-MO) Acute myeloblastic leukemia without maturation (AML-M I) Acute myeloblastic leukemia with maturation (AML-M2) Acute promyelocytic leukemia (AML-M3) Hypergranular type Microgranular variant Acute myelomonocytic leukemia (AML-M4) Increased marrow eosinophils (AML-M4-EO) Acute monocytic leukemia (AML) Acute monoblastic leukemia (AML-M5A) Acute monocytic leukemia. 5-19. L2. 5-19). which usually stain with oil red O and are periodic acid–Schiff (PAS) negative (Fig. or L3.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . based on the primary cell of origin. the leukemias are further classified as acute or chronic. percent of cases of AML. monoblasts. The type II myeloblast (II) has a few azurophilic granules in the cytoplasm at the lower right. The promyelocyte (Pro) has numerous azurophilic granules in the cytoplasm. The spleen contains fibrotic scars. Sickle cell anemia. Spleen is shrunken and has a gray. nodular external surface. depending on the blast morphology. the diagnosis of AML is made if the bone marrow contains 30 percent or more blasts. 5-21). Acute myeloid leukemia. The L1 lymphoblast is a small cell. AML is characterized by the appearance of blast cells in the bone marrow. The promyelocyte is the predominant abnormal cell in acute promyelocytic leukemia (Fig. 5-22). clear vacuoles.Fig. myeloid and lymphocytic. a homogeneous smooth nuclear chromatin. Two types of myeloblasts generally are recognized: type I and type II (Fig. They are classified as two major cytologic types. The major blast populations include myeloblasts. 5-17. 5-20). erythroblasts. In approximately 60 11 Pro Classification of Acute Myeloid Leukemias ' Acute myeloblastic leukemia. L2 lymphoblasts are larger than L 1 lymphoblasts and have moderate amounts of lightly basophilic cytoplasm and fine nuclear chromatin with distinct and sometimes prominent multiple nucleoli (Fig. and inconspicuous or no identifiable nucleoli (Fig. myeloblasts contain linear azurophilic structures known as Auer rods (Fig. and megakaryoblasts. with a high nuclear-cytoplasmic ratio. differentiated (AML-M5B) Erythroleukemia (AML-M6) Acute megakaryoblastic leukemia (AML-M7) Fig. 5-18. 5-23). The monoblasts and promonocytes are the major immature cells in acute monocytic leukemia (Fig. Acute Leukemias Acute myeloid leukemias (AML) are classified into eight subgroups (Table 5-2). Sickle cell anemia. Acute lymphoblastic leukemia is classified as L1. L3 lymphoblasts have a moderate amount of intensely basophilic cytoplasm that contains sharply defined. 5-23). approximately twice the size of a normal lymphocyte. 5-24). The type I myeloblast (I) is agranular.

Acute monoblastic leukemia (M5A).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . frequently with delicate. 5-20. Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Fig. The cytoplasm of L3 lymphoblasts in a marrow aspirate contains sharply outlined cytoplasmic vacuoles. Acute lymphoblastic leukemia. 5-23. Fig. azurophilic granules. Acute myeloblastic leukemia with maturation (M2). Acute lymphoblastic leukemia.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Promyelocytic leukemia. The bone marrow contains monoblasts. 5-22. scattered. Fig. 5-21. The blast at the upper right is small with sparse cytoplasm and coarser nuclear chromatin and inconspicuous nucleoli.79 Fig. Cells with multiple intertwining Auer rods ("faggot" cells) are characteristic of hypergranular promyelocytic leukemia. 5-24. Variation in size and amount of cytoplasm is shown in this bone marrow smear. which are larger than normal myeloblasts and usually have abundant cytoplasm. LI and L2 lymphoblasts show characteristic morphology in marrow aspirates. All of the blasts contain Auer rods.

less than 5% blasts in blood I. 5-26. Peripheral blood smears contain numerous relatively uniform lymphocytes that have condensed nuclear chromatin and sparse cytoplasm (Fig. In CML the bone marrow is markedly hypercellular and contains an increased number of neutrophils and megakaryocytes and their precursors (Fig. 20% to 29% blasts in marrow. 5% to 29% blasts in blood 3. 5-25. The peripheral blood smear shows marked leukocytosis and basophilia. Chronic B-cell lymphocytic leukemia is characterized by lymphocytosis that varies from 4 X 10 9 /L to more than 400 X 109 /L. dysgranulopoiesis -!> I X I09/L monocytes in blood and one of the criteria listed for RAEB-T Chronic myelomonocytic leukemia (CMML) Chronic myelomonocytic leukemia in transformation (CMML-T) Myelodysplastic syndrome. less than 5% blasts in marrow 5% to 20% blasts in marrow. In adult T-cell leukemia. granulocytes and megakaryocytes usually normal. On the basis of immunohistochemical markers these disorders represent either B-cell or T-cell neoplasms (Table 5-4). unclassified Less than 5% blasts in marrow.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Classification of Primary Myelodysplastic Syndromes Refractory anemia (RA) Refractory anemia with ringed sideroblasts (BARS) Refractory anemia with excess blasts (RAEB) Refractory anemia with excess blasts in transformation (RAEB-T) Anemia refractory to hematinic therapy. dyserythropoiesis 6. The peripheral blood leukocytosis exceeds 100 X 10 9/L in 70 percent to 90 percent of patients. 5-26). 5-28). it forms a group if disorders known as primary myelodysplastic syndromes (Table 5-3).Chronic Leukemias Chronic myeloid leukemia (CML) is a myeloid stem cell disorder. Chronic myeloid leukemia.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 5-25). 5-27)." markedly convoluted nuclei (Fig. peripheral blood smears contain abnormal lymphocytes. significant dysplasia in two or more myeloid cell lines 66417308 : ¸Ÿ±U 24 ¥°Q . 5-29). <20% blasts in marrow. a disease associated with human T-cell leukemia/lymphoma virus (HTLV-1) infection. 2. Fig. no blasts in blood More than 15% of red cell precursors in marrow "ringed" sideroblasts. myeloblasts do not exceed 2 percent to 3 percent of all cells (Fig. Fig. Bone marrow is markedly hypercellular and infiltrated with numerous myeloid cells. 5-30). Neutrophils at the myelocyte and segmented stages predominate. Chronic lymphoproliferative disorders are a heterogeneous group of diseases that are characterized by a proliferation of small well-differentiated lymphocytes. Together with several other closely related diseases of the bone marrow. Chronic myeloid leukemia. In hairy cell leukemia the peripheral blood contains medium-sized lymphocytes with an oval or lobated nucleus and shaggy cytoplasm extending into surface projections (Fig. marrow blasts less than 5%. In granulated cell lymphocytic leukemia peripheral blood smears contain medium-sized to large lymphocytes with abundant cytoplasm that is rich in coarse azurophilic granules (Fig. which are described as having " flower-shaped. Auer rods (any one criterion suffices) > I X I09/L monocytes in blood.

·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig. The blood smear contains lymphoid cells that have a shaggy cytoplasm. Adult T-cell leukemia/lymphoma. 5-29.81 Chronic Lymphoproliferative Disorders B-cell lymphoproliferative disorders Chronic lymphocytic leukemia Typical Mixed cell type Prolymphocytic leukemia Chronic lymphocytic leukemia/prolymphocytic leukemia Hairy cell leukemia Splenic lymphoma with villous lymphocytes T-cell chronic lymphoproliferative disorders T prolymphocytic leukemia Granulated T-lymphocyte leukemia Sezary syndrome Adult T-cell leukemia Fig. The smear contains lymphoid cells with lobulated ("flower-shaped") nuclei. Hairy cell leukemia. 5-28. B. 66417308 : ¸Ÿ±U 24 ¥°Q . 5-30. A. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Chronic lymphocytic leukemia. Electron microscopy shows slender surface villi. Granulated lymphocyte leukemic CD8+ lymphocytes have abundant cytoplasm filled with coarse azurophilic granules. 5-27. A B Fig. The smear contains numerous well-differentiated lymphocytes with a high nuclearcytoplasmic ratio and condensed nuclear chromatin.

Renal amyloidosis is a common complication (Fig. Waldenstrom macroglobulinemia is a monoclonal gammopathy of the immunoglobulin M class. focal. Plasma cell Plasma Cell Dyscrasias and Related Disorders Monoclonal gammopathy of undetermined significance (MGUS) Solitary plasmacytoma Multiple myeloma Waldenstrom macroglobulinemia Heavy chain disease Primary amyloidosis infiltrates cause lytic punched-out lesions in the bones (Fig. Light chains of immunoglobulin are excreted in urine as Bence Jones protein. Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The bone marrow is involved focally or diffusely in 85 percent of patients. B. immature. 5-34). 5-32. 5-33). interstitial. expressing either kappa (K) or lambda (K) light chains (Fig. A.. 66417308 : ¸Ÿ±U 24 ¥°Q .e. 5-35). This group of diseases includes several closely related entities (Table 5-5). 5-32). Fig. The neoplastic infiltration of the bone marrow seen in trephine biopsies may be diffuse.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 5-3 I. A B Fig.82 PLASMA CELL DYSCRASIAS Plasma cell dyscrasias are proliferations of B immunocytes accompanied by the production of monoclonal immunoglobulin. Multiple myeloma. monoclonal). Bone marrow aspirate contains mostly plasma cells. or a combination of these patterns (Fig. 5-31). Multiple myeloma is a neoplastic proliferation of plasma cells associated with a monoclonal gammopathy. or plasmablastic (Fig. The criteria for the diagnosis are summarized in Table 5-6. Bone marrow is infiltrated with atypical plasma cells. Multiple myeloma. Immunohistochemistry typically shows that the cells are light chain restricted (i. It is associated with plasmacytoid lymphoma cells infiltrating the bone marrow or the lymph nodes (Fig. The radiograph shows lytic lesions. The skull contains lytic ("punched-out") lesions. Multiple myeloma. 5-33. Bone marrow aspirates of these lesions contain plasma cells. 5-36). which can be classified as mature. Tumor cells appear as either small or plasmacytoid lymphocytes.

5-36. and plasma cells. Amyloidosis. lymphoplasmacytic cells. B. A. Fig. 5-35. Arrow shows intranuclear inclusions (Dutcher bodies). The plasma cells are kappa light chain restricted.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Multiple myeloma. Congo red stained amyloid examined under polarized light appears green. B Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Semin Oncol 13:300.83 Diagnostic Criteria for Multiple Myeloma Modified from Durie BG: Staging and kinetics of multiple myeloma. 66417308 : ¸Ÿ±U 24 ¥°Q . The infiltrate consists of small lymphocytes. which are known to be composed of immunoglobulin. 5-34. A Fig. Waldenstrom macroglobulinemia. Renal amyloidosis affecting the glomeruli and blood vessels is a common complication of monoclonal gammopathies. The bone marrow biopsy was stained immunohistochemically with antibodies to kappa (K) and lambda (X) light chains. 1986.

The enlarged lymph nodes contain hyperplastic germinal centers with little intervening interfollicular tissue. The hyperplastic germinal center contains small and large cleaved and noncleaved germinal center cells. resulting in a histologically bizarre " geographic pattern" (Fig. 5-41 and 5-42). occurs in two forms: the more common hyaline vascular type (Fig. Fusion of adjacent germinal centers results in bizarre structures. or Kikuchi disease. (4) diffuse. (3) mixed follicular and interfollicular. Follicular hyperplasia. Fig. or angiofollicular lymph node hyperplasia. The hyperplastic follicles contain expanded germinal centers composed of small and large cleaved and noncleaved cells (Fig. Follicular lymph node hyperplasia. The histologic findings are diagnostic. 5-38). 5-42). (2) interfollicular. Histologically the enlarged lymph nodes contain patchy areas of necrosis confined to paracortical and cortical areas. and plasma cells (Figs.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and (5) sinusoidal (Table 5-7).84 REACTIVE LYMPHADENOPATHIES The term lymphadenopathy is used to describe nonneoplastic enlargement of lymph nodes caused either by infection or by any other antigenic stimulation. tingible body macrophages. Fusion of adjacent germinal clusters may take place. 5-40). Five histologic patterns are recognized: (1) follicular. Histiocytic necrotizing lymphadenitis. 5-39) and plasma cell variant (Fig. Follicular hyperplasia. 5-38.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Human immunodeficiency virus. 5-37). 66417308 : ¸Ÿ±U 24 ¥°Q . Patterns of Reactive Lymphadenopathies Follicular pattern Nonspecific follicular hyperplasia Rheumatoid arthritis/Sjogren syndrome Syphilis Angiofollicular hyperplasia (Castleman disease) HIV-related Progressive transformation of germinal centers Interfollicular pattern Nonspecific interfollicular hyperplasia Dermatopathic lymphadenitis Histiocytic necrotizing lymphadenitis (Kikuchi disease) Granulomatous lymphadenitis Mixed follicular and interfollicular pattern Toxoplasmosis lymphadenitis Cat-scratch disease Lymphogranuloma venereum Mesenteric lymphadenitis Kimura disease Diffuse pattern Infectious mononucleosis and other viral lymphadenitis Abnormal immune response/angioimmunoblastic lymphadenopathy Drug-induced hypersensitivity reactions Systemic lupus erythematosus Mucocutaneous lymph node syndrome (Kawasaki disease) Sinus pattern Sinus histiocytosis Hemophagocytic syndrome Sinus histiocytosis with massive lymphadenopathy Lymphangiography effect Whipple disease HIV. surrounded by macrophages. a condition known as persistent generalized lymphadenopathy (Fig. Human immunodeficiency virus (HIV) infection leads to lymph node enlargement. Castleman disease. immunoblasts. In other cases the sinuses are distended by monocytoid B-cells and scattered neutrophiles. Fig. 5-37. and scattered plasma cells. is characterized by an increased number and size of follicles. is a benign self-limited disease that predominantly affects young women. the most common form of reactive lymphoid proliferation.

hyaline vascular type.85 Fig. A B Fig. Part of a follicle is seen adjacent to a dense interfollicular plasma cell infiltrate. 5-42. Castleman disease.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Interfollicular vascularity is prominent. Two follicles with progressively transformed germinal centers are surrounded by concentrically arranged mantle zone lymphocytes. 5-41. Most of the node is replaced by large germinal centers in which there is a prominent starry sky appearance. plasma cell variant. Monocytoid B-cells occupy the paracortex between two large germinal centers.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Castleman disease. immunoblasts. "Lollipop" appearance of a follicle (right) is evident. Fig. such as macrophages. B. 5-39. Higher magnification shows that the necrotic area is surrounded by a mixture of large cells. Kikuchi disease. B. A. 66417308 : ¸Ÿ±U 24 ¥°Q . A B Fig. A. 5-40. and plasmacytoid monocytes. HIV-related lymphoadenopathy. An irregular patchy focus of paracortical necrosis devoid of neutrophils is characteristic of this disease.

This cell has the characteristics of a diagnostic Reed-Sternberg cell but with a single round or oval nucleus. The nucleolus is not large and prominent. Lacunar variant: the cell has a lobated nucleus with small-to moderately prominent nucleoli in a clear lacuna produced by the retraction of cytoplasm from the plasm membrane. A. Mummified (necrobiotic) cells frequently seen in nodular sclerosis type HD with pyknotic nucleus and darkly eosinophilic cytoplasm. Mononuclear variant. Diagnostic Reed-Sternberg cells and variants. D. E. Electron microscopy of a typical ReedSternberg cell. B. Diagnostic Reed-Sternberg cell: a large multinucleated or multilobated cell with inclusion body–like nucleoli surrounded by a halo of clear nucleoplasm. A large cell with a polyploid nucleus and high nuclear-cytoplasmic ratio.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . C.86 A B C D E F Fig. F. L&H variant. 5-43. A small amount of cytoplasm often is observed around the nucleus. There is a moderate amount of amphophilic cytoplasm.

5-45. Axillary lymph nodes are enlarged. R-S cells have characteristic features and are pathognomonic of HD (Fig. The relationship of this classification to the older classification by Jackson and Parker and the simplified version adopted at the Rye conference is shown in Table 5-8 Lymphocyte predominance type HD is characterized by a dense lymphocytic infiltrate with some histiocytes. The spleen. macrophages. Hodgkin disease. Bands of collagen extend inward from 5-45). eosinophils. Hoppe RT. *Two percent of the cases were considered unclassifiable. 66417308 : ¸Ÿ±U 24 ¥°Q . Radicular Rye Conference Lymphocytic predominance Frequency (%)* 5 Nodular sclerosis Mixed cellularity Lymphocytic depletion 70 22 Granuloma From Colby TV. and plasma cells. 5-44). Histopathologic Subtypes of Hodgkin Disease The pathologic classification of Hodgkin disease (HD) in current use continues to be the one proposed by Lukes and Butler in 1966. Inc. In addition to classic R-S cells the tumors contain varying numbers of large pleomorphic neoplastic cells known as R-S variants (Fig. which nevertheless show some common pathologic and clinical features that distinguish them from non-Hodgkin lymphomas. Fig. Hodgkin disease tends to involve cervical and axillary lymph nodes in a contiguous manner (Fig. L&H Hodgkin disease. It occurs in a diffuse and a nodular form (Fig. Large nodules with small round lymphocytes. Diffuse 2. Diagnostic R-S cells are very difficult to find. a subsidiary of John Wiley & Son. 5-43). Reprinted by permission of Wiley-Liss. and liver also may be involved (Fig. which occasionally may be abundant. and scattered L&H cells are seen. The L&H variants of R-S cells are scattered in this infiltrate. 5-43). Mixed cellularity 4. Nodular sclerosis type HD is characterized by a thickened lymph node capsule. Copyright 1981 American Cancer Society. bone marrow. 5-45). Fig. macrophages. Histologically the tumor consists of neoplastic Reed-Sternberg (R-S) cells that typically are found in a background of reactive cells such as small lymphocytes. The Pathologic Classification of Hodgkin Disease Jackson & Parker Paragranuloma Lukes & Butler I. Nodular sclerosis 3.87 HODGKIN DISEASE Hodgkin disease (HD) is a neoplastic disease of lymph nodes. occasionally even in the form of small aggregates. thymus. Current evidence suggests that HD may be a syndrome that comprises several entities. Diffuse fibrosis 5. Inc. Lymphocytic and histiocytic a. 5-44.. Nodular b. neutrophils. Warnke RA Cancer 49:1848-1856. 1981.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . nodular type.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

Scattered R-S variant cells are seen. Fig.88 the capsule and separate the tumor into nodules composed of a variety of reactive cells and R-S variants called lacunar cells (Fig. Reticular type. eosinophils. Lymphocyte depletion type HD occurs as diffuse fibrosis type (Fig. 5-46). The lymph node is largely replaced by a proliferation of R-S cells and R-S variant cells. 5-49. Nodular sclerosis type HD. Bands of thick collagen extend from the thickened capsule to divide the lymph node into smaller nodules. Areas of necrosis or microabscess formation may be prominent (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . eosinophilic. Much of the lymph node has been replaced by a pink. 5-48). 5-46. Fig. which may be pleomorphic and bizarre. and plasma cells (Fig. histiocytes. Fig. Diffuse fibrosis type. Mixed cellularity type HD is characterized by a mixed cellular background of lymphocytes. In the latter there is marked proliferation of R-S cells. 5-50). 5-50. 5-48. 66417308 : ¸Ÿ±U 24 ¥°Q . 5-49) or reticular type (Fig. Fig. In the former R-S cells are not necessarily numerous. Fig. Microabscess is surrounded by a ri m of R-S variant cells. Lymphocyte depletion type HD. 5-47.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Mononuclear R-S variant cells are scattered in a mixed cellular background. Nodular sclerosis type HD. Typical R-S cells and mononuclear variant R-S cells are readily identified. 5-47). Mixed cellularity type HD. amorphous material with depletion of lymphocytes.

Burkitt-like Clin Peripheral T-cell.5 to 2. Follicular. ATUL. Follicular. mixed small cleaved and large cell D. LGL. diffuse small cell Lymphoplasmacytoid Marginal zone/MALT Mantle cell Diffuse large B-cell lymphoma ATUL Angioimmunoblastic Angiocentric Diffuse large B-cell lymphoma G. 5-52). SLL. permission. Morphologically the tumor cells resemble small mature lymphocytes (Fig. Categories D–H are also called aggressive lymphomas. follicular. 66417308 : ¸Ÿ±U 24 ¥°Q . a German system. J . grade I Mantle zone Marginal zone Follicle center. MALT. PLL. Lymphoblastic Small noncleaved cell Burkitt Non-Burkitt 5 6 Precursor B-lymphoblastic Burkitt High-grade B-cell. unspecified 47:351-372. large cell 22 H. follicular. Non-Hodgkin lymphomas can be classified according to the Working Formulation developed by the National Cancer Institute. Comparison of Working Formulation (WF) and Revised European-American Lymphoma (REAL) Classification WF Category* A. unspecified ATUL Angioimmunoblastic Angiocentric Peripheral T-cell. predominantly small cleaved cell C. which is widely used in Europe. CLL. small lymphocytic lymphoma. H –J = high grade (survival 0.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . which is referred to as REAL (Revised European-American Lymphoma. mucosa-associated lymphoid tissue. Large cell Immunoblastic 9 Peripheral T-cell. unspecified ATUL Angioimmunoblastic Angiocentric Anaplastic large-cell Precursor T-lymphoblastic I.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . follicular. unspecified ATUL Angioimmunoblastic Angiocentric Peripheral T-cell. large cell E. *Categories A–C = low-grade (survival 5 to 10 or more years untreated). Diffuse. Reproduced with From Skarin AT. Table 5-9). mixed small and large cell 7 Large B-cell lymphoma (rich in T-cells) Follicle center. chronic lymphocytic leukemia. unspecified REAL Classification T-cell Neoplasms T-cell CLUPLL LGL Plasmacytoid B. called the Kiel classification. D–G = intermediate grade (survival 2 to 5 years untreated). diffuse small cell Marginal zone/MALT T-cell CLUPLL LGL Peripheral T-cell. Small lymphocytic consistent with CLL Frequency (%) 4 B-cell Neoplasms B-cell CLUSLUPLL Marginal zone/MALT Mantle cell Lymphoplasmacytoid 26 Follicle center. grade II Marginal zone/MALT Follicle center. large granular lymphocyte leukemia. or the new classification developed by the International Lymphoma Study Group.89 NON-HODGKIN LYMPHOMA The term non-Hodgkin lymphoma includes all malignant lymphomas other than Hodgkin disease. CA Cancer / . 1997. Small lymphocytic lymphoma is a low-grade B-cell neoplasia that diffusely infiltrates the lymph nodes (Fig. prolymphocytic leukemia. grade III Mantle cell Follicle center. Dorfman DM: Non-Hodgkin's lymphoma: current classification and management. Adult T-cell lymphoma/leukemia.0 years untreated). Diffuse. 5-51). Follicular. Diffuse. small cleaved cell 9 4 8 F.

These B cells are normally present external to follicular mantle cells and are particularly prominent in the spleen. In approximately 40 percent of cases monoclonal plasma cells or plasmacytoid cells also are found in the infiltrate. The lymph node is infiltrated by a uniform population of small to intermediate-sized lymphocytes with bland nuclei and a moderate rim of clear cytoplasm. 5-5I. The infiltrate is composed of small to medium-sized lymphocytes with a mature chromatin pattern and slightly irregular nuclear membranes. In later stages lymphoma cells diffusely infiltrate the lymph nodes or the mucosa (Fig. They are thought to be capable of differentiating into reactive monocytoid B cells and plasma cells. Involved lymph nodes show a variety of architectural patterns.to intermediate-grade lymphoma that grows in a follicular pattern. mixed small cleaved and large cell (Fig. with occasional colonization of the germinal center (Fig. The infiltrate typically is composed of intermediate-sized monocytoid B cells (Fig. 5-59). Fig. The lymph node is composed of loosely packed cells of intermediate size with discernible nucleoli. There are several architectural patterns.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig. Marginal zone lymphoma.90 Fig. and predominantly large cell (Fig. 5-54. such as signet ring—like cells. Small lymphocytic lymphoma. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Marginal zone lymphoma. 5-53). The normal architecture of the lymph node may be completely effaced or a vaguely vascular pattern may be retained. Mantle cell lymphoma is a low. 5-53. Marginal zone lymphoma is a low-grade lymphoma composed of cells that resemble normal B cells of the marginal zones. 5-55 and 5-56). Note the presence of scattered neutrophils. The normal lymph node architecture has been completely effaced. 5-53). Lymphoma cells tend to invade epithelia. 5-60). Cytologically several variants have been recognized: small cleaved cell (Fig. whereas those arising in mucosa-associated lymphoid tissue are called maltomas. 5-62). 5-58). Small lymphocytic lymphoma. 5-54). Follicular lymphoma is a low.to intermediate-grade lymphoma. 5-57). It represents the neoplastic counterpart of germinal center B lymphocytes (Fig. Occasionally the neoplastic cells take unusual forms. 66417308 : ¸Ÿ±U 24 ¥°Q . Nucleoli are inconspicuous and the cytoplasm is scant (Fig. 5-61). Cases involving lymph nodes are often referred to as monocytoid lymphoma. There is preferential infiltration of the marginal zone of splenic white pulp. In early stages lymphoma cells infiltrate the marginal zone surrounding reactive germinal centers. Mantle zone pattern results from a broad infiltrate around the reactive germinal centers (Fig. 5-52. or they may show plasmacytoid differentiation. forming " lymphoepithelial lesions " (Figs.

5-58. Marginal zone lymphoma of the stomach ("maltoma"). 5-56. Fig. invade gastric glands. Many crowded nodules of relatively even size and lacking well-defined mantle zones are present. Marginal zone lymphoma of salivary gland. 5-59. Fig. 5-57. many of which have a clear perinuclear halo. Germinal center is surrounded by a broad zone ("mantle"). The infiltrate consists of a monotonous population of small lymphocytes. The infiltrate is composed of a monotonous population of small cells with contorted nuclei (cleaved cells). The nuclei of these cells have a mature chromatin pattern and slightly irregular outlines.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 66417308 : ¸Ÿ±U 24 ¥°Q . forming a socalled "lymphoepithelial lesion. Small to medium-sized lymphocytes." Fig. predominantly small cleaved cell lymphoma. Follicular. Mantle cell lymphoma. The epithelial gland is infiltrated with lymphocytes. Follicular lymphoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig. 5-55. Fig.91 Fig. Mantle cell lymphoma. 5-60.

Peripheral T-cell lymphomas are difficult to recognize morphologically because they can assume a variety of histologic appearances. such that neither element dominates (Fig. They 66417308 : ¸Ÿ±U 24 ¥°Q .y lymphoma. and plasma cells. predominantly large cell lymphoma. 5-64). 5-63) or immunoblasts (Fig. In diffuse mixed lymphomas there is a significant admixture of small lymphoid cells. 5-68). Follicular. mixed large cell and large cell immunoblastic lymphomas of B-cell lineage are classified according to the Working Formulation as intermediate. erythrophagocytic T. intestinal T-cell lymphoma. Diffuse large cell lymphoma. angioimmunoblastic lymphadenopathy with dysproteinemia-like (AILD-like) T-cell lymphoma.or high-grade malignancies composed of T cells. The hallmark of these lymphomas is the presence of a significant number of large lymphoid cells (Fig. hepatosplenic T-cell lymphoma. 5-62. The neoplastic cells infiltrate the lymph node. Large tumor cells have vesicular nuclei in contrast to occasional normal lymphocytes that have condensed chromatin. Necrosis or sclerosis may be prominent in large cell lymphomas (Fig. 5-65). Fig. Follicular. 5-61. 5-64. Peripheral T-cell lymphomas (PTCL). The cytoplasm is abundant and shows plasmacytoid features. These tumors usually are designated T-cell rich B-cell lymphomas (Figs. causing partial or complete effacement of the lymph node architecture. mixed small cleaved and large cell lymphoma. Typically there is an admixture of reactive cells. Two cell populations are clearly seen. 5-66 and 5-67). such as epithelioid and nonepithelioid histio - cytes. The infiltrate is composed predominantly of large noncleaved cells. Fig. The term PTCL encompasses several clinicopathologic entities. adult T-cell leukemia/lymphoma. lymphoepithelioid T-cell lymphoma. also known as postthymic T-cell lymphomas. eosinophils.92 Fig. includipg mycosis fungoides/Sezary syndrome. The tumor cells are large. Diffuse. 5-63. In other cases the small round cells represent reactive T cells that are not part of the neoplastic process.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . T-cell lymphoma associated with erythrophagocytosis.or high-grade lymphomas. Large cell immunoblastic lymphoma. morphologically and immunophenotypically equivalent to mature T cells. and many cases of CD30+ lymphoma. Fig. with vesicular nuclei containing a single prominent nucleolus. are intermediate. respectively. angiocentric T-cell lymphoma. small lymphocytes.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

5-67. numerous arborizing vessels. a B cell marker. Scattered eosinophils are present. preferential paracortical infiltration. some of which have multilobated nuclei (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . which may vary from one cell to another and may include highly pleomorphic forms. T-cell rich B-cell lymphoma. 5-68.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . When the neoplastic cells increase in number and cells with clear cytoplasm appear. In early stages of the disease the definitive diagnosis of this lymphoma cannot be made easily.93 Fig. Fig. Large cell lymphoma. The cell infiltrate usually is composed of a mixture of atypical intermediate-sized to large lymphoid cells (Fig. and absence or repression of germinal centers. 5-70). 5-69. The large cells stain with antibodies to CD20. AILD-like T-cell lymphoma is characterized by cell-poor diffuse effacement of lymph node architecture. The tumor contains prominent areas of sclerosis. The perivascular infiltrate is composed of both large and intermediate-sized atypical lymphoid cells. never show a follicular architecture but may show effacement. 5-66. Fig. Diffuse mixed small and large cell lymphoma. Peripheral T-cell lymphoma. 66417308 : ¸Ÿ±U 24 ¥°Q . The large tumor cells are embedded in a background of smaller T cells. Deposits of intercellular PAS-positive amorphous material may be prominent. 5-69). or preferential sinusoidal involvement. The atypical cells often have irregular nuclear contours. T-cell rich B-cell lymphoma. Fig. A relatively even admixture of small and large atypical lymphoid cells is seen. often forming clusters around the Fig. 5-65.

These cells often form small groups. Atypical lymphoid cells are admixed to epithelioid histiocytes.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. macrophages. 5-72). Angiocentric T-cell lymphoma is a term that encompasses a group of previously poorly characterized entities. In Burkitt lymphoma the infiltrate begins in the germinal centers. Many of the large lymphoid cells have hyperlobated nuclei. such as lymphomatoid granulomatosis and polymorphic reticulosis. the diagnosis of AILD-like T-cell lymphoma can be made readily (Fig.94 Fig. The infiltrates consist of atypical T cells. is characterized by a proliferation of atypical T lymphocytes surrounded by epithelioid histiocytes (Fig. The tumor consists of a mixed population of small. Fig. 5-70. 5-71). Small noncleaved cell lymphoma (SNCL) is a high-grade malignancy of two subtypes: Burkitt type and non-Burkitt type. evoking a fibrous response (Fig. It occurs in extranodal sites. it represents the tissue equivalent of acute lymphoblastic leukemia. The tumor cells have round or highly irregular nuclear contours with finely dispersed chromatin and inconspicuous nucleoli. Plasma cells and eosinophils usually are present. 5-74). 5-73. small lymphocytes.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The unifying feature of the various forms of this lymphoma is the infiltration of small arteries and veins (Fig. The infiltrate contains prominent intermediate-sized atypical lymphoid cells with pale cytoplasm. 5-72. The atypical small to medium-sized lymphoid cells tend to efface the lymph node architecture and spread into the pericapsular tissue. AILD-like T-cell lymphoma. 5-71. vessels. intermediate-sized. Lymphoblastic lymphoma is a high-grade malignant lymphoma. 5-73). or Lennert lymphoma. A small artery in the center is infiltrated with atypical lymphoid cells that occlude its lumen. often with pleural or pericardial effusion. Eosinophils and plasma cells also may be present. Angiocentric lymphoma. and large lymphoid cells. subsequently leading to an effacement of the 66417308 : ¸Ÿ±U 24 ¥°Q . and eosinophils. Lymphoepithelioid T-cell (Lennert) lymphoma. Lymphoepithelioid T-cell lymphoma. which represent the most abundant cells in the tissue. A lymphoblastic lymphoma typically presents as a mediastinal mass. plasma cells. Fig. particularly the upper and lower respiratory tracts and the skin. The mitotic rate is high and extensive single cell necrosis may be present. Peripheral T-cell lymphoma.

The chromatin is not dispersed as finely as it is in lymphoblastic lymphoma. Each nucleus contains several nucleoli. 5-78. 5-76. 5-78). and multiple nucleoli (Fig. lymph node architecture (Fig. A starry sky pattern is seen at low magnification. A population of intermediate-sized lymphoid cells with a high mitotic rate is present. Burkitt lymphoma. Burkitt lymphoma. 5-74. OTHER HEMATOPOIETIC PROLIFERATIONS IN LYMPH NODES Neoplasms that originate from other cellular components of lymph nodes are much less common than lymphomas. There are numerous mitoses and tangible body macrophages. The neoplastic cells of the non-Burkitt subtype are similar to those in Burkitt lymphoma except that the cells show more pleomorphism and fewer but often more prominent nucleoli (Fig. Lymphoblastic lymphoma. The neoplastic Fig. The sinusoid of the lymph node is distended by sheets of Langerhans cells and an aggregate of eosinophils. A single cell file pattern of infiltration is seen in the perinodal tissue. 5-75. Langerhans cell histiocytosis. Fig. non-Burkitt type. 5-76).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 66417308 : ¸Ÿ±U 24 ¥°Q . The tumor is composed of a uniform population of medium-sized lymphoid cells. Small noncleaved cell lymphoma. The cells are somewhat more pleomorphic than those typically seen in Burkitt lymphoma. Fig.95 Fig. coarse chromatin.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . which impart to the lymph node a starry sky appearance. 5-77). Fig. The neoplastic cells are B lymphocytes of intermediate size with round nuclei. Langerhans cell histiocytosis presents with neoplastic infiltrates in lymph node sinuses (Fig. 5-75). 5-77.

5-82). Follicular dendritic cell sarcoma. and lymphoma Hemolytic anemias Hereditary spherocytosis. 66417308 : ¸Ÿ±U 24 ¥°Q . 5-80. leukemia. folded delicate nuclear membranes. High-grade B-cell lymphomas. 5-79.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . T-cell lymphomas are less common in the spleen. etc. on the other hand. Fig. The pattern of splenic involvement depends on the type of the disease. Lowand intermediate-grade lymphomas involve the white pulp and produce a "miliary" pattern (Fig. which give them a coffee bean—like appearance. The infiltrate consists of spindle cells. 5-79). Niemann-Pick disease Amyloidosis NEOPLASMS INVOLVING THE SPLEEN Splenomegaly may be caused by a variety of neoplastic and nonneoplastic diseases. elliptocytosis Thalassemias. brucellosis. Sepsis Congestion Cirrhosis of the liver Budd-Chiari syndrome Chronic congestive heart disease Storage diseases Gaucher disease. All leukemias. produce one or more solid tumors or masses (Fig. toxoplasmosis. and lymphomas may involve the spleen and cause splenomegaly (Fig. Myeloid leukemia may involve the lymph nodes or may present as a soft tissue mass ( "chloroma " ). etc. 5-81). where they usually involve the T zones and the red pulp (Fig. Tumors are composed of a uniform population of cells with vesicular nuclei (Fig. In acute myeloid leukemia the cords and sinuses are filled with blast cells (Fig. Malaria.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The infiltrates are always in the white pulp. Dendritic cell sarcomas include follicular dendritic cell sarcoma and interdigitating cell sarcoma. 5-84). which are listed in Table 5-10.96 Fig. Langerhans cells have grooved nuclei with complex. essential neutropenia Systemic lupus erythematosus Rheumatoid arthritis Sarcoidosis Infections Infectious mononucleosis. 5-85). myeloproliferative diseases. The mitotic rate is high and occasionally there is a starry sky appearance. There are numerous small lymphocytes between the tumor cells. Acute myeloid leukemia involving a lymph node. Splenic involvement is found in approximately one third of cases of Hodgkin disease. A few scattered lymphocytes are still present. 5-83). A diagnosis of "atypical" lymphoblastic lymphoma was favored histologically because this patient did not have a history of leukemia. sickle cell anemia Autoimmune disorders Autoimmune hemolytic anemia Thrombocytopenia. Causes of Splenomegaly Neoplasia Myeloproliferative and myelodysplastic disorders. 5-80). In hairy cell leukemia the neoplastic cells infiltrate the red pulp and surround the trabecular vessels of the white pulp (Fig. The neoplastic cells have elongated nuclei and pale eosinophilic cytoplasm (Fig. 5-86).

Hairy cell leukemia. Fig. high-grade. 5-86. Replacement of normal sinus-lining cells by hairy lymphocytes leads to pooling of blood and the formation of "blood lakes. Tumor cells form a discrete mass in the spleen. Fig. T-cell lymphoma. Mantle cell lymphoma. Fig. Chronic myeloid leukemia.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 5-85. 66417308 : ¸Ÿ±U 24 ¥°Q . simulating malignant histiocytosis. Fig. The tumor involves the sinusoids of the red pulp. 5-84. The cords and sinuses are filled with blast cells. Spleen also shows infarcts. 5-81. Lymphoblastic lymphoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Splenomegaly is a common finding." which are typical of this disease. The tumor cells diffusely infiltrate the red pulp. Acute myeloid leukemia.97 Fig. 5-83. Fig. 5-82. The enlarged follicles of the white pulp infiltrated with tumor cells impart a "miliary" pattern to the cross section of the spleen.

dysplasia with pseudoglandular appearance. also known as lymphoid follicular hyperplasia. Patient had SCID caused by purine nucleoside phosphorylase (PNP) deficiency. (2) welldifferentiated thymic carcinoma. Histologically the thymus shows either simple dysplasia (Fig. A. predominantly cortical (organoid). 66417308 : ¸Ÿ±U 24 ¥°Q . and (3) anaplastic carcinoma (Fig. They are composed of spindle-shaped epithelial cells admixed to mature lymphocytes (Fig. The enlargement of the thymus is as- sociated with an increased number of lymphoid follicles with germinal centers (Fig. (3) thymitis and hyperplasia. 5-91). Thymic hypoplasia.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 5-89). L. A severely hypoplastic thymus (arrowheads) was found close to the aortic arch at the autopsy of a six-month-old infant who died of sepsis superimposed on severe combined immunodeficiency (SCID). A B Fig. 5-87. 5-88. but no Hassall corpuscles are seen. Fig. There are three forms of thymic carcinomas: (1) low-grade. malignant thymoma. which includes squamous cell carcinoma. Thymomas are classified as benign or malignant. and (4) thymic neoplasia. Thymic dysplasia with stromal corticomedullary differentiation. 5-89. clear cell carcinoma. Fig. or severe atrophy. 5-90). In primary immunodeficiency states the thymus is very small (Fig. Thymus.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Lymphofollicular thymitis. Tumors of the thymus originate from the thymic epithelium or lymphocytes. dysplasia with stromal corticomedullary differentiation (Fig. Larnyx.98 DISEASES OF THE THYMUS The most important pathologic changes involving the thymus are (1) developmental disorders such as thymic aplasia. Epithelial thymic lobules are almost devoid of lymphoid cells. 5-87). Lymphomas are of B-cell or T-cell type. 5-93). Rudimentary cortical medullary demarcation is evident. without corticomedullary demarcation and with a lack of Hassall corpuscles. Simple thymic dysplasia. hypoplasia. is found in 50 percent to 70 percent of cases of myasthenia gravis. or dysplasia. Benign thymomas are well encapsulated (Fig. or carcinoid. Hodgkin disease also may involve the thymus. 5-92). T. Incomplete DiGeorge syndrome shows incompletely descended hypoplastic thymus. B. 5-88). (2) accelerated involution of the thymus.

Am J Surg Pathol 20:519-552. Skarin AT. 1996. Jaffe ES. Kuo Ti': Kikuchi's disease (histiocytic necrotizing lymphadenitis). Kikuchi M et al: Angioimmunoblastic lymphoma (AILD-type T-cell lymphoma) with hyperplastic germinal centers. 1995. Chang KL. 1995. Stein H et al: A revised European-American classification of lymphoid neoplasm: A proposal from the International Lymphoma Study Group. 1993. Fig. Kingma DW et al: Hodgkin's disease following non-Hodgkin's lymphoma. Arber DA et al: Pathologic features of nodular lymphocyte predominance Hodgkin's disease in extranodal sites. Madeiros LJ. Hammer RD. Epithelial tumor cells form solid nests that contain only a few scattered lymphocytes. Clinical and pathologic features. Dorfman DM: Non-Hodgkin's lymphoma: Current classification and management. Am J Clin Pathol 99:486-493. 1996. A clinicopathologic study encompassing 50 years. 5-92. immunohistology. Masih AS et al: T-cell—rich B-cell lymphoma. 66417308 : ¸Ÿ±U 24 ¥°Q . The thymus contains numerous lymphoid follicles in the perivascular spaces and the medulla. Isaacson PG: Recent developments in our understanding of gastric lymphomas. Kurtin P1.99 Fig. Thymic carcinoma. 1995. Glick AD. Stuckey JH. 1996. Am' SurgPathol 17:123-132. Suster S. Am J SurgPathol 20:1469-1480. 1994. A clinicopathologic and immunophenotypic study of nine cases. Thymoma. Fig. 1997. Lieberman PH. The tumor is composed of spindle-shaped epithelial cells in a background of mature lymphocytes. and DNA ploidy. 1995. Harris NL. Am J Surg Pathol 19:1313-1324. A distinct B cell neoplasm. Medullary thymoma. Ree HJ. CA Cancer J Clin 47:351-372. Bank PM: Extranodal lymphocyte predominance Hodgkin's disease. Jones CR. A clinicopathologic study of 79 cases with an analysis of histologic subtypes. Zarate-Osorno A. A diagnostic guide. Steinman RM et al: Langerhans cell (eosinophilic) granulomatosis. 5-90. Am J Surg Pathol 19:798-809. The borders of the tumor nests may be scalloped or infiltrating. Am JSurg Pathol 20(suppl 1):S1-S7. Kadin ME. 5-91. Blood 84:1361-1392. 1998. Am J Surg Pathol 20:613-626. Am J Surg Pathol 22:643-655. 5-93. The tumor is encapsulated and appears lobulated on cross section. Kamel OW. Am J Clin Pathol 103:6575. Chan WC. 1993. Am J Clin Pathol 103:485-491.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Burke JS: Splenic lymphoid hyperplasias versus lymphomas/leukemias. Siebert JM. A clinicopathologic study of eight cases.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. Moran C: Primary thymic epithelial neoplasms showing combined features of thymona and thymic carcinoma. Further Reading Baddoura FK. 1996. Greer et al: Splenic marginal zone lymphoma. Follicular thymitis in myasthenia gravis.

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and the mandible is even more complex because it involves the fusion of anlagen that are symmetrically formed on each side. the periodontal ligaments. 6-1). 66417308 : ¸Ÿ±U 24 ¥°Q . 6-3. Anomalies of tongue include macroglossia (a common feature of Down syndrome. the maxilla. The receding chin is associated with a hypoplastic mandible. Fig. congenital hypothyroidism. with recessed mandible and low-set ears. 6-5 and 6-6). and hamartomas such as giant hemangioma (Figs. Prognathia.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The teeth primordia develop through an intricate interaction of epithelial-mesenchymal precursors of the various layers of the teeth. Complex facial malformations maybe associated with incomplete formation of the mouth. fissured tongue. 6-3). Fig. and other parts of the face (Fig. nose. is a feature of Potter syndrome. Cleft palate. 6-4). congenital tumors. 6-2. Micrognathia. The pregnancy was marked by oligohydramnios related to renal agenesis. Fig. 6-1. Cleft lip and cleft palate are dysraphic malformations of polygenic origin that result from incomplete fusion of the facial embryonic structures (Fig. and several other conditions). 6-2). Complex facial malformation in a stillborn infant. in which the kidneys are not formed or the fetal urinary tract is obstructed (Fig.102 DEVELOPMENTAL ANOMALIES The upper digestive system develops from the embryonic foregut through a sequence of highly regulated events. The morphogenesis of the mouth and especially the lips. Fig. and the gingiva. Prognathia is abnormal protrusion of the mandible beyond the maxilla (Fig. 6-4. Potter syndrome.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

and coloration.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 6-7. Macroglossia. bacterial. and esophagitis may occur as isolated diseases or as a manifestation of generalized infection and/or various systemic diseases. It could have many causes. shows papillary hyperplasia with numerous downward projections of epithelium and a chronic submucosal inflammation. all of these infections show a predictable. eruption. vesicular. vesiculation. 6-5. and tracheoesophageal fistula. Giant congenital cavernous hemangioma of the tongue. formation. or fungal. caused by ill-fitting denture. pharyngitis. suppurative. Ill-fitting dentures may cause fibrous hyperplasia or inflammatory papillary hyperplasia. 6-7). shape. I NFLAMMATORY LESIONS Stomatitis (inflammation of the mouth). Hyperplastic granulation tissue on the gingiva. and typically are prone to ulceration.103 Fig. 6-8). Anomalies of teeth may be numerical or may involve positioning. Grayish fibrinous material covers the ulcer on the ventral surface of the tongue. Anomalies of the esophagus include congenital atresia. Stomatitis may be classified as acute or chronic and according to its etiology as viral. aphthous. or acanthosis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . which typically occurs on the mucosa of the hard palate (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . size. sialadenitis (inflammation of the salivary glands). enamel. Acute stomatitis presents in many forms such as erythematous. or pseudomembranous inflammation (Fig. Inflammatory papillary hyperplasia. may present in the form of nodular masses known as pyogenicgranuloma or epulis (Fig. Chronic stomatitis often is seen in smokers or may be caused by chronic irritation from illfitting dentures. 6-8. stereotypic pathol - ogy. dentinogenesis. 6-6. presumably caused by infection or trauma. stenosis. Fig. This hard palate lesion. Fig. Because the upper digestive tract is lined by squamous epithelium from the oral orifice to the lower end of the esophagus. Fig. Aphthous ulcer.

Presenting symptoms include erythema. and pseudomembrane formation. Ludwig angina. The lesion presents as a sharply demarcated nodule. Severe bacterial infection occasionally may spread to the neck and cause necrotizing neck gangrene known as Ludwig angina (Fig.104 6-9). In most instances oral infections can be treated effectively or may heal spontaneously. The infiltrates are most prominent around the small ducts. swelling or suppuration. such as Candida and Aspergillus (Fig 6-12). Fig. whereas viral infections are hematogenous. such as mumps virus. Oral Manifestation of AIDS Chronic thrush Hyperplastic stomatitis Recurrent apthae Condyloma acuminatum Necrotizing ulcerative gingivitis Kaposi sarcoma Angular cheilitis Erythematosus stomatitis Herpangina Hairy leukoplakia Submandibular cellulitis Fig. Esophagitis usually is found in immunosuppressed persons who have AIDS. Pharyngitis is a common manifestation of numerous viral and bacterial infections ( " strep throat " ). Sialadenitis may be caused by bacteria or viruses. Oral lesions are common features of acquired immunodeficiency syndrome (AIDS) (Table 6-1). 6-10). those who are receiving treatment for cancer. 6-11. Pyogenic granuloma of gingiva. Sialadenitis also may be immune mediated (Fig. or fungi. Bacterial infections typically ascend through Stensen's excretory duct from the mouth. Chronic sialaderiitis. 6-9. 6-11). Fig. such as herpes simplex and cytomegalovirus (CMV). Necrosis and ulceration are accompanied by marked inflammation and edema of underlying neck tissue.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 6-10. The salivary gland is infiltrated focally by mononuclear cells. or those who are debilitated.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . In most instances esophagitis is caused by viruses. 66417308 : ¸Ÿ±U 24 ¥°Q .

A. Herpes simplex—infected cells have multinucleated "ground glass" nuclei. Dentigerous cyst.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . It usually is associated with the crown of an impacted or unerupted tooth.105 B Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . which are cavities in bone that are surrounded by granulation tissue or fibroosseous tissue.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The parakeratotic OKC is lined by a layer of squamous epith- A B C Fig. ORGAN-SPECIFIC LESIONS Dental Cysts Dental cysts are classified as developmental or inflammatory (Table 6-2. B. The wall of this dentigerous cyst contains foci of ameloblastoma penetrating into the connective tissue wall of the cyst. C. True cysts are lined by epithelium. stratified squamous epithelium. 6-13. Viral particles can be demonstrated by immunohistochemistry. Esophagitis. The cyst usually is lined by nonkeratinizing. A. B. It is lined by a thin non- keratinizing squamous epithelium that resembles the enamel epithelium. It occurs in two types: the more common parakeratotic OKC and the orthokeratotic OKC. in contrast to pseudocysts. Dentigerous cyst is the most common developmental odontogenic cyst. Odontogenic keratocyst ( OKC) accounts for 5 percent to 10 percent of all jaw cysts. Diagram 6-1). Mucous or ciliated cells may be present and the wall of dentigerous cysts may contain foci of ameloblastoma (Fig. 6-12. The stratified squamous epithelium lining the cyst shows mucous metaplasia. 6-13). Such unicysticameloblastomas occur in teenagers and are readily cured by enucleation.

C. Baltimore. ed 2. 1979. nasolabial cyst. globulomaxillary cyst. (From Batsakis JG: Tumors of the head and neck: clinical and pathological considerations. ed 2. residual. nasopalatine cyst. lateral periodontal. Springer-Verlag. 5. 6. A. periapical (radicular). 66417308 : ¸Ÿ±U 24 ¥°Q . 6-14.10 6 WHO Classification of Cysts of the Jaws Developmental Odontogenic Gingival cysts of infants (Epstein pearls) Odontogenic keratocyst (primordial cyst) Dentigerous (follicular cyst) Eruption cyst lateral periodontal cyst Gingival cyst of adults Glandular odontogenic cyst. dentigerous. 1992.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . B. 6. Shear M: Histological typing of odontogenic tumors. A B Diagram 6-I. cyst of palatine papilla. B: I. in the mandible and maxilla respectively. Higher power view shows typical parakeratosis. Daughter cysts are present in the connective tissue capsule. gingival. corrugated. B. The cyst is lined by partially detached. squamous epithelium. mandibular infected buccal) cyst From Kramer IRH. Parakeratotic cyst. 3. Diagrams of the site of odontogenic. median palatal cyst. 4. nasoalveolar cyst. eruption. 7. Pindborg JJ.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The squamous epithelium shows palisaded basal cell proliferation and surface parakeratosis.) A B C Fig. 4. A: I. sialood NonodontogeniC Nasopalatine duct (incisive canal) cyst Nasolabial (nasoalveolar) cyst Inflammatory Radicular cyst Apical and lateral cysts Residual cyst Paradental (inflammatory collateral. 5. 2. 3. and fissural (nonodontogenic) cysts. A. Williams & Wilkins. Berlin. 2. primordial.

nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The persistent inflammation stimulates the proliferation of the epithelium derived from odontogenic residues in the periodontal ligament. 6-16. Radicular cyst is the most common cyst of the jaws.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The orthokeratotic OKC does not have a palisading basal layer. Radicular cyst. It develops from a periapical abscess or granuloma. A B C Fig. 6-14). The luminal surface is corrugated and is at least partially lined by parakeratotic cells. Rushton bodies and remnants of squamous epithelium are found in the inflamed cyst wall. hemosiderin pigment. The cyst is lined by keratinizing epithelium covered with a keratin layer. 66417308 : ¸Ÿ±U 24 ¥°Q . C. which provide partial lining of the cavity (Fig. The surface keratin layer lies on a prominent granular cell layer but without surface corrugation (Fig. and cholesterol clefts. prominent granular layer. Orthokeratotic cyst. and the epithelial lining appears flattened. B. 6-16). Radioluscent area is seen in association with the remaining roots of the right maxillary bicuspid and first molar. A. the rests of Malassez. Cyst wall contains inflammatory cells. The lumen is filled with keratin. The epithelium lining the radicular cysts is squamous but it shows no tendency toward keratinization. B. extravasated blood. 6-I S. The surrounding connective tissue is heavily inflamed and may be hyalinized. The wall of the cyst is lined by keratinizing epithelium. A. with flattened basal layer. and surface orthokeratin. elium that is five to eight cells thick and shows maturation from the palisading basal layer toward the lumen (Fig.107 A B Fig. 6-15). The connective tissue capsule may contain daughter cysts.

·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Mucocele. A B Fig. The epithelial nests represent ducts that have undergone squamous metaplasia.109 Fig. Fig. 6-19. 6-21.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Mucous retention cyst. B. The cyst is lined by squamous epithelium. Focal chronic sialoadenitis. 66417308 : ¸Ÿ±U 24 ¥°Q . 6-22. The myoepithelial nests are surrounded by lymphoid cells in a follicular arrangement. The nests are surrounded by loose connective tissue. Mucus is infiltrated with inflammatory cells. Myoepithelial sialoadenitis of Sjogren syndrome. Sjogren syndrome. Fig. A. 6-20. Necrotizing sialometaplasia.

The wall of these lesions may show nonspecific inflammation. These syndromes do not have a distinct anatomic substrate and show no pathologic changes except in rare instances. "nutcracker esophagus" ). and stenosis are common complications. Diverticula and hernia. or lower esophagus and are either of traction or pulsion type. such as in systemic sclerosis.11 0 Diagram 6-2. 6-25). capillary proliferation in the papillae. A. and corrosive chemicals. Diaphragmatic hernia and esophageal diverticula can be diagnosed best by radiograph (Diagram 6-2). and congestion (Fig. B. Prolonged reflux leads to ulceration and glandular metaplasia (Barrett esophagus) (Fig. Esophageal Lesions Dysphagia. A. strong acids. or blackened (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The dilated veins are located in the lower third of the esophagus (Fig. C. which typically are caused by prolonged vomiting in alcoholics. Outpouchings of the esophagus may occur in the upper. A B Fig. middle. 6-23. is a cause of bleeding in Mallory-Weiss syndrome (Fig. which typically is caused by cirrhosis. Mucosal ulceration maybe extensive in terminally ill patients. 66417308 : ¸Ÿ±U 24 ¥°Q . The mucosa typically is eroded. Rupture of the esophagus. Dilated veins filled with blood are seen in the wall of the esophagus. 6-24). Rolling hernia. 6-26). Sliding hernia. usually is caused by dysmotility syndromes related to spasms (e. Dilated tortuous veins are seen bulging underneath the intact epithelium of the lower esophagus. Esophageal varices are a complication of portal hypertension. B.. or in Chagas disease involving autonomic ganglia. 6-23). even in those who have not previously had reflux esophagitis (Fig. fistulas. 6-28).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . elongation of the papillae beyond the normal 50 percent extension into the epithelium. The epithelium shows basal cell hyperplasia. Erosive or corrosive esophagitis may be caused by accidental or suicidal ingestion of lye. Eosinophils have been described as characteristic but they rarely are actually seen.g. in muscle diseases such as myotonic dystrophy. Lacerations at the level of the gastroesophageal junction. 6-27). Reflux esophagitis is an inflammatory disease that is caused by the reflux of acidic gastric juice into the esophagus. the most common esophageal symptom. Esophageal varices. hemorrhagic.

6-26. The papillae are elongated and congested.Fig. 6-24. Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The mucosa replacing the normal squamous epithelium is composed of glands rich in goblet cells. Corrosive esophagitis and gastritis caused by ingestion of hydrochloric acid. There also is basal cell hyperplasia. Fig. 6-27. The normal squamous epithelium (white) is missing over broad areas. Mallory-Weiss syndrome. Mucosa appears black. Hematemesis in this chronic alcoholic was caused by deep mucosal tears at the gastroesophageal junction. Reflux esophagitis. Barrett esophagus. 6-28. Fig. 6-25. 66417308 : ¸Ÿ±U 24 ¥°Q . Fig. Ulcerative esophagitis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

6-29. Histologically tumors that originate from minor salivary glands are identical to those seen in major salivary glands. Ameloblastomas originate mostly in the mandible from the rests of enamel organ epithelium. Important variants are (1) poorly differentiated nonkeratinizing SCC. 6-30). Erythroplakia of the hard palate. beginning as carcinoma in situ and progressing to invasive carcinoma that shows varying degrees of keratinization. and (4) verrucous SCC (Fig. Histologically the tumors have the usual features of squamous cell carcinoma (SCC). other patterns are less common (Fig. 6-32). mostly because of its size . indurations. They can occur in the major or minor salivary glands. 66417308 : ¸Ÿ±U 24 ¥°Q . 6-31). Tumors also can originate from the tooth-related structures and primordia and from minor salivary glands. calcifying epithelial odontogenic tumor (Fig. Cuboidal or columnar tumor cells form ductlike structures. Fig. Odontogenic adenomatoid tumor.112 TUMORS Oral Tumors Most tumors of the mouth originate from the squamous epithelium lining the oral cavity. or ulcerations (Fig. Ameloblastoma is the most common odontogenic tumor. 6-3 I. Ameloblastoma. epithelial lining of dentigerous cysts. Verrucous carcinoma. (3) papillary SCC. (2) basaloid SCC. Benign tumors are more common than malignant tumors. Most ameloblastomas present in a follicular or plexiform histologic pattern. and ameloblastic fibroma (Fig. 6-33).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 6-32.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 6-34) are less common. The interdigitating cords of palisading epithelial cells surround areas composed of stellate reticulum cells. Salivary Gland Tumors Salivary gland tumors occur in several histologic forms (Table 6-4). Benign tumors are more common than malignant tumors. 6-30. or occasionally from the basal layer of the oral mucosa. Tumors of the squamous epithelium present clinically as white or red plaques (leukoplakia and erythroplakia). Pleomorphic adenoma is the most Fig. The neoplastic epithelium forms rounded nests extending into the underlying stroma. Dental tumors occur in several forms (Table 6-3). Fig. 6-29). Most patients are in the third to fifth decade of life. The parotid gland is the most commonly involved site. Fig. Other odontogenic tumors such as odontogenic adenomatoid tumor (Fig.

Odontogenic Tumors Benign . NOS Epidermoid (squamous cell) carcinoma Sebaceous carcinoma Basal cell adenocarcinoma Undifferentiated carcinoma • Large cell lymphoepithelial • Small cell lymphoepithelial Carcinosarcoma NNW NOS. The islands of polyhedral epithelial cells are surrounded by extracellular eosinophilic material with foci of calcification.113 Fig. Calcifying epithelial odontogenic tumor. 6-33. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº ." ' Epithelial Ameloblastoma Odontogenic adenomatoid tumor Calcifying epithelial odontogenic tumor Mesenchymal Myxoma Odontogenic fibroma Cemental tumors Mixed epithelial and mesenchymal origin Ameloblastic fibroma Ameloblastic fibroodontoma Complex and compound odontomas Malignant Epithelial Malignant ameloblastoma Ameloblastic carcinoma Mesenchymal Ameloblastic fibrosarcoma Classification of Epithelial Salivary Gland Tumors Benign Pleomorphic adenoma (mixed tumor) Papillary cystadenoma lymphomatosum (Warthin tumor) Monomorphic adenoma • Basal cell • Ductal • Oncocytic Myoepithelioma Ductal papilloma • Intraductal • Sialadenoma papilliferum • Inverted Cystadenoma Sebaceous adenoma Sebaceous lymphadenoma Malignant Arising from Preexisting Benign Tumor Carcinoma • Ex pleomorphic adenoma • Ex monomorphic adenon cell a oma. 66417308 : ¸Ÿ±U 24 ¥°Q . Not otherwise specified. 6-34. Ameloblastic fibroma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Odontogenic epithelium forms islands surrounded by highly cellular stroma. Ex Warthin tumor Ex myoepithelioma Malignant Mucoepidermoid carcinoma Adenoid cystic carcinoma Acinic cell carcinoma Epimyoepithelial (clear cell) carcinoma Salivary duct carcinoma Papillary and nonpapillary adenocarcinoma Mucinous adenocarcinoma Cystadenocarcinoma Adenocarcinoma.

6-40). A. A B Fig. Pleomorphic adenoma of the parotid gland. Neoplastic papillae. 6-38). or interlocking cords (Fig. Epithelial cells are intermixed or surrounded by mesenchymal stroma that may be myxoid. Fig. 6-39). It is composed of columnar and cuboidal cells covering papillae embedded in a lymphocyte-rich stroma. sheets. The interlacing epithelial nests form occasional lumina and are surrounded by fibrous stroma. 66417308 : ¸Ÿ±U 24 ¥°Q . nests. Adenocarcinoma arising in pleomorphic adenoma. Basal cell adenoma is a benign tumor composed of bluish basaloid cells that form solid sheets or nests that have a palisaded outer layer (Fig. The tumor has an invasive growth pattern. 6-37). can be lined by oncocytic cuboidal or squamous cells (Fig. which are typical of the tumor. Sialadenoma papilliferum is a benign tumor composed of an exophytic and an endophytic component. In approximately 5 percent of patients mixed tumors give rise to adenocarcinomas (Fig. Myoepithelioma is a benign tumor composed of myoepithelial cells (Fig. 6-35). B.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 6-36. accounting for 60 percent to 70 percent of all parotid tumors and for 40 percent to 70 percent of tumors in other glands. and may even show ossification.114 common tumor. 6-36). 6-35. Papillary cystadenoma lympho- matosum is a benign slow-growing tumor of older adults. chondroid. or fibrous. (Fig. Pleomorphic adenoma is a benign tumor that presents as a sharply demarcated mass.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Oncocytoma is an uncommon benign tumor composed of mitochondria-rich cells with eosinophilic or clear cytoplasm. Histologically it is an adenocarcinoma. Histologically it consists of an epithelial component forming ducts.

Clear cells are arranged in an alveolar pattern. 6-39. 6-37. Eosinophilic cells form solid nests. Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Sialadenoma papilliferum. 6-40. A.115 Fig. Oncocytoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The tumor nests are composed of small basaloid cells. B. 6-38. A B Fig. The cells at the periphery of these nests are cuboidal and palisaded.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Basal cell adenoma. The papillae are lined by a double layer of oncocytic cells. Myoepithelioma: Tumor is composed of spindleshaped myoepithelial cells. Fig.

B. 6-41.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . B. A. 66417308 : ¸Ÿ±U 24 ¥°Q . C. Acinic cell adenocarcinoma. Well-differentiated serous acinar cells form solid sheets (solid pattern). Cribriform pattern. 6-42. Adenoid cystic carcinoma. Cells form follicles that vary in size and shape (follicular pattern). A.11 6 A B Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Tubular pattern. Solid pattern. A B C Fig.

The cells grow in three patterns: cribriform. Other malignant tumors. 66417308 : ¸Ÿ±U 24 ¥°Q . solid. 6-45). sebaceous carcinoma (Fig. Mucoepidermoid carcinoma is the most common malignancy. cystic. Epithelial-myoepithelial carcinoma. vacuolated. Adenoid cystic carcinoma accounts for 3 percent to 10 percent of all salivary gland tumors. and salivary duct carcinoma (Fig. 6-43). 6-46. polymorphous low-grade adenocarcinoma (Fig. Atypical basaloid cells show central sebaceous differentiation . and tubular (Fig. more often arising in minor than major glands. 6-43. acinar. 6-46). Cytologically bland and uniform basaloid cells grow in an infiltrating manner.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Microscopically these tumors are composed of rather uniform populations of basaloid tumor cells with little cytoplasm. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The ratio of benign to malignant tumors is 4:1.Malignant tumors of salivary glands are less common. 6-41). such as epithelial-myoepithelial carcinoma (Fig. or follicular pattern (Fig. Such cells have clear cytoplasm. 6-42). Fig. Numerous ductlike structures are lined by eosinophilic and clear cells. are less common. Fig. Salivary duct carcinoma. The tumor may be composed of several cell types including serous. usually in the center of epithelial nests. This tumor has the general features of squamous cell carcinoma but it also contains mucous cells. Fig. 6-44. accounting for 10 percent of major salivary gland tumors and 90 percent of minor salivary gland tumors. and intercalated ductlike cells arranged in a solid. clear or-granular. Sebaceous carcinoma. 6-45. papillary. Tumor nests are composed of cells arranged in a cribriform pattern that resembles breast carcinoma. 6-44). Polymorphous low-grade carcinoma. Acinic cell carcinoma accounts for 2 percent to 3 percent of salivary gland tumors.

·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . It usually presents as ulcerated or indurated lesions (Figs. Fig. Barrett's esophagus with dysplasia. The tumor appears ulcerated. are extremely rare (Fig. Fig. such as small cell carcinoma. which typically present as intramural subepithelial masses. 6-49. Carcinoma of the esophagus.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Squamous cell carcinoma is the predominant form of esophageal tumor. 6-49 and 6-50) and are preceded by dysplasia (Fig. Nuclei in dysplastic glands appear crowded and are not restricted to the basal parts of the cells. 66417308 : ¸Ÿ±U 24 ¥°Q . Adenocarcinomas arise from the glandular epithelium of Barrett esophagus and often are located at the gastroesophageal junction (Figs. 6-53). 6-50. Other malignant tumors of the esophagus. 6-51 and 6-52). 6-47 and 6-48). sharply demarcated from the surrounding tissues. 6-48. Squamous tumor cells form solid nests.118 Esophageal Tumors Carcinoma of the esophagus is the most important tumor in this anatomic site (see Diagram 6-2). Such adenocarcinomas do not differ from those in the stomach (Figs. Fig. Fig. Carcinoma of the esophagus. sarcoma. or melanoma. 6-50). The most common are leiomyomas. 6-47. Barrett esophagus with early carcinoma. Benign tumors of the esophagus are less common than malignant tumors.

Brown pigment is seen focally. A clinicopathologic and flow cytometric analysis. Ellis GL: Clear cell neoplasms in salivary glands: clearly a diagnostic challenge. Am J Surg Pathol 16:845-858. Haggitt RC: Barrett's esophagus. Some squamous epithelium remains between the neoplastic gland-like structures. Bleckner Set al: Carcinoma of the esophagus. 1995. Pignon J-P et al: Surgical pathology of adenocarcinoma arising in Barrett's esophagus: Analysis of 67 cases. Albores-Saavedra J: Salivary duct carcinoma. B. Semin Diagn Pathol 13:118-127. Adenocarcinoma of the esophagus. Cancer 76:922-927. dysplasia and adenocarcinoma. Melanoma of esophagus. Wenig BM. 66417308 : ¸Ÿ±U 24 ¥°Q . 1994. Delgado R. Ellis GL. Am J Gastroenterol 92:586-591. Fig. 6-53. 1992. Hitchcock CL. Huvos AG: Oncocytic tumors of the major salivary glands. Bittinger F. 1995. Pathol Annu 30:209-226. Ann Diag Pathol 2:61-78. 1995.I19 Fig. Amer J Surg Pathol 15:514-528. 1995. 1994. Eveson JW: Granulomatous disorders of the oral mucosa. Sarbia M. 1993. Shriver CD. Paraf F. 1991. 1998. Tumor is composed of polygonal cell with a large nuclei. Lieberman MD. 1995. Semin Oncol21:425-430.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The tumor at the gastroesophageal junction appears bulky and ulcerated. prognostic significance of histologic type. Fl@jou J-F. Am J Surg Pathol 19:183-191. Carpenter HA: Barrett's esophagus. Adenocarcinoma. J Thor Cardiovasc Surg 109:130-138. Klimstra D: Pathologic prognostic factors in esophageal carcinoma. A. Dawsey SM. Cameron AJ. Gnepp DR: Metastasizing mixed tumor of salivary glands. and early adenocarcinoma: A pathologic study. high-grade dysplasia. 6-5I. Simpson RH: Classification of salivary gland tumors—a brief histopathological review. Vuitch F. 1997.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Histol Histopathol 10:737-746. Lewin KJ: Histologic precursors of squamous esophageal cancer. Cancer 72:1503-1512. Porschen R et al: Prognostic factors in esophageal squamous carcinoma: A study of histologic parameters of esophageal squamous cell carcinoma. Hum Pathol 25:982-993. A black mass is seen protruding into the lumen. A B Fig. 1996. 6-52. Further Reading Brandwein MS.

nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .66417308 : ¸Ÿ±U 24 ¥°Q .

·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .66417308 : ¸Ÿ±U 24 ¥°Q .

and malrotations. It represents a remnant of the fetal vitelline duct (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . diverticula. Projectile vomiting in the first weeks of life is the presenting symptom. Fig. which protrude through the defect of the abdominal wall. 7-6). Fig. 7-3). 66417308 : ¸Ÿ±U 24 ¥°Q .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . As a result of incomplete formation of the anterior abdominal wall. Pyloric stenosis is the most common form of congenital gastrointestinal stenosis (Fig. The cysts are lined by intestinal epithelium. Intestinal duplication. persistent embryonic rests. 7-3. 7-2. 7-5). Fig. dilatations. The dilated lymphatics may be seen by the naked eye as cystic spaces that distort segments of the intestine (Fig. 7-4). Intestinal lymphangiectasia is a rare developmental disorder that is associated with protein-losing enteropathy. Inappropriate development of innervation in the distal colon is the main cause of proximal dilatation of the large intestine in Hirschsprung disease. such as diaphragmatic hernia or omphalocele. two feet proximal to the cecum. in which the normal body compartments have not been formed and parts of the gastrointestinal system are located outside their normal abdominal location (Fig. 7-I. It forms a cystic mass protruding into the intestinal lumen. Microscopically the intestinal wall is devoid of ganglion cells (aganglionosis) but it contains numerous hypertrophic nerves. Proliferation of small nerves may be demonstrated immunohistochemically using antibodies to acetylcholinesterase (Fig. stenoses. Males are affected four times more often than females. Meckel diverticulum is an example of a persistent embryonic structure. a sac forms at the site of the insertion of the umbilical cord.122 DEVELOPMENTAL DISORDERS Developmental disorders of the gastrointestinal tract include positional anomalies. It contains intestinal loops. It usually is two inches long and causes clinical symptoms in 2 percent of those who have it. duplications. Intestinal duplications are cystic structures included in the intestinal wall or attached to it (Fig. This blind intestinal loop of the il eus is found in 2 percent of the population. Omphalocele. 7-2). Positional anomalies include conditions. congenital atresias. Meckel diverticulum. 7-1). It may be limited to the bowel or it may be part of generalized familial lymphedema (Milroy disease).

7-4. NJ.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . B. The lamina propria of the colon contains numerous proliferated fine nerve fibers visualized immunohistochemically with the antibody to acetylcholinesterase. Lausanne. Camden.) 66417308 : ¸Ÿ±U 24 ¥°Q . (Courtesy of Dr. Congenital lymphangiectasia. Fred Bosman.V. W. Harrer. Dilated sigmoid colon tapers off toward the lower stenotic part. A. (Courtesy of Dr. Pyloric stenosis. Hirschsprung disease. 7-5.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .) A B Fig.) Fig. (Courtesy of Dr.123 Fig. The pylorus of this adult who was operated on for congenital pyloric stenosis still shows muscular hypertrophy. 7-6. James Dimmick. Cystic spaces distorting the wall of the resected intestinal loop represent dilated lymphatics. Vancouver. Canada. Switzerland.

Dieulafoy ulcer. Intestinal angiodysplasia is another important cause of gastrointestinal blood loss. Chronic intestinal ischemia. 7-8. Fig. both congenital and acquired. Acute ischemia of large bowel.which typically is related to the progressive stenosis and gradual occlusion of smaller branches of the arterial system. are important causes of gastrointestinal hemorrhage. 7-11). Necrotic epithelium has been sloughed off and only a few crypts remain. causes focal ischemic necrosis and ulceration of intestinal mucosa. 7-7. forms over an arteriovenous malformation (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . they include mucosal aneurysmal dilatations of small vessels (congenital hemorrhagic telangiectasia) and multiple congenital hemangiomas (Fig. a bleeding ulcer of the stomach. The intestinal loops have undergone hemorrhagic infarction. Fig. Mesenteric artery thrombosis. Acute systemic circulatory collapse as typically seen in shock is commonly associated with gastrointestinal mucosal bleeding ulcerations. which typically are hemorrhagic (Figs. Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 7-10). Fig. Typically seen in Osler-Weber-Rendu disease. Surface ulcerations of gastric mucosa appear as dark red defects. Thrombosed artery attached to the aorta (arrow). 7-8 and 7-9). Vascular anomalies. Hypoperfusion of intestinal mucosa in shock causes similar ischemic mucosal ulcers (Fig. 7-7).124 CIRCULATORY DISTURBANCES Circulatory disturbances are common in the gastrointestinal tract. 7-10. 66417308 : ¸Ÿ±U 24 ¥°Q . The mucosa shows hemorrhagic discoloration. 7-9. Curling ulcers. Occlusion of the mesenteric arteries or veins by thrombi or thromboemboli causes intestinal infarcts. Acute stress erosions and ulcers found in the proximal duodenum or stomach following burns or trauma traditionally are called Curling ulcers. Ischemic colitis. and those found in the stomach and associated with brain lesions are called Cushing ulcers (Fig. 7-12).

Rupture of the obstructed intestine leads to meconium peritonitis. intussusception. Histologically viscous mucus may be seen filling the crypts. are called hernias. Fig. 7-14. peritoneal adhesions. gallstones. Meconium ileus. which is found in children who have cystic fibrosis.125 Fig. The ulcer contains ruptured superficial tortuous arteries.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 7-13. Inspissated meconium.7 . B. A B Fig. such as trichobezoars. Trichobezoar. 7-12. which appears as a black intestinal plug. or fecaliths (Fig. or new cavities formed by defects or weakening of the abdominal wall. This large mass removed from the stomach was composed of hair. 7-15 to 7-17). Intestinal crypts contain viscid mucus. 7-13). Fig. and tumor-like lesions such as endometriosis (Figs. Protrusions of the intestines or any other abdominal organ into another body cavity. Herniated intestinal loops may become obstructed and may require surgery. 7-14).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The dilated intestine of this neonate is obstructed by thick meconium. also may cause intestinal obstruction (Fig. Other causes of intestinal obstruction are volvulus. OBSTRUCTIONS AND DILATATIONS OF INTESTINAL LUMEN The gastrointestinal tract may be obstructed by a number of intraluminal foreign bodies. 66417308 : ¸Ÿ±U 24 ¥°Q . Dieulafoy ulcer.1I . A. tumors. Intestinal hemangiomas.

A. which most often is caused by nonsteroidal antiinflammatory drugs. The serosa of this intestinal loop is covered with hemorrhagic tissue specks. The normal mucosal architecture is preserved and there is no atrophy (Fig. B. or fungal) or chemical. Diverticulosis. Intestinal loops twisted around mesocolon have undergone hemorrhagic necrosis. irritants in food. 7-16. Gastritis and Peptic Ulcer Inflammation of the gastric mucosa is classified as acute or chronic. Neutrophils and H. Diverticula are outpouchings of the mucosa through weakened muscularis propria. The outpouchings typically occur between the anti mesenteric taeniae (Fig. Volvulus.g. pylori may 66417308 : ¸Ÿ±U 24 ¥°Q .1 26 Fig. or intestinal epithelium (Fig. 7-18.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 7-15.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Type B gastritis is associated with Helicobacter pylori infection and is characterized by pronounced inflammatory infiltrates.. 7-19 and 7-20). Type A gastritis preferentially involves the fundus and oxyntic corpus and is characterized by inflammatory cell infiltrates and progressive replacement of the normal mucosa by patches of antral. Fig. bacterial. Diverticula may occur in any part of the intestine but are most common in the sigmoid colon. as seen on cross section blackened. pseudoantral. Endometriosis. 7-22). Acute gastritis is subclassified as infectious (e. Intussusception. viral. A B Fig. 7-18). 7-17. Loops of bowel invaginating one into another. Subserosal protrusions. Chronic gastritis is classified as autoimmune atrophic (type A) gastritis or chronic nonatrophic (type B) gastritis (Table-7-1). The mucosa protrudes through a defect of the muscle layer. or alcohol (Figs. 7-21). Fig. ORGAN-SPECIFIC DISEASES Each of the anatomic parts of the gastrointestinal tract may be affected by a site-specific type of inflammation or other organ-specific diseases.

Fig.127 Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . associated with pernicious anemia. There also is mild edema and chronic inflammation. The foveolae show mild reactive changes. Neutrophils are invading the epithelium of gastric pits. Fungal gastritis. A. The oxyntic mucosa shows atrophy and is replaced to a large extent by pseudoantral metaplasia. A B Fig. 7-20. Gastritis type A (autoimmune). B. The fungi form slightly raised mucosal plaques. The lamina propria is expanded by inflammatory cells. 7-21. The inflammatory cells are prominent in the lamina propria and the lumen contains H. Chemical gastritis caused by aspirin. Gastritis type B (nonatrophic).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 7-22. pylori organisms. Fig. which are stained black. 7-19.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The mucosa shows multiple hemorrhagFc erosions.

7-23.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . deep hemorrhagic defects of gastric mucosa. 7-24).128 Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Infection with H. Other less common forms of gastritis include eosinophilic. lymphocytic. 7-25. Comparison of Type A and Type B Gastritis ?~'? Location Distribution Cause Autoantibodies Gastric acidity Cancer risk Prevalence ype A (atrophic) Fundus Diffuses Autoimmune + — +/— Type B (nonatrophic) Antrum Focal Helicobacter pylori — + + Uncommon Common be seen in the mucosal pits. Hypertrophic gastritis (gastropathy) includes so-called Menetrier disease and gastric mucosal hyperplasia/hypertrophy resulting from an excess of gastrin in Zollinger-Ellison syndrome. Menetrier disease. B. Two ulcers appear as sharp. granulomatous. pylori also is associated with gastric and duodenal peptic ulcers (Fig. 7-23). 66417308 : ¸Ÿ±U 24 ¥°Q . and xanthomatous gastritis. It is associated with marked rugal thickening and histologically characterized by variable degrees of hyperplasia of foveolar or glandular compartments (Fig. 7-24. Fig. B A Fig. Biopsy specimen of the same patient shows that the mucosa has recovered almost completely after 6 months of gluten-free diet. Celiac disease A. The gastric mucosal folds are markedly thickened. Intestinal biopsy specimen shows atrophy of the villi and lengthening of the crypts. Peptic ulcer.

Celiac disease is a multifactorial disease of uncertain pathogenesis. Several diseases of neoplastic or unknown etiology such as Waldenstrom macroglobulinemia... pancreatic biliary disease Inborn errors of metabolism (disaccharidase deficiency) Short bowel syndrome Alcohol abuse Drug induced enteropathy Identifiable pathogens Viruses (e. The best examples are infections caused by Mycobacterium avium-intracellulare and Tropheryma whippelii (Figs. rota virus) Bacteria (e. A. These changes are reversible.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Whipple disease) Fungi (e. or fungi may cause diarrhea and malabsorption (Fig. Intestinal infection with Mycobacterium avium-intracellulare ( MAI).g. viruses. In many instances the causative pathogens are recognized by biopsy of the small intestine. Giardia lamblia) Metazoa (e. A B Fig.129 Small Intestinal Diseases That Cause Malabsorption According to small intestinal mucosal biopsy findings the diseases that cause malabsorption syndrome are classified into four major groups (Table 7-2). 66417308 : ¸Ÿ±U 24 ¥°Q . which are acid fast in this Ziehl-Neelsen–stained slide. 7-27.. B. Mycobacterium avium-intracellulare. 7-26).g. Small intestinal mucosa shows atrophy of the villi and lengthening of the crypts (Fig. 7-25).g.g. it is related to hypersensitivity to gluten. Complete recovery is possible if a patient follows a gluten-free diet. Macrophages are filled with MAI. Cryptococcus neoformans) Protozoa (e. or lipoid Classification of Malabsorption Syndromes According to the Small Intestinal Biopsy Findings Normal histologic features Gastric.. 7-27 and 7-28). and the intestinal mucosa resumes its normal morphology.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fungal enteritis in an immunosuppressed person. Fig. Strongyloides stercoralis) Diagnostic tissue changes Abetalipoproteinemia Amyloidosis Lymphangiectasia Waldenstr6m macroglobulinemia Lipoid proteinosis Nonspecific inflammatory mucosal changes Celiac disease (sprue) Tropical sprue Graft versus host disease Intraluminal bacterial overgrowth MAI. 7-26. amyloidosis. MAI. Patches of mucosa infiltrated with fungi appear raised and necrotic. The lamina propria contains numerous foamy macrophages. Infectious enteritis caused by bacteria.g..

Ectors. 7-33). Detroit. neutrophils. MI. Leuven.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 7-32). which maybe recognized on histologic examination of the intestines (Fig. Amebic colitis typically produces ulcers in the cecum. (Courtesy of Dr. Detail of lamina propria with macrophages. B. mucin. Histologically the pseudomembranes consist of fibrin. and cellular debris covering the surface of the damaged mucosa (Fig.) proteinosis are characterized by deposition of proteinaceous extracellular material. 7-31). Inflammation of the Appendix and the Large Intestine Acute appendicitis is one of the most common infections of the gastrointestinal tract that requires surgical intervention. Caccamo. (Courtesy of Dr. The lumen of the appendix may be obstructed with inspissated feces or worms such as Enterobius vermicularis (Fig. The appendix appears swollen and congested and histologically shows signs of transmural inflammation (Fig. 7-34). Whipple disease. The necrotic cell debris in the bottom of ulcers contains pathogenic Entamoeba histolytica (Fig. D.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . A. N. Infectious colitis presents as localized or diffuse inflammation and often is associated with ulceration or pseudomembrane formation. 7-30). The lamina propria contains deposits of fibrillar proteinaceous material. Fig.13 0 B A C Fig. C. 7-29. Segments of the intestine are covered with yellow or brown flat-topped plaques (Fig. Pseudomembranous colitis typically is a complication of Clostridium difficile infection. Light microscopy shows prominent macrophages and dilatation of lacteals in the lamina propria. Electron microscopy shows the pathogenic bacteria in the cytoplasm of these macrophages. 7-28. 7-29).) 66417308 : ¸Ÿ±U 24 ¥°Q . Belgium. Lipoid proteinosis.

Inflammation extends to the serosa. Pseudomembranous colitis. B. Acute appendicitis. The surface of the large intestine is covered with yellow. A. 66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . which appears hyperemic. The lumen of the appendix contains Enterobius vermicularis in cross section. Cross section shows transmural inflammation (blue) and foci of hemorrhange (red). Fig. flat-topped plaques. 7-3I.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 7-32.131 A B Fig. 7-30. Fig. Acute appendicitis.

Amebiasis. Fig. 7-33. Pseudomembranous colitis. or it may be ulcerated. Broad bands of collagen are seen underlying the surface epithelium in this trichrome-stained slide. 7-37). appears on colonic biopsy specimen as typical subepithelial collagen bands (Fig. A. Volcano-like appearance of early lesions. There are several histologic forms of noninfectious colitis of uncertain etiology. 7-38). As the disease progresses the inflammation spreads over the surface of the entire large intestine (Fig. 7-36). The trophozoites of Entamoeba histolytica are found in the area of "dirty necrosis" scraped from the bottom of a colonic ulcer. Eosinophilic colitis is an occasional manifestation of food allergy that presents with mucosal eosinophilia. Collagenous colitis. Inflammatory Bowel Disease (IBD) The term inflammatory bowel disease (IBD) includes two closely related entities of unknown etiology: ulcerative col - itis and Crohn disease. Fig. alternating with pseudopolypous transformation of the intervening mucosa that has not been destroyed (Fig. In chronic colitis the luminal surface may be flat and featureless.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . which is characterized by intermittent diarrhea unrelated to a known pathogen. The pseudomembrane has a layered appearance. producing crypt abscesses (Fig. The morphologic features that distinguish ulcerative colitis from Crohn disease are listed in Table 7-3. 7-35). Collagenous colitis. fibrin. Ulcerative colitis is characterized by superficial inflammation that is limited to colonic mucosa and does not extend 66417308 : ¸Ÿ±U 24 ¥°Q . Ulcerative colitis begins as acute inflammation of the mucosa. 7-35.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .13 2 A B Fig. B. 7-34. The exudate covering the damaged mucosa consists of mucus. inflammatory cells. Lymphocytic colitis is characterized by lymphocytic infiltration of colonic mucosa. and cell debris.

The intestine has a thick wall and narrowed lumen. Comparison of Ulcerative Colitis and Crohn Disease Feature Macroscopic Location Pattern Wall Mucosa in chronic stages Complications Ulcerative colitis Colon Diffuse Thin Flat or pseudopolyposis Megacolon Crohn disease Ileum and colon Patchy with skip areas Thick Cobblestone-like Adhesions Fistulas Transmural Superficial +(50%) + + Microscopic Inflammation Ulcerations Pseudopolyps Granulomas Fibrosis Peritonitis Mucosal Deep Fig." Crohn disease is a transmural inflammation of the terminal ileus and segments of the colon. Pseudopolyps represent hyperplastic mucosa surrounded by ulcers. Fig. 7-39.133 Fig. although the terminal ileum may show signs of " backwash ileitis. there are no skip areas. 7-37." The intestinal wall is thickened (Fig. into the deeper layers of the intestinal wall. Ulcerative colitis. The inflammation extends into the deeper layers of the intestine up to the serosa and in approximately 50 percent of cases there are granulomas (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Crohn disease. The weakened intestine may undergo massive dilatation ( "toxic megacolon " ). Ulcerative colitis. Crypt abscesses (aggregates of neutrophils in the intestinal crypts) are early signs of the disease.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fat tissue covers the antimesometrial serosal surface. 7-41). Because of the segmental nature of the disease the inflamed areas alternate with uninvolved " skip areas. The thickened ulcerated mucosa has a "cobblestone " appearance (Fig. In the chronic stages of the disease there is inflammatory polyposis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 7-36. 7-38. The small intestine is not involved. Ulcerative colitis. The entire colon is involved. Fig. 7-39). 7-40).

Histologically these tumors are adenocarcinomas of two types: intestinal or diffuse (Fig. TUMORS Tumors of the gastrointestinal tract are clinically classified as benign or malignant. A. Foci of chronic inflammation are seen in the muscle layers of the large intestine. and from the mucosa-associated lymphoid tissue (MALT). Crohn disease. 7-42). Fungating tumor has a cauliflower-like appearance. The stomach is the site of origin of approximately 50 percent of all gastrointestinal stromal tumors. Gastric Tumors Carcinoma of the stomach is the most important gastric neoplasm.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. 7-44 and 7-45).134 Fig. The irregularly shaped ulcerated area appears indurated and shows areas of necrosis. 7-42. 66417308 : ¸Ÿ±U 24 ¥°Q . Carcinoids and lymphomas are less common but nevertheless important tumors of the stomach. Crohn disease. Carcinoma of the stomach. The ulcerated thickened inflamed mucosa has a "cobblestone" appearance. B. 7-40.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Ulcerated tumor. of borderline malignancy. B A Fig. Fig. These tumors most often arise from the epithelium but also may be derived from the smooth muscle and other stromal cells. 7-41. and are composed of either smooth muscle cells. These submucosal tumors may be benign. 7-43). Schwann cells. or malignant. or nondescript stromal cells (Figs. Several types are recognized on gross examination ( Diagram 7-1.

Type III. Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . protruding. superficial elevated. Type IIc. excavated. The tumor cells have elongated nuclei with round tips and eosinophilic cytoplasm. superficial depressed. Type I. Type Ila. Gastric carcinoma. Leiomyoma of the stomach. The tumor forms a submucosal mass. Adenocarcinoma of the stomach. Diffuse type. Intestinal type. superficial flat.135 TYPE I A TYPE Ila TYPE Ilb TYPE Ilc B TYPE III Diagram 7-I.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. A. Fig. 7-45. B. Spindle cell leiomyoma. Type Ilb. The neoplastic glands are composed of stratified pleomorphic cells. 7-43. 7-44. The tumor is composed of scattered individual cells that have a clear and sometimes vacuolated cytoplasm and appear signet ring—like.

lipoma. 7-47 to 7-49). Fig. and so forth.) Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Histologically these tumors have the same features as the more common colonic neoplasms of the same type. Kansas City. tumors of the small intestine are rare. Most tumors are small and appear as I to 2 cm submucosal nodules. Mantle cell lymphoma of the intestine.136 Tumors of the Small Intestine Overall.V. 7-50 and 7-51). Lipoma of the small intestine. the goblet cell carcinoid (Figs. The tumor is composed of uniform cells with round nuclei forming nests and strands. noncystic. Tumors of the Appendix The most important tumors of the appendix are (1) adenoma. carcinoids. Fig. W. and (4) carcinoid and its most important variant. MO. resembling normal fat tissue. Approximately 60 percent to 75 percent of all tumors are thought to be benign and are classified as epithelial (adenomas) or mesenchymal neoplasms such as leiomyoma. colonic-type. Harrer. (Fig. NJ. Fig. (2) cystadenoma or circumferential adenoma. Carcinoid tumors. Camden. malignant stromal tumors (sarcomas). Carcinoid. 7-47. Polyps are classified as nonneoplastic or neoplastic (Table 7-4).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Malignant tumors include adenocarcinomas. The tumor presented in the form of multiple small mucosal nodules (lymphomatous polyposis). 7-48. and lymphomas (Figs. 7-46. 7-49. Intestinal Polyps Polyp is a term used to describe any mass that projects into the lumen of the intestine.) 66417308 : ¸Ÿ±U 24 ¥°Q . or signet ring-type. The submucosal tumor appears yellow. mucinous. hemangioma. which may be colonic. Rachel Cherian. (Courtesy of Dr. (3) adenocarcinoma. (Courtesy of Dr. 7-46).

Fig. 66417308 : ¸Ÿ±U 24 ¥°Q .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Mutinous cystadenoma of the appendix. 7-51. Lymphoid hyperplasia Mucosal prolapse Solitary rectal ulcer syndrome Diverticular disease Pneumatosis intestinalis Inflammatory bowel disease. The cystic tumor is filled with mucus. Villi lined by mucous cells protrude into the lumen.137 B Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .> . Goblet cell carcinoid. B. Neoplastic polyps Adenoma Tubular Villous Tubulovillous Carcinoma _ cinoid Stromal tumor Leiomyoma Lipoma GIST Lymphoma . The tumor is composed of uniform mucin-rich cells that form small nests. gastrointestinal stromal tumor. 7-50. A. GIST. Intestinal Polyps Nonneoplastic polyps Hyperplastic polyp Hamartomatous polyp Juvenile polyp Peutz-Jeghers polyp Inflammatory polyps IBD-related pseudopolyps Inflammatory fibroid polyp IBD.

66417308 : ¸Ÿ±U 24 ¥°Q . 7-55. The glands. 7-56.138 Fig. The polyp is composed of normal glands and strands of smooth muscle. 7-57. The polyp is lined by glands that have a serrated lumen. Fig. Fig. which are lined by normal epithelium.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 7-54. Tubular adenoma. Tubular adenoma. 7-53. Juvenile polyp. The tumor protrudes into the lumen of the large intestine. 7-52.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The finger-like villi are lined by mucin-secreting columnar cells. Peutz-Jeghers polyp. Fig. Fig. are focally dilated. Villous adenoma. Hyperplastic polyp. Fig. Histologically the tumor is composed of dysplastic but nevertheless uniform glands. The surface is ulcerated and the stroma is congested and inflamed.

Peutz-Jeghers polyps are sessile arborizing lesions that most commonly are found in the small intestine. 7-60 and 61). 7-59). Adenocarcinoma arising in a tubular adenoma. Tubular adenomas are the most common neoplastic polyps. 7-57). 7-52).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Adenocarcinomas of the colon that arise in tubular adenomas invade the stalk and thereafter the submucosa of the underlying bowel (Fig. 7-58). Mixed tubulovillous polyps show both growth patterns. 7-59. They typically are pedunculated and often are multiple (Fig. Fig. 7-54). Histologically they consist of stroma that contains dilated crypts lined by normal intestinal epithelium (Fig. they may be well differentiated or poorly differentiated. On gross examination adenocarcinomas of the cecum and the right colon have the appearance of endophytic fungating or ulcerated masses. Familial adenomatous polyposis coli. approximately 5 mm in diameter and composed of glands that have a serrated luminal surface (Fig. Polyps are composed of dysplastic columnar epithelium forming tubular glands (Fig. 7-58. Numerous polyps cover the luminal surface of the colon. Many colorectal carcinomas have a mucinous component but the designation mucinous carci- Fig. Histologically the tumors are adenocarcinomas. an autosomal dominant disorder. 7-53). 7-56). is the best defined premalignant condition. 66417308 : ¸Ÿ±U 24 ¥°Q . Patients with this condition have multiple neoplastic colonic polyps (Figs. The malignant glands have more irregular contours and are lined by cells that show marked nuclear irregularities and pleomorphism. it invariably leads to colon cancer. Fig.139 Hyperplastic polyps are minute dewdrop-like lesions. Fig. whereas the carcinomas of the sigmoid colon and rectum tend to produce circumferential narrowing ( "napkin ringlike lesions " ) (Figs. The tumor forms a circumferential mass narrowing the intestinal lumen. The fungating endophytic mass shows central ulceration. Carcinoma of the Large Intestine Carcinoma of the large intestine may arise in preexisting tubular or villous adenomas or may appear de novo. 7-55). Juvenile polyps are hamartomas. Adenocarcinoma of the right colon. Familial adenomatous polyposis coli.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 7-60. Villous adenomas are sessile lesions composed of finger-like villous projections lined by columnar mucin-secreting cells (Fig. 7-61. The polyps have a smooth muscle core covered with normal mucosal epithelium (Fig. Adenocarcinoma of the sigmoid colon. which usually are diagnosed during the first five years of life.

Anal Tumors and Related Lesions Condyloma acuminatum. combined adenocarcinoma-carcinoids. 7-63.140 noma is reserved for those neoplasms that have at least a 60 percent mucinous component. Fig. The lesion is composed of finger-like protrusions of keratinizing squamous epithelium covering fibrovascular cores. The entire thickness of the disorganized epithelium contains dysplastic atypical epithelial cells. Carcinoid is composed of groups of cells with uniform round nuclei. Two thirds of anal invasive cancers are keratinizing squamous cell carcinomas. Anal condyloma acuminatum. Neuroendocrine tumors include hindgut carcinoids. 7-64. Small cell neuroendocrine carcinoma is composed of undifferentiated small blue cells that have oval nuclei and very little cytoplasm. 7-62. clear cell. 7-65). Benign tumors are rare. which macroscopically resembles condyloma acuminatum. is a human papillomavirusinduced tumor-like epithelial lesion that occurs in the anus (Fig. Neuroendocrine tumors of the colon. A B Fig. It resembles genital extramammary Paget disease. and neuroendocrine cell carcinomas (Fig. 7-67). and choriocarcinomatous are less common. Other forms of carcinoma such as adenosquamous. and (3) mucoepidermoid carcinoma (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . 7-64). Anal intraepithelial neoplasia. Fig. which may present clinically as a wartlike intraluminal mass. (2) mucinous carcinoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . spindle cell. 7-63). The remaining one third are nonkeratinizing and are classified as basaloid (cloacogenic) (Fig. 7-66). The earliest lesions are intraepithelial and re- semble the more common cervical lesions (Fig. Anal gland carcinomas are of three histologic types: (1) welldifferentiated adenocarcinoma. Paget disease associated with carcinoma of the anal glands or rectum may affect the anus or the perianal skin (Fig. Histologically the tumor is composed of well-differentiated squamous epithelial cells (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . A. 7-68). pure squamous. 7-62). B. goblet cell carcinoids. Malignant tumors originate from the epithelium and represent mostly as squamous cell neoplasms. An important variant is the so-called verrucous carcinoma.

141 Fig. Patterns of involvement in colorectal biopsies and changes with time. Hum Pathol 25:994-1005. Sobin LH: Epithelial noncarcinoid tumors and tumor-like lesions of the appendix. Walley VM: Pigments of the gastrointestinal tract. Pascal RR: Dysplasia and early carcinoma in inflammatory bowel disease and colorectal adenomas. 66417308 : ¸Ÿ±U 24 ¥°Q . The small hyperchromatic tumor cells form . Correa P: Helicobacter pylori and gastric carcinogenesis. 7-65. 7-67. 1994. 1997. Lewin KJ: Gastric epithelial dysplasia and adenoma: historical review and histological criteria for grading. Genta RM. 1996. Further Reading Antonioli DA: Precursors of gastric carcinoma. Cancer 74:556-564. Isaacson PG: Recent developments in our understanding of gastric lymphomas. Am J Surg Pathol 20:11611181. 7-66. 1995. Franquemont DW: Differentiation and risk assessment of gastrointestinal stromal tumors. Stemmermann GN: Intestinal metaplasia of the stomach. Riddell RH: Premalignant and early malignant lesions in the gastrointestinal tract: definitions. Kleer CG. Semin Gastrointest Dis 7:94-104. relatively uniform squamous cells. 1994. Dixon MF. Fig. 1995. 1996. Lewin KJ: Collagenous colitis: A study of the distribution of morphological abnormalities and their histologic detection. Carr NJ. Galperin C. 1995. Torres C. A critical review with a brief description of early (curable) gastric cancer. JAMA 278:1946-1955. Ultrastruct Pathol 19:213-220. Hum Pathol 25:1160-1171. Am J Gastroenterol 91:864-872. Goldstein NS. Appelman HD: Ulcerative colitis. Am I Clin Pathol 103:41-47. A clinicopathologic study of 184 patients with a multivariate analysis of prognostic factors. Hum Pathol 28:127-133. The basal portion of the squamous epithelium contains nests of mucin-rich carcinoma cells. 1995. Anal carcinoma of the basaloid type. A comparison of light microscopic and electron microscopic findings. Fig. Am J Surg 22:1043-1047. Adenocarcinoma cells surround an obstructed anal duct. terminology. Fig. 1998. Hum Pathol 30:451-457. 1997.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Anal gland carcinoma. Willenbucher RF: Inflammatory bowel disease. A status report. Antonioli D. 1996.nests that show peripheral palisading. Suster S: Gastrointestinal stromal tumors. 7-68. Yardley JH et al: Classification and grading of gastritis. Jao RV. 1998. McCarthy WF. Am J Surg Pathol 22:983-989. Paget disease of the anus. Ghadially FN. Gershwin ME: Immunopathogenesis of gastrointestinal and hepatobiliary diseases. Sem Diagn Pathol 13:297313. Lewin KJ: Nomenclature problems of gastrointestinal epithelial neoplasia. Cancer 75:757-768. Am J Surg Pathol 20(suppl)S1-S7.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and problems. Verrucous carcinoma. 1994. 1996. A clinical. 1996. Offner FA. The updated Sidney system. Am J Surg Pathol 19:S37-S43. Odze RD: Polypoid dysplasia and adenomas in inflammatory bowel disease. 1999. 1998. Am J Surg Pathol 22:275-284. The tumor is composed of well-differentiated. pathologic and follow-up study of 89 polyps from 59 patients.

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·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

and bile duct cells (Fig. Alpha j -antitrypsin deficiency is characterized by the presence of cytoplasmic globules. Glycogenosis type I (von Gierke disease) is characterized by an accumulation of glycogen in liver cells. These globules are round. Microscopic. 66417308 : ¸Ÿ±U 24 ¥°Q . Dubin Johnson syndrome. and periodic acid-Schiff (PAS) positive. All of these diseases may become clinically evident in infancy and childhood or may present clinically in adult life. mostly in the periportal hepatocytes. Liver changes include steatosis. 8-4). and giant cell transformation of hepatocytes. Hepatocellular changes are most pronounced in the Dubin-Johnson syndrome. which give the liver a black or dark brown appearance. Wilson disease may progress to cirrhosis (Fig. Pseudoglandular transformation of hepatocytes. Fig. Fig. glycogenated nuclei.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . They contain a l -antitrypsin. Genetic hemochromatosis is characterized by an accumulation of hemosiderin. lobular disorganization. 8-1. B. Gross. brown pigment in hepatocytes. Hereditary tyrosinemia is associated with steatosis and cholestasis. A. Liver cells have clear cytoplasm. lipid. 8-3.-antitrypsin deficiency or hemochromatosis. eosinophilic. or protein metabolism affect the liver. Hepatocytes contain coarse brown granules in their cytoplasm. 8-6). Glycogen storage disease. A B Fig. and rare foci of necrosis or apoptotic bodies. The liver appears brown-black on gross examination and the hepatocytes contain large amounts of cytoplasmic brown pigment (Fig. Wilson disease is characterized by an accumulation of copper in liver cells. Glycogen and lipid storage diseases typically are accompanied by hepatomegaly and intrahepatic accumulation of intermediate metabolites. Like many other storage diseases such as a. Liver changes are prominent in diseases that involve the metabolism of heavy metals such as copper or iron. Prussian blue-positive. and nodular regeneration develop early in childhood (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .144 HEREDITARY METABOLIC DISEASES Numerous hereditary diseases of carbohydrate. 8-1). Hereditary hyperbilirubinemias reflect defects in bilirubin conjugation or excretion. The liver shows steatosis. cholestasis. or both (Table 8-1). intraacinar and periportal fibrosis. 8-5). the iron-rich. Diseases of bilirubin conjugation and the excretion of bile also may be hereditary. Hereditary tyrosinemia. Glycogen-rich hepatocytes have clear cytoplasm (Fig. Kupffer cells. which may be demonstrated immunohistochemically (Fig. 8-2. 8-3). 8-2).

whereas cytoplasm in other hepatocytes is eosinophilic. 66417308 : ¸Ÿ±U 24 ¥°Q . or excretion Excretion Histopathologic Changes in the Liver Canalicular cholestasis None None or excess lipofuscin in zone 3 and 2 hepatocytes None Pigmented brown granules in hepatocytes Fig. Hepatocytes of this cirrhotic liver have glycogenated nuclei. a i -Antitrypsin deficiency. type II Gilbert Rotor Dubin Johnson Principal Defect in Bilirubin Metabolism Conjugation Conjugation Conjugation and/or uptake Unknown but may include uptake. B. which appear clear. A B Fig. 8-4. type I Crigler-Najjar. 8-5. Some hepatocytes have clear cytoplasm. 8-6. A. Kupffer cells.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Brown pigment (hemosiderin) accumulates in hepatocytes. Hemochromatosis. Fig. and bile ductular cells. conjugation. The liver cells contain typical PAS-positive round cytoplasmic bodies. Wilson disease.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .145 Histopathology of Viral Hepatitides Disease Crigler-Najjar. Hemosiderin granules in bile ductular cells appear blue after the Prussian blue reaction.

Acute passive congestion. The changes resemble those seen in Budd-Chiari syndrome but are limited to the intrahepatic veins. Fig. 8-10. 8-9. Venoocclusive disease maybe a consequence of irradiation. The fixed liver has a nutmeg-like appearance. 8-8). 66417308 : ¸Ÿ±U 24 ¥°Q . which has a dual blood supply in that it receives blood from both the hepatic artery and the portal vein. In typical cases intimal edema of the terminal hepatic venules is followed by the subendothelial deposition of reticulin and collagen fibers. Many hepatocytes have been lost from those areas or are ischemic and are undergoing necrosis. Sudden heart failure causes acute passive congestion with or without centrilobular (zone 3) hepatocellular necrosis (Fig. 8-7). and replacement of liver cells by fibrous tissue. Venous outflow obstruction of Budd-Chiari syndrome is reminiscent of changes produced by congestive heart disease.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The vein containing an organized thrombus is surrounded by areas of necrosis of zone 3 hepatocytes. or drinking bush tea produced from Senecio or Crotalaria alkaloids. but the liver typically shows a spectrum of changes. A nutmeg is included for comparison. 8-7. Coagulative necrosis commonly is seen. On gross examination such livers have a nutmeg-like appearance (Fig. Chronic passive congestion. cytotoxic drug therapy. or may show fibrous mural thickening (Fig. Chronic passive congestion leads to zone 3 liver cell atrophy and loss. Fig. which is most pronounced in zone 3 but sometimes extends to the portal tracts. 8-8. 8-9). The terminal hepatic venule and the sinusoids of zone 3 are filled with blood. Inflammation is sparse and thrombi are not seen. Budd-Chiari syndrome. Progressive sinusoidal dilatation is accompanied by atrophy of hepatocytes and zone 3 fibrosis. Venoocclusive disease caused by Senecio alkaloids.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 8-10). These thrombotic changes are not seen in congestive heart failure. Fig. which have undergone necrosis. often is affected by circulatory disorders. In other areas the central hepatic venules and intercalated veins may contain thrombi or recanalized thrombi. Fig. Terminal hepatic venule (center) is almost completely occluded and is surrounded by areas devoid of hepatocytes. Those acini with acute changes show severe sinusoidal dilatation and congestion. and progressive narrowing and complete obliteration of their lumen (Fig.146 CIRCULATORY DISORDERS The liver.

·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . 8-13. The liver shows marked lobular disarray. In acute viral hepatitis the liver shows acinar disarray. Peliosis most often is induced by drugs or steroid hormones. Viral hepatitis. 8-12. cytomegalovirus (CMV).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . most prominently in the periportal areas. variable degrees of ballooning of hepatocytes. Peliosis hepatis. and prominence of Kupffer cells. hepatitis C virus (HCV). 8-12). focal necrosis of hepatocytes. The severity of the acute disease and its histology vary from case to case. 8-14. Bacterial hepatitis is a feature of biliary tract infection or sepsis. Portal vein thrombosis is a common complication of hepatocellular carcinoma (Fig. Viral Hepatitis Unless otherwise specified. Various viruses induce different changes. Blood also contains leukemia cells. hepatitis D virus (HDV). the term viral hepatitis denotes an infection caused by one of the hepatotropic viruses—hepatitis A virus (HAV). Deposits of fibrin may be accompanied by spotty hepatocellular necrosis and liver cell dropout. Hepatocytes appear swollen and the Kupffer cells are prominent. 8-13 and 8-14). The comparative histopathologic features of the major forms of acute viral hepatitis are listed in Table 8-2. Portal vein thrombosis. but it also may be found in patients infected with other pleiotropic viruses such as herpes simplex virus. Fig. hepatitis E virus ( HEV ). 8-11. Fibrin thrombi in sinusoids typically are found in toxemia of pregnancy and severe disseminated intravascular coagulation (DIC) syndromes. which are not always predictable.1 47 Peliosis hepatis is a consequence of endothelial cell injury leading to an accumulation of blood in the spaces of Disse and sinusoids that become transformed into blood-filled cavities (Fig. The cirrhotic liver contains hepatocellular carcinoma (left). and others. Blood-filled cavities do not have endothelial lining. I NFECTIOUS HEPATITIS Hepatitis most often is caused by hepatotropic viruses. Sinusoids appear narrow. 8-11). or hepatitis G virus (HGV). Fig. Viral hepatitis. scattered apoptotic bodies. and prominence of Kupffer cells (Figs. Fig. but it also may be a complication of infection with Rochalimaea henselae in acquired immunodeficiency syndrome (AIDS) or chronic debilitating infections such as tuberculosis. Infections with protozoa and parasites occur in tropical countries. Prominent apoptotic cells are being pushed into the sinusoids. hepatitis B virus (HBV).

Eosinophils. 8-16. L. There also is considerable chronic inflammation and piecemeal necrosis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . tMicrovesicular steatosis. The bile ducts are inflamed and surrounded by a dense lymphocytic infiltrate. lymphocytes. Chronic HBV infection. neutrophils. plasma cells. 66417308 : ¸Ÿ±U 24 ¥°Q . unicellular acidophilic and ballooning degeneration. Chronic HCV infection. Only some periportal hepatocytes have survived the infection. N. The cytoplasm of hepatocytes has a "ground glass " appearance.148 Histopathology of Viral Hepatitides *Includes apoptosis. Fig. 8-15. Fig. 8-18. Fig. Fibrous bands bridge the space between neighboring portal tracts." $E. P. HBV carrier state. 8-17. and focal necrosis. seen only in posttransplantation "reinfection. Fig. Massive hepatic necrosis caused by HBV.

Infectious mononucleosis. The hepatocellular changes are relatively mild and include focal apoptosis and only mild ballooning. Coagulative liver cell necrosis with almost no inflammation. which typically contain basophilic intranuclear inclusions. Q fever hepatitis is characterized by noncaseating granulomas with a fibrin ring often surrounding a centrally located fat vacuole (Fig. cirrhosis. 8-22). 8-18) are the hallmark of the chronic carrier state of hepatitis B. 8-17). 8-20. 8-20). CMV infection causes enlargement of bile ductal cells. The hepatocytes contain Cowdry type A intranuclear inclusions. Entrapment of isolated hepatocytes or small groups of liver cells by the expanding portal fibrous tissue is highly typical of chronic hepatitis. 8-19). Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Fibrin rings are typical. Chronic hepatitis. Extension of strands of fibrous tissue and inflammatory cells from portal tracts into the acini with focal liver cell necrosis and dropout ("piecemeal necrosis") commonly is present.149 Complications of acute viral hepatitis include massive necrosis. and Fig. 8-21). such as typhoid. Hepatocytes with a finely granular "ground glass " cytoplasm (Fig. is characterized by portal and/or lobular inflammation and fibrosis (Fig. Hematogenous hepatic infection occurs in many acute bacterial diseases. 8-22. tularemia. Fig. Infectious mononucleosis is characterized by sinusoidal lymphocytic infiltrates and prominence of Kupffer cells (Fig. Herpesvirus hepatitis. Cowdry type A intranuclear inclusions typically are present (Fig. Serology is the best way to diagnose specific forms of hepatitis virus infection. Herpesvirus hepatitis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . HCV causes steatosis and bile duct inflammation and destruction (Fig. albeit not diagnostic of this disease. Q fever. Fig. and hepatocellular carcinoma. 8-15). chronic hepatitis. Severe viral infection may cause massive hepatic necrosis (Fig. Hepatitis Caused by Pathogens Other Than Hepatitis Viruses Herpesvirus hepatitis is characterized by foci of necrosis with a relatively sparse inflammatory response (Fig. The liver shows sinusoidal Iymphocytosis and prominence of Kupffer cells. 8-16). a complication of all viral hepatitides except those caused by HAV. 8-19. 8-21. brucellosis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

8-26. or through portal veins from the intestines. 8-24). Mycobacterium avium-intracellulare ( MAI) infection presents in the form of granulomas composed of MAI-filled macrophages (Fig. B. A B Fig. 8-24. 8-25. Fig. 8-23.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Typhoid fever. and causes foci of hepatic necrosis and inflammation (Fig 8-23). Liver contains sharply demarcated foci of necrosis. Macrophagic granulomas. Fig. usually in sepsis. Pus is oozing from bile ducts on a cross-sectioned liver. Biliary Infections Ascending biliary infection is a common complication of bile stone impaction in the common bile duct and other diseases of the biliary system. 8-25). Cholangitic abscesses. Abscesses contain bile-tinged pus. Hematogenous infections may reach the liver through arteries. Biliary hepatic abscesses may persist as encapsulated pus-filled cavities inside the liver (Fig. Ziehl-Neelsen stain shows numerous acid-fast bacilli inside macrophages.150 so forth. Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Acute bacterial cholangitis often is a suppurative infection (Fig. A. MAI infection.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Histologically there is bile ductal dilatation with infiltrates of neutrophils. 8-26). Bacterial cholangitis.

(From Damjanov I: Pathology for the health related professions. 8-28. WB Saunders.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Philadelphia. Infections with Schistosoma haematobium and Opisthorchis sinensis are accompanied by granulomas and periportal hepatic fibrosis of "pipe stem " type (Fig. 8-27. Although these lesions are also known as amebic abscesses. A B Fig. with permission. A. which contain black hemozoic pigment (Fig. The cavitary lesion is filled with yellow putty-like material. A B Fig. a complication of amebic colitis. 1996. Malaria is accompanied by pronounced hypertrophy of Kupffer cells. is characterized by hepatic lesions called amebomas. they do not contain pus but are filled with putty-like material formed from necrotic liver cells (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . It does not contain pus and thus is not a true abscess but rather a localized area of hepatic necrosis. 8-28).) B. B. 8-27). 8-29). Necrotic material occupies space surrounded by fibrous tissue. Cyst contains cross-sectioned scolices of the parasite. Amebic abscess. Cyst has a hyaline fibrotic wall. 66417308 : ¸Ÿ±U 24 ¥°Q . Infections with parasites such as Echinococcus granulosus lead to the formation of hep- atic cysts (Fig.151 Hepatic amebiasis. Echinococcus granulosus cyst. A. 8-30).

zone I halothane • Massive necrosis Isoniazid. phosphorus • Microvesicular • Macrovesicular Vascular changes • Venoocclusive disease ▪ Peliosis hepatis Hyperplastic changes Amiodarone Methotrexate Cytotoxic drugs Senecio or Crotalaria alkaloids Anabolic steroids. Massive hepatic necrosis induced by acetaminophen. This patient developed a hepatitis-like disease after treatment for tuberculosis with isoniazid. pure cholestasis.- Toxins Mushrooms. DRUG-INDUCED LIVER DISEASES Most drugs absorbed into the portal or systemic circulation are metabolized in the liver. 8-31. Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . and hyperplastic and/or neoplastic lesions (Table 8-3. copper sulfate Phosphorus. CCII . acetaminophen necrosis. zone 3 • Submassive Paraaminosalicylic acid. 8-31 to 8-36). oral contraceptives Fatty change Tetracycline. ferrous sulfate CCI4 Fig. The parasite in tissue is surrounded by chronic inflammation and fibrosis. These substances also may produce an immune response. In general. Schistosomiasis. tamoxifen Oral contraceptives Fig. the morphologic features of drug-induced liver injury parallel those of viral hepatitis but also include fatty change. Some drugs may induce an unpredictable idiosyncratic adverse response in the liver. Figs. necrosis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . chlorinated naphthalenes Granulomas Methyldopa.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . mushrooms. vascular changes. halothane. The enlarged Kupffer cells contain black hemozoic pigment. 8-30. 152 Fig. Falciparum malaria. Drug-induced hepatitis. During this metabolic process the liver cells may be injured as a result of the direct toxicity of the drug or its metabolites. and such a hypersensitivity reaction also may indirectly affect the liver. salicylates Ps„. Drug-induced Liver Diseases Drug Examples Isoniazid = `ds-like Spotty necrosis Methyldopa Submassive Halothane. sulfonamides phenylbutazone Cholestasis Chlorpromazine. 8-29. 8-32.

8-37. Fatty change often is associated with hepatomegaly. Drug-induced chronic hepatitis. 8-34. Microscopically it presents with macrovesicular steatosis (Fig. Drug-induced fatty change. Androgen-related jaundice was associated with bile plugs and cholestatic rosettes. Cholestasis. Fig. but in essence it causes no clinical symptoms and is reversible. These granulomas were found in a patient treated with phenylbutazone. which are classified morphologically as (1) fatty change. 8-33. The liver appears yellow. Fig. 8-37).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . (2) alcoholic hepatitis. Fig. The most prominent changes are seen in zone 3. Hepatic granulomas. which shows pronounced unrest (pleomorphism) of hepatocytes. 8-36. and (3) alcoholic cirrhosis. Liver changes in this patient treated with methyldopa resemble those of chronic hepatitis. 8-35. Mallory Fig.153 Fig. In a minority of chronic alcoholics the liver injury presents as alcoholic hepatitis. ALCOHOLIC LIVER DISEASES Chronic abuse of alcohol may produce a spectrum of overlapping hepatic changes. Fatty liver. 8-38). Many hepatocytes show cytoplasmic dissociation (clumping of part of the cytoplasm around the nucleus with rarefaction of the remainder) and Mallory body formation (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

There is noticeable unrest of hepatocytes.and macronodular. 8-39. 8-41). Fig. 8-40. bodies may be demonstrated immunohistochemically with antibodies to ubiquitin (Fig. Fig. 8-42.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Alcoholic hepatitis. The connective tissue may become confluent. 66417308 : ¸Ÿ±U 24 ¥°Q . Fig. In this Mallory trichrome—stained slide zone 3 shows periventricular fibrosis extending between hepatocytes. Fibrosis tends to occur around the terminal hepatic venules extending into the spaces of Disse and sinusoids enveloping individual hepatocytes or groups of hepatocytes ( "chicken wire " fibrosis) (Fig. which ultimately leads to cirrhosis (Fig. Alcoholic hepatitis. The liver shows steatosis and fibrosis of zone 3 in the center of the field. some of which contain Mallory bodies (arrows). Groups of neutrophils tend to surround hepatocytes with Mallory bodies ( "neutrophilic satellitosis " ). in many cases the liver is devoid of fat and appears macronodular or mixed micro. 8-41. Fig. In this immunohistochemical preparation Mallory bodies stain brown with antibodies to ubiquitin. 8-42). Alcoholic liver disease. Fibrosis may progress. However.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 8-39). Cirrhosis typically is micronodular and the liver appears yellow because of a high fat content. Steatosis usually is mild to moderate but may even be absent. In typical cases alcoholic cirrhosis is micronodular and the liver is yellow and fatty. replacing zone 3 hepatocytes and obliterating efferent veins ( " sclerosing hyaline necrosis " ). Alcoholic cirrhosis. In some biopsy specimens of patients with portal hypertension. 8-38. dissecting acini into small segments. Venoocclusive lesions may be associated with variable degrees of periportal fibrosis. perivenular fibrosis of zone 3 and steatosis may be the only findings (Fig.154 Fig. Mallory bodies. 8-40).

severe intraacinar necrosis. Primary sclerosing cholangitis. is mentioned here only because many patients with this disease have perinuclear antineutrophil cytoplasmic antibodies (pANCA) and may have an altered immune system. Cholangi- Fig. in contrast to the normal liver in which 87 percent or more portal tracts have bile ducts. 8-45. Fig. Autoimmune hepatitis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 8-43. 8-44). 66417308 : ¸Ÿ±U 24 ¥°Q . Primary biliary cirrhosis. Primary biliary cirrhosis is an autoimmune disease that is characterized by destruction of intrahepatic bile ducts. The presence of plasma cells is considered to be useful for distinguishing autoimmune chronic hepatitis from chronic hepatitis C. 8-45). The presence of lteriportal cholestasis and foci of pseudoxanthomatous cells is useful for diagnosis but is not pathognomonic of primary biliary cirrhosis (Fig. Some authors believe that hypocellular areas of collapse. 8-46). with or without actin antibody) and (lb) which is only actin antibody—positive.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .155 AUTOIMMUNE LIVER DISEASES Autoimmune hepatitis and primary biliary cirrhosis are the best known autoimmune diseases of the liver. Connective tissue bridges connect portal areas. Fig. Primary biliary cirrhosis. As the disease progresses the bile ducts are replaced by fibrosis. 8-43). 8-44. There are no histologic findings that reliably distinguish autoimmune chronic hepatitis from chronic hepatitis B or drug-induced chronic hepatitis. The bile duct is distorted by inflammatory cells. which leads to biliary cirrhosis. and (3) liver-pancreas antibody—positive (with or without other antibodies). which typically are devoid of bile ducts in advanced stages of the disease. Autoimmune chronic hepatitis includes three subgroups: (l a) lupoid hepatitis (antinuclear antibody-positive. the chronic inflammatory cells in the portal tracts infiltrate and destroy the bile ducts ( "chronic nonsuppurative destructive cholangitis") (Fig. 8-46. An increased titer of antimitochondrial antibodies is seen in 90 percent of patients. However. plasma cells may be abundant in viral hepatitis B and in some druginduced lesions. Clusters of xanthomatous cells are found in the dilated sinusoids. and the disease often is associated with other autoimmune disorders such as Hashimoto thyroiditis or atrophic gastritis. many other investigators do not find any specificity in these findings. Histologically. a disease of unknown pathogenesis. In liver biopsy specimens more than half the portal tracts lack bile ducts. in which the portal infiltrates consist predominantly of lymphocytes (Fig. which extends from one portal area to another (Fig. Primary biliary cirrhosis. (2) liver-kidney microsomal antibody—positive. in early stages of the disease. and inflammation with rosettes and multinucleated hepatocytes are more suggestive of autoi mmune hepatitis than other forms of chronic hepatitis. The inflammatory infiltrate in this chronic hepatitis contains numerous plasma cells. It should be noted that some drug reactions also are immune mediated. which surround and invade it. Fig.

Other causes of obstruction are listed in Table 8-4. 8-47). The epithelium of the intraacinar bile ducts may show irregularity. edema. Cirrhosis usually is micronodular and maybe associated with marked cholestasis. 8-48). 8-52). In acute biliary obstruction the first changes are seen in acinar zone 3 and sometimes in zone 2. The liver is nodular and shows greenish nodular discoloration. 8-49). and cholangiolar proliferation are typical but not diagnostic (Fig. or edema. B. Possible causes of biliary obstruction such as bile stones are readily identified clinically (Fig. which show focal stenosis alternating with dilatation ( " beading" on cholangiography). Biliary cirrhosis develops terminally in most patients. 8-47. Intrahepatic bile ducts compressed by concentric. Periportal Mallory bodies are found in approximately one fourth of all cases. BILIARY OBSTRUCTION Obstruction of extrahepatic biliary ducts causes jaundice and is associated with typical hepatic changes. Bile ducts have been replaced by round scars.156 A Fig. 8-53 and 8-54). Xanthomatous cells and foreign body giant cells with phagocytosed bile may be present. hyperplasia. which are characterized by prominent piecemeal necrosis and nodular regeneration. Hepatocytes are relatively spared except in advanced cirrhotic stages of the disease. 8-50). Ductopenia is accompanied by residual chronic inflammation. The medium-sized bile ducts are surrounded by collagenous fibrous tissue. A. In severe cases the bile ducts rupture and cholangitic abscesses form (Fig. These abscesses contain remnants of disrupted biliary epithelium. Zone 3 hepatocytes show slight unrest (Fig. olar proliferation may be prominent. Causes of Biliary Obstruction Congenital • Atresia • Agenesis Gallstones Inflammation/Fibrosis • Primary sclerosing cholangitis • Bacterial cholangitis • Surgical stricture Tumors • Carcinoma of head of pancreas • Carcinoma of ampulla of Vater • Carcinoma of common bile ducts • Lymphoma of hilar lymph nodes Fig. 8-48. Extravasated bile ("bile lakes " ) and dissolution of liver cells resulting from the detergent action of bile ( " bile infarcts" ) are seen only in advanced cases. Bile plugs sometimes are present in the bile ducts. Extrahepatic ducts also are narrowed and fibrotic and ultimately are transformed into fibrous strands devoid of any lumen. The disease affects the intrahepatic bile ducts. and are of limited diagnostic value in liver biopsies (Figs. usually at autopsy. Primary sclerosing cholangitis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and bile mucin admixed with neutrophils in various stage of disintegration. In some cases it may be associated with ulcerative colitis or retroperitoneal fibrosis. 8-51). 66417308 : ¸Ÿ±U 24 ¥°Q . Histologic changes in the liver resemble those caused by other forms of extrahepatic biliary obstruction and include periductal fibrosis and variable cholestasis (Fig. Portal tract infiltrates of neutrophils and acute cholangiolitis. Biliary cirrhosis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .(` onionskin " ) fibrosis ultimately disappear and are replaced by round fibrotic scars (Fig. Primary sclerosing cholangitis usually is idiopathic and occurs sporadically.

The acinar zone 3 shows unrest and canalicular cholestasis. Fig. The portal tract is inflamed and there is cholangiolar proliferation. Bile infarct. Extrahepatic biliary obstruction. 8-49. The dilated and ruptured bile duct is filled with neutrophils and bile. 8-50. 8-54. Pigmented stones were found in dilated ducts.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig.157 Fig. 8-52. Dissolution of liver cells is a late consequence of chronic biliary obstruction. Extrahepatic biliary obstruction. Darkly stained extravasated bile surrounded by xanthomatous cells is found in late stages of biliary obstruction. 66417308 : ¸Ÿ±U 24 ¥°Q . Cholangitic abscess. Fig. Gallstones in the hepatic ducts. 8-5 I. Bile lake. 8-53. Fig. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Morphologically it is classified as (1) micronodular if the nodules are smaller than 3 mm in diameter. are found in most cases (Fig. Dilated branches of portal veins. 8-58. 8-57. Cirrhosis.-antitrypsin deficiency Galactosemia Immune-mediated hepatic diseases Primary biliary cirrhosis Primary sclerosing cholangitis Autoimmune ("lupoid") hepatitis Toxic and drug-induced hepatitis Biliary obstruction Cryptogenic cirrhosis Fig. Large nodules.158 CIRRHOSIS Cirrhosis. Cirrhosis. 8-55 and 8-56). chronic inflammatory cells. and dilated veins. The most important causes of cirrhosis are listed in Table 8-5. Macronodular cirrhosis. The nodules are small and of approximately even size. (2) macronodular if the nodules are larger than 3 mm in diameter. Septa contain reticulin fibers that extend between the liver cells. Fig. Micronodular cirrhosis. Histologic features of cirrhosis are typical and usually reflect the gross findings. accentuating their abnormal structure (Fig. These septa may contain proliferating bile ducts and chronic inflammatory cells. 8-60). and (3) mixed if the liver contains an equal number of large and small nodules (Figs. 66417308 : ¸Ÿ±U 24 ¥°Q . are surrounded by broad areas of fibrosis. Nodules of liver cells are surrounded by fibrous septa. which vary in size and shape. Causes of Cirrhosis Viral hepatitis Alcohol abuse Metabolic diseases Hemochromatosis Wilson disease a. strands. is characterized by replacement of normal liver parenchyma by abnormal liver cell nodules and fibrosis. The fibrous septa contain proliferating bile ducts. The hepatocellular nodules are composed of pleomorphic liver cells arranged into groups. a term used as a synonym for advanced liver disease or end-stage liver disease. Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 8-56. and nests that lack normal sinusoidal blood supply (Fig. 8-55. 8-59). Fig. In all instances groups of liver cells are arranged into nodules surrounded by fibrous septa (Fig 8-57). which reflect intrahepatic vascular obstruction and portal hypertension. 8-58).

The cyst wall contains small bile ducts surrounded by fibrous tissue. but occasionally the change may be widespread (Fig. Reticulin stain highlights broad septa giving rise to fine fibers that extend into the hepatocellular nodules. or autosomal dominant polycystic kidney disease (ADPKD). 8-60. autosomal recessive polycystic kidney disease (ARPKD). TUMOR-LIKE CONDITIONS AND TUMORS Tumor-Like Conditions Extensive cystic changes in the liver are uncommon. Kansas City. 8-62). The hepatic changes vary from mild to severe. Cirrhosis. The most common finding in mild hepatic forms of ADPKD are minute nodules. The liver contains numerous large cysts.) 66417308 : ¸Ÿ±U 24 ¥°Q . A. Kansas. Polycystic liver disease. (Courtesy of Dr. 8-61). Reticulin fibers of this kind are not seen in hepatocellular carcinoma. B. measuring 1 to 3 mm in diameter. Fig. 8-59. 8-61. composed of small bile ductules embedded in collagenous stroma (von Meyenburgcomplexes) (Fig. Paramjit Bhatia. Hepatocellular nodules lack normal sinusoidal blood supply and are composed of pleomorphic liver cells arranged into groups rather than plates.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Cirrhosis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .159 Fig. A B Fig. Cysts usually occupy only part of the liver. Cysts of the liver are found in several hereditary conditions such as Caroli disease.

Focal nodular hyperplasia. Groups of small bile ducts are enclosed in connective tissue stroma. Focal nodular hyperplasia. and telangiectasia) syndrome and polyarteritis nodosa. The average mass measures 5 cm in diameter. The lobular mass has a central fibrotic scar. Reticulin stain shows the difference between the nodule composed of two cell—thick plates and the compressed normal liver to the right. inflammatory bowel disease.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 8-64). also known as nodular regenerative hyperplasia. The nodule typically has a central fibrous scar radiating toward the periphery ("wagon wheel" pattern). On cross section it appears lobulated and is well demarcated from the rest of the liver (Fig. sclerodactyly. von Meyenburg complex. Fig. Fig. focal nodular hyperplasia is composed of normalappeanng hepatocytes arranged into two cell-thick plates between septa of fibrous tissue (Fig. Histologically. The nodules are composed of hepatocytes that are larger and paler than those of the surrounding normal liver. including CREST (calcinosis. Fig. Fig. lymphoma and myeloproliferative diseases. 8-63. represents diffuse hepatic nodularity without fibrosis or cirrhosis. 8-62.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The central scar extends peripherally into thinner septa. 8-63). Focal nodular hyperplasia may present as solitary or multiple nodules in noncirrhotic livers of adults: It is twice as common in women as in men. 8-66. Nodular transformation. 8-65. Nodular transformation. It has been associated with a number of diseases such as autoimmune diseases.160 Fig. 8-64. and it most often is asymptomatic and is discovered accidentally. esophageal dysfunction. Raynaud 's phenomenon. or bacterial endo - 66417308 : ¸Ÿ±U 24 ¥°Q . Nodular transformation.

Reticulin stain clearly shows the differences between the nodule and the compressed atrophic normal liver cells (Fig. 8-67). Hepatocellular adenoma. The tumor may be classified on gross examination as solitary. (Courtesy of Dr. Hepatocellular carcinoma. 8-69. or diffuse (Figs.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . It maybe pathogenetically related to hepatitis B or hepatitis C virus infection. Smaller satellite nodules are seen left of the main mass. and the nuclei appear uniform. Hepatocellular carcinoma is a malignant liver cell tumor that most often originates in a cirrhotic liver. Kansas. It usually is asymptomatic. Histologically. Kansas City. This cirrhotic liver contains a solitary malignant nodule. which appears yellow. 8-67. 66417308 : ¸Ÿ±U 24 ¥°Q . hepatocellular carcinoma occurs in several patterns such as trabecular. 8-70. massive. 8-65). The tumor appears as a partially hemorrhagic yellow mass. James Fishback. Some cases have been related to prolonged intake of anabolic steroids or oral contraceptives. The nodules are composed of hyperplastic hepatocytes arranged into two cell–thick plates compressing the adjacent liver without any intervening fibrous tissue (Fig. Hepatocellular carcinoma. The tumor is composed of hepatocytes resembling those of the normal liver. Fig. 8-66). 8-69 and 8-70). The massive tumor is poorly demarcated from the remaining liver. Fig. 8-68. multinodular. which makes their cytoplasm appear clear (Fig. but morphologically it may be confused with cirrhosis.) Fig. and contain glycogen. compact.161 carditis. congested or hemorrhagic nodule in an otherwise normal liver (Fig. The tumor is composed of clear cells arranged into two cell—thick plate. Hepatocellular adenoma. are arranged into two cell–thick plates. pseudoglandular Fig. The cells have a low nuclear-cytoplasmic ratio. Epithelial Tumors Hepatocellular adenoma is the most important benign liver tumor. 8-68). It occurs as a yellow. Tumor cells usually are larger.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

Fibrolamellar hepatocellular carcinoma.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 8-71 and 8-72).162 (acinar). Hepatoblastoma. The cytoplasm of tumor cells appears granular because the cells contain numerous mitochondria. Irrespective of its growth pattern. 8-75. 66417308 : ¸Ÿ±U 24 ¥°Q . The five-year survival rate is in the range of 60 percent to 80 percent. Fig. 8-73. 8-74. It often is associated with a variety of congenital anomalies such as Fig. Tumor cells also may contain globular PAS-positive inclusions and socalled pale bodies. Hepatoblastoma is a tumor of childhood. The tumor is composed of large cells with well-developed eosinophilic cytoplasm. Hepatocellular carcinoma. hepatocellular carcinoma has a poor prognosis. Fig. Connective tissue scars also are seen. Hepatocellular carcinoma. Fig. Fig. The tumor is composed of cuboidal cells that resemble fetal hepatocytes. 8-73). Hepatoblastoma. The tumor has a pseudoglandular pattern. 8-72. Histologically the tumor is composed of large polygonal cells with intensely eosinophilic cytoplasm (Fig. The tumor has a trabecular pattern.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . It is not associated with hepatitis virus infection and occurs in normal rather than cirrhotic livers. Fibrolamellar hepatocellular carcinoma is a distinct subtype of hepatocellular carcinoma that occurs in adolescents and young adults. On gross examination the tumor presents as a mass that is demarcated from the remaining liver and crisscrossed with fibrous scars. 8-71. The tumor has a lobular appearance with areas of necrosis. and scirrhous (Figs.

angiosarcoma. lung. They most often originate from vascular cells.163 B Fig. Malignant mesenchymal tumors are rare. Epithelioid hemangioendothelioma. 7-78). Tumor cells. Other benign tumors such as lipoma and fibroma are rare. Histologically the tumors are adenocarcinomas. often of a tubular pattern evoking a strong desmoplastic reaction. Cholangiocellular carcinoma is a malignant epithelial tumor derived from the intrahepatic bile ducts. They most often originate from primary tumors in the colon. or familial adenomatous polyposis coli.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . necrosis. 8-76). Fetal type cells are larger and have more eosinophilic or clear cytoplasm filled with fat and glycogen (Figs. are supported by delicate stroma. Sinusoidal vascular spaces are seen as clefts between tumor cells. Beckwith-Wiedemann syndrome. 8-75). 8-77). 8-74). The tumor appears grayish-white. Histologically the tumor has a tubular pattern. 8-76. On gross examination the tumor usually is well circumscribed with foci of cystic degeneration. B. Embryonal type cells are small fusiform cells with hyperchromatic nuclei. A. Mesenchymal Tumors Hemangioma is the most common benign mesenchymal tumor. Metastatic Tumors Metastases to the liver are the most common malignancy in this organ. It usually is asymptomatic and clinically insignificant. Fig. On gross examination metastases appear as multiple spherical nodules with a central indentation ("umbilication") (Fig. hemihypertrophy. The most important are epithelioid hemangioendothelioma. 8-77. (Fig. or breast. Histologically it consists of cells that resemble embryonic fetal hepatocytes embedded in a mesenchymal matrix. but in the rest of the world it seems to be sporadic. In Southeast Asia this tumor has been associated with liver fluke infestation. 66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Cholangiocellular carcinoma. or hemorrhage (Fig. congenital absence of the portal vein. which typically show cytoplasmic vacuoles (lumens). and undifferentiated sarcoma (Fig. Two thirds of these tumors are solitary and one third are multifocal.

and radiographically opaque or translucent (Fig. They may be solitary or multiple. which were removed after surgery. Sarcomas are extremely rare. Transmural Iymphocytic infiltrates in a follicular pattern account for the term follicular cholecystitis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . It often is found in association with gallstones even though there is no pathogenetic link between these two diseases. 880 and 8-81). which in chronic cholecystitis may be accompanied by fibrosis and epithelial metaplasia. If extensive lymphoid hyperplasia is found. Fig. many of which show central indentation ("umbilication") corresponding to the areas of necrosis. Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Carcinoids.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 8-79). DISEASES OF THE GALLBLADDER The most important diseases of the gallbladder and biliary ducts are biliary stones (cholelithiasis). The gallbladder contained stones. and tumors.164 Fig. Gallstones. The mucosa appears red and swollen. 8-84). Gallstones are predominantly composed of cholesterol and bile pigment. 8-81. 8-83). firm or soft. The gallbladder is distended and filled with clear fluid. Hydrops of the gallbladder typically is caused by impacted gallstones. Chronic cholecystitis. 8-82). but some appear as mixed adenosquamous or squamous cell carcinomas. Gallstones often are accompanied by inflammation. inflammation of the gallbladder (cholecystitis). The liver contains numerous spherical nodules. Metastatic carcinoma. Histologically most tumors are adenocarcinomas. 8-78. Cholecystitis may be classified as acute or chronic (Figs. endocrine carcinoma. It is more common in women than in men and is especially common in Native Americans. Acute cholecystitis. The tumor grows into the lumen or through the wall and infiltrates the liver (Fig. which may be related to mechanical or chemical irritation of the mucosa or to bacterial infection. Histologically the wall of the gallbladder shows signs of inflammation. Fig. 8-80. the term chronic active cholecystitis is used (Fig. the term follicular cholecystitis is used. If infiltrates of neutrophils are found in chronic cholecystitis. Porcelain gallbladder is a term that is used for fibrosed and/or calcified gallbladders in chronic states of disease. or carcinosarcomas are rare. 8-79. Carcinoma of the gallbladder is clinically the most important tumor of the gallbladder. Its wall may be fibrosed (Fig. The gallbladder is filled with multifaceted stones.

Hum Pathol 26:956-964. Weiss JB Jr. Carithers RL Jr. Steiner PE: Primary carcinoma of the liver. Hepatology 20:349-355. 1997. Meyer zum Buschenfelde K-H. International Working Party. Guerret S. Nolberg K. Terminology of nodular hepatocellular lesions. James 0. Hepatology 21:240-252.900 necropsies. gallbladder. 1997. 66417308 : ¸Ÿ±U 24 ¥°Q . Persing DH: Hepatitis C. 1994. 1995. 1978. Chatila R: Differential diagnosis of bile duct injury and ductopenia. 1998.165 Fig. 1994. 1995. Gerber M. Gold JH. Seeff LB: Natural history of viral hepatitis. 1995. 1995. Henson DE: Liver. Walters MNI: Premalignant epithelial lesions of the gallbladder. Hydrops of the gallbladder. Mayo Clin Proc 70:296-297. Ishak KG: Chronic hepatitis. Adachi E. Definition—classification—histopathology—immunopathogenesis. NEngl JMed 337:1733-1745. 1995. 8-82. Sem Diag Pathol 15:270-284. 1996. Kajiyama K et al: Combined hepatocellular and cholangiocarcinoma. Day C: Non-alcoholic steatohepatitis: another disease of affluence. Medicine (Baltimore) 71:139-164. 1992. Shilken KB. Am J Clin Pathol 70:6-17.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Carcinoma of the gallbladder. An update on terminology and reporting. Chronic active cholecystitis. Yuzbasiyan-Gurkan V: Wilson disease. Guzman IJ. Semin Gastrointest Dis 6:20-27. Comparison with morpholometric studies. Lancet 353:1634-1636. Hoofnagle JH et al: Classification of chronic hepatitis: Diagnosis. Hoofnagle JH. Pathologic examination of 45 cases. Dilated gallbladder contains an impacted stone in its neck region. Ojeda VJ. type C. Wands JR: Hepatitis C virus: epidemiology and transmission. Chossegross P et al: A histological semiquantitative scoring system for evaluation of hepatic fibrosis in needle liver biopsy specimens. Summary of a workshop. Rosai J: Benign tumors of the liver. Cancer 75:175-190. Am J Surg Pathol 19:1409-1417. 1994. Fig. 1954. whereas the surface mucosa is infiltrated with neutrophils. 8-84. Virchows Arch 429:1-12. The gallbladder is partially filled and infiltrated with neoplastic tissue Further Reading Albores-Saavedra J. Henson DE: Unusual malignant epithelial tumors of the gallbladder. 1999. Hepatology 22:983-993. Carriaga MT. A study of 100 cases among 48. 8-83. Hepatology 3:521-526. Advances in diagnosis. Shapiro C et al: Fulminant hepatic failure. grading and staging. Proposed criteria according to cytokeratin expression and analysis of clinicopathologic features. Morphology and nomenclature. The wall of the gallbladder is infiltrated with chronic inflammatory cells. A prospective study of 120 cholecystectomy specimens. Hepatology 19:1513-1520.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Sem Diag Pathol 13:326-338. Chevallier M. Cancer 7:462-503. Maeda T. Desmet VI. 1996. 1995. Fig. 1985. Lee WM: Hepatitis B virus infection. West AB. Edmonson HA. Brewer GJ. Dienes H-P: Autoimmune hepatitis. 1995. Ludwig J: Chronic hepatitis. and pancreas. Heintges T. Mod Pathol 7:690-713. Pathology 17:451-454. extrahepatic bile ducts. Batts KP.

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Dysfunction of the CFTR is associated with increased viscosity of the mucus of many exocrine glands. which most often are composed of splenic or intestinal tissue (Figs. forming a ductuloinsular complex. The irregularly shaped islet is attached to a small duct. Diffuse nesidioblastosis. and heterotopic inclusions or choristomas. 9-1 and 9-2). In advanced stages of the disease chronic obstruction of the pancreas is associated with compression and atrophy of acini. Histologically the main criteria for establishing the diagnosis are (1) distinct 13-cell hypertrophy with nuclear enlargement. 9-2. and (4) endocrine cell complexes. In the diffuse form there are distinct insular changes. 9-3 and 9-4). (3) irregularly sized and poorly defined endocrine cell clusters scattered in the acinar parenchyma.. (2) the presence of islets of variable size.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . pancreas divisum. small intestine. often resulting in giant and bizarre nuclei. Annular pancreas. Fig. Cyst is lined by cuboidal epithelium. Cystic fibrosis is one of the most common autosomal recessive diseases of man and it always involves the pancreas. These abnormalities occur sporadically and usually are asymptomatic. Fig. The viscous mucus stagnates and accumulates in the pancreatic ducts (Fig. Cyst of the pancreas. Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . usually are asymptomatic.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 9-I. B. Nesidioblastosis is an anomaly of the endocrine pancreas that is characterized by persistent neonatal hyperinsulinemic hypoglycemia. often intimately connected with small or larger ducts (ductuloinsular complexes) (Figs. including the pancreas. in the stomach.168 DEVELOPMENTAL AND GENETIC DISORDERS Developmental disorders of the exocrine pancreas include (1) anatomic anomalies such as annular pancreas. and ectopic pancreas (e. Diffuse nesidioblastosis. which then are replaced by fibrous tissue (Fig. 9-6). often of somewhat irregular outline. Many cells in this enlarged islet have hypertrophic nuclei. and (2) hamartomas. The disease is related to mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). These cysts. but an annular pancreas occasionally causes intestinal obstruction. 9-4.g. A. which may be multiple. or Meckel diverticulum). which are widespread. cysts. A B Fig. 9-3. In the focal form islet cells form small nodules. The narrowed duodenum is only probe patent. 9-5). It occurs in both focal and diffuse forms.

9-9. contain a few inflammatory cells. Viral pancreatitis may be caused by the mumps virus.169 Fig. Interstitial pancreatitis. Viral pancreatitis. 9-7. Dilated ducts contain inspissated proteinaceous material. results from acinar cell injury and intrapancreatic activation of pancreatic lytic enzymes (Diagram 9-1). Fig. Acute hemorrhagic pancreatitis. 9-8). PANCREATITIS Acute interstitial pancreatitis occurs in the course of many systemic diseases. 66417308 : ¸Ÿ±U 24 ¥°Q . and some pancreatic cells contain CMV nuclear inclusions. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . which is the most important clinical form of pancreatitis. Blood-filled cavities (pseudocysts) form in the pancreas (Fig. 9-8. which appear dilated because of edema.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Acute hemorrhagic pancreatitis. 9-9). 9-7). Fig. 9-5. which leads to massive hemorrhagic necrosis of the pancreas and adjacent tissues (Fig. Histologically it presents as interstitial edema accompanied by a sparse inflammatory infiltrate (Fig. The pancreas appears disorganized. The loose connective tissue stroma contains scattered inflammatory cells. 9-6. The pancreas has been completely obliterated by blood. Proteolytic enzymes digest the walls of blood vessels. Cystic fibrosis. In later stages of the disease the dilated ducts filled with eosinophilic material are surrounded by fibrotic parenchyma and atrophic acini. Cystic fibrosis. 9-10). and some other viruses (Fig. The interstitial spaces. Fat necrosis characterized by saponification of fatty acids re - Fig. It may be associated with elevated blood amylase or lipase but usually causes no symptoms. cytomegalovirus (CMV).

9-10. 9-12. The mesentery shows foci of fat necrosis and hemorrhage.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Acute pancreatitis. Fig. A. fat necrosis. Pathogenetic relationships of acinar cell injury and duct obstruction to pancreatitis. 66417308 : ¸Ÿ±U 24 ¥°Q .17 0 Diagram 9-I. Peritonitis complicating acute pancreatitis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Intrapancreatic mechanisms of enzyme activation in pancreatitis Fig. 9-1 I. Acute pancreatitis. Fig. Acute hemorrhagic pancreatitis. Hemorrhage. 9-13. The necrotic pancreatic acinar cells have been transformed into amorphous bluish granular material. Foci of fat necrosis appear as white opaque patches. Fig. In the areas of fat necrosis the fat cells have left their normal outlines and appear eosinophilic. B. The bloody ascites has been removed. and a pseudocyst filled with blood are seen on cross section.

but the fibrous capsule remains (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Pancreatic pseudocyst. continuously promoting necrosis and inflammation (Fig. 9-16). 9-I5. 66417308 : ¸Ÿ±U 24 ¥°Q . After drainage of its content. Treatment by marsupialization (i. 9-18). which act on the adjacent tissue. and focally calcified. which typically is accompanied by shock and massive necrosis of mesenteric and omental fat tissue (Fig. 9-18. 9-14. Chronic pancreatitis may be a late consequence of acute pancreatitis. Fig. 9-15). 9-13). Clinically it is marked by chronic pancreatic insufficiency and malabsorption. Large pseudocysts may form at the site of pancreatic tissue destruction (Fig. Complications of acute pancreatitis are massive bloody peritonitis. Pancreatic pseudocyst. Chronic pancreatitis. Histologically the acini are replaced by fibrous tissue and chronic inflammatory cells. Its obstructed and dilated ducts contain calculi (Fig. 9-16.e. exteriorization of the cyst. Connective tissue and foci of chronic inflammatory cells are found surrounding a few scattered ducts and remnants of acini and islets. Fig. The main pancreatic duct is dilated and contains calculi. the pseudocyst appears as a fibrous sac. 9-11 and 9-12). The disease is a well-known complication of chronic alcoholism. Fig. 9-17. The normal lobular architecture of the pancreas has been lost because most acini have been replaced by fibrous tissue. Fig. Fig. allowing its drainage to the outside of the body) may eliminate the enzymes.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . but more often it is the end result of clinically undetected bouts of recurrent pancreatitis.171 leased from damaged fat cells through the action of pancreatic lipase is a typical finding (Figs. The lumen is lined by necrotic material that lacks an epithelial layer. Diabetes is seen in approximately 25 percent to 35 percent of cases. fibrotic. 9-17). These pseudocysts typically are filled with pancreatic enzymes. Cyst filled with hemorrhagic fluid in the tail is extending into the hilum of spleen. which surround the few remaining ducts and islets of Langerhans (Fig. The pancreas usually is firm.. Pancreatic pseudocyst. 9-14). Chronic pancreatitis.

The World Health Organization histologic classification of tumors of the exocrine pancreas is presented in Table 9-1. The cystic spaces in serous cystadenoma are filled with clear fluid and lined by flattened cuboidal epithelium (Fig. indicating that the malignancy arose through an adenoma-carcinoma sequence similar to the histogenesis of carcinoma of the colon in familial adenomatous polyposis coli. also known as solid cystic tumor. Intraductal papillary mucinous neoplasms represent a group of closely related neoplasms. acinar. They measure from 2 to 20 cm in diameter.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . These tumors are either benign or borderline malignant. including benign. B. 9-19). Tumor cells contain both zymogen and neuroendocrine granules. The benign variant. Malignant tumors of this group are indistinguishable from other mucinous adenocarcinomas (Fig. and malignant neoplasms. The tumor is well circumscribed. These tumors typically occur in young women and present in the form of a solid or partially cystic mass. also called intraductal papilloma. Mucinous cystadenomas are lined by cuboidal mucin—rich epithelium. Histologically they are composed of solid nests of cuboidal cells that have clear or eosinophilic cytoplasm and round to oval nuclei (Fig. Serous cystadenoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . On cross section it appears microcystic. A. borderline malignant. The tumor is traversed by fibro- Histologic Classification of Tumors of the Exocrine Pancreas Proposed by the World Health Organization A B Fig. or malignant. or villous adenoma of the pancreatic ducts. Solid pseudopapillary tumor. papillary adenoma. Malignant tumors predominate. 9-21). 9-22). they grow slowly and measure from 2 to 4 cm in diameter at di- agnosis.172 TUMORS OF THE EXOCRINE PANCREAS Benign or malignant neoplasms of the exocrine pancreas may arise from ductal. Some of these tumors contain foci of borderline and even benign mucinous epithelium. and some from the latter group may give rise to invasive cancer. is composed of papillae lined by well-differentiated mucin-rich epithelium (Fig. Overall. 9-23). Intraductal papillary mucinous tumors of borderline malignancy have complex papillae lined by tall columnar epithelium with moderate nuclear dysplasia (Fig. and stromal cells. 9-19. ductal adenocarcinoma accounts for 80 percent to 85 percent of pancreatic neoplasms. 66417308 : ¸Ÿ±U 24 ¥°Q . Benign Tumors and Tumors of Borderline Malignancy Cystadenomas of the pancreas are multicystic tumors that are classified as serous or mucinous (Fig. 9-24). refers to a group of tumors that may be benign. 9-20). borderline.

Fig.173 Fig. Fig. In the pseudopapillary part of the tumor. Intraductal papillary mucinous adenoma. hyperchromasia. 9-20. cells line or are attached to fibrovascular cores that project into the cystic space. 66417308 : ¸Ÿ±U 24 ¥°Q . Intraductal papillary-mucinous tumor of borderline malignancy. Solid pseudopapillary tumor. 9-23.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . A. Intraductal papillary-mucinous carcinoma. and mild to moderate atypia. Serous cystadenoma. 9-22. 9-21. Solid areas are composed of uniform cuboidal cells. Fig. B.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The long papillary folds are lined by tall columnar epithelium showing nuclear crowding. Small cystic spaces are lined by flattened cuboidal epithelium. A B Fig. The duct epithelium forms intraluminal folds lined by well-differentiated mucin-rich epithelium. 9-24.

C. Moderately differentiated carcinoma. It is composed of a few poorly formed ducts and scattered anaplastic or signet ring—like cells in small clusters. 9-26. or undifferentiated with osteoclast-like multinucleated giant cells (Fig. 9-33). adenosquamous (Fig. 9-32). Carcinoma of the Pancreas Carcinoma of the pancreas not otherwise specified is a term that usually is reserved for malignant tumors that originate from ductal epithelium. The tumor has metastasized to the liver. Poorly differentiated carcinoma (grade III). (grade II). most of which also show a high degree of nuclear atypia. Invasion and metastases are found in 10 percent to 20 percent of cases. There is a moderate desmoplastic reaction. Carcinoma of the body of the pancreas. Approximately 60 percent of these tumors are located in the head of the pancreas. The tumor invades the spleen. Well-differentiated carcinoma (grade I). 9-27). Necrosis occurs in more than half of all tumors. Adenocarcinoma of ductal origin. Fig. Cuboidal cells form irregular glands that vary in size and shape. or poorly differentiated (Fig. Carcinoma of the tail of the pancreas. moderately differentiated. and the remaining 30 percent are in the body or are diffuse (Figs. Histologically most tumors are adenocarcinomas that are graded on a scale from Ito III or are described as well-differentiated. 9-28). Acinar cells may form acini and lobules or solid sheets (Fig. which gives the tumor a pseudopapillary histologic appearance. Some tumors are classified as mucinous (Fig. 9-27. eliciting a strong desmoplastic reaction. In this process only the cells close to the vasculature remain viable. 9-30). 66417308 : ¸Ÿ±U 24 ¥°Q . undifferentiated (Fig. Columnar hyperchromatic cells form irregular glands with a "gland within gland" and "back to back " growth pattern. A B C Fig. 9-29). Other tumors are extremely rare. 10 percent are in the tail. 9-25.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 9-25 and 9-26). Acinar cell carcinomas are rare tumors composed of cells that resemble acinar cells.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 9-31). Fig. B. It is composed of primitive undifferentiated cells that differentiate into epithelial and neuroendocrine cells.174 vascular septa. A. occasionally arranged into organoid structures (Fig. Pancreatoblastoma is a tumor of children and adolescents.

The tumor is composed of pleomorphic and spindle-shaped cells. A B Fig. Acinar cell carcinoma. 9-28. 9-30.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Mucin-filled spaces are partially lined by columnar mucin-secreting epithelium.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Well-differentiated acinar carcinoma is composed of uniform cells with well-developed eosinophilic cytoplasm arranged into acini or acinar tubules. 9-32. Solid acinar carcinoma. Fig. 9-3I. Adenosquamous carcinoma.175 Fig. Mucinous (noncystic) carcinoma. 9-29. Undifferentiated carcinoma. B. A. Fig. Undifferentiated carcinoma. Fig. The tumor contains numerous osteoclast-like multinucleated giant cells. 66417308 : ¸Ÿ±U 24 ¥°Q . Both glandular and squamous elements are evident. The tumor is composed of uniform cells that have round nuclei and welldeveloped eosinophilic cytoplasm. The cells form solid sheets.

176

A

B

Fig. 9-33. Pancreatoblastoma. A, The tumor is composed predominantly of primitive cells and only occasional ductlike structures. B, The tumor is composed of duct-like and endocrine cells.

TUMORS OF THE ENDOCRINE PANCREAS
Islet cell tumors are rare neoplasms that are found in the general population at a rate of 1 per 100,000. Because the tumors have the features of neuroendocrine cells and presumably have the same origin as islets of Langerhans, they are referred to as neuroendocrine tumors of the pancreas. Clinically they are either benign or malignant. It is not possible to determine on the basis of histology whether a particular tumor is benign or malignant, and the presence of metastases is the only definitive sign that a tumor is malignant. On gross examination neuroendocrine tumors appear as well-circumscribed nodules (Fig 9-34). Some tumors are multiple, and malignant tumors may have local metastases

in the lymph nodes or liver. Histologically, islet cell tumors resemble neuroendocrine tumors (carcinoids) of the intestine or the bronchi and present in several patterns such as trabecular, insular, glandular, or solid (Fig. 9-35). Some tumors are composed of endocrine and exocrine cells. In some patients with multiple endocrine neoplasia type 1 (MEN 1), islet cell tumors are seen only on microscopic examination and are classified as microadenomas (Fig. 9-36). Islet cell tumors are classified functionally according to which hormone they produce as: (1) insulinoma; (2) glucagonoma; (3) somatostatinoma; (4) PPoma (pancreatic polypeptide—secreting tumor); (5) gastrinoma; (6) VIPoma (vasoactive intestinal polypeptide-secreting tumor); (7) nonfunctioning tumors; and (8) ectopic hormone—secreting tumors. By light microscopy all of these tumors have the same features and cannot be distinguished one from another. Somatostatinomas may contain calcifications (Fig. 9-37), but

Fig. 9-34. Islet cell tumor. The tumor presented as a small mass, which was sharply demarcated from the remainder of the pancreas.

Fig. 9-35. Islet cell tumor. Uniform tumor cells with round nuclei are arranged in solid sheets.

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177

Fig. 9-36. Microadenoma in MEN I. The tumor cells are arranged in a trabecular pattern.

Fig. 9-37. Somatostatinoma. The tumor has a trabecular pattern with focal calcifications.

Fig. 9-38. Islet cell tumor. Immunohistochemically this insulinoma reacted strongly with antibodies to insulin.

this finding does not have enough specificity to allow one to make a definitive diagnosis. Immunohistochemistry and electron microscopy are essential for diagnosis and in most cases provide morphologic confirmation and correlation with the clinical and biochemical laboratory data (Figs. 9-38 and 9-39). Many neuroendocrine tumors of the pancreas are, however, composed of more than one cell population and are i mmunohistochemically polyhormonal.

Fig. 9-39. Islet cell tumor. Immunoelectron microscopy with antibodies to insulin proves that the tumor is an insulinoma.

DIABETES MELLITUS
refers to a group of disorders characterized by hyperglycemia that is related to either absolute or relative insulin deficiency. On the basis of clinical, genetic, and immunologic features diabetes is classified as (1) type 1, insulindependent diabetes mellitus (IDDM); (2) type 2, non– insulin-dependent diabetes mellitus (NIDDM); (3) diabetes
Diabetes mellitus

secondary to pancreatic disease; (4) diabetes related to overproduction of hormones that antagonize the action of insulin; and (5) gestational diabetes (Table 9-2). Type I diabetes is characterized by an immune-mediated injury of the islets of Langerhans. Infiltrates of T lympho -

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178

Features of the Main Types of Diabetes Mellitus

Fig. 9-40. Type I diabetes (IDDM). Islet of Langerhans is infiltrated with lymphocytes on the left. On the right side the islet still contains many cells that stain brown with the antibody to insulin.

Fig. 9-41. Type I diabetes (IDDM). The islet cells stain with fluorescein-labeled anti-islet autoantibodies typically found in patients with IDDM.

A

B

Fig. 9-42. Type I diabetes (IDDM). A, After 21 years of disease this patient shows few remaining 13 cells staining with antibodies to insulin (INS). B, There is hyperplasia of a cells staining with antibodies to glucogen (GLU).

Fig. 9-43. Type I diabetes (IDDM). The islets have been replaced to a great extent by fibrous tissue.

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Fig. 9-44. Type 2 diabetes-(NIDDM). Amyloid deposits are seen in the stroma of the islet.

Fig. 9-45. Chronic pancreatitis with diabetes. Fibrous tissue has replaced the acini but has spared the islets, which appear in clusters.

Diabetes of chronic pancreatitis is related to destruction of the pancreas, with fibrosis replacing the lost parenchyma (Fig. 9-45). Although fibrosis preferentially replaces acini, many islets also are destroyed and the number of f3-cells is reduced (Fig. 9-46). The remaining islets usually form irregular clusters surrounded by fibrotic tissue, which impedes the release of insulin into the circulation. Further Reading
Klimstra DS: Pancreatoblastoma. A clinicopathologic study and review of the literature. Am J Surg Pathol 19:1371-1389, 1995. Kloppel G, Maillet B: Chronic pancreatitis. Evaluation of the disease. Hepatogastroenterology 38:408-412, 1991. Le Bodic M-F, Heyman M-F, Lecomte M et al: Immunohistochemical study of 100 pancreatic tumors in 28 patients with multiple endocrine neoplasia, type 1. Am J Surg Pathol 20:1378-1384, 1996. Marshall JB: Acute pancreatitis. A review with an emphasis on new developments. Arch Intern Med 153:1185-1198, 1993. Oertel JE: The pancreas. Nonneoplastic alterations. Am J Surg Pathol 13(suppl 1):50-65, 1989. Pettinato G and others: Papillary cystic tumor of the pancreas. A clinicopathologic study of 20 cases with cytologic, immunohistochemical, ultrastructural and flow cytometric observations, and a review of the literature. Am I Clin Pathol 98:478-488, 1992. Steer ML, Waxman I, Freedman S: Chronic pancreatitis. NEngl JMed 332:1482-1490, 1995. Steinberg W, Tenner S: Acute pancreatitis. NEngl JMed 330:1198-1210, 1994. Talamini MA, Pitt HA, Hruban RH et al: Spectrum of cystic tumors of the pancreas. Am )"Surg 163:117-124, 1992. Warshaw AL, Fernandez-del Castillo C: Pancreatic carcinoma. N Engl J Med 326:455-65, 1992.

Fig. 9-46. Pancreas in advanced chronic pancreatitis. Islets with reduced 13 cell number. (Immunostaining for insulin.)

cytes are seen in early stages of the disease (Fig. 9-40). Affected patients typically develop autoantibodies to islet cells (Fig. 9-41). In the course of the disease the islets lose R cells, an event that maybe accompanied by a hyperplasia of a cells (Fig. 9-42). In some fulminant cases islets may be destroyed (Fig. 9-43). In such cases patients survive only by receiving daily injections of insulin. Type 2 diabetes usually is not associated with specific insular changes. Some patients show hyalinization and/or amyloid deposition in islets (Fig. 9-44).

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182

Diseases of the endocrine glands present clinically as hypofunctional or hyperfunctional states or as space-occupying lesions caused by neoplastic or nonneoplastic enlargement of the glands. The hypofunction of endocrine glands may be traced to a destruction of parenchymal cells by inflammation, circulatory disturbances, or tumors; hyperfunction may be related to hyperplasia or neoplasia. Major endocrine glands are interrelated, and changes in one gland may produce reactive changes in another gland.

DISEASES OF THE PITUITARY GLAND Hypopituitarism
Hypofunction of the pituitary gland maybe related to (1) agen-

esis or congenital hypoplasia; (2) circulatory disturbances; (3) inflammatory disease caused by infections or autoimmune disorders; (4) compression or destruction of the pituitary gland or hypothalamus by space-occupying lesions such as tumors, abscesses, or hematomas; (5) trauma, irradiation, or surgical procedures (Fig. 10-1). Pathologic changes de -

Diagram 10-I. Primary empty sella syndrome. The pituitary is compressed as a result of the increased cerebrospinal fluid pressure. CSF, Cerebrospinal fluid.

Fig. 10-1. Pituitary necrosis caused by ischemia.

Fig. 10-2. Lymphocytic hypophysitis. The anterior pituitary is infiltrated with lymphocytes.

Fig. 10-3. Craniopharyngioma. The tumor is located at the base of the brain and consists of nests of epithelial cells. Calcifications are prominent.

Fig. 10-4. Histiocytosis X. The pituitary gland is infiltrated with Langerhans cells (histiocytes) and eosinophils.

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1 83

pend on the primary disease, but ultimately the entire content of the sella turcica may be destroyed, resulting in the socalled empty sella syndrome. Empty sella syndrome related to incomplete or absent sellar diaphragm is called primary empty sella syndrome (Diagram 10-1). If the cause of empty sella syndrome is traced to a destructive disease, it is classified as secondary. Lymphocytic hypophysitis is thought to be an autoimmune disease (Fig. 10-2). Granulomas may be infectious or-idiopathic, as in sarcoidosis. Tumors such as craniopharyngioma or Langerhans cell histiocytosis (histiocytosis X) may destroy the pituitary gland or the hypothalamus, causing hypopituitarism (Figs. 10-3 and 10-4).

Reactive Changes
Reactive changes may be seen in the pituitary gland (1) under physiologic conditions, as in pregnancy; (2) as a result of hypofunction of other endocrine glands, as in hypothyroidism or adrenocortical hypofunction (Addison disease); (3) as a result of hypefunction of other endocrine glands, as in hyperadrenocorticism; or (4) as a consequence of a drug effect. The reactive cells enlarge or decrease in size, or show typical cytoplasmic changes such as Crooke hyaline in hyperadrenocorticism (Figs. 10-5 and 10-6). Tumors Tumors of the pituitary gland are mostly benign and are composed of cells equivalent to those normally seen in the pituitary gland. Immunohistochemically they are classified as prolactinomas, or as adrenocorticotropic hormone (ACTH), growth hormone (GH), thyroid-stimulating hormone, (TSH), or gonadotropic hormones (FSH or LH) secreting adenomas. If the immunochemical results are negative or inconclusive, pituitary adenomas are designated null cell adenomas or unclassified adenomas. Tumors composed of oncocytic cells are called oncocytomas. The frequency of various types of pituitary adenomas is listed in Table 10-1.
Frequency of Pituitary Adenomas Adenoma Type GH cell adenoma, densely granulated GH cell adenoma, sparsely granulated PRL cell adenoma, densely granulated PRL cell adenoma, sparsely granulated Mixed (GH cell—PRL cell) adenoma Mammosomatotroph adenoma Acidophil stem cell adenoma Corticotroph adenoma Silent "corticotroph" adenoma, subtype I Silent "corticotroph" adenoma, subtype 2 Silent adenoma, subtype 3 Thyrotroph adenoma Gonadotroph adenoma Null cell adenoma Oncocytoma Unclassified adeno Percentage 7.2 6.4 0.4 26.5 3.7 I.3 1.7 9.9 1.5 2.1 1.4 1.0 9.3 12.7 13.1 1.8 Fig. 10-7. Pituitary adenoma. The tumor protrudes from the sella turcica. Fig. 10-5. Reactive hyperplasia of thyrotroph cells in hypothyroidism. The enlarged thyrotroph cells are arranged into acini.

Fig. 10-6. Crooke hyaline. In hyperadrenocorticism adrenocorticotropic cells enlarge because of an accumulation of intermediate filaments in their cytoplasm. These cytoplasmic bodies displace the secretory granules to the subplasmalemmal periphery of cell cytoplasm.

GH, Growth hormone; PRL, prolactin. *Based on unselected surgical material involving 1910 cases.

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184

On the basis of their size, pituitary tumors are classified as microadenomas (if they are smaller than 10 mm in diameter) or macroadenomas (if they are larger than 10 mm in diameter) (Figs. 10-7 and 10-8). On the basis of their morphology on routine hematoxylin-eosin—stained slides, pituitary adenomas traditionally were classified as acidophilic, basophilic, or chromophobic (Fig. 10-9). This classification did not provide useful correlates with clinical or biochemical data, and it has been replaced by a functional classification based on immunohistochemical and electron microscopic typings of tumor cells (Figs. 10-10 and 10-11). Pituitary carcinomas are rare, locally invasive tumors that account for 2 percent to 3 percent of all pituitary neoplasms. Histologically it is not possible to distinguish with confidence adenomas from carcinomas, except in rare cases in which the malignant tumor is highly anaplastic.
A B

Fig. 10-8. Pituitary adenoma. On cross section the tumor nodule is sharply demarcated from the normal pituitary. C

Fig. 10-9. Pituitary adenomas A, Acidophilic. B, Basophilic. C, Chromophobic. A B

Fig. 10-10. Prolactin cell adenoma. A, Small tumor cells are staining with antibody to prolactin. B, By electron microscopy the tumor cells show extrusion of small granules at the lateral cell membranes ("misplaced exocytosis").

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Idiopathic nodular goiter is the most common cause of thyroid enlargement. ACTH-positive tumor cells form solid nests. Thyroid Hyperplasia Hyperplasia typically causes enlargement of the thyroid gland (goiter). A. 10-I I. B.185 A B Fig. affecting 3 percent to 5 percent of the population at large. By electron microscopy the tumor cells contain 250 to 450 nm granules. Nodular goiter. Follicles are lined by cuboidal or flattened epithelium. (2) antibodies to TSH receptor. hyalinization. 10-12. 10-12). calcification. which may show focal papillary hyperplasia (Fig. which may be either nodular or diffuse. The thyroid gland is enlarged and consists of nodules that vary in size and shape. cholesterol crystals. (4) goitrogens in food. A B Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Hypothyroidism or hyperthyroidism may be associated with distinct morphologic changes. imparting a nodular appearance to the gland. Some nodules may acquire adenoma-like properties. and cystic degeneration. Histologically it is composed of colloid-filled follicles that vary in size and shape. or (5) drugs. (3) iodine deficiency. B. DISEASES OF THE THYROID GLAND Disorders of thyroid function are commonly diagnosed in clinical practice. A.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . which otherwise are composed only of large dilated follicles. It presents as a mass that causes enlargement of the thyroid gland without hormonal abnormalities.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Corticotroph adenoma. 10-12). In one form or another it is found in ap- proximately 50 percent of autopsies in adults. Foci of secondary proliferation composed of cells arranged in a microfollicular or solid pattern may be seen in some nodules. Secondary degenerative changes are common and include fibrosis. but in general nodular goiter is not a direct precursor of thyroid cancer. The thyroid gland is asymmetrically nodular and may compress surrounding structures (Fig. but in most instances it is not possible to predict functional thyroid abnormalities from the morphologic data alone. Foci of hemorrhage and chronic inflammation are present. foci of hemorrhage. Hyperplasia of the thyroid gland may result from hyperstimulation by (1) TSH. The thyroid gland is composed of follicles arranged into clusters.

It most often occurs in women. The epithelium often projects into the lumen of follicles in the form of small papillary infoldings. Occasionally there is Diagram I0-2. Histologically it is characterized by a granulomatous giant cell and lymphocytic reaction around the colloid released from ruptured follicles. and soft (Fig. The excess of T 3 and T4 results in the suppression of thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) production. usually following a viral infection. Other forms of thyroiditis that may cause clinical symptoms are less common but may be associated with specific clinical symptoms (Table 10-2). Hashimoto thyroiditis is an autoimmune thyroid disease that may occur either in an isolated form or conjointly with other autoinunune diseases such as atrophic gastritis or primary biliary cirrhosis. A defect in suppressor T-lymphocytes is responsible for the excessive production of autoantibodies to TSH receptor causing enlargement of the thyroid gland and excessive production of triiodothyronine (T 3 ) and thyroxine (T 4). Most patients initially are euthyroid. 10-15). Graves disease is an autoimmune disorder caused by stim- ulation of the thyroid gland by antibodies to the receptor for TSH (Diagram 10-2). and the female-male ratio is 8:1. The colloid is pale and often shows peripheral scalloping (Fig. low-grade fever. and on cross section it appears hyperemic. also known as granulomatous or de Quervain thyroiditis. 10-14). A. On cut section the thyroid gland appears moist and hyperemic and lacks normal colloidal appearance. The stroma is vascular and mildly fibrotic and may contain lymphoid cell aggregates. 66417308 : ¸Ÿ±U 24 ¥°Q . Graves disease. Subacute thyroiditis. 10-13.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . is characterized by painful enlargement of the thyroid gland. and hyperthyroidism of sudden onset. 10-16). Histologically the follicles are lined by hyperplastic. commonly diagnosed at autopsy (Fig. (Fig. Pathophysiologic mechanism of Graves disease. Thyroiditis Nonspecific lymphocytic thyroiditis is a disease of no clinical significance. 10-13. The thyroid gland is diffusely enlarged. vacuolated cells with basally located nuclei. moist.18 6 B A Fig. B). but as destruction of the thyroid gland advances they may develop signs of hypothyroidism. The thyroid gland is symmetrically enlarged. B.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . tall columnar. Oncocytic changes may be evident but usually are not prevalent.

The thyroid gland is infiltrated focally with lymphocytes and plasma cells. Nonspecific lymphocytic thyroiditis. sudden onset of painful swelling Clinically the most important autoimmune thyroiditis. Some follicles contain very little colloid. related to head and neck infections. which form lymphoid follicles with germinal centers.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . I0-14. Thyroid follicles are destroyed and replaced in part by the infiltrate. A.187 A B Fig. 10-15. and the follicles contain almost no colloid. Graves disease. Subacute granulomatous thyroiditis. sepsis. The remaining follicles are atrophic and often devoid of colloid. granular cytoplasm) is typical. leads to hypothyroidism but often euthyroid. Hashimoto thyroiditis is associated with an increased risk for lymphoma. The thyroid gland typically is enlarged to three or four times its normal size (Fig. The stroma contains lymphocytes. Other epithelial changes such as nodular hyperplasia or squamous metaplasia are less common. or surgery Rare. Widespread oncocytic change (i. which accounts for 10 percent of cases (Fig. Follicles are lined by tall columnar epithelium. 10-17). Fig. Fig. Marked hyperplasia of the epithelium is seen.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Forms of Thyroiditis Type of Thyroi Nonspecific lymphocytic Acute bacterial Subacute (granulomatous) Hashimoto Clinical Features Common finding at autopsy. Histologically the gland is infiltrated with lymphocytes and plasma cells. The colloid adjacent to the epithelium appears vacuolated and scalloped. B. Multinucleated giant cells surround residual colloid in a follicle.. The most common is the fibrous variant. 10-16. "hashitoxicosis" rare Rare.e. probably related to viral disease. fibrosing destruction of thyroid extending into adjacent tissue ("ligneous" thyroiditis) Riedel 66417308 : ¸Ÿ±U 24 ¥°Q . The follicular epithelium shows no significant changes. hyperthyroidism ( " hashitoxicosis"). Several histologic and clinical variants of Hashimoto thyroiditis have been recognized. eosinophilic. asymptomatic Rare. transformation of epithelium into cuboidal cells with mitochondria-rich.

which stems from lymphoid infiltrates and loss of colloid-filled follicles. a minority arise from stromal cells or lymphoid tissue. which replaces most of the thyroid parenchyma and extends into adjacent neck structures. The process may be focal or diffuse. Riedel thyroiditis. Lymphocytes and plasma cells are found between the strands of connective tissue. also known as invasive fibrous thyroiditis. is a rare cause of hypothyroidism that is characterized by extensive fibrosis. Histologically it may present as lymphocytic or granulomatous inflammation but without multinucleated giant cells.188 A B C Fig. the epithelium does not show oncocytic changes but may be hyperplastic. Benign tumors are more common than malignant tumors. which typically produces multiple nodules. or macrofollicular (colloid) adenoma. C.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . B. Thyroid follicles devoid of colloid are lined by oncocytic cells that have eosinophilic granular cytoplasm and round vesicular nuclei. It should not be confused with nodular hyperplasia. also known as silent thyroiditis or self-resolving lymphocytic thyroiditis with hyperthyroidism. Hyalinized trabecular adenoma shows 66417308 : ¸Ÿ±U 24 ¥°Q . The epithelium shows either oncocytic or hyperplastic changes. It presents as a solitary " cold" nodule on isotopic scanning with radioactive iodine . A. Hyperplastic changes in the form of papillary or pseudopapillary structures may occur (Fig. and although its etiology is not known this disease might represent an outcome of Hashimoto disease. however. present a more formidable challenge from both the diagnostic and the therapeutic point of view. Closely related to it is the so-called painless thyroiditis. (2) hyalinized trabecular adenoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . solid (embryonal). Histologically. The remaining follicles are atrophic. It is characterized by fibrosis and prominent hypothyroidism. Atrophic thyroiditis (idiopathic myxedema) is characterized by a loss of follicles and atrophy of the gland. 10-20 and 10-21). and (4) oncocytic (HUrthle cell) adenoma. 10-18). The epithelium of the remaining follicles shows oncocytic transformation. 10-17. and typically in the walls of small veins (Fig. which. 10-19). Juvenile thyroiditis is a variant that occurs in children and young women. The enlarged thyroid has a multinodular. A lymphoid follicle with a germinal center and diffuse lymphocytic infiltrates replace the thyroid follicles. Hashimoto thyroiditis. Atypical follicular adenomas show less regular architectural and cytologic features than typical adenomas. Benign Thyroid Tumors Most thyroid tumors are of epithelial origin. around the blood vessels. whitish appearance. Variants of follicular adenoma that deserve additional studies are (1) atypical follicular adenoma. In contrast to classic Hashimoto thyroiditis. microfollicular (fetal).and is surrounded by normal or compressed thyroid follicles. 10-22). (3) adenoma with bizarre nuclei. Follicular adenoma is a benign encapsulated tumor that shows evidence of follicular differentiation (Figs. collagenous bands are found replacing thyroid follicles. even though the thyroid gland is enlarged. Microscopically the tumor may present in one of several patterns and is classified as trabecular. normofollicular (simple). These descriptive terms have no biologic or clinical implications.

Fig. 10-22. 10-19. Fibrous tissue infiltrated with lymphocytes is replacing the follicles.189 Fig. Fig. Follicular adenoma. Diffuse fibrosis and inflammatory cells such as lymphocytes and plasma cells have replaced the thyroid follicles. Riedel thyroiditis. The well-circumscribed nodule has a fibrous capsule separating it from the normal parenchyma. 66417308 : ¸Ÿ±U 24 ¥°Q . A medium-sized vein shows signs of vasculitis (arrow). Fig. Follicular adenoma with papillary hyperplasia. Tumor cells form small follicles.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 10-20.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig. microfollicular pattern. Follicular adenoma. 10-18. Fibrous variant of Hashimoto thyroiditis. 10-21. On cross section the tumor appears yellow-tan with focal hemorrhage. Short papillary projections lined by follicular cells have almost no fibrovascular cores. few of which remain.

5:1. 10-24). Oncocytic (Hurthle cell) adenoma consists of solid nests of cuboidal cells that have round uniform nuclei and eosinophilic granular or clear cytoplasm (Fig. prominent perivascular hyalinization and collagenous strands that subdivide the parenchyma into trabeculae or solid nests reminiscent of " Zellballen" of paragangliomas (Fig.190 Fig. 10-23). 10-25. with a ratio of 2. Tumor cells arranged into solid sheets have abundant eosinophilic cytoplasm. sarcomas. and lymphomas. Follicular adenomas. Natural History of Different Types of Thyroid Carcinoma Arising from Follicular Cells 66417308 : ¸Ÿ±U 24 ¥°Q . which account for the vast majority of tumors. Adenoma with bizarre nuclei is characterized by clusters of cells that have gigantic hyperchromatic nuclei (Fig. The salient features of carcinomas. Fig. Papillary carcinoma is the most common malignant tumor of the thyroid gland. Fig. Clusters of cells with huge. Malignant Thyroid Tumors Malignant thyroid tumors include carcinomas.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . irregularly shaped nuclei are admixed with smaller cells that have a solid growth pattern. 10-23. large nuclei. are given in Table 10-3. 10-25). Hurthle cell adenoma. and prominent nucleoli. 10-24. Tumor cells are arranged into nests reminiscent of the "Zellballen" of paraganglioma. It occurs more often in women than in men. It may occur at any age. Follicular adenoma with bizarre nuclei. hyalinizing trabecular pattern.

In addition to papillary proliferation. (5) tall cell variant.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and the average age at diagnosis is 10 years more than 66417308 : ¸Ÿ±U 24 ¥°Q .5 cm. 10-29 to 10-31). 10-26). almost all tumors also show a follicular component. Fig. Tumor cell nuclei have a clear " "ground glass appearance. Numerous blue-stained psammoma bodies are seen in the connective tissue stroma. The microscopic diagnosis of papillary carcinoma is made on the basis of architectural features. Follicular carcinoma is a tumor composed of neoplastic cells that form follicles. It may be solid or cystic. with the mean being 2. Wide fibrous strands incompletely divide the tumor into lobules. 10-28. and (6) columnar cell variant (Figs. Papillary carcinoma. (3) follicular variant. which almost completely replaces one thyroid lobe. Variants of papillary carcinoma include (1) papillary microcarcinoma. It occurs more often in women than in men. 10-27. 10-26. Papillary carcinoma.191 Fig. Fig. Tumor cells line branching papillae.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Papillary carcinoma. 10-29. such as papillae. 10-27 and 10-28). and multicentric foci are seen in 20 percent of cases on gross examination (Fig. Cuboidal tumor cells with clear cytoplasm line colloid-filled spaces. but the mean age of patients at diagnosis is 35 to 40 years. (4) diffuse sclerosing variant. Fig. appears solid with some unevenness on cross section. and nuclear features. follicular variant. such as optically clear nuclei ( "ground glass" or "Orphan Annie " nuclei). (2) encapsulated variant. Papillary carcinoma. This large tumor. The size of the tumor varies from microscopic to several centimeters in diameter. or nuclear pseudoinclusions and grooves (Figs. Metastases to local lymph nodes are common.

Tumor cells form irregular. minimally invasive type. Papillary carcinoma. Fig. 10-30. 10-31. widely invasive type. solid growth pattern. Papillary carcinoma. Fig. 10-33. Fig. Papillae lined by tumor cells project into the lumen of endothelium-lined spaces. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . On gross examination this tumor appears well circumscribed. The tumor contains prominent connective tissue strands infiltrated with lymphocytes and psammoma bodies. The neoplastic cells extend across the full thickness of the capsule into the normal parenchyma. almost solid sheets. minimally invasive type. Follicles are lined by cells that have clear cytoplasm.192 Fig. 10-35. The tumor has a predominantly solid pattern. Follicular carcinoma. 10-34. Follicular carcinoma. Follicular carcinoma. 66417308 : ¸Ÿ±U 24 ¥°Q .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Follicular carcinoma. Fig. diffuse sclerosing variant. 10-32.

45 to 50 years). 10-37. They may be encapsulated. Histologically it resembles follicular adenoma. Oncocytic (Hiirthle cell) carcinoma. 10-33). Widely invasive follicular carcinoma usually is not encapsulated but shows widespread invasion of the adjacent thyroid parenchyma and blood vessels. Nuclear atypia. Two subtypes are recognized: a minimally invasive or encapsulated form and a widely invasive form.e. 10-36. The larger lesions are sharply circumscribed but not encapsulated (Fig. usually in a multinodular manner (Fig. Clear cell change may occur focally but also may be widespread (Fig. Medullary carcinoma is composed of cells that show differentiation into C cells. 10-38). 10-35). for papillary carcinomas (i. Histologically the tumors are composed of oncocytic cells arranged in a follicular pattern (Fig 10-37). 66417308 : ¸Ÿ±U 24 ¥°Q .. and areas of necrosis are prominent. some tumors show a trabecular pattern. type MEN 2A has occurred in association with hereditary cutaneous lichen amyloidosis. most often are seen in the lungs and bones. A solid or trabecular growth pattern is seen (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Individual Type 2 Multiple Endocrine Neoplasia (MEN) Syndromes* *Rarely. familial forms of medullary carcinoma may occur in the absence of other endocrine abnormalities. which usually are blood borne. and a papillary pattern is even more rare. hyperchromasia.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 10-32). These tumors occur in sporadic and familial forms in the context of multiple endocrine neoplasia ( MEN) syndromes types 2A and 2B. Tumor cells penetrate the capsule and extend into the surrounding thyroid tissue (Fig. numerous mitoses. but they also may invade the adjacent parenchyma. This encapsulated tumor has a tan color with central areas of necrosis and hemorrhage Fig. Medullary carcinomas range in size. especially the embryonal. Oncocytic carcinoma. they may be barely visible or may replace the entire thyroid. 10-34). 10-36). Rarely.1 93 Fig. Minimally invasive follicular carcinoma grows as an encapsulated nodule that usually exceeds 1 cm in diameter (Fig. They account for 10 percent of all thyroid malignancies (Table 10-4). Metastases. Tumor cells invade capsular vessels. tin a small number of families. and atypical types. fetal. Oncocytic carcinomas are more aggressive than classic follicular carcinomas and are thus a distinct entity.

Histologically they show three distinct patterns known as spindle cell. (8) melanocytic. a "peritheliomatous " pattern may be prominent. A. Cellular pleomorphism. 10-43). metastasize widely.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . with broad areas of necrosis that invade the surrounding neck structures. 10-39). lobular. polygonal. and in- vasion into adjacent structures typically are found. Immunohistochemically the tumors are positive for thyroglobulin and keratin and negative for calcitonin. and (10) amphicrine types (Fig. (5) giant cell. (3) pseudopapillary. They present as a rapidly enlarging mass. Medullary carcinoma. Histologically the tumor may have a solid. or spindleshaped. (9) squamous. 10-40). 66417308 : ¸Ÿ±U 24 ¥°Q . giant cell. The thyroid gland contains well-demarcated tan nodules. Groups of cells form lobules. imparting an " insular" pattern. tumor cells may be round. (7) clear cell. but occasionally they may arise from papillary carcinomas. (6) oncocytic. These tumors typically occur in old age and are as common in women as in men. accounting for 10 percent to 25 percent of thyroid malignancies. Poorly differentiated carcinoma is a recently described type of thyroid cancer that occupies an intermediate position between well-differentiated follicular and papillary carcinomas and undifferentiated (anaplastic) carcinomas. Lobular growth pattern. and have a poor prognosis. Undifferentiated (anaplastic) carcinomas are rare. Metastases are common and occur hematogenously. or insular growth pattern (Figs. high mitotic activity. and squamoid. oval. The stroma is abundant and typically contains amyloid (Fig. Fig. (2) papillary. As a result of widespread necrosis that spares only the perivascular cells.194 Fig. 10-39. Medullary carcinoma. These tumors grow fast. Medullary carcinoma. In most cases these tumors represent poorly differentiated follicular carcinomas. 10-38. areas of necrosis. B. A B Fig. 10-42). Solid nests tend to retract from the connective tissue stroma. (4) small cell.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 10-41). Histologically these tumors show a solid trabecular or microfollicular pattern (Fig. 10-40. Variants of medullary carcinoma include (1) follicular or tubular. These different cell types often are intermixed (Fig. which distinguishes them from medullary carcinoma. which are surrounded by stroma containing deposits of amyloid that stain red with Congo red. Solid growth pattern.

195 A B Fig. DISEASES OF THE PARATHYROID GLANDS Hypoparathyroidism is a rare disease that most often is related to inadvertent removal of the parathyroid glands during neck surgery or radiotherapy. metabolic disorders that destroy the parathyroid glands such as hemochromatosis. sheets. The neoplastic cells form solid nests surrounded by connective tissue stroma that shows artificial retraction from tumor nests. Medullary carcinoma. Follicular variant. bone. Parathyroid hyperplasia. The tumor is composed of spindle-shaped and giant cells.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . In the latter case the glands become hyperfunctioning in response to the altered homeostasis of calcium and phosphate caused by a kidney. Small cell variant. and follicles (Fig. A. Poorly differentiated carcinoma. 10-41. Hyperplastic glands composed exclusively of clear cells rarely are found but usually are associated with severe hypercalcemia. Hyperparathyroidism is classified clinically as primary if the cause lies primarily in the parathyroid glands or secondary if the cause is outside the parathyroid glands. Histologically most parathyroid adenomas are composed of chief cells 66417308 : ¸Ÿ±U 24 ¥°Q . and pluriglandular endocrine autoimmune disorders. Parathyroid adenoma usually presents in the form of nodular enlargement of one parathyroid gland while the other three glands are of normal size (Fig. 10-46). All four glands are enlarged. although not to the same extent (Fig. Fig. oxyphil. and transitional oxyphil cells arranged into cords.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 10-43. Undifferentiated carcinoma. 10-42. Histologically the glands are composed of a mixture of chief. Fig. shows the same morphologic changes. Other causes include genetic diseases such as DiGeorge syndrome. B. 10-45). 10-44). or intestinal diseases (Diagrams 10-3 and 10-4). whether primary or secondary.

10-45. In humans calcitonin appears to play a relatively insignificant role in the rapid regulation of calcium metabolism. Parathyroid hormone (PTH) acts primarily on the bone and kidneys. Histologically it is composed of cells that resemble watermelon seeds arranged into solid sheets rimmed by thick ocellular fibrous bands (Fig. percent to 2 percent of all cases of primary hyperparathyroidism. Of the total dietary calcium 200 mg per day is actually absorbed and excreted through the kidneys and sweat glands. Human calcium balance in a young adult in calcium balance. Nuclei of tumor cells usually are of normal size and uniform. All effects of PTH and vitamin D (+) tend to elevate the ionic serum calcium. variation. and parathyroid glands. Parathyroid hyperplasia. All four glands are enlarged. albeit not to the same extent. that form solid sheets. The tumor has an invasive growth pattern and tends to metastasize. The presence of nuclear atypia. 10-44. and such elevation results in a negative feedback on PTH. 10-49). 10-48). whereas vitamin D (D) metabolites act on the intestines. 10-47). Parathyroid hyperplasia. Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The bone exchange is 640 mg per day. nests. and giant cells speaks against the diagnosis of malignancy. Only a few fat cells remain inside the parenchyma. such cellular changes more often are found in adenomas than in carcinomas of the parathyroid glands. Calcium-ion concentration acts on the parathyroid glands and the thyroid C cells.196 Diagram I0-3. bone. 66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Calcitonin acts in opposition to PTH in most experimental conditions. Adenomas of oxyphil cells are less common. Parathyroid carcinoma is a rare tumor. Cells tend to be uniform. or acini (Fig. accounting for 1 Fig. but in 10 percent of adenomas there are multinucleated cells and even giant cells (Fig. Control of calcium metabolism. Diagram I 0-4. Indistinct nodules composed of chief and oxyphil cells are surrounded by loose connective tissue stroma.

I 0-48.5 cm) is teardrop-shaped. The enlarged gland (3 X 2. 66417308 : ¸Ÿ±U 24 ¥°Q . cords.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Parathyroid adenoma. and yellow-tan beneath its thin translucent capsule. nodular. 10-49. 10-47. A. which are best seen in the left lower portion of the photograph. 10-46. Tumor cell nuclei vary in size and shape. Parathyroid adenoma. Large watermelon-shaped cells have regular nuclei. Parathyroid adenoma. Fig. Cells show palisading around a centrally placed vessel. A B Fig. Fig. as seen in this trichrome-stained specimen. The tumor is composed almost entirely of chief cells arranged into uniform sheets.197 Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Parathyroid carcinoma. and pseudofollicles. B. Solid sheets of tumor cells are traversed by thick fibrous septa.

·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . which includes adrenocortical insufficiency and hypothyroidism. Fig. Eosinophilic hyaline material has replaced most of the cortical cells. Lipid accumulation is thought to have cytotoxic defects in both the adrenal glands and the brain. 66417308 : ¸Ÿ±U 24 ¥°Q . Adrenocortical insufficiency accompanies the more prominent central nervous system symptoms. and viral infections with cytomegalovirus (CMV). Amyloid deposits are found in the sinusoids and in the walls of larger blood vessels. herpes simplex. such as congenital adrenal hypoplasia. Infection is associated with necrosis. probably is such an autoimmune disease. 10-53. 10-50). The cytoplasm of large ballooned cortical cells contains cleftlike spaces caused by extraction of lipid. 10-51). Amyloidosis is a rare cause of adrenocortical insufficiency.198 DISEASES OF THE ADRENAL CORTEX Adrenocortical Insufficiency Insufficiency or hypofunction of the adrenal cortex may be diagnosed in any age group and may be related to (1) congenital disorders. CMV infection. Adrenoleukodystrophy is an inborn defect of metabolism of fatty acids that affects peroxisomes. If no obvious causes are found. Amyloidosis. Fig. (2) deposition of amyloid in amyloidosis or hemosiderin in hemochromatosis. Histoplasmosis. (4) infections. and ultimately the entire gland may be replaced by amyloid (Fig. histoplasmosis. familial glucocorticoid deficiency. Adrenal cells appear enlarged and contain viral inclusions. which may be limited to the adrenal glands or may be part of a pluriglandular syndrome. or adrenoleukodystrophy. Three clinical forms are recognized: infantile. (3) circulatory disorders such as massive bilateral hemorrhage in Waterhouse-Friderichsen syndrome. juvenile (childhood onset). adrenocortical insufficiency is designated idiopathic Addison disease. such as tuberculosis. (5) autoimmune adrenalitis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . but the cortical cells appear enlarged and have a striated or ballooned cytoplasm (Fig. 10-51. and adult. 10-50. Amyloid deposits cause atrophy of adrenal cells. 10-52. The adrenal glands are small. or varicella-zoster virus. Such deposits usually are found in secondary amyloidosis and represent AA amyloid. Schmidt syndrome. Fig. Histiocytes filled with round to oval structures are found between adrenocortical cells. Adrenoleukodystrophy. Fig.

10-54). the cortex is thicker than 2 mm because of an increase in the thickness of the zona fasciculata (Fig. viruses. Caseating granulomas are partially replacing the parenchyma of the adrenal gland. 10-53). Adrenal gland is infiltrated with lymphocytes arranged into a follicle. Adrenocortical Hyperplasia and Hyperfunction Hyperfunction of the adrenal cortex may present as several clinical syndromes: (1) hyperaldosteronism (Conn syndrome). Adrenocortical hyperplasia may be diffuse or nodular (Figs. A B Fig. or (3) adrenogenital syndrome. Fig. (2) hypercortisolism (Cushing syndrome).199 Infectious adrenalitis caused by bacteria.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . or fungi is accompanied by adrenocortical cell loss. B. Autoimmune adrenalitis. Macronodular hyperplasia rarely occurs. Macronodular hyperplasia more often is a sign 66417308 : ¸Ÿ±U 24 ¥°Q . forming microscopic nodules. 10-52). 10-54. and in advanced stages it often is accompanied by calcifications (Fig. A. 10-56 and 10-57). 10-55. CMV has a distinct tropism for adrenocortical cells. In typical Cushing disease caused by an ACTH-secreting pituitary adenoma. 10-58). In tuberculosis the gland is replaced to a large extent by caseating granulomas. The adrenal glands are infiltrated with lymphocytes that destroy the adrenocortical cells until no cortex remains (Fig.Adrenocortical cells of the inner zona fasciculata have eosinophilic cytoplasm as a result of the conversion of lipid-rich cells to more compact lipid-depleted cells. Tuberculosis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . In chronic stages of Addison disease the adrenal glands have almost no cortex and are reduced to only the medulla. Hypercortisolism is considered primary if it is caused by adrenocortical hyperplasia or neoplasia. In severe cases the entire adrenal gland may be destroyed. Most of the cortex has been destroyed. In systemic histoplasmosis the adrenal glands often are involved (Fig. and adrenal involvement is found in 50 percent of patients with acquired immunodeficiency syndrome (AIDS) (Fig. Hyperplastic cells may extend into periadrenal fat. Immune-mediated adrenalitis is currently the most common cause of adrenal inflammation. 10-55). secondary hyperplasia develops as a result of overstimulation of the adrenal cortex by the pituitary gland or ACTH-secreting tumors (Diagram 10-5).

Fig. I0-58. 10-6I. The adrenal gland shows several yellow nodules that measure up to I cm in diameter. I 0-57. Fig. The adrenal contains darkly pigmented nodules. Fig. 10-56. Primary pigmented nodular adrenocortical disease (PPNAD). The cortex appears thickened. Macronodular hyperplasia of adrenal in Cushing syndrome. Adrenal cells have eosinophilic cytoplasm that is rich in lipofuscin (brown).200 Fig. I0-59. The zona fasciculata consists of clear and lipid-depleted compact cells. The nodules are composed of pale lipid-rich cells. Fig. PPNAD.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . There also is an area of lipomatous metaplasia. Nodular adrenocortical hyperplasia on cross section. Fig. 10-60. Adrenocortical hyperplasia in Cushing disease. Diffuse adrenocortical hyperplasia.

Some tumors may secrete corticotropinreleasing factor (CRF) of primary adrenal disease in which the Cushing syndrome is caused by autonomous hyperfunction of adrenocortical cells (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Adrenal adenoma. The tumor is composed of pale li pid-rich cells.201 Ectopic ACTH (or CRF) Syndrome Diagram 10-5. Adrenocortical Tumors Adrenocortical tumors are classified as benign (adenomas) or malignant (carcinomas). Pituitary-dependent form of hypercortisolism (Cushing disease) is usually caused by an ACTH-producing microadenoma of the pituitary gland. Autonomous secretion of cortisol by an adrenocortical neoplasm. Adrenal adenoma on cross section. sharply circumscribed nodules that are attached to the adrenal gland or more often completely replace it. 10-60). The tumor appears deep orange with tan-brown geographic areas composed of lipid-depleted cells that are rich in lipofuscin. Most of the cells in these nodules have compact eosinophilic cytoplasm and contain variable amounts of lipochrome pigment. Tumors removed from patients with Cushing syndrome usually weigh less than 50 g and measure 3 to 4 cm in diameter (Fig. Fig. On cross section most tumors are Fig. Hormone-producing tumors may be associated with typical adrenocortical syndrome (Cushing. 10-63. 66417308 : ¸Ÿ±U 24 ¥°Q . C. ACTH levels tend to be very low or undetectable. or adrenogenital syndrome) or with generalized adrenocortical hyperfunction that combines some features of all three syndromes. Conn.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . With ectopic secretion of ACTH (or rarely corticotropin-releasing factor) levels of circulating ACTH typically are higher than in Cushing disease and sometimes are greatly elevated. A. Histologically the micronodules appear to reside in the zona reticularis and may encroach slightly on the medulla (Fig. 10-59). PPNAD is a descriptive term that has no particular reference to underlying pathogenesis. 10-61). Adenomas are benign. B. The adrenal glands are enlarged and show pigmented nodules on their surface and on cross section (Fig. ACTH levels may be in the normal range or only mildly elevated. These tumors may secrete one or more hormones and are classified clinically as inactive or active. 10-62. 10-62). Primary pigmented nodular adrenocortical disease (PPNAD) is a rare ACTH-independent hypercortisolism.

or anastomosing trabeculae (Fig. but sometimes there is considerable nuclear variation. and occasional intranuclear pseudoinclusions are seen. but some are brown and may have a variegated appearance. Fig. Aldosterone-secreting adenomas of Conn syndromes usually are small intraadrenal nodules that measure less than 3 cm in diameter (Fig. Aldosterone-producing adrenocortical adenoma. 10-63). Inset shows spironolactone bodies stained with Luxol fast blue. Adrenocortical carcinoma resected from a teenaged girl with virilization. Tumor cells have voluminous compact eosinophilic cytoplasm and large pleomorphic nuclei with prominent pseudoinclusions. B. short cords. 10-66. On cross section these tumors are homogeneously yellow-orange or canary-yellow. 10-64. 10-64). The tumor weighs more than 1000 g. Histologically the tumor is composed of cells arranged into broad trabeculae. and on cross section it is coarsely nodular with extensive areas of necrosis. 66417308 : ¸Ÿ±U 24 ¥°Q . 10-67. but larger tumors may show degenerative changes. Nuclei are round and uniform.202 yellow. Aldosterone-producing adrenocortical adenoma. The tumor is composed of cortical cells that have granular cytoplasm. 10-65. A B Fig. Fig. Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 10-65). The tumor is yellow-orange and sharply circumscribed. Spironolactone bodies appear as round cytoplasmic inclusions.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . A. Histologically they are composed of alveolar ducts. Histologically they are composed of pale lipidladen cells resembling those of normal zona fasciculata (Fig. Adrenocortical carcinoma. Cells may have clear or granular eosinophilic cytoplasm.

90 percent are unilateral and 10 percent are bilateral. 10-66). and (5) atypical mitoses. On cross section they appear grayish or dusky red. cystic degeneration. Histologically three major architectural patterns are seen: (1) trabecular. Pheochromocytoma is a tumor composed of cells that resemble normal adrenal medullary cells. I0-68. Tumors vary in size. arbitrary. (2) diffuse growth pattern. it is not possible to predict the biologic behavior of tumors. grayish or brownish-tan nodules that may resemble adrenocortical neoplasms (Fig. Nuclei are round and vesicular. 90 percent are located in the adrenal. Pheochromocytoma. 66417308 : ¸Ÿ±U 24 ¥°Q . Areas of necrosis. Degenerative changes such as fibrosis. On microscopic examination the following features are most predictive of malignancy: (1) broad fibrous bands. however. In larger tumors there is considerable nuclear variation and pseudoinclusions. These tumors may be found in any age group. and 10 percent are nonfunctional. Intracytoplasmic hyaline globules are found in 45 percent of pheochromocytomas. Growth patterns have been described as trabecular. A spindle cell pattern occasionally is seen. 10-71). 10-69. 10-67). whereas those that weigh more than 95 g tend to be malignant. (3) vascular invasion. On gross examination the tumors are sharply circumscribed. and functionally they are either active or inactive. Pheochromocytomas occur in the general population at a rate of 8 per million. Adrenal medullary hyperplasia. The distinction between hyperplasia and small pheochromocytomas is. and invasion of adjacent tissues are apparent in large tumors.203 Some tumor cells contain round cytoplasmic bodies that are known as spironolactone bodies. By convention most nodules larger than 1 cm in diameter are considered to represent true neoplasms. 10-68). in which cells grow in solid sheets (Fig. Most surgically resected tumors weigh approximately 100 g and measure 3 to 5 cm in diameter. causing hypertension. Such globules are periodic acid–Schiff positive and diastase resistant.Histologically the cells show considerable pleomorphism. DISEASES OF THE ADRENAL MEDULLA Hyperplasia of adrenal medullary cells is seen most convincingly in patients with MEN syndrome type 2 (Fig. 10-69).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . cystic degeneration. necrosis. and hemorrhage are seen in larger tumors. 90 percent are benign and 10 percent are malignant. As a general rule. and atypical mitoses may be seen (Fig. typically measuring over 12 cm in diameter and weighing on average 1000 g (Fig. In a small but significant number of cases. alveolar. Adrenocortical carcinomas are highly malignant tumors that metastasize through the lymphatics or hematogenously. hemorrhage. Fig. The histologic appearances may vary from one microscopic field to another.. There is nodular expansion of the medulla. most of which weigh between 100 and 400 g. In most cases they cause death within 12 months of diagnosis. (4) mitotic rate greater than 5 per 50 high-power fields. or diffuse. By electron microscopy tumor cells contain typical neurosecretory granules (Fig. but this should not be considered a sign of malignancy. Adrenocortical carcinomas are rare malignant tumors that occur at a rate of 2 per million. Individual tumor cells are polygonal with a lightly eosinophilic granular cytoplasm. The cytoplasm of tumor cells may be lavender. There are no reliable differences between adrenocortical adenomas and carcinomas. Fig. and 10 percent are located in sympathetic ganglia. 90 percent of tumors are functional. It also occurs in Beckwith-Wiedemann syndrome and in some patients with paroxysmal attacks of hypertension that are suggestive of pheochromocytoma. The cross-sectioned surface of this encapsulated tumor appears grayish or red because of areas of congestion and hemorrhage. resembling normal medullary chromaffin cells. Invasive growth is a feature of malignant types. in which cells form anastomosing cords. in which groups of cells are surrounded by connective tissue septa. and (3) diffuse. Empiric data indicate that in adults most tumors that weigh less than 50 g are benign.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . (2) alveolar. 10-70).

B. Pheochromocytoma. By electron microscopy tumor cell cytoplasm contains numerous dense granules. A B Fig. B. Epinephrine is stored in granules that appear more symmetric. Cells form solid sheets. Diffuse pattern. Pheochromocytoma. which are intranuclear invaginations of the cytoplasm. Trabecular pattern. 10-70. A. lacking the wide halo around the dense core (curved arrow). Their lavender cytoplasm contains fine pinpoint granules. 10-71. A few tumor cells have unclear pseudoinclusions. A.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Tumor cells form anastomosing cords partially surrounded by fibrous septa.20 4 A B C Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Norepinephrine is stored in granules that have an eccentric dense core surrounded by a wide halo (straight arrow). Dense-core neurosecretory granules vary in size and shape.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . C.

The tongue is studded with neuromatous nodules. Fig. 10-73. Pheochromocytomas are sporadic in 90 percent of cases.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Patients with MEN 2B have typical oral neuromatous nodules (Fig. soft ("encephaloid" ) adrenal mass that often invades the surrounding tissues (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . 10-72. but 10 percent occur in the context of MEN 2A or 2B conjointly with medullary carcinoma of the thyroid gland. It is the most common malignancy in infants under the age of one year. The tumor is composed of sheets of closely packed cells that have very little cytoplasm. ganglioneuroblastoma. Pale fibrillar areas are composed of neuritic processes. The bisected tumor attached to the kidney appears lobulated and blood-stained. On cross section the tumor is lobulated and shows prominent areas of necrosis and hemorrhage. 10-73). Neuroblastoma. with an incidence of 9. neuroblastoma. MEN 2B. or ganglioneuroma.6 per million. and approximately 5 percent of tumors have composite features of pheochromocytoma. 10-74. 10-72). Neuroblastoma is a tumor of neural crest–derived neuroblastic precursors of adrenal medullary cells and sympathetic ganglia. Fig. Metastases through the lymphatics or blood vessels are common. Fig. Neuroblastoma. The tumor presents as a partially encapsulated.205 Scattered neuronal or ganglion cells often are present.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

with more distinct cell borders and more pronounced eosinophilia of the cytoplasm. The tumor consists of spindleshaped Schwann cells and round ganglion cells. Cells appear loosely arranged.206 A B C Fig. Most ganglioneuromas are. A. densecore. The spaces between the nuclei contain pink fibrillar material that represents neuritic processes. Histologically the tumors are composed of small blue cells that are separated focally by eosinophilic fibrillar material representing neuritic processes (Fig. Ganglioneuroma. usually in school-aged children (average age seven years). but brain metastases are unusual. which are the most characteristic feature of neuroblastomas (Fig. may be arranged around vessels or connective tissue cores. membrane-bound neurosecretory granules. Ultrastructurally the fibrillar matrix of neuroblastoma and ganglioneuroblastomas consisfs of a tangled Skein of neuritic process that contains arrays of microtubles and intermediate filaments. Other sites of metastasis are the lymph nodes. 10-74). however. 10-76. Nests of small cells are enclosed by fibrous septa with foci of calcification.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 10-77). 10-77. 10-76). Approximately 10 percent to 15 percent of ganglioneuromas originate in the adrenal glands. 10-75. These neuritic processes extend between cells. Tumor cells form Homer Wright rosettes. The tumor consists of ganglion cells that have eosinophilic cytoplasm. neoplastic cells develop neuronal or ganglion-like features. Fig. Neuroblastoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . with a predilection for the cortex of long bones and short bones. Ganglioneuroblastoma. Ganglioneuromas are benign tumors that are composed of ganglion cells and Schwann cells (Fig. liver. and skull. 10-75). Stroma is inconspicuous. C. Such tumors are called ganglioneuroblastomas (Fig. and form so-called Homer Wright rosettes. skin. found in the posterior mediastinum. As differentiation or maturation of neuroblasts proceeds. An important diagnostic feature is the presence of small. 66417308 : ¸Ÿ±U 24 ¥°Q . B. The dura may be involved. Fig. bone marrow.

Kane LA. An i mmunocytochemical and ultrastructural analysis of 300 cases. Auguste LJ: Multiple parathyroid adenomas: Report of thirtythree cases. 1998. Bonsib SM. 1995. 1990. Lin BT-Y. Bailliere's Clin Endocrin Metab 9:243-270. and gonadotroph adenomas of the human pituitary. 1996. Mierau GW et al: Oncocytic adrenocortical neoplasms. 1991. Mizukami Y. Nonomura A et al: Autonomously functioning (hot) nodule of the thyroid gland. Samaan NA. 1993. Udelsman R: Intraoperative confirmation of parathyroid tissue during parathyroid exploration. A 30-year experience. Schlumberger MJ: Papillary and follicular thyroid carcinoma. subacute and chronic. 1995. 1987. 1998. Kontogeorgos G. Surgery 110:704-708. Am J Surg Pathol 20:964-974. N Engl J Med 338:297-306. Grimelius L. Brodeur GM: Molecular pathology of human neuroblastomas. 1995. Schwartz SI: Carcinoma of the parathyroid gland. Am I Clin Pathol 101:29-35.1994. Am J SurgPathol 22:538-544. Muller PJ: Clinical-pathological correlation of pituitary tumours. 1998. Kovacs K. 1991. A clinical and histopathologic study of 17 cases. Horvath E et al: Null cell adenomas. Pritchett DD. Michigishi T. Leinung MC. Scheithauer BW et al: Pituitary adenomas in childhood and adolescence.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . A report of seven cases and review of the literature. Westra WH. Oelkers W: Adrenal insufficiency. 1996. 1998. Frkovic-Grazio S. Semin Diagn Pathol 11:118-125. NEngl J Med 335:1206-1212. Shortell CK. 66417308 : ¸Ÿ±U 24 ¥°Q .207 Further Reading Attie JN. Arch Pathol Lab Med 122:63-68. Am J Surg Pathol 22:603-614. Hickey RC: Pheochromocytoma. Ohta TI et al: Cortico-medullary mixed tumor (pheochromocytoma and cortical adenoma) of the adrenal gland. Semin Oncol 14:297-305. A retrospective evaluation of the frozen section. 1992. Phillips CE Jr. Acute. Thapar K. Endocr Pathol 4:20-27. J Urol Pathol 3:157164. Ostrowski ML. A reassessment and immunohistochemical study with comparison to the usual type of papillary carcinoma of the thyroid. Bondeson L: Histopathological diagnosis of parathyroid diseases. Kovacs K.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Surgery 108:1014-1019. Andrus CH. Endocr Pathol 3:517-518. Lamovec J. Singer PA: Thyroiditis. 1994. A clinicopathologic study of the Mayo Clinic experience. oncocytomas. Med Clin North Am 75:61-77. Path Res Pract 191:353-365. Bracko M: Nonsporadic and unusual morphologic features in pheochromocytoma and paraganglioma. Merino MJ: Tall cell variant of papillary thyroid carcinoma.

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66417308 : ¸Ÿ±U 24 ¥°Q .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

Developmental disorders of the kidneys and the urinary tract reflect disturbances of this complex morphogenesis. B. adrenal. which gives rise to ureteric buds. Metanephric blastema establishes contact with the ureteric bud and is induced to form the definitive kidney. 11-2). mesonephros. in which renal agenesis is accompanied by oligohydramnios. The right kidney is located lower than the left one. Ectopia and malrotation of the kidney.210 DEVELOPMENTAL AND GENETIC DISORDERS The kidneys and the urinary tract form during prenatal life in a complex sequence of interrelated morphogenetic processes. Exstrophy. Agenesis. and Related Defects The definitive kidney results in incomplete induction (renal hypoplasia) or aplasia (renal agenesis). Bilateral agenesis results in a developmental sequence called Potter syndrome. Urinary bladder.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . St. The urethra and the urinary bladder form from the cloaca. 11-1. Malposition. and its hilum is facing anteriorly. Positional renal abnormalities.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Ectopia also may be associated with abnormal rotation of the kidney. and a small recessed mandible and low-set ears (see also Fig. B Diagram 11-1. Crossed ectopia. but the ureters and kidneys are missing. and metanephros. (From Carlson BM: Human embryology and developmental biology. Both kidneys may be on the same side of the vertebra (crossed ectopia). and testes are normally developed. 5-4). Louis. Ureteric buds grow upward and interact with the primordium of the kidney. Ectopia of one or both kidneys results from malpositioning of the kidneys (Diagram 11-1). A. The right kidney has crossed the left ureter and has migrated only part of the normal distance. Renal agenesis. Fig. Horseshoe kidney results from the fusion of left and right renal anlage into a simple kidney (Fig. 11-3). Pelvic kidney. 1994. Mosby) Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . which may be unilateral or bilateral (Fig. 11-2. and in such cases the hilum may face anteriorly or posteriorly (Fig. Ectopic kidneys usually are located caudal to their normal lumbar position but may be cranial to their normal location or even in the thorax (thoracic ectopia or dystopia). 11-1). pulmonary hypoplasia. which has passed through three sequential stages: pronephros.

Abnormalities of the penis such as agenesis or micropenis are rare and usually are associated with other urogenital anomalies or chromosomal changes. Fig. The kidneys are multicystic and dysplastic. I I-S. Fig. is an opening of the urethra on the dorsum of the penis. which is less common than hypospadia. Hypospadia. (Courtesy of Dr. Smith.21I The ureters may form incompletely and may show focal stenosis or atresia. Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . 11-3. Horseshoe kidney. I 1-4. 11-5). Cincinnati. The urethra opens on the lower side of the shaft of the penis rather than on the tip of the glans penis. I 1-6.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The ureters are dilated and tortuous. Ohio. Exstrophy of the urinary bladder.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Congenital megaureters are dilated and tortuous and usually are associated with abnormal urinary conduit (Fig. Red mucosa of the urinary bladder may be seen through the defect of the anterior abdominal wall. Megaureters. In males these anomalies maybe associated with abnormal development of the penis.) Fig. An abnormal opening of the urethra on the lower side of the penile shaft is called hypospadia (Fig. Roger D. Epispadia.l1-4) Exstrophy of the urinary bladder represents incomplete formation of the urinary bladder combined with a defect of the anterior abdominal wall (Fig. 11-6). Developmental defects of the urethra include agenesis and stenosis. and GRIPE.

The solid areas comprise homologous renal and heterologous (nonrenal) elements. E. A. The cysts are small and elongated. the most important of which are (1) autosomal dominant polycystic kidney disease. extending in the form of slits from the corticomedullary junction toward the subcapsular cortex (Fig.) Fig. Because symptoms of ARPKD appear in infancy and childhood. weighing up to 2000 to 3000 g and measuring up to 40 cm in length. 11-7). 11-8. results in polycystic kidney disease. 11-7. (2) autosomal recessive polycystic kidney disease. (From Damjanov I: Histopathology. These cysts are lined by nondescript flattened cells derived from the epithelium of tubules. Childhood polycystic disease is autosomal recessive. The cysts Diagram 11-2. Kidney parenchyma typically is replaced by fluid-filled cysts that vary in size and shape (Fig. 1996. Both kidneys are enlarged. which are the basic anatomic and functional units of the kidneys. and the disease therefore is known as adult polycystic kidney disease. B. (3) familial juvenile nephronophthisis-medullary cystic disease complex. 11-8). Symptoms of renal disease appear in the third or fourth decade. Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease that occurs at a rate of 1 per 1000.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . but also shows microcystic changes in all parts of the nephron. Fig. Both kidneys are enlarged but retain their normal shape. The cysts are lined by flattened epithelium and contain proteinaceous fluid. Autosomal dominant polycystic kidney disease is characterized by widespread cystic dilatation of all parts of the nephron. D. Autosomal recessive polycystic kidney disease (ARPKD) is less common than ADPKD. both infantile and childhood forms are recognized. 11-9). and (4) renal dysplasia (Diagram 11-2). Nephronophthisis shows cystic dilatation of juxtacortical medullary tubules. Williams & Wilkins. Baltimore. Cystic dysplasia contains solid and cystic areas. collecting ducts. C. The enlarged kidneys consist of cysts that have replaced the normal parenchyma. ADPKD. or Bowman capsule (Fig. A color atlas and textbook. 66417308 : ¸Ÿ±U 24 ¥°Q .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .212 Polycystic Kidney Disease Abnormal morphogenesis of nephrons. Cystic developmental kidney diseases. Several clinicopathologic subtypes are recognized. Medullary sponge kidney shows cystic dilatation of collecting ducts of the papillae. ADPKD.

Multicystic renal dysplasia. The kidneys are enlarged because of diffuse dilatation cystic transformation of tubules and collecting ducts. which compress the remaining tubules. Alport syndrome is a form of hereditary nephritis that is caused by a defect in the synthesis of collagen type IV. which show Fig. ARPKD. Renal dysplasia is a disorder of differentiation of the metanephros. often in association with other developmental disorders.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 11-12. The enlarged kidney consists of cysts ( " multicystic dysplasia " ) and solid tissue replacing to a variable extent the normal renal parenchyma (Fig. causing either atrophy or dilatation of the remaining parts of the nephron (Fig. Fig. 11-10). The biochemical defect is associated with morphologic changes of the glomerular basement membrane (GBM). The cortex contains numerous dilated collecting ducts lined by flattened epithelium. causing an abdominal mass in neonates and infants. which appear as dilated channels crossing from the cortex to the medulla. Fig. Histologically the cysts varyin size and shape and are lined by cuboidal or flattened epithelium. The deformed kidney consists of several large cysts and solid tissue replacing the normal renal parenchyma. Fig. 11-9. The remaining portions of the nephrons are either compressed or dilated. 11-10. Remnants of two fetal glomeruli are seen surrounded by atrophic tubules. It may be bilateral. The solid areas consist of primitive ducts lined by columnar epithelium surrounded by concentric layers of fibromuscular stroma that often contains islands of cartilage (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Renal dysplasia. 11-12). ARPKD. The normal parenchyma has been almost completely replaced by fibromuscular tissue and cartilage. Hereditary Glomerular and Tubular Diseases Many multisystemic genetic disorders affect the kidneys.213 represent dilated collecting ducts. I 1-I I. 66417308 : ¸Ÿ±U 24 ¥°Q . 11-11). but more often it is unilateral. but only in certain disorders do renal symptoms represent the main clinical manifestation of such diseases.

B. Thinning is caused by the reduction of the width of the lamina densa. These changes are best appreciated by electron microscopy (EM) (Fig. and slowly evolving but progressive renal failure. The disease is more common. Presenting symptoms include proteinuria. which become vacuolated (Fig. A. Clinically the disease presents with mild hematuria with or without proteinuria. The capillary wall is very thin. In glycogenosis type I the renal tubules are vacuolated and filled with glycogen (Fig. and is more severe in men than in women. Thin basement membrane nephropathy may occur in familial and sporadic forms. EM reveals accumulation of lipid-rich myelin figures in the cytoplasm of these cells (Fig. Fig. By EM the thickened basement membrane consists of alternating dense and lucent segments. Similar changes are seen in arteries and arterioles. has an earlier onset. The epithelial cell foot processes are discrete and show no effacement. Many inborn errors of metabolism affect the renal tubules. which contains strands of banded collagen (Fig. Normal basement membrane. A.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and the disease has a good prognosis. By light microscopy the glomeruli are normal. In the kidneys ceramide trihexoside accumulates in glomerular epithelial cells.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Nail-patella syndrome is a hereditary disease whose presenting symptoms include typical nail changes. and renal symptoms. Chronic renal failure evolves over 10 to 20 years. 11-13). Fabry disease is an X-linked hereditary disease caused by the mutation of the gene for a-galactosidase A. thickening. congenital absence of the patella. Renal function remains preserved. B. 11-14). 11-17). Glomerular changes are prominent and are related to changes in the glomerular membrane. By EM the glomeruli have membranes that measure 80 to 250 nm in width. A A B B Fig. 1 I-13. I 1-14. Damage of the glomeruli ultimately leads to proteinuria. Alport syndrome. 66417308 : ¸Ÿ±U 24 ¥°Q . 11-16). There also is subepithelial scalloping of the basement membrane and partial effacement of the epithelial cell foot processes. hematuria. and occasionally in interstitial cells.214 focal thinning. Thin basement membrane nephropathy. and cutaneous manifestations. 11-18). The tubules appear atrophic and there are foam cells in the interstitium. measuring 90 nm in width. and layering. measures 360 nm in width. 11-15). shown here for comparison. The en- zyme deficiency results in accumulation of the glycosphingolipid ceramide trihexoside in plasma and many tissues. neurologic. The disease has renal. which is much thinner than normal (340 to 360 nm) (Fig. The glomerulus appears unremarkable by light microscopy.

Abnormal nails. GBM contains banded collagen fibrils.215 Fig. 11-18.. Fig. I 1-17. A B Fig. Fig.The visceral epithelial cells are enlarged and have vacuolated cytoplasm.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . A. Nail-patella syndrome. 66417308 : ¸Ÿ±U 24 ¥°Q . Renal tubules have clear cytoplasm as a result of glycogen accumulation. 11-15. I 1-16. Fabry disease. Fabry disease. B. Glycogenosis type I. The cytoplasm of epithelial cells is filled with dense myelin figures representing stored sphingolipid.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

11-23). thrombotic thrombocytopenic purpura. Fig. with increased cytoplasmic volume. Nephroangiosclerosis. Atrophic tubules filled with colloid ( " thyroidization " ) typically are found as evidence of blocked flow of solutes through nephrons that have been dis - rupted or obstructed by interstitial scarring (Fig. and malignant hypertension. Atherosclerosis most prominently involves the main renal arteries.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Two types of glomerular changes are seen: those that result from fibrin deposition and those that result from ischemia (Fig.216 VASCULAR DISORDERS The most important vascular disease that affects the kidneys is atherosclerosis. 11-19). 11-21. scarred and granular external surface. which may be indistinguishable from scars caused by pyelonephritis (Fig. 11-20). Thrombotic microangiopathy is a term that encompasses several diseases. 11-21). 11-24). Fig. Nephrosclerosis accounts for 15 percent of end-stage kidney disease worldwide. Atrophic tubules are filled with eosinophilic proteinaceous casts that resemble thyroid follicles ("thyroidization of the kidney"). Mesangial regions are widened. It is especially prevalent among the elderly. 11-22). Nephroangiosclerosis. Aorta shows marked atherosclerosis. The kidney on the right contains a cyst. Fig. but it also is associated with intimal and medial fibrosis of the intrarenal arteries. arteriolosclerosis. Nephroangiosclerosis. Clinically nephrosclerosis is accompanied by a loss of renal function. The glomeruli are hyalinized. and the atrophic tubules are surrounded by fibrous tissue. Severe surface scarring may be indistinguishable from changes caused by pyelonephritis. Capillary lumens may contain fibrin thrombi. Histologically the glomeruli are hyalinized. Because the entire kidney is affected. 11-19. 11-22. Mesangiolysis (dissolution of matrix) Fig. Kidneys have . including hemolytic uremic syndrome. 66417308 : ¸Ÿ±U 24 ¥°Q . 11-20. Larger cortical infarcts may cause more profound multiple scarring.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Capillary walls are thickened because of endothelial cell swelling and widening of subendothelial spaces. and the tubules appear atrophic and are replaced by fibrous tissue and scattered lymphocytes (Fig. which sometimes gives the capillaries a double contour. the term nephroangiosclerosis (nephrosclerosis) is used as a synonym for ischemic changes in the kidney caused by prolonged ischemia in atherosclerosis. All thrombotic microangiopathies are characterized by intravascular deposition of fibrin and lesions that primarily involve arterioles and glomerular capillaries (Fig. On gross examination the kidneys are smaller than normal and show cortical atrophy and V-shaped indentations that correspond to small infarcts (Fig. Nephroangiosclerosis. which slowly progresses to renal failure. scleroderma. and glomerulosclerosis.

Focal and segmental glomerulosclerosis (FSG) is a term used to describe two entities: a glomerulopathy that causes nephrotic syndrome. IgM. remains obscure. The arteriole contains a thrombus that extends into the glomerulus. has been elucidated to a great extent. but the epithelial foot processes show complete effacement (Fig. Clinically glomerulopathies present with proteinuria.217 may produce microaneurysms. "Primary" Glomerulopathies Responsible for Nephrotic Syndrome Minimal change disease Mesangial injury glomerulonephritis with IgM deposits Focal and segmental glomerulosclerosis Membranous glomerulonephritis Membranoproliferative glomerulonephritis Fig. or visceral epithelial cell disease. Some capillary loops have wrinkled membranes. I MMUNE-MEDIATED GLOMERULAR DISEASES I mmune-mediated glomerular diseases may involve any part of the kidney but most often they present as glomerulonephritis. Minimal change disease. is a disease of unknown etiology and poorly understood pathogenesis. and are diagnosed as nephrotic or nephritic syndromes. 11-23. Double contours of glomerular capillaries are seen in segments of the glomerulus. Thrombotic microangiopathy. 66417308 : ¸Ÿ±U 24 ¥°Q . Immunoglobulin. Segmental sclerosis (i. Fig. or both. During the healing process there is sclerosis of glomeruli. Lesions of interlobar and arcuate arteries may be present and are most prominent in scleroderma. 11-25). respond well to treatment with corticosteroids. whereas the pathogenesis of others. In this slide stained with PAS— methenamine silver the glomeruli appear normal. Hypertension is evident in 50 percent of cases. such as systemic lupus erythematosus (SLE). 11-26). which often has a lobular pattern that is reminiscent of membranoproliferative glomerulonephritis type I.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The etiology and pathogenesis of FSG are not known. Thrombotic microangiopathy. such as minimal change disease. such as poststreptococcal glomerulonephritis. whereas others. Clinically all of these disorders are characterized by diminished renal function and oliguria. are slowly progressive and unresponsive to treatment. Some glomerulopathies. lipoid nephrosis. By light microscopy the glomeruli appear normal (Fig.. By EM the GBMs are normal. such as membranous nephropathy.e. The sclerotic lesions may correspond to an occluded capillary obliterated with plasma protein deposits ( " hyalinosis " ) or may represent expanded mesangium associated with collapsed capillary base- Fig. also known as nil disease. such as minimal change disease. Glomerular disease may occur in an isolated form or as part of a systemic disease. and morphologic changes that may occur in association with a variety of systemic diseases that affect the kidneys (Table 11-2). The pathogenesis of some glomerulopathies. 11-25.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . It is one of the "primary" glomerulopathies responsible for nephrotic syndrome (Table 11-1). Minimal change disease. hematuria. There are no diagnostic immunofluorescence (IF) microscopy findings. obliteration of segments of a single glomerulus) is seen affecting some glomeruli (hence called focal). 11-24.

Hyaline material appears finely granular by EM and may contain lipid droplets. The hyalinized portions of the glomerulus appear blue in this Masson trichrome—stained slide. 11-30). I 1-27. 11-27 and 11-28). Focal and Segmental Glomerulosclerosis "Primary" Parts of minimal change disease spectrum Unique disease Secondary Heroin-associated nephropathy HIV-associated nephropathy Complicating Other Renal Disorders Reflux nephropathy and other sclerotic interstitial disorders Glomerulonephritis (many types) Nephrosclerosis Familial-metabolic diseases Chronic transplant rejection Variants Collapsing glomerulopathy Tip lesions HIV. there are no other findings by IF microscopy. in which there is complete collapse of the capillary loops (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig. 11-29). Human immunodeficiency virus. Human immunodeficiency virus (HIV)—associated nephropathy may present as FSG. I 1-28. 66417308 : ¸Ÿ±U 24 ¥°Q . The tubules contain proteinaceous casts and may undergo microcystic dilatation. The most typical is the so-called collapsing glomerulopathy.218 ment membrane (Figs. "Hyaline" occludes the lumen of the hilar capillaries. Fig. Fig. but in many cases the glomeruli also show changes that might represent precursor lesions of typical hyalinosis. There is complete effacement of the foot processes of the visceral epithelial cell. Minimal change disease. Except for deposits of immunoglobulin (IgM) and third component of complement (C3) in the areas of hyalinosis. Numerous tubuloreticular structures are seen by EM in the cytoplasm of endothelial cells but also in other cells (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . A normal mesangial cell is seen to the right. I 1-26. Focal and segmental glomerulosclerosis. Focal and segmental glomerulosclerosis.

which shows interposition of mesangial cell cytoplasm between the original basement membranes and the newly formed basement membranes (Fig. 11-33. and prominent reduplication (double contours) of basement membranes (Fig. which is interposed between the layers of basement membrane. MPGN-I. MPGN-I. 11-33). and III) are recognized. The cytoplasm of this endothelial cell contains a large tubuloreticular structure. lobular appearance of glomeruli. lesion that may represent different disease entities. Granular deposits of C3 are seen along the capillary loops and in the mesangium by IF microscopy. MPGN-1 is an immune complex— mediated disease that is characterized by mesangial hypercellularity. These double contours are better seen by EM. Fig. 11-32).219 Fig. II. Membranoproliferative Glomerulonephritis Membranoproliferativeglomerulonephritis ( MPGN) is a renal Fig. Peripheral capillary loops have double contours. IgA maybe found in a few patients. Three subtypes (I. I 1-30. 11-31. 11-29.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . HIV-associated nephropathy. 11-31).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . HIV-associated nephropathy. Glomerular capillary has a narrow lumen because of peripheral extension of mesangial cell cytoplasm. Fig. Fig. which are grouped here for historical reasons. IgG and IgM deposits are present focally but may be missing entirely. 11-32. The glomerulus has a lobular configuration with mesangial widening and hypercellularity. MPGN-I. Immune deposits seen by EM 66417308 : ¸Ÿ±U 24 ¥°Q . The glomerulus in the center shows collapse of capillary loops. IF microscopy shows granular deposits of C3 along the peripheral capillary loops and in the mesangium (Fig. and the tubules filled with proteinaceous casts show microcystic dilatation.

is an immune complex— mediated disease that presents with proteinuria and nephrotic syndrome. capillary walls. Glomerulus shows coarse granular staining of mesangial regions. C3 nephritic factor. may be demonstrated in the blood. and tubules. MPGN-II.220 are located in the basement membranes or inside the capillaries in a subendothelial location. I 1-36. The basement membranes appear thickened and may have double contours (Fig. Double contours are seen segmentally. 11-35). I 1-34. Membranous Glomerulonephritis Membranous glomerulonephritis (GN). EM shows segmental replacement of the lamina densa by electron-dense finely granular material. or dense deposit disease. 11-36). Common Associations with Secondary Membranous Glomerulonephritis Infections Hepatitis B Syphilis Autoimmune Diseases Systemic lupus erythematosus Rheumatoid arthritis Sjogren syndrome Thyroiditis Drugs Gold Penicillamine Captopril Malignancies Diabetes mellitus Renal transplantation Fig. 11-37). which become more prominent in the course of disease progression (Fig. Circulating C3 typically is decreased. The basement membranes of the glomeruli are biochemically abnormal. I 1-35. The glomerular capillary basement membranes are thickened and have a ribbon-like quality. which may contribute to glomerular pathology. By IF microscopy deposits of C3 are seen in a finely granular pattern along the GBMs and in the mesangial areas (Fig. MPGN-II. involves activation of the alternate complement pathway. also known as membranous nephropathy. 11-34). Dense Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 11-38). 66417308 : ¸Ÿ±U 24 ¥°Q . MPGN-III is a heterogeneous group of diseases that produce changes similar to MPGN-I. By EM the early deposits (stage I) are epimembranous and subepithelial. which may be seen as fuchsinophilic material in Masson trichrome—stained slides.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . an IgG that enhances clearance of C3. Silver impregnation techniques show subepithelial projections ( " spikes ") of the basement membrane between the deposits of immune complexes. It may occur as a primary kidney disease or secondary to other systemic diseases (Table 11-3). MPGN-II. By light microscopy the glomeruli show thickening of basement membranes. Dense deposits are seen along the basement membranes by EM (Fig. MPGN-II. which results in consumption of complement. Fig. In stage II the deposits are larger and are located between the spikes of the basement membrane. In stage III or IV of the disease the deposits may be completely covered with the basement membrane (Fig. A resorbing subendothelial deposit is indicated by an arrow. By light microscopy the glomeruli appear lobular and show mesangial expansion and hypercellularity. The mesangial areas are expanded and hypercellular segmentally and show some nodularity.

11-38.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . A B C Fig. Early (stage I) disease shows small subepithelial electron-dense deposits (arrows). A. B. 66417308 : ¸Ÿ±U 24 ¥°Q .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . C. A. In this slide stained with PAS—methenamine silver the thickened basement membranes have fine spikes along their subepithelial surface. Stage II is characterized by larger deposits between the intervening projections of newly formed basement membrane ("spikes"). The lucent areas correspond to partially resorbed immune complexes. In this Masson trichrome–stained slide immune complexes appear red ( " fuchsinophilic"). Stage IV disease is characterized by large lucent spaces enclosed by basement membrane. B. 11-37. Membranous glomerulonephritis.221 A B Fig. Membranous glomerulonephritis.

partially confluent deposits of IgG and C3. Henoch-Schonlein purpura ( HSP). round. IgA Nephropathy and Henoch-Schonlein Purpura IgA nephropathy (Berger disease) is an immune complex— Fig. The glomerulus shows mesangial widening and segmental mesangial hypercellularity in this slide stained with PAS—methenamine silver. In extreme cases the damaged capillaries rupture. IF microscopy shows that the mesangial areas contain diffusely finely granular deposits of IgA. 11-39). mediated glomerulonephritis with IgA as the sole or dominant antibody in the complexes.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . By IF microscopy the capillary loops are covered with granular. also known as anaphylactoid or rheumatoid purpura. Fig. The number of mesangial cells is not increased. HSP glomerulonephritis is classified as Fig. In mild cases there are only mesangial deposits of IgA. The disease presents with widening of mesangial areas. Clinically. which usually is a sign of their resorption. which localize preferentially in the mesangium. Its etiology and pathogenesis are not known. IgA nephropathy. IgA mesangial deposits recur in transplanted kidneys but are clinically insignificant in most cases. 11-40.222 deposits may become lucent. and gastrointestinal lesions. which contains IgA. I 1-41. Accordingly. I 1-39. The glomerular changes vary from mild to severe. and a crescentic glomerular nephritis ensues. increased mesangial cellularity. The primary abnormality is a small vessel vasculitis in the IgA deposits of affected vessels. IgA nephropathy. It is the most common primary immunemediated glomerulopathy worldwide. Fig. A capsular adhesion and an area of sclerosis are seen at 12 o'clock. with an exceptionally high incidence in Asia and in Mediterranean countries. Several widened mesangial and paramesangial areas contain large. Approximately one third of all patients develop end-stage renal disease over 20 years and require renal transplantation. IgA nephropathy. fuchsinophilic deposits in this Masson trichrome—stained slides. The renal changes result from deposition of immune complex. presenting symptoms of the disease are asymptomatic proteinuria and hematuria but it also may manifest in the form of other renal syndromes and thus is considered to have a protean nature.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . on the basis of glomerular lesions. Membranous glomerulonephritis. 11-40 to 11-43). By IF microscopy the immune complexes appear as finely granular deposits along the basement membrane (Fig. and mesangial or paramesangial deposits of IgA (Figs. 66417308 : ¸Ÿ±U 24 ¥°Q . dermal. In severe cases the deposits also are found in the glomerular capillaries. is a clinical syndrome that comprises renal. I 1-42.

Large subepithelial deposits of osmiophilic material ( " lumps" ) are seen by EM. EM shows electron dense deposits in the mesangial area. The capillary loops appear unremarkable. Immune complexes attract neutrophils and evoke a proliferative response by glomerular cells. B. 11-45). Deposits of IgG and complement are seen in the capillaries and mesangial areas (Fig. B). (1) mesangiopathic. Postinfectious Glomerulonephritis Postinfectious glomerulonephritis is a form of immune com- plex—mediated acute glomerulonephritis that occurs as a sequela of certain bacterial infections. The capillary loops are normal in this Masson trichromestained slide. it shows IgA predominance. 11-43. and 1. renal disease occurs in 10 percent to 25 percent of affected children and young adults. The paramesangial areas are widened by round electron-dense deposits. Histologically the glomeruli appear hypercellular and typically contain inflammatory cells in the capillaries (Fig. A.22 3 A B Fig. and (4) endocapillary/extracapillary (crescentic). If microscopy is required for diagnosis. 66417308 : ¸Ÿ±U 24 ¥°Q . 11-44. (3) diffuse proliferative (endocapillary). but in general the outcome of the disease correlates with the severity of glomerular changes. usually belonging to types 12. and in such cases HSP resembles SLE. It is believed that the antigens of these microorganisms are planted in the glomeruli. Certain strains of group A streptococci. whereas others appear normal. IgA nephropathy. 4. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . which usually are more diffuse and not as round as in IgA nephropathy (Fig. 11-46). where they form immune complexes with the antibodies deposited into the glomeruli from circulation. 11-44. By light microscopy there always is mesangial widening and hypercellularity (Fig. In more severe cases hump-shaped subepithelial and subendothelial capillary deposits are seen. Symptoms vary. Some mesangial areas appear expanded and hypercellular. Henoch-Schonlein purpura. are the most common cause. EM demonstrates mesangial deposits.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Clinically. (2) focal and segmental. A). 11-44.

50 percent of whom may ultimately show signs of chronic kidney disease.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The glomerulus appears hypercellular and contains numerous intracapillary neutrophils. These morphologic findings are. Crescents may be seen in several diseases (Table 11-4). such as the globular noncollagenous domain of type IV collagen. and end-stage kidney disease occurs in less than 2 percent to 3 percent of all patients. 66417308 : ¸Ÿ±U 24 ¥°Q . The disease may be limited to the kidneys or may Diseases That May Present as Crescentic Glomerulonephritis Anti-GBM disease Idiopathic glomerulonephritis with anti-GBM antibodies Goodpasture disease Wegener granulomatosis Polyarteritis nodosa Systemic lupus erythematosus Henoch-Schonlein purpura Essential cryoglobulinemia Postinfectious glomerulonephritis Fig. 11-48. I 1-46. Glomerular crescents are a sign of severe glomerular injury associated with rupture of GBMs and exudation of fibrin and macrophages into the glomerular urinary space. nonspecific and also are seen in a variety of other kidney diseases that progress to end-stage renal disease. however. Fig. Most children recover. interstitial fibrosis. Symmetrically shrunken kidneys have a uniformly granular surface. Crescentic Glomerulonephritis Fig. Acute postinfectious glomerulonephritis. IF microscopy shows irregular deposits of C3 in the mesangium and the capillaries. Acute poststreptococcal glomerulonephritis. 11-47). There is extensive glomerular hyalinization and tubular atrophy accompanied by interstitial fibrosis (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 1 I-45. Fig.224 Clinically. Unfavorable outcome is more common in adults. poststreptococcal glomerulonephritis usually presents as a transient self-limited nephritic syndrome of childhood. and scattered mononuclear cells. Chronic glomerulonephritis. Glomeruli are hyalinized and surrounded by atrophic tubules. Chronic glomerulonephritis. Anti glomerular basement membrane disease is an i mmune-mediated disease that is characterized by destructive glomerular lesions caused by antibodies to GBM antigens. 11-47. In such cases the kidneys are uniformly shrunken and small (Fig. 11-48).

Wegener granulomatosis probably is the most common cause of crescentic glomerulonephritis. Damaged glomeruli undergo scarring. 11-49. Because all of these diseases produce the same morphologic changes.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . karyorrhexis* Crescents—cellular* "Wire loops" "Hyaline thrombi" TUBULOINTERSTITIAL Chronic Lesions Sclerosis Fibrous crescents Active Lesions Mononuclear leukocyte infiltration Chronic Lesions Interstitial fibrosis Tubular atrophy Each lesion is assigned a grade of 0. Some tubules contain red blood cells as evidence of severe glomerular injury and glomerular hematuria. In this slide stained with PAS–methenamine silver the collapsed capillary loops are compressed by a crescent composed of fibrin and macrophages. additional immunologic data. Typical Goodpasture disease. such "crescents " also contain exudated macrophages and proliferated epithelial cells compressing the collapsed capillary loops. presenting with pulmonary hemorrhage and RPGN. Crescentic glomerulonephritis of the type found in Goodpasture disease may be found in other kidney diseases that present as RPGN. is rare. such as tests for antinuclear antibody (ANA) and antineutrophil cytoplasmic antibody (ANCA). 11-51). In mesangial lupus glomerulonephritis there is mild mesangial widening accompanied by mild mesangial hypercellularity (Fig. Anti–glomerular basement membrane nephritis. 11-49). Systemic Lupus Erythematosus (SLE) SLE glomerulonephritis is an immune complex–mediated renal disease that occurs in more than 75 percent of patients who have this systemic autoimmune disease. and end-stage kidney disease may evolve over a few weeks or months. the renal lesions are graded on a scale from mild to severe and are classified into five categories (Tables 11-5 and 11-6). 11-50. 2. and immunofluorescence microscopies Mesangial (injury. IF microscopy shows linear staining of the capillaries with antibodies to IgG or IgM .225 be part of a renal-pulmonary syndrome (Goodpasture disease). (Fig. In addition to fibrin. In focal and segmental proliferative World Health Organization Classification of Lupus Nephritis Class Lesion No abnormalities by light. Fibrin is seen in the crescents. electron. 11-50). The capillary loops stain in a linear manner with antibodies to IgG. those with an asterisk are doubled. Anti–glomerular basement membrane nephritis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . or 3. 66417308 : ¸Ÿ±U 24 ¥°Q . The glomeruli show typical extracapillary exudation of fibrin into the urinary space between the Bowman capsule and the capillary loops (Fig. I. Add all active lesions for activity index (maximum number 27) and chronic lesions for chronicity index (maximum number 12). which are listed in Table 11-4. Fig. are essential for proper diagnosis. Clinically this is recognized as rapidly progressive glomerulonephritis (RPGN) characterized by relentless loss of renal function. Fig. proliferative glomerulonephritis) No increased cellularity Mild increases in mesangial cellularity Focal and segmental glomerulonephritis Diffuse proliferative glomerulonephritis Membranous glomerulonephritis "Pure" membranous glomerulonephritis With mesangial glomerulonephritis With focal proliferative glomerulonephritis With diffuse proliferative glomerulonephritis Lupus Nephritis Scoring System of Renal Pathology GLOMERULAR II A B III IV V A B C D Active Lesions Hypercellularity Leukocytic infiltration Necrosis. According to the World Health Organization classification.

Lupus nephritis. mesangial proliferative. The glomerulus is hypercellular and has expanded mesangial areas and partially obliterated capillary lumens. 11-54 and 11-55). Deposits of immune complexes may be found by IF microscopy in the mesangial areas. diffuse proliferative. Fig. EM shows a large subendothelial electron-dense deposits and "hyaline capillary thrombus. Glomerulus shows segmental loss of normal architecture of the tufts because of deposition of eosinophilic material and cell proliferation. focal proliferative.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . but they also contain mesangial deposits (Fig. The lower part of the glomerulus is relatively spared. Intracapillary eosinophilic hyaline thrombi and wire loops are seen segmentally. Endothelial cells typically contain tubuloreticular structures (Fig.226 GN and diffuse proliferative GN. Fig. deposits of immune complexes are accompanied by proliferation of mesangial cells. I 1-53. I 1-52. Capillary deposits are classified by EM as subendothelial. 11-54. Fig." 66417308 : ¸Ÿ±U 24 ¥°Q . Lupus nephritis. and in capillaries (Figs. or subepithelial. expansion of mesangial areas. In membranous GN the glomeruli show subepithelial deposits like in any other membranous GN. along the GBM. intramembranous. 11-56). 11-54).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and obliteration of capillary lumina (Figs. Lupus nephritis. Mesangial areas are widened and contain an increased number of mesangial cells in this slide stained with PAS–methenamine silver. 11-52 and 11-53). Deposits of immune complexes also may be seen in the interstitial peritubular spaces (Fig. Lupus nephritis. diffuse proliferative. Fig. I 1-51. 11-55).

Deposits of dense material corresponding to immune complexes are seen in a subepithelial location along the capillaries and in the mesangium. macrophages. Clinically and pathologically they are classified as acute or chronic.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and (4) ischemic. 11-55. The interstitium contains a dense infiltrate of lymphocytes. 11-58). Numerous interstitial deposits are located around a peritubular capillary. and eosinophils. may have many causes (Table 11-7). In this Masson trichrome–stained slide the edematous interstitium is infiltrated with mononuclear cells. Acute interstitial nephritis. Tubules show focal signs of injury. Acute interstitial nephritis. membranous. A B Fig.227 Fig. Interstitial nephritis also may present as a granulomatous reaction (Fig. The kidneys typically are enlarged and edematous and show extensive interstitial infiltrates composed of lymphocytes. Lupus nephritis. 11-57. also known as acute tubulointerstitial nephritis. plasma cells. or eosinophils (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . B. TUBULOINTERSTITIAL DISEASES Tubulointerstitial diseases are classified etiologically as (1) immune-mediated. (3) metabolic and/or toxic. 11-56. Lupus nephritis. A. These diseases have many common morphologic features. 11-57).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. (2) infectious. and their etiology is not always apparent. macrophages.

11-60). In chronic pyelonephritis. 11-60. which tend to replace the tubules (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . rickettsial. Fig. 11-58. The interstitium contains epithelioid granulomas. Acute tubular necrosis (ATN) is a reversible lesion of the tubular epithelium that is associated clinically with acute renal failure. Chronic pyelonephritis. leptospiral. Infections may be caused by hematogenous spread of bacteria or reflux of infected urine. Granulomatous interstitial nephritis. Histologically the kidneys are infiltrated with lymphocytes. Fig.22 8 Pyelonephritis is a term that refers to bacterial tubulointerstitial infections. and plasma cells. 1 1-61. 11-59. Bilateral chronic pyelonephritis is associated with end-stage kidney disease. Metabolic and/or toxic disorders that affect the kidneys cause tubular injury. Neutrophils are found in the tubules and the edematous interstitium. which often is associated with urinary obstruction. which may or may not be associated with glomerular and vascular changes. Chronic pyelonephritis. which may fill the tubules or form interstitial abscesses (Fig 11-59). The kidneys are enlarged and swollen and may contain abscesses. idiopathic) Infection-associated Reactive (viral. but the glomeruli appear preserved in this Masson trichrome–stained slide. Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . 11-61). In acute pyelonephritis the kidney is infiltrated with neutrophils. Extensive mononuclear infiltrates have replaced most of the tubules. Acute pyelonephritis. mycobacterial) Hereditary and metabolic Crystal formation Paraprotein-mediated Toxins Hereditary Irradiation Idiopathic Fig. Pyelonephritis may be unilateral or bilateral. the loss of renal parenchyma typically results in shrinkage of the kidneys and hydronephrosis (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . macrophages. bacterial) Direct (viral. This kidney from a patient with urinary obstruction shows dilatation of calices and pelvis and loss of renal parenchyma. It may be caused Etiologies of Acute Interstitial Nephritis Drug-induced Allergic (hypersensitivity) Toxic Idiopathic Immune-mediated Antitubular basement membrane disease Immune complex deposition T cell–mediated (sarcoid.

The desquamated cells fragment and form granular casts that are most prominent in the medullary tubules. 11-64. accounting for the term lower nephron nephrosis. and focally cells are missing altogether (Fig. Diabetic glomerulosclerosis occurs in diffuse and nodular forms (Figs.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . By microscopy the basement membranes and mesangial areas appear to be impregnated with IgG and albumin. In nodular glomerulosclerosis there is nodular expansion of the mesangial regions. in multiple organ failure. The vasa recta of the medulla typically are congested and contain nucleated blood cell precursors (Fig. ATN. Recovery is associated with normalization of renal function. The expanded mesangial areas and the nodular material also consist of basement membrane–like material. by a variety of toxins (Table 11-8). Histologically the earliest changes are those in which the proximal tubules lose their brush borders. 11-66). 11-62). and in essentially all conditions that are associated with anoxia or hypoperfusion of the kidneys. which is best seen in slides stained with period acid–Schiff reagent.229 Causes of Toxic Acute Tubular Necrosis Fig. The medullary tubules contain casts. The glomerulus contains a mesangial nodule composed of basement membrane–like material. which imparts to them a " pseudolinear " staining pattern (Fig. and (4) papillary necrosis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . (2) hyalinization of arterioles (hyaline arteriolosclerosis). Fig. 11-62. 11-64 and 11-65). Renal tubular epithelium may regenerate. In diffuse glomerulosclerosis the GBMs are uniformly thickened and the amount of mesangial matrix is increased. 11-63). which contain cellular debris in the form of granular proteinaceous material. 11-63. Typical renal lesions include (1) diabetic glomerulosclerosis. The epithelium of the tubules is flattened. Some tubules contain granular casts. which typically is found in various forms of shock. ATN. Fig. The kidneys are enlarged and have a pale cortex and congested medulla. and in the recovery phase of ATN the tubules are lined by cells that have basophilic cytoplasm. Diabetic glomerulosclerosis. Necrosis of tubular cells leads to widening of the tubules. The tubules are lined by flattened epithelium. which previously was used to describe ATN in autopsy specimens. By EM the basement membranes of the capillary loops appear uniformly thickened. Ischemia may also cause ATN. (3) pyelonephritis. Diabetes mellitus is a major cause of kidney disease. and the congested vasa recta contain nucleated red blood cells. 66417308 : ¸Ÿ±U 24 ¥°Q . which is focally missing altogether.

in several other metabolic diseases such as hyperoxaluria and cystinosis.230 Fig. The basement membranes are diffusely thickened.. and the mesangial areas appear widened. and in urinary tract infections. 11-67. Small stones that obstruct the ureter cause colic. (2) magnesium ammonium phosphate. and (4) cysteine. 11-68. Papillae missing their tips appear blunted and partially calcified (arrows). Diabetic glomerulosclerosis. Antibody to IgG stains the GBM and Bowman capsule in a linear way. 66417308 : ¸Ÿ±U 24 ¥°Q . Diffuse diabetic glomerulosclerosis. 11-67). 11-68). and clinical symptoms depend on their size and location. Fig. Calcium phosphate crystals may precipitate in renal tubules or renal interstitium. The arterioles show hyalinization. Large stones that are impacted in the pelvis cause obstructive hydronephrosis and progressive renal failure (Fig. Deposits of other metabolites that may be found in the kidneys include uric acid crystals in gout and oxalate crystals in oxalosis or ethylene glycol poisoning (Figs 11-69 and 11-70). Urinary stone. Fig. I 1-65. This complication is not unique to diabetes. Biochemically. (3) uric acid. which may slough off into the pelvis (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The dilated pelvis contains irregular stones. Bowman capsule thickening ("hyaline drop") also is seen. uri- nary stones are composed of (1) calcium (oxalate or phosphate. Fig. especially in end-stage kidney disease (nephrocalcinosis). The stones may be small or large. Papillary necrosis is characterized by an infarction of the renal papillae. It is especially common in diabetic patients who have obstruction of urine flow or pyelonephritis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Urolithiasis (urinary stones) also occurs in gout. 11-66. Papillary necrosis also occurs in women who abuse aspirin and phenacetin ( " analgesic abuse nephropathy " ). Papillary necrosis. Metabolic changes associated with the excretion of calcium and phosphates often result in the formation of urinary stones.

B. Fig. 11-71. Gout. Birefringent crystals in the tubules are seen under polarized light. I 1-69. Deposits of uric acid crystals have caused yellowish discoloration of the papilla. Amyloid fibrils have a typical appearance by EM. Oxalosis. Amyloid. 11-70. Uric acid crystals appear as birefringent deposits in the medulla.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . A.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .231 A B Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Fig.

or epididymis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . which usually leads to lobular transformation of the hypercellular glomerular tufts reminiscent of MPGN (Fig. but most often the pathogens do not respect the anatomic boundaries and the inflammation involves the major part of the lower urinary tract. 11-75. Deposition of cryoglobulins. The mucosa is focally hemorrhagic. In males it may spread to the prostate. Acute cystitis. Renal deposits of amyloid are found in both primary and secondary amyloidosis. vas deferens. Cryoglobulinemia typically is associated with glomerulonephritis.232 Fig. Fig. Cryoglobulinemia. such as urethritis or cystitis. 66417308 : ¸Ÿ±U 24 ¥°Q . blood vessels. 11-74. The mucosa of the urinary bladder is congested and shows foci of hemorrhage. Fig. and some contain pink-staining plasma protein casts in their lumen.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The wall of the bladder is thickened. 11-72. The glomerulus shows lobular expansion and hypercellularity. predominantly occurs in renal vessels. LOWER URINARY TRACT I NFECTIONS Infections of the lower urinary tract may occur as an isolated form. Chronic cystitis caused by prostatic hyperplasia. Fig. which may cause urinary obstruction (Fig. Many capillary loops have double contours. Multiple myeloma. 11-73). and tubular basement membranes (Fig. 11-72). multiple myeloma kidney disease is characterized by tubular casts of immunoglobulin light chains. plasma proteins that precipitate at low temperature. 11-71). 11-73. These deposits are seen in the glomeruli. Tubular proteinaceous casts elicit a giant cell reaction. Besides amyloid.

Fig. and (5) squamous metaplasia (Figs. Acute cystitis usually is caused by coliform bacteria. It often is associated with predisposing conditions such as urinary stones or prostatic hyperplasia. The urinary bladder appears congested and may show shallow bleeding ulcerations that result in hematuria (Fig 11-74). but these cells also may occur in other forms of cystitis. Interstitial cystitis is a persistent form of cystitis of unknown etiology that typically affects women. Malacoplakia (see Chapter 12) is characterized by the presence of Michaelis-Gutmann bodies and von Hansemann histiocytes. I 1-78. It is less common in men than in women.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The urinary bladder has a thick wall and may show trabeculation as a result of smooth muscle hypertrophy and hyperplasia (Fig. Inflammation and glandular metaplasia are seen. Pseudomembranous cystitis may be a complication of chemotherapy. I 1-77. Histologic features of chronic cystitis generally are nonspecific and provide few if any clues to the etiology of the disease. Fig. Interstitial cystitis. 11-76. Massive hemorrhagic cystitis. The mucosa of the urinary bladder of patients receiving chemotherapy may necrotize and the urinary bladder may fill with blood and necrotic debris (Fig. who have shorter urethra and are more likely to develop an ascending urinary tract infection. It presents with thickening of the wall of the urinary bladder and mucosal ulceration (Hunner ulcer) (Fig. and the surface of the bladder subsequently is covered with a pseudomembrane that is composed of fibrin and cell debris. which are known in the urinary bladder as (1) von Brunn nests. 11-78). Chronically inflamed epithelium of the lower urinary tract may show hyperplastic and metaplastic changes. Chronic cystitis may result from recurrent bouts of acute infection. Several pathologic variants of chronic cystitis are recognized. In this disease the urinary bladder undergoes necrosis of the epithelium. 11-77). In interstitial cystitis the chronic inflammatory infil- trate contains an increased number of mast cells. The wall of the contracted bladder is edematous and thickened and the mucosa shows hemorrhagic ulceration. 11-76). Granulomatous cystitis has been observed in patients treated by intravesical instillation of bacille Calmette-Guerin (BCG) vaccine. 66417308 : ¸Ÿ±U 24 ¥°Q . and they do not necessarily have distinct clinical symptoms.233 Cystitis is a very common disease. Chronic cystitis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Histologically pseudomembranes may be recognized by their content of fibrin and amorphous cell debris. Fig. (3) cystitis glandularis. 11-75). (4) nephrogenic metaplasia. Urinary bladder of this patient treated for Burkitt lymphoma is filled with clotted blood and necrotic detritus. (2) cystitis cystica.

Most tumors are of clear cell type. Renal cell carcinoma. I 1-79.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . clear cells arranged into alveoli surrounded by thin fibrovascular strands. of yellow color. necrosis. 11-79). and (3) urothelial carcinoma. Grading of Nuclei of Renal Cell Tumors Grade I Rund.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . In comparison with these tumors. On cross section they are solid. the contour of nuclei.234 TUMORS The most important tumors of the kidney and the urinary tract are (1) renal cell carcinoma. Unfavorable features are large hyperchromatic nuclei and multipolar mitotic figures.m with nucleoli visible at 400x Grade 3 Moderately to greatly irregular nuclear contours and diameters of approximately 20 p. Tumors of the Kidney and Renal Pelvis the most common renal tumor. On gross examination nephroblastomas may replace the whole kidney. which account for most neoplasms at this site. or cystic degeneration are common. The stroma component is composed of loose connective tissue that occasionally may show differentiation into skeletal muscle or cartilage. all other benign and malignant tumors are rare. but often they appear as circumscribed multinodular masses. and the appearance of nucleoli (Table 11-10).m with large nucleoli visible at IOOx Grade 4 Nuclei similar to those of grade 3 but also multilobular or multiple nuclei or bizarre nuclei and heavy clumps of chromatin Fig. Histologically the tumors are composed of clear cells arranged in an alveolar or diffuse pattern (Fig. Histologically they are composed of a mixture of blastema-like epithelial and stromal cells and cells forming tubules and cords (Fig. Wilms tumor. rhabdoid tumor. Areas of hemorrhage.m in diameter with minute or absent nucleoli Grade 2 Slightly irregular contours and diameters of approximately I5 p. and grayish-white (Fig. soft. A relatively well demarcated yellow tumor occupies the upper pole of the kidney. 66417308 : ¸Ÿ±U 24 ¥°Q . which account for 80 percent of the renal tumors of childhood. 11-80). must be differentiated from mesoblastic nephroma. Nephroblastomas. The tumors may be unilateral or bilateral. On the basis of histologic features and the presence or absence of anaplasia. 11-82). nephroblastomas are classified as tumors of a favorable or an unfavorable nature. Renal cell carcinoma. clear cell sarcoma. It occurs in several histologic subtypes (Table 11-9). 11-80. The tumor is composed of Fig. is a tumor of infancy and childhood that arises from nephrogenic nests. and with areas of necrosis or hemorrhage (Fig. uniform nuclei approximately 10 p. 11-81). or nephroblastoma. and cystic nephroma. (2) Wilms tumor. solid lobulated masses. On gross examination tumors appear as well-circumscribed. The tuRenal cell carcinoma is Classification of Renal Cell Tumors Benign Neoplasms Renal oncocytoma Carcinomas Renal cell carcinoma Clear cell Chromophil Eosinophil Basophil Chromophobe Typical Eosinophil Collecting duct carcinoma Neuroendocrine tumors Carcinoid Small cell carcinoma mors are graded on a scale from 1 to 4 according to size.

only a small fraction of all bladder tumors are of mesenchymal origin. conventional type Verrucous squamous cell carcinoma Villous adenoma Adenocarcinoma Papillary. TCC of the renal pelvis. In all respects these tumors resemble the more common urinary bladder tumors. The tumor is composed of blastema. I 1-83. 11-83). Wartlike tumor masses protrude into the lumen of the pelvis. I 1-84. signet-ring cell. Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Wilms tumor. Fig. and 1 percent to 2 percent of tumors show glandular differentiation and are classified as adenocarcinomas.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .235 Fig. 11-81. and loose stroma. glandular. 11-84).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Classification of Urinary Bladder Tumors (Epithelial Neoplasms) Transitional cell (urothelial) neoplasms Papilloma Inverted Everted Carcinoma Papillary Nonpapillary (solid) Carcinoma in situ and possible precursor lesions Variants of TCC TCC. Approximately 10 percent of tumors are squamous cell carcinomas. and clear cell Small cell carcinoma (neuroendocrine carcinoma) Mixed carcinoma Other epithelial neoplasms Carcinosarcoma Carcinoid tumor Urothelial carcinomas of the renal pelvis and ureter present as exophytic and papillary masses that often fill the pelvis and obstruct the ureter (Fig. Fig. A histologic classification of epithelial bladder tumors is given in Table 11-11. The tumor is composed of papillary and solid components. mucinous. nested type TCC with glandlike lumens Lymphoepithelial carcinoma Squamous cell carcinoma. Histologically most tumors are transitional cell carcinomas (TCC) (Fig. arising from the smooth muscle or stromal cells. I 1-82. The multinodular tumor is replacing a large portion of the renal parenchyma. Wilms tumor. Tumors of the Urinary Bladder Most tumors of the urinary bladder arise from the urothelium. primitive tubules. TCC of the renal pelvis.

236 Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . I 1-85.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . hyperchromasia. Fig. 11-86. B. The central fibrovascular core is lined by transitional epithelium that has a surface umbrella cell layer. This exophytic tumor protrudes into the lumen of the bladder. TCC. Transitional cell papilloma. Carcinoma of the urinary bladder. everted type. A. Grade II TCC is composed of cells showing mild nuclear pleomorphism. C. Grade I TCC is composed of slightly atypical cells forming a thickened transitional epithelium-like layer. Grade III TCC is composed of pleomorphic cells showing variation in the size and shape of their nuclei and a complete loss of polarity. and loss of polarity. I 1-87. A B C Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 66417308 : ¸Ÿ±U 24 ¥°Q . Minnesota. Everted papillomas have a connective tissue core lined by seemingly normal transitional epithelium that is less than seven cells thick and a surface umbrella cell layer (Fig. J Clin Pathol 47:126-132. Bladder tumors appear on gross examination as polyps or exophytic cauliflower-like masses that protrude into the lumen of the bladder (Fig. (2) interruption of basement membrane.237 Fig. Further Reading Berden JHM: Lupus nephritis. (5) invasion of blood vessels or lymphatics. 1997. Coyne JD. Cohen MB: Urinary system. polypoid masses or a solitary large mass that replaces the wall of the bladder. Small cell carcinoma of the urinary bladder with foci of TCC. In addition to the stage of the tumor. They are rare and represent less than 1 percent of all bladder tumors. 11-88. (6) tentacular invasion. Some tumors appear as flat plaquelike lesions. Pleomorphic cells have completely lost polarity. Am J Kidney Dis 23:451-460. Cancer 75:316-329. (3) invasion into or below the muscularis mucosae. 1995. Reuter VR et al: The World Health Organization/ International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of urinary bladder. which is determined by its size and the extent of local and metastatic spread. Epstein JI. Adjacent epithelium may contain carcinoma in situ (Fig. (4) detrusor muscle involvement. Rennke HG: Secondary membranoproliferative glomerulonephritis. are rare. 11-87). Transitional cell carcinomas (TCC) occur in three grades (Fig. Rochester.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 1998. Grade II lesions are multilayered. Emancipator SN: IgA nephropathy: Morphologic expression and pathogenesis. Amin MB. McWilliams LJ. 1995. the recurrence or progression and a clinically unfavorable outcome are related to (1) high tumor grade. Inverted papillomas are composed of similar cells that form solid nests. Lancet 353:1509-1515. Wetzels JFM: Prognostic factors in idiopathic membranous nephropathy. Pathologic findings are of prognostic significance. Grade I tumors are papillary lesions that are lined by slightly disorganized epithelium showing minimal nuclear abnormalities and measuring more than seven layers in thickness. Approximately 25 percent of bladder tumors are multifocal. 1994. Couser WG: Glomerulonephritis. 11-86). 1999. Bostwick DG. 9 percent are squamous cell carcinomas. Approximately 90 percent of urinary bladder tumors are TCC. Curry A: Value of electron microscopy in diagnosis of renal disease. 11-89). 1997. Am J Surg Pathol 22:1435-1448. most of which are leiomyosarcomas. and (8) multiple tumors. Koene RAP. Kidneylnt 47:643-651. Sarcomas. Fig. Kidney hit 52:538-558. The tumor presents in the form of multiple. whereas others show both an exophytic and an endophytic invasive component. Cancer 80:975-976. Rhabdomyosarcoma is the most common malignancy of the urinary bladder in children. Am 'Kidney Dis 31:1-11. and the epithelium appears disorganized throughout its entire thickness. Carcinoma in situ of the urinary bladder. Reichert LJM. 1998. Grade III tumors are composed of nests of disorganized cells that show marked nuclear polymorphism. glistening. Histologically it shows features of embryonal rhabdomyosarcoma (Fig. Murphy GP: Conference summary: Diagnosis and progression of renal cell carcinoma: 1997 workshop. 1994. and to a large extent the cells have lost their polarity. Eble IN. 1 1-89. (7) associated carcinoma in situ in adjacent epithelium. Papillomas are benign lesions of transitional epithelium that occur in two forms: everted and inverted papillomas. and the remaining 1 percent are adenocarcinomas and small cell carcinomas. 11-85). Lynch CF. Pearson JM. 11-88).

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including cryptorchidism. Fig. The seminiferous tubules have been replaced by fibrous tissue.) Fig. Copenhagen. The tubules appear dilated and show hypospermatogenesis. 12-3. and the treatment that has been carried out. Germ cell aplasia. testicular ectopia. or polyorchidism. which may be unilateral or bilateral. (4) gonadal dysgenesis. Approximately 25 percent of contralateral descended testes show similar changes. The remaining tubules have thick hyalinized basement membranes and contain no spermatogenetic cells (Courtesy of Drs. (Courtesy of Drs N. Maturation arrest of spermatogenesis. Klinefelter syndrome is a chromosomal anomaly that usually is associated with a 47. (2) numeric aberrations. monorchidism. Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . including anorchia. including germ cell aplasia. and severe atrophy in 17 percent of patients (Fig. Cryptorchidism. 12-4. Giwercman. Denmark.XXY karyotype. and (5) abnormal spermatogenesis. Cryptorchidism. Marked germinal hypoplasia is found in 24 percent. (3) structural malformations of the testes or epididymis. Histologic changes are minimal in 26 percent of patients. " is generally used as a synonym for undescended testes. Spermatogenesis has not progressed beyond the stage of spermatocytes.240 GENETIC AND DEVELOPMENTAL DISORDERS The abnormal development of the testis may result in (1) abnormal positioning of one or both testes. and in many cases there also are epididymal abnormalities. and various forms of maturation arrest associated with oligospermia or azoospermia.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Klinefelter syndrome. The testes are atrophic and show no signs of spermatogenesis (Fig. Skakkebaek and A. 12-1. The histologic features vary depending on the age of the patient. Copenhagen. or dystopia. Denmark. 12-2). 12-1). 12-2. the location of the testis. a term derived from Greek words meaning "hidden testis. Skakkebaek and A. Undescended testes are smaller than normal and remain small even after orchidopexy. N. Fig. The tubules contain only Sertoli cells.) 66417308 : ¸Ÿ±U 24 ¥°Q . diffuse tubular hypoplasia in 33 percent. hypospermatogenesis. Giwercman. which almost always is associated with sex chromosome abnormalities and intersexuality.

The germ cells are sparse. Mixed infections with uropathogens such as Escherichia coli or Pseudomonas aeruginosa are common causes of infection in older men over the age of 60 years. and herpesvirus infection are typical sexually transmitted diseases. and reduced sperm counts (Fig. Ascending bacterial infections that reach the testes usually also affect the epididymis and cause a suppurative epididymoorchitis (Fig. or in a diffuse form that involves all of the genital organs and the lower urinary tract. and there is no evidence of spermatogenesis. This form of hypogonadism is typical of Prader-Willi prepubertal syndrome. Maturation arrest may occur at any stage of spermatogenesis. In this disease the seminiferous tubules are infiltrated with numerous macro - 66417308 : ¸Ÿ±U 24 ¥°Q . The testis contains abscesses. dilatation of seminiferous tubules. Spermatogenesis also may be reduced as a result of hypothalamic or pituitary disorders that are characterized by a lack of gonadotropin and hypogonadotropic hypogonadism. Hypogonadotropic hypogonadism. Infections most often are acquired through sexual transmission or from ascending urinary tract infections. 12-6.241 Fig. Only one seminiferous tubule contains spermatozoa. Chronic infections cause severe testicular destruction. The testes are small and never attain normal adult size. The arrest typically is at the level of spermatocytes or round spermatids (Fig. in which the seminiferous tubules contain only Sertoli cells (Fig. Follicle-stimulating hormone and luteinizing hormone deficiencies result in incomplete maturation of the testes. syphilis. or hypothalamic tumors. The most severe form is aplasia of germ cells. Kallmann syndrome. The small seminiferous tubules contain immature (fetal) Sertoli cells and a few spermatognia. Fig. Hypospermatogenesis is associated with hypoplasia of germinal epithelium. In contrast to bacterial infections. also known as granulomatous orchitis. 12-6). The seminiferous tubules are small and are lined by immature Sertoli cells that have round nuclei and inconspicuous nucleoli (Fig. Suppurative epididymoorchitis. or balanoposthitis. Gonorrhea. viral infections cause an interstitial orchitis. 12-3). pituitary apoplexy. 12-7). Fig. urethritis. Disturbances of spermatogenesis occur in several forms. which usually is associated with spermatogenetic arrest (Fig. 12-4). 12-5. epididymitis. INFECTIONS Infections of the male genital organs may occur in a localized form as orchitis. Viruses such as the mumps virus reach the testes hematogenously. 12-5). Pathogens may reach the genital organs hematogenously. The best known example of such chronic infection is malacoplakia. 12-7. prostatitis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 12-8).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Hypospermatogenesis.

Mononuclear infiltrate is associated with spermatogenic arrest. Malignant tumors are more common than benign tumors. which are devoid of spermatogenesis (Fig. and focal lymphocytic infiltrates (Fig. 12-12). tubular hyalinization. The tubules are obliterated by a mononuclear infiltrate. All age groups may be affected. 12-9). A B Fig. Mumps orchitis.242 phages. These bodies have a characteristic targetoid appearance by electron microscopy (EM). In most patients who histologically show extensive tubular atrophy. 12-9. CIS cells give rise to seminoma or embryonal carcinoma (EC). lymphocytes. Germ Cell Tumors The histogenesis of germ cell tumors has not been entirely clarified. With an exception of some tumor types. The macrophages have a prominent cytoplasm filled with residues of phagocytosed bacteria and concentrically calcified round inclusions called Michaelis-Gutmann bodies. TUMORS OF THE TESTIS Testicular tumors account for approximately 1 percent of all tumors of the internal organs in men. 12-10). and plasma cells (Fig. Malacoplakia A. interstitial fibrosis. hyalinization and loss (so-called end-stage testis disease). the cause of testicular injury usually cannot be determined (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . appears in the form of large atypical cells inside the tubules. In acquired immunodeficiency syndrome (AIDS) the testes show atrophy of germinal epithelium. which are developmentally pluripotent cells that resemble early embryonic cells. which reflects our ignorance about the initiation and promotion of malignancy in this cell system. CIS. Sex cord cell tumors such as Leydig cell and sertoli cell tumors account for 2 percent to 5 percent of all tumors. all other germ cell tumors pass through a preinvasive carcinoma in situ (CIS) stage (Diagram 12-1). 66417308 : ¸Ÿ±U 24 ¥°Q . By EM this typical Michaelis-Gutmann body has a dark calcified center surrounded by a halo and a distinct rim. whereas the remainder are tumors of nonspecific stromal cells and metastases. Germ cell tumors account for 92 percent to 95 percent of all neoplasms. also known as intratubular testicular neoplasia (ITTN). but the peak incidence for germ cell tumors typically is in the range of 25 to 40 age years (Table 12-1). cells. 12-11).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The testes may be damaged by a variety of systemic infections even if there is no direct invasion of testicular tissue by pathogens. EC cells may mimic normal embryonic cells and form embryo- Fig. 12-8. a reduced number of Leydig cells. B. such as spermatocytic seminoma and yolk sac tumor of infancy and childhood.

66417308 : ¸Ÿ±U 24 ¥°Q . Most tubules are hyalinized. 12-I I. CIS.243 Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Large neoplastic cells with centrally located nuclei and clear cytoplasm are located along the basement membrane.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. Pathogenesis of germ cell tumors. Classification of Testicular and Epididymal Neoplasms Germ cell tumors Tumors of sex cord cells Leydig cell tumors Sertoli cell tumors Mixed germ cell–sex cord cell tumors Tumors of the rete testis Tumors of the epididymal epithelium Tumors of mesothelial origin Tumors of nonspecific stromal cells Tumors derived from epithelial rests and choristomas Tumors of hematopoietic cells Diagram 12-1. 12-12. and the interstitial spaces are dilated and fibrotic. The seminiferous tubules are dilated hypocellular and show reduced spermatogenesis. 12-10. Fig. End-stage testis disease. AIDS.

Fibrous septa are infiltrated with lymphocytes. 12-16). macrophages. 12-15). 12-14. however. For clinical purposes germ cells are divided into two groups: seminomas and nonseminomatous germ cell tumors (NSGCT). 66417308 : ¸Ÿ±U 24 ¥°Q . It consists of an embryonic shield and primitive amniotic and yolk sac cavities. Embryonal carcinoma is a tumor that grows much faster than a seminoma. important to note that the malignancy of NSGCT tumors resides primarily with EC cells. 12-17). Fig. plasma cells. i mmature and mature teratomas. Histologically it is composed of clear glycogen-rich cells arranged into nests that are surrounded by fibrous septa (Fig. Tumors composed of EC cells and their derivatives are called teratocarcinomas.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 12-13. On gross examination it has a variegated appearance because of broad areas of necrosis and hemorrhage (Fig. 12-13). In approximately 20 percent to 30 percent of tumors there are scattered trophoblastic giant cells. and resembles early human embryo. A. which have vesicular. Fig. 12-14). which are called embryoid bodies (Fig. The latter is a heterogeneous group that encompasses embryonal carcinoma. The tumor cells are positive for placental alkaline phosphatase (PLAP) and negative for keratin. Clear tumor cells form nests surrounded by fibrous strands infiltrated with lymphocytes. B. and occasionally multinucleated giant cells. which distinguishes them from EC cells. such as trophoblast or yolk sac epithelium. which are PLAP-negative and keratin-positive. The tumor is homogeneously yellow and lobulated. A B Fig. such as nerve. and scant cytoplasm with indistinct borders (Fig. Seminoma. Placental alkaline phosphatase is demonstrated in tumor cells. 12-15.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The histologic components of these tumors most often are intermixed. Seminomas are radiosensitive and have a good prognosis. Seminoma. it is only of academic interest to enumerate all elements identified in the tumor. It is. Histologically it is composed of a single population of undifferentiated cells. The tumor appears lobulated and homogeneously yellowish on cross section (Fig. or glands.244 like structures. irregularly shaped nuclei. Embryoid body. choriocarcinoma. and after a diagnosis of malignant NSGCT has been established. EC cells also may differentiate into various somatic tissues. Seminoma is the most common germ cell tumor. or into extraembryonic tissues. An abundance of EC cells in a given tumor and extensive invasion of EC cell into the blood vessels and lymphatics are related to an unfavorable prognosis. muscle. and yolk sac carcinomas. teratocarcinoma.

On cross section the tumor shows irregular nodularity and appears to be composed of heterogeneous elements. Embryonal carcinoma. 12-18 to 12-20). Extraembryonic tissues include trophoblastic and yolk sac elements. 12-16. On cross section the tumor has an inhomogeneous texture. Fig. Teratoma. many of which actually are capable Fig. The tumor is composed of neural tissue.245 Teratocarcinoma is a tumor that is composed of EC cells and their somatic and extraembryonic derivatives (Figs. The tumor is composed of hyperchromatic EC cells and other loosely arranged elements. 12-20. squamous epithelium. 12-21). The tumor is composed of undifferentiated cells with scant cytoplasm. 12-20). one can never be sure that all malignant cells have disappeared from such tumors. Pure yolk sac carcinomas and choriocarcinoma are rare in the testis (Fig. 12-17. and connective tissue stroma. However. Teratoma of adult testis ostensibly is a histologically benign tumor composed of somatic tissues that are devoid of EC cells. Fig. Teratocarcinoma. In some tumors these cells may proliferate and overshadow all others. Trophoblastic cells secrete human chorionic gonadotropin (hCG). The nuclei appear crowded and overlap. Embryonal carcinoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 12-18. 66417308 : ¸Ÿ±U 24 ¥°Q . Such teratomas develop from teratocarcinomas in which all EC cells have differentiated into histologically benign somatic tissues (Fig. and yolk sac carcinoma cells secrete alpha-fetoprotein (AFP).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. 12-19. Teratocarcinoma. Fig. Antibodies to hCG and AFP are used to demonstrate these tumor components immunohistochemically in tissue sections.

and giant cells. Leydig cell tumors are composed of cells that resemble normal Leydig cells and therefore may be hormonally active. There are few mitoses. On gross examination they appear as well-circumscribed brown nodules. and granulosa cell tumors.to 60-year age group. 12-23. Small cells that resemble lymphocytes are scattered at random or form small clusters. Sertoli cell tumors. Histologically it consists of yolk sac—like tissue that is similar to the yolk sac components of teratocarcinoma (Fig.246 Fig. Yolk sac tumors of infancy have a good prognosis. even in those tumors that are clinically malignant and metastasize. Histologically they are composed of polyhedral cells that have welldeveloped eosinophilic cytoplasm and vesicular round nuclei (Fig. is the most common tumor of infancy. 12-22). Yolk sac tumor. Spermatocytic seminoma is a germ cell tumor of older adults. although a few malignant ones have been described. and the presence of metastases is the only reliable sign of malignancy. These tumors account for 2 percent to 3 percent of testicular neoplasms. androgen-secreting tumors are not different from estrogen-secreting tumors. a neoplasm composed of pure yolk sac elements. Sex Cord Stromal Tumors Tumors of specialized gonadal stroma include Leydig cell tumors. They most often occur in the 30. but approximately 20 percent of Leydig cell tumors are found in children. Fig. Benign Leydig cells cannot be histologically distinguished from malignant Leydig cells. are the least common (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . which probably have a histogenesis entirely different from that of tumors of adult testis. It apparently is unrelated to NSGCT tumors and is not associated with CIS. Choriocarcinoma. which measure up to 100 pm in diameter. The tumor consists of three types of cells: medium-sized principal cells. 12-23). Hormonally inactive tumors do not differ from those that are hormonally active. Typical Reinke crystals are sparse and are found in only one third of tumors. Spermatocytic seminoma. It is composed of three cell types ar- 66417308 : ¸Ÿ±U 24 ¥°Q . 12-21. Clear cytotrophoblastic and multinucleated syncytiotrophoblastic cells are surrounded by extravasated blood. Yolk sac tumor. Giant cells. Fig. Medium-sized principal cells with round nuclei and scant cytoplasm predominate. The cytoplasm may be vacuolated because of fat droplets or may contain brown pigment (lipofuscin). 12-22. small cells. Spermatocytic seminoma generally is a benign tumor.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . of progressive growth and metastasis. Most Leydig cell tumors are benign. Teratomas of infancy and childhood are benign tumors. The tumor is composed of epithelial cells forming solid nests and strands lining irregular cavities. 12-24). but 10 percent are malignant. ranged into dense sheets.

They occur in all age groups. 12-27). (3) sclerosing. and well-developed eosinophilic cytoplasm. the most common site of their occurrence. large cell calcifying type. The tumor is composed of solid nests of uniform cells that have vesicular round nuclei. Sertoli cell tumor. Histologically Sertoli cell tumors are composed of cells that form nests and cords reminiscent of seminiferous tubules (Fig. children. Histologically they are composed of nests of germ cells and sex cord cells surrounding round bodies composed of basement membrane–like material (Fig. which are known as tubular adenoma of Pick. Other variants are (1) tubular. Gonadoblastomas are tumors of dysgenetic gonads and are found in infants. Foci of calcification may be seen in epithelial nests. Tumors form cords and groups that resemble tubules. Sertoli cell tumors are composed of cells that resemble adult or fetal Sertoli cells. 66417308 : ¸Ÿ±U 24 ¥°Q . Invasive germ cell tumors may evolve from gonadoblastomas. The abundant stroma surrounding these nests may contain lymphocytes.247 Fig. which may invade and metastasize (Fig. Fig. 12-25. Sertoli cell. It contains prominent foci of calcification. Tumor is composed of tubules lined by Sertoli cells. Gonadoblastoma. and adolescents. and (5) anaplastic. 12-25). Tumor nests composed of germ cells and sex cord cells are surrounded by dense stroma that contains lymphocytes. Fig. often replacing them. The latter tumor is benign and resembles such tumors in the dysgenetic ovary. Areas of calcification are common. Clinically they are benign or malignant. (2) large cell calcifying. 12-26. Mixed Germ Cell Stromal Tumors Tumors composed of germ cells and sex cord stromal cells occur in two forms: gonadoblastoma and mixed germ cell tumor of the adult testes. (4) sex cord tumor with annular tubules.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Sertoli cells account for 1 percent of all testicular tumors. Leydig cell tumor. 12-24. prominent nucleoli. Fig. 12-26). Almost all gonadoblastomas described so far were found in persons who have a Y chromosome. 12-27.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

they often show nuclear enlargement. malignant tumors are called malignant mesotheliomas and are similar to peritoneal or pleural mesotheliomas. Shelled-out prostate contains numerous nodules. and the glands contain mucin. Histologically it appears as adenocarcinoma with papillary and tubular features (Fig. BPH is a common disorder. The hyperplastic basal cells usually are larger than normal. 12-28).248 Fig. Microscopically BPH typically is nodular and is composed of varying proportions of epithelium and stroma comprising fibrous connective tissue and smooth muscle (Fig. Tumors of Bete Testis. and Tunica Vaginalis Testis Tumors of rete testis are very rare. The enlarged prostate contains rubbery. yellow-gray nodules that bulge from the surface (Fig. 12-28. and stromal fibrosis. Adenomatoid tumors are small nodules that measure from a few millimeters to 5 to 6 cm in diameter. in which clear cells proliferate in an atrophic background. Cuboidal tumor cells form tubules and papillae that project into their lumen. elongated or spindled basal cells. Tissue spaces are lined by flattened epithelial cells surrounded by cords of cuboidal cells in connective tissue stroma. These lesions may be benign or malignant. Histologically these tumors are composed of epithelial cells arranged into cords or strands in dense connective stroma. TUMORS AND TUMOR-LIKE LESIONS OF THE PROSTATE The two most important diseases of the prostate are benign prostatic hyperplasia (BPH) and carcinoma of the prostate. The enlarged median bar may protrude into the urinary bladder. hyperchromatic nuclei. 12-29.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 66417308 : ¸Ÿ±U 24 ¥°Q . Such cells often show nuclear atypia. 12-30.000 partial prostatectomies per year in the United States. 12-30). but it is apparent that it is hormonally mediated and that androgens play an important role in its development. several histologic variants are recognized (Figs. 12-32). The mesothelium of the tunica vaginalis may give rise to benign and malignant tumors. The pathogenesis of BPH is not understood. 12-33 to 12-35). 3. Basal cell hyperplasia. The incidence of atrophy increases with age. lining glandlike or cystic spaces (Fig. Epithelial tumors of the epididymus resemble miillerian serous or mucinous adenomas and adenocarcinomas of the female genital system. 12-31). Benign tumors are called adenomatoid tumors. which is characterized by several layers of basal cells at the periphery of the prostatic glands and acini. which is characterized by small distorted glands. Atrophy.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . In addition to this most prevalent form of hyperplasia. 2. The prostate nodules may compress and deform the urethra (Fig. acting as a ball valve. accounting for approximately 400. Fig. Benign Prostatic Hyperplasia BPH is a disease of old age that results from proliferation of epithelial and stromal cells of the periurethral and transitional zone of the prostate. Fig. Epididymis. Carcinoma of rete testis is a tumor that occurs in men over the age of 40 years. Adenocarcinoma of rete testis.lined by flattened epithelium. The most important histologic variants are 1. Adenomatoid tumor. Benign prostatic hyperplasia (BPH). Postatrophic hyperplasia. 12-29).

Adenoid cystic–like tumor (adenoid basal cell tumor). Cribriform hyperplasia. 6. 12-34. circumscribed nodules composed of basal cells arranged into solid nests or cystically dilated glands.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Atypical basal cell hyperplasia. 66417308 : ¸Ÿ±U 24 ¥°Q . which consists of large. including clear cell cribriform hyperplasia. 12-32. Peripheral invasion may be seen. BPH. Fig. BPH. In contrast to basal cell adenoma. The cells from such glands usually have pale to clear cytoplasm and small uniform nuclei with inconspicuous nucleoli. Stromal cell nuclei vary in size and shape and appear hyperchromatic. Stromal connective tissue often traverses the adenomatous nodule. Peripheral basaloid cells have elongated nuclei and often show palisading. creating incomplete lobulation. 4. Basal cell adenoma. and the lumina surrounded by such cells vary in size and shape. The glands have a cribriform appearance. 12-35. which usually presents as a nodule composed of glands that have a distinctive cribriform pattern. 12-3I. Fig. atrophic variant. but there are no metastases. 5. The cell nests frequently are large and round to angular. Fig. 12-33. Stromal hyperplasia with atypia. 7. which is composed of nests of basaloid cells that infiltrate the stroma. The lesions typically are composed of hyperplastic glands and stroma. Cell crowding is prominent.249 Fig. Fig. BPH. which is composed of large basal cells with prominent nucleoli. The distorted glands are lined by flattened epithelium. Cribriform hyperplasia. Periurethral prostate appears nodular. this lesion is not circumscribed.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

The cells show nuclear atypia but are enclosed by a basement membrane (Fig. 11. according to the disease continuum concept. The glandular epithelium is distorted. however. including the ratio of stroma to epithelium and the degree of stromal cellularity. Adenomatous hyperplasia. and acini (Diagrams 12-2 and 12-3). High-grade PIN (formerly grades 2 and 3) corresponds to moderate to severe dysplasia and CIS. Benign and malignant phyllodes tumors are differentiated on the basis of a number of factors. mitotic activity. 12-36). D. Morphologic continuum from normal prostatic epithelium through increasing grades of PIN to early invasive carcinoma. Several architectural patterns. 1993. which is composed of fibroblasts and smooth muscle cells. a localized proliferation of small glands with varying degrees of nuclear atypia. this invasion occurs where the basal cell layer is disrupted. A.25 0 8. Brawer MK: Cancer 59:788. The precursor state ends when malignant cells invade the stroma. 1987. The basal cells react positively with antibodies to S-100 protein and smooth muscle–specific actin. or cribriform. Disruption of the basal cell layer accompanies the appearance of the architectural and cytologic features of high-grade PIN and appears to be a necessary prerequisite for stromal invasion. micropapillary. Carcinoma of the Prostate Prostatic intraepithelial neoplasia (PIN) represents the putative precancerous end of the morphologic continuum of cellular proliferations that occur within prostatic ducts.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . tufting. Carcinoma of the prostate is the most common form of cancer among men in the United States. The architectural patterns assumed by high-grade PIN. perhaps in response to lumina) carcinogens. and the stroma is exuberant and contains loose ground substance surrounding fibroblasts. 9. Sclerosing adenosis. which is a rare benign tumor that has the features of a fibroadenoma and resembles the more common breast tumors. ductules. B.Phyllodes tumor. 12-37). as evidence of myoepithelial metaplasia.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and cytologic atypia. Estimates are that in 1998 more than 45.) Diagram 12-3. appears proliferative. in which a localized but circumscribed proliferation of small glands within the prostate may be mistaken for carcinoma. and such stromal nodules should not be considered malignant. Notice that the dysplastic changes occur in the superficial (luminal) secretory cell layer.) 66417308 : ¸Ÿ±U 24 ¥°Q . is another possible preinvasive lesion (Fig.000 men will die of prostate cancer and A B C D Diagram 12-2. are recognized. lining slitlike spaces. hyperchromasia. Stromal hyperplasia with atypia composed of hypercellular nodules that show crowding of cells. There are. C. 10. no mitoses or necrosis. The stroma. (From Bostwick DG et al: Hum Pathol24:298. Flat pattern. Solid stromal nodules composed of smooth muscle cells are referred to as atypical leiomyomas. Low-grade PIN (formerly grade I) corresponds to very mild to mild dysplasia. such as flat. Cribriform pattern. and nuclear enlargement with atypia. Atypical adenomatous hyperplasia (adenosis). (From Bostwick DG. in which there is striking myoepithelial metaplasia of the basal cell compartment. Micropapillary pattern. Tufting pattern.

. It extends into the . B A Fig. Atypical adenomatous hyperplasia. Transition zone cancer is characterized by a bulging asymmetric mass that is present in association with BPH (arrow). Cross section of tumor Fig.nlA 16 ·IMIÃi : urinary bladder. yellowwhite mass in the lateral peripheral zone of the prostate. Carcinoma of the prostate. «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº ¸Ÿ±U 24 ¥°Q . 12-38. Small proliferating atypical glands form a cluster adjacent to the normal prostatic glands.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ Fig. The main tumor appears as a circumscribed. 12-39.Fig. Carcinoma of the prostate. A. B. PIN. Additional microscopic foci were found bilaterally in the periphery. Fig. This high-grade lesion has a flat pattern. 12-40. 12-36. shows that rectum and ºIzº yºHjn¼º 66417308it:has invaded the seminal vesicles and the fat tissue. 12-37. Carcinoma of the prostate.

prostatic carcinoma most often consists of small glands that exhibit a myriad of patterns. The clinical and pathologic features of these variants are summarized in Table 12-2. Carcinoma invades the seminal vesicles (Fig. 12-40).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . small gland subtype. 12-38 and 12-39) but also may occur in the transition zone.000 cases will be diagnosed. with fused glands. The diagnosis is dependent on confirmation of architectural and cytologic findings (Fig. 12-39) and may extend into other pelvic organs (Fig. 12-41. E. Gleason pattern 3. B. 12-41).252 more than 250. Carcinoma of the prostate tends to occur in peripheral parts of the gland (Figs. Several histologic variants of prostatic carcinoma are recognized. F. C. A. Gleason pattern 3. with little or no glandular differentiation. Microscopically. Gleason pattern I. Approximately 80 percent of all 80-year-old men have been found to have prostate cancer at autopsy. A B C D E F Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . indicating that only a fraction of these tumors become clinically apparent. 12-42. cribriform subtype. Gleason pattern 5. Carcinoma of the prostate. Gleason pattern 2.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and the salient features are shown in Fig. Gleason pattern 4. D.

Mucinous (colloid) adenocarcinoma. 12-41. Adenocarcinoma after androgen deprivation therapy. the composite histologic score is derived by including the scores for the dominant and secondary patterns.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .253 Carcinoma of the prostate is graded according to the system developed by Gleason (Table 12-3. Small cell carcinoma. F. Typical histologic patterns used for Gleason grading are shown in Fig. Diagram 12-4). 66417308 : ¸Ÿ±U 24 ¥°Q . Ductal (endometrioid) carcinoma. D.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The Gleason system takes into account the degree of glandular differentiation. A B C D E F Fig. accommodating tumor heterogeneity by assigning a primary pattern for the dominant grade and a secondary pattern for the nondominant grade. Variants of prostatic carcinoma. Urothelial carcinoma of the prostate. C. 12-42. Signet-ring cell carcinoma. E. A. B.

Am J Surg Pathol 18:1240-1246. Hum Pathol 25:1035-1042. unknown prognostic significance Adenocarcinoma after androgen deprivation therapy Histologic features: Shrunken. and smooth muscle) Clinical features: Poor prognosis. which rarely may extend along the ejaculatory ducts through the prostate to the seminal vesicles Clinical features: Unfavorable prognosis. apparently the same as sarcomatoid carcinoma Transitional cell carcinoma of the prostate Histologic features: May be primary in the prostate or prostatic urethra but usually is secondary to bladder involvement. undifferentiated carcinoma (high-grade neuroendocrine carcinoma) Histologic features: Identical to counterpart in lung and other sites Clinical features: Very poor prognosis. 1998. Reuter VE. PSA. Am J Surg Pathol 22:755-761. The impact of margin status. no long-term follow-up studies of this histologic pattern Further Reading Blute ML. main differential diagnosis is carcinosarcoma. 1993. Prostatic acid phosphatase. usually with typical acinar carcinoma. 1998. usually mixed with typical acinar adenocarcinoma Clinical features: Very rare in pure form. 1993. Ayala G. keratin proteins. but this pattern usually is a result of contiguous spread from rectal cancer Clinical features: Similar or slightly worse than those of conventional adenocarcinoma Signet-ring cell carcinoma Histologic features: Typical signet-ring cell features. Cancer 82:902-908.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Amin MB. 1998. important to distinguish from adenocarcinoma because tumor is refractory to androgen deprivation therapy Adenoid basal cell tumor (adenoid cystic carcinoma or basal cell carcinoma) Histologic features: Nests of basaloid round to oval cells. and other epithelial markers.25 4 Variants of Prostate Adenocarcinoma Ductal (endometrioid) adenocarcinoma Histologic features: Florid papillary. 1994. with mean survival less than 2 years.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Bostwick DG. SeayTM et al: Pathologic classification of prostate carcinoma. some with extraglandular mucin and mucin lakes. 1994. Bostwick DG. Pure squamous cell carcinoma is rare and carries a very poor prognosis. Bostwick DG. often with a cribriform pattern. 66417308 : ¸Ÿ±U 24 ¥°Q . closely packed glands with optically clear cytoplasm and inconspicuous nucleoli Clinical features: Unknown. Bostwick DG: Grading prostate cancer. Rare variant includes colonic-type carcinoma of the prostate. and others Mutinous (colloid) carcinoma Histologic features: At least 25 percent of tumor is composed of extracellular mucin. Cheville JC. Dundore PA. Wollan PC: Neuroendocrine differentiation in prostatic intraepithelial neoplasia and adenocarcinoma. may be associated with paraneoplastic syndromes such as Cushing syndrome. Cubilla AL. Tumor may be in situ or invasive within the prostate. 1998. with no definite metastatic tumors or deaths Lymphoepithelioma-like carcinoma Histologic features: Islands of closely packed glands set in a dense lymphocytic stroma Clinical features: Only one reported case. Am J Clin Pathol 102:S38-S56. Cubilla AL. Bostwick DG et al: Transitional cell carcinoma of the prostate. bone. look for luminal mucin and eosinophilic basement membrane–like material Clinical features: Very rare. or solid epithelial proliferation in large periurethral prostatic ducts Clinical features: Often presents at an advanced stage without elevation of serum PSA level Small cell. prostate-specific antigen. Hum Pathol 24:298-310. very poor prognosis Squamous cell carcinoma of the prostate Histologic features: Most commonly seen as mixed adenosquamous carcinoma but may be pure squamous cell carcinoma with typical malignant features Clinical features: Mixed adenosquamous and pure squamous cell carcinoma pattern may appear after irradiation or hormonal therapy for typical acinar adenocarcinoma. cartilage. Riveros M: Pathologic features of epidermoid carcinoma of the penis. Gregoire L et al: Basaloid squamous cell carcinoma: a distinctive human papilloma virus-related penile neoplasm: a report of 20 cases. it is refractory to androgen deprivation therapy Sarcomatoid carcinoma of the prostate Histologic features: Spindle cell carcinoma. immunohistochemical results may be positive for PSA. cribriform. with tumor cells showing PAP and PSA immunoreactivity. Barreto JE. J Urol Pathol 8:3-20. Am J Surg Pathol 17:753-776. 1994. inappropriate antidiuretic hormone secretion. Eble JN: Spermatocytic seminoma. Eble JN: Variants of prostatic hyperplasia that resemble carinoma. Dousa MK. Crawford BG. Dundore Petal: Architectural patterns of highgrade prostatic intraepithelial neoplasia. mucin may or may not be present. Cancer 82:703-707. Carcinosarcoma Histologic features: Adenocarcinoma with sarcomatous elements (for example. Clinicopathologic study of 50 cases. look for pagetoid spread. death in less than 48 months PAP. and some authors do not make this distinction Clinical features: Poor prognosis.

and margins of resection. 1995. 1994. Baldewijns M. 1998. Epstein JI: Pathology of prostatic intraepithelial neoplasm and adenocarcinoma of the prostate. Murphy WM: Prognostic factors in the pathological assessment of prostate cancer. Am J Surg Pathol 22:709-721. 1998.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . volume. Egawa S. Scully RE: Malignant mesothelioma of the tunica vaginalis. 1995. Gleason grading system of prostatic adenocarcinoma Epstein JI: Diagnostic criteria of limited adenocarcinoma of the prostate on needle biopsy. Heidenreich A. 1995. Berger Net al: Clinical value of fine-needle aspiration cytology and biopsy in the evaluation of male infertility. A comparative study of 48 infertile patients. Sesterhenn IA. Arch Pathol Lab Med 119:722-726. 1994. Jones MA. 1994. Histopathology 24:341-348. Ohori M. Mostofi FK. Lauweryns J: Florid basal cell hyperplasia of the prostate. Prognostic influences of stage. 1998. Hum Pathol 29:427-430. 1993.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Ayala AG: Histologic variants of adenocarcinoma and other carcinomas of prostate: pathologic criteria and clinical significance. 66417308 : ¸Ÿ±U 24 ¥°Q . A clinicopathologic analysis of 11 cases with review of the literature.25S Gleason Grading System for Prostatic Adenocarcinoma: Histologic Patterns Diagram 12-4. 1998. Am J Surg Pathol 17:1075-1098. 1998. not otherwise specified. J Urol Pathol 8:31-44. Mod Pathol 10:612-629. van de Voorde W. J Urol Pathol 2:223-234. Young RH. Hum Pathol 26:223-229. grade. Fendler J-P. Am J Surg Pathol 19:815-825. Ro JY. Young RH. A clinicopathologic analysis of 60 cases. Randolph TL. Moul JW: Prognostic risk factors that identify patients with clinical stage I nonseminomatous germ cell tumors at low risk and high risk for metastasis. Ulbright TM: Germ cell neoplasm of the testis. Cancer 83:1002-1011. Semin Oncol 21:527-541. Piaton E. tumor. Grignon DJ: Minimal diagnostic criteria for adenocarcinoma of prostate. Wheeler TM: Nodules resembling nodular hyperplasia in the peripheral zone of the prostate gland. Amin MB. Koelliker DD. Scully RE: Sertoli cell tumors of the testis.

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Intersex Syndromes Affecting Females. 13-1 to Fig.258 DEVELOPMENTAL DISORDERS The development of the female genital organs is complex for two main reasons: various parts of the system develop from distinct embryonic primordia such as genital ridges. and cloaca. 66417308 : ¸Ÿ±U 24 ¥°Q . Denver. 13-6. Robert H. Colorado. or Female Genitalia Courtesy of Dr. Shikes. and some of these conditions are illustrated in Figs. mullerian ducts.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and proper development de - pends on genetic and hormonal regulation.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Apparent Females. Clinically important conditions that involve abnormal sexual development are listed in Table 13-1.

Androgen insensitivity (testicular feminization) syndrome. Persistent miillerian duct syndrome (hernia uteri inguinalis) secondary to deficiency of miillerian inhibitory substance ( MIS).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Turner syndrome. Left testis has descended into the scrotum. 13-2. Histologically the testis consists of immature solid tubules lined by Sertoli cells. Fig. Bisected testis appears dark brown and contains hamartomatous nodules. Fig. The hernia sac of this phenotypic male contains endomyometrium. 13-3.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . B. Fig. 13-5. Streak gonad consists of ovarian type of stroma without follicles. Turner syndrome and gonadal dysgenesis. External genitalia in mixed gonadal dysgenesis. Fig. Streak gonad is attached to a hypoplastic uterus. 13-4. 66417308 : ¸Ÿ±U 24 ¥°Q . I3-I. Androgen insensitivity (testicular feminization) syndrome. Hilar vessels and rete ovarii are seen in the lower portion of the figure. 13-6. A. The dysgenic gonad contains a gonadoblastoma that appears like a small nodule.259 A B Fig. the right gonad was a streak in the abdomen. Fig.

vaginitis. The infections may be acute or chronic and are caused by various pathogens. wartlike excrescences (Fig. which is an infection of the internal genital organs. (Courtesy of Dr. The flagellate protozoan resides in the lumen of the vagina and maybe recognized in Pap smears (Fig. Fig. are found on the vulva but also may occur on the cervix. Exuberant keratotic papillary processes cover and obliterate large areas of the vulva. endometritis. The fallopian tubes are distorted. may occur in the form of a recurrent acute infection or as a chronic infection. including gram-negative coliform bacteria.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and thick-walled (Fig. Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and Ureaplasma. 13-8). Infection tends to occur in the form of vesicles. which are caused by a mixed flora. 13-10. cervicitis. Chlamydia. 13-7). swollen. Herpesvirus infection of the vulva. Kansas City. These infections. Histologically these lesions are squamous cell papillomas composed of cells that show typical nuclear and cytoplasmic changes (koilocytosis). In Pap smears the bacteria tend to adhere to squamous cells. 13-10. Herpes simplex virus 2 is a very common cause of infection of the vulva. PID. 13-12). or giant genital warts. Infection with the bacterium Gardnerella vaginalis is yet another cause of vaginitis and leukorrhea. which assume a peculiar appearance and are known as "clue cells " (Fig. Missouri. may cause tumor-like periovarian and peritubal abscesses or may spread to the peritoneal cavity. 66417308 : ¸Ÿ±U 24 ¥°Q . some of which have ruptured. 13-11). which ulcerate and then heal spontaneously (Fig. Mucosa shows numerous vesicles. Condyloma acuminatum.) Fig. 13-9. each supported by a fibrovascular connective tissue stalk. salpingitis. Trichomas vaginalis is the most common cause ofvaginitis in sexually active women. and salpingitis is almost a sine qua non for the diagnosis of PID. or they may involve the entire reproductive system as a chronic inflammation known as pelvic inflammatory disease (PID). Cynthia Caputo. gram-positive bacteria. Most of these infections are sexually transmitted or are related to infections in other parts of the body. 13-7. A). Condyloma acuminatum. or oophoritis. These lesions are caused by several types of human papillomavirus (HPV) and present as whitish-gray. Papillary processes are covered by orderly squamous epithelium. B).260 INFECTIONS Infections of the female reproductive system may be localized to external or internal genital organs and occur in an isolated form such as vulvitis. 13-9). 13-8. Intraluminal fibrosis and adhesions impart the tube's complex and multiglandular appearance on cross section (Fig. which may be recognized in histologic sections and Papanicolaou (Pap) smears (Fig. Infections tend to center on the fallopian tubes. Condyloma acuminatum.

261 A B Fig. 13-13). estrogen and progesterone act in a cyclic manner. and when the endometrial mucosa exceeds its capacity to respond. but it also may respond to male hormones. Fig. 13-I I. Excess of endogenous or exogenous estrogens leads to endometrial hyperplasia. B. 13-13. Chronic follicular salpingitis. Anovulatory cycles result in prolonged estrogenic stimulation. Vaginal infections. which is classified histologically as simple. I3-I0. most prominently in the uterus. This cycle ends at the time of menopause but also is interrupted by pregnancy and lactation and may be perturbed by exogenous hormones." Fig. During the reproductive life of a woman. HORMONALLY INDUCED CHANGES The entire female reproductive system normally is under the influence of female sex hormones. Lack of sex hormones or their excess may cause typical changes. corn - Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . swollen villi infiltrated with mononuclear cells.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Chronic salpingitis. it undergoes necrosis and a hemorrhage ensues (Fig. A Trichomonas vaginalis infection. A. and hormone antagonists. 13-12. Gardnerella vaginalis showing "clue cells. Both fallopian tubes are retortshaped and swollen and show adhesions to the ovaries. Epithelial hyperplasia may be prominent and may simulate adenocarcinoma. 66417308 : ¸Ÿ±U 24 ¥°Q . Anovulatory cycle. and various drugs. contraceptive pills. Protozoans are seen between the epithelial cells. Endometrium has failed to enter the secretory phase and shows ischemic stromal necrosis. hormone-like drugs. The lumen of the fallopian tube is partially obliterated by deformed.

B Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Endometrial glands are dilated and cystic. A Fig. B. Cytologic atypia is absent.262 Fig. Polycystic ovarian disease (PCOD). Complex hyperplasia with atypia. Prominent stroma and follicles are seen in the histology section. Cells within these closely packed glands lack polarity and show stratification and nuclear atypia resembling to some extent well-differentiated adenocarcinoma. On cross section the enlarged ovary has abundant central stroma and subcapsular follicles. 13-14.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . A. 66417308 : ¸Ÿ±U 24 ¥°Q . Simple (cystic) hyperplasia. There are thrombosed vessels in the abundant stroma between the glands. Complex hyperplasia (adenomatous hyperplasia). 13-16. 13-17. Fig. Glands are fairly widely separated by stroma but exhibit architectural complexity. 13-15. The follicles show theca cell hyperplasia and atrophy of the granulosa cells.

which may present clinically as leukoplakia or kraurosis vulvae. measuring only a few millimeters in diameter. Larger nodules (endometriomas). such as lichen plan us et acuminatus atrophicans. VIN with anal interepithelial neoplasia (VIN-AIN). traepithelial neoplasia (VIN). ovary. a term that has replaced older terms such as carcinoma in situ. Hyperthecosis may be seen in deeper parts of the cortex. VIN. the dysfunctioning ovaries are enlarged and contain numerous follicular cysts (Fig. PCOD may be treated hormonally. which respond to hormonal stimulation and tend to become hemorrhagic at the time of normal menstruation. Ovarian endometriosis. VIN. Many atypical cells are scattered through all layers of the epidermis. but in some cases. "Chocolate cyst. 13-19. it may progress to endometrial carcinoma.g. 13-18. 13-18). Endometriosis is a disease of unknown etiology. Carcinoma of the vulva is believed to begin as an intraepithelial malignancy that progresses over time to invasive cancer (Fig. which are composed of nonluteinized granulosa cells and an outer layer of luteinized theca cells.. A.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and erythroplasia of Fig. Bowen disease. represent the most important neoplastic vulvar lesions. and less often on other sites. Most foci of endometriosis are small. intestinal adhesions) may require surgery. Disturbances of this system are considered to be the major cause of polycystic ovarian disease (PCOD). pelvic peritoneum. or complex with atypia (Figs. 13-17). but large endometriomas and some complications (e. vulvar in- B Fig. 13-14 to 13-16). In this relatively common hor- A monal disorder. 13-19). especially if it is associated with atypia." B. It involves the left labium minus. Histologically the nests are composed of endometrial glands and stroma. which usually are found on the ovary. Histologically endometriosis consists of endometrial glands and stroma. These lesions must be distinguished clinically and pathologically from viral warts (condyloma acuminatum) and nonneoplastic vulvar dystrophies. Endometriosis may be treated hormonally.263 plex. 13-20. The ovaries function as part of the hypothalamicpituitary-ovarian and adrenal system.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . which is associated with menstrual irregularities and infertility. Endometrial hyperplasia is a reversible benign lesion. are surrounded by dense cortical stroma that may form an external fibrous capsule. The follicles. Lesion is white and well circumscribed. albeit with varying results. Fig. It is characterized by the appearance of ectopic endometrial tissue on the serosal surface of the fallopian tube. 66417308 : ¸Ÿ±U 24 ¥°Q . are filled with old blood and are colloquially called " chocolate cysts " (Fig. TUMORS OF THE VULVA Squamous cell carcinoma and its precursor lesions.

13-21). The neoplastic process tends to spread horizontally. It usually affects women under the age of 40 years. 13-23). Squamous cells of the epidermis itself are histologically benign and compressed by tumor. Radical vulvectomy and bilateral inguinal lymphadenectomy were performed for this squamous cell carcinoma of the left labia. myxoid mass that is composed of hypocellular myxoid tissue with numerous muscular medium-sized arteries (Fig. 13-21. 66417308 : ¸Ÿ±U 24 ¥°Q . The epithelium of hair follicles and apocrine glands also is typically involved. The tumor may recur locally but metastases have not been reported. Fig. 13-20).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . such as melanoma. Invasive cancer usually presents as indurated ulcers (Fig. Histologically the epidermis contains pale vacuolated adenocarcinoma cells scattered between the compressed but otherwise normal squamous cells (Fig. It may involve large portions of the vulva and may even extend to the anus (Fig. 13-23. Neoplastic cells infiltrate the epidermis in small clumps. circumscribed. Locally invasive aggressive angiomyxoma is a rare but i mportant lesion of the labia. Invasive squamous cell carcinoma of vulva. Fig. An underlying adenocarcinoma is found in approximately one third of all cases. Grossly it appears as an eczematoid patch with discrete borders and white keratotic areas and typically begins on the labia majora. are rare. Other tumors of the vulva. and the underlying dermis is not involved by cancer cells. The tumor cells are fibroblasts and myofibroblasts that lack significant nuclear atypia but nevertheless have a propensity to invade local tissues. and stromal neoplasms. 13-22. The lesion appears as a soft. In the presence of invasive growth and metastasis the tumor has a poor prognosis. The tumor appears ulcerated. Carcinoma of the vulva. Vulvar Paget disease. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . but they also occur in the pelvic and abdominal lymph nodes and hematogenously may reach distant organs. Vertical growth with invasion of the underlying stroma ensues in untreated cases (Fig. 13-22). Metastases are found first in inguinal lymph nodes.264 Queyrat. may be graded histologically on the basis of the extent of cytologic atypia. adenocarcinoma of Bartholin glands. Extramammary Paget disease is an intraepidermal neoplasm that has features of adenocarcinoma. 13-24).

well-circumscribed mass. Fig. 13-25). A. B. 13-26. Clear cell adenocarcinoma of the vagina subsequent to in utero exposure to diethylstilbestrol. 13-25. Aggressive angiomyxoma. Carcinoma appears as an ulcerated nodule (right). Tumor cells are rich in glycogen. 66417308 : ¸Ÿ±U 24 ¥°Q . Other tumors are less common but deserve to be mentioned because of their unique features.265 A TUMORS OF THE VAGINA The most common malignant tumor of the vagina is squamous cell carcinoma. Histologically the lesions are composed of glands lined by mucinous columnar epithelium (Fig. soft. and electron microscopy (EM) shows that they have prominent apical microvilli. Fig. pale pink normal vagina. 13-24. which has the same features as the more common carcinomas of the vulva and the cervix.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Vaginal adenosis is a benign condition that has been reported in young women who were exposed to diethylstilbestrol (DES) during fetal life. Mucosa of the exocervix and adjacent vagina contains mucinous glands in place of normal squamous epithelium. Invasive adenocarcinoma may evolve from some of these lesions (Fig. The tumor presented as a large. in contrast to the more opaque. 13-27). 13-26). Histologically these tumors are clear cell adenocarcinomas and are similar to those in the ovary or uterus (Fig. Vaginal adenosis. myxoid. On gross examination foci of vaginal adenosis appear red and velvety. The cervix (left) shows an abnormal configuration. The tumor occurs in young women (median age 30 years) and is located in or just above the hymenal ring. Mucus is PAS-positive (red). Benign mixed tumor of the vagina is a rare tumor that may be confused with sarcoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Hypocellular myxoid tissue surrounds numerous medium-sized blood vessels. Histologically this small (1 to 5 cm in di- B Fig.

13-28. Clear cell adenocarcinoma arising in vaginal adenosis from a young women exposed in utero to diethylstilbestrol. adenocarcinomas are considerably less common. Fig. Cells show no significant atypia. These lesions maybe recognized by colposcopy (Fig. 13-27. Embryonal rhabdomyosarcoma (botryoid sarcoma) is the most common malignant vaginal tumor in girls under the age of five years. Tumor cells may show crossstriations and react with antibodies to desmins. 13-30). Both the spindle-shaped cells and the epithelial cells appear to be of epithelial origin. The tumor is composed of embryonic rhabdomyoblasts. CIN II. or CIN III. Fig. 13-28). 13-29. Embryonal rhabdomyosarcoma of vagina (botryoid sarcoma).266 ameter) tumor is composed of bland spindle-shaped " stromal" elements admixed with epithelial foci (Fig. A mixture of stromal and squamous cells is seen in the submucosa. Embryonal rhabdomyosarcoma of the vagina (botryoid sarcoma). Fig. 13-29). Tumors also originate from the squamous epithelium itself. It is graded on the basis of cellular and architectural atypia as CIN I. Benign mixed tumor of the vagina. but the neoplastic transformation of the glandular epithelium of the endocervix is less common. A fleshy mass protrudes into the lumen of the vagina. The tumor is composed of tubulocystic glands. Carcinoma of the cervix begins as an intraepithelial neoplasm that is termed cervical intraepithelial neoplasia (CIN). The tumor presents as a grapelike polypoid mass protruding from the vagina (Fig. indicating that they represent rhabdomyoblasts. TUMORS OF THE CERVIX Most tumors of the cervix originate from the squamocolumnar junction between the squamous epithelium of the exocervix and the glandular epithelium of the endocervix (transitional zone).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 66417308 : ¸Ÿ±U 24 ¥°Q . 13-30. 13-31). Histologically it is composed of malignant spindle-shaped cells that forming dense aggregates that are separated from the surface squamous epithelium by a lucent loosely textured zone ( "cambium layer " ) (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig. Most tumors are classified as squamous cell carcinomas.

and simple koilocytotis now are grouped under one heading. Fig. The lesions that formerly were designated CIN I. is characterized by koilocytotic atypia and usually is related to HPV 6 or HPV I I infection. Clear cell carcinoma of the cervix may be similar to Fig. therapy. 13-33. It is becoming increasingly obvious that LSIL represents a productive viral infection. HSIL. HSIL (CIN II) of the cervix. 13-31. mild koilocytic dysplasia. HPV 6 and HPV 11 account for 70 percent to 90 percent of HPV associated with flat and exophytic condy- lomas. and prognosis. an indurated mass. Carcinoma of the cervix spreads by direct invasion of contiguous tissues and lymphogenously to local lymph nodes. 13-32. Lesions that previously were classified as CIN II and CIN III are called high-grade squamous intraepithelial lesion (HSIL) (Figs. High-grade lesions are aneuploid and are more likely to progress. but they vary considerably in size and shape and have a relative abundance of cytoplasm.267 The National Cancer Institute recently proposed a new terminology (Bethesda System) according to which the three-grade CIN scheme was reduced to two grades of squamous intraepithelial lesion (SIL). also known as flat condyloma. Staging and grading of cervical cancer are important for clinical assessment. Adenocarcinoma of the cervix occurs in several histologic patterns. and the two entities do not appear to be related. This lesion. Abnormal squamous epithelial cells appear atypical. 13-34. Invasive carcinoma of the cervix may appear as an ulcer. 13-35). Maturation is evident at the surface. 66417308 : ¸Ÿ±U 24 ¥°Q . Distant metastases are found at autopsy in the lungs and liver in 25 percent of patients. Fig. whereas HSIL is a true neoplastic intraepithelial lesion. 13-33 and 13-34). HSIL (CIN III) of the cervix. or a polypoid cauliflower-like lesion (Fig. Low-grade lesions usually are diploid or polyploid and tend to regress. 13-32). The main reason for the change in terminology is the apparent differential distribution of HPV in these lesions. low-grade squamous intraepithelial lesion (LSIL) (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . HPV 16 is found in nearly one half of CIN III and invasive carcinomas. Fig. Colposcopy shows a mosaic pattern and accentuated punctate vessels against a background of white-red opaque epithelium. There is no evidence of maturation. Abnormal cells have uniform size and shape and relatively scant cytoplasm.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . LSIL (CIN I) of the cervix.

carcinosarcomas. 13-38 and 13-39). Ulcerated invasive lesion extends into the endocervix. Other variants. Malignant mixed miillerian tumors. Villoglandular adenocarcinoma of the cervix. clear cell carcinoma. The more aggressive forms of endometrial cancer (serous.268 Fig. Endometrial Adenocarcinoma Adenocarcinoma of the uterus occurs in menopausal and postmenopausal women. Villoglandular papillary adenocarcinoma is a newly recognized variant. Classification of Endometrial Carcinoma* Endometrioid Typical Variants With squamous differentiation Secretory carcinoma Ciliated carcinoma Serous papillary adenocarcinoma Clear cell adenocarcinoma Mucinous adenocarcinoma Squamous cell carcinoma Mixed carcinomat Un_ i _. 13-37. The tumor resembles a colonic polyp. slightly atypical cuboidal cells (Fig. No stromal invasion is seen. Endometrioid carcinoma. and clear cell carcinoma) that occur in women of reproductive age do not seem to be related to hyperestrinism. 66417308 : ¸Ÿ±U 24 ¥°Q .OF THE UTERUS Tumors of the body of the uterus may arise from endometrial glands. and smooth muscle tumors similar to those in the body of the uterus rarely are found in the cervix. Several histologic patterns are recognized (Table 13-2). Estrogenic stimulation plays an important pathogenetic role in lowgrade ( "endometrioid") cancer of post menopausal women and cancer that is associated with endometrioid hyperplasia. but the stage of the tumor is the most important prognostic parameter (Table 13-3). 13-36. Obvious myometrial invasion in seen. t o carcinoma containing more than 10 percent of a second cell type. It is characterized by exophytic growth. such as serous papillary carcinoma. and in the United States it is estimated that 1 in 100 women will de - velop endometrial cancer during her life span.tiated carcinoma *Modified from the World Health Organization and International Society of Gynecological Pathologists classifications of endometrial carcinoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and adenocarcinoma with squamous differentiation. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 13-37). In industrialized countries its incidence has surpassed the incidence of cervical cancer. Endometrial carcinoma presents as an intrauterine lesion that invades the myometrium and extends into the cervix (Fig. or the myometrium. TUMORS . 13-40 to 13-42). is graded histologically according to the scheme adopted by the International Federation of Gynecology and Obstetrics (FIGO) (Figs. adenosquamous. the most common subtype. Fig. Histologic features have prognostic implications. Invasive squamous cell carcinoma of the cervix. endometrial stroma. 13-36). elongated fibrovascular papillae that are lined by well-differentiated. 13-35. A well-differentiated mucinous adenocarcinoma may be difficult to distinguish from reactive changes in the normal endocervix. Adenocarcinoma of the endometrium. the clear cell carcinoma of the vagina or endometrium. have typical histologic features (Figs. The tumor fills the endometrial cavity.

269 Fig. Clear cell carcinoma. Fig. 13-40. The glands are malignant but the squamous epithelium appears benign. 13-41. Serous papillary adenocarcinoma of the endometrium. International Federation of Gynecology and Obstetrics (FIGO) Staging of Endometrial Adenocarcinoma (1988) Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Tumor cells have cytoplasmic vacuoles. Fig. Glands show back to back and gland within gland arrangement. FIGO grade I.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 13-39. 13-42. Endometrial adenocarcinoma. Adenocarcinoma with squamous differentiation (adenoacanthoma). Thick connective strands forming papillae are lined by stratified anaplastic cells. Glands are lined by clear hobnail-like cells. Endometrial adenocarcinoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . FIGO grade I. Fig. secretory type. 13-38.

These tumors are composed of cells that resemble endometrial stromal cells even less than those of the low-grade ESS (Fig. 13-45). 1992) Fig. well-circumscribed masses that often resemble leiomyomas but differ from them by their yellow color and softer consistency.270 Endometrial Stromal Tumors Tumors that originate from the endometrial stromal cells include benign endometrial stromal nodules. Low-grade ESS occur as grossly circumscribed nodules with or without extensive intravascular extension (endolymphatic stromal myosis). The lesions often are found under the serosa of the uterus and are called plexiform tumorlets. Endometrial stromal nodule. 13-43. 13-44). The large multinodular tumor has a variegated cross section with areas of hemorrhage and necrosis. Histologically these nodules resemble endometrial stroma. 13-45. 13-46. with numerous evenly distributed small vessels. Fig. Tumor cells resemble endometrial cells of proliferative endometrium and are separated by a network of small blood vessels. Prat J: Int J Pathol 11:293. A well-circumscribed nodule protrudes into the endometrial cavity. Mitotic figures may be prominent. Malignant mixed miillerian tumor. The most characteristic feature is the presence of numerous wormlike masses that protrude from the vascular spaces on cut surface. the cells of ESS infiltrate the adjacent myometrium (Fig. Low-grade ESS. (From Lloreta J. Stromal lesions of distinct trabecular architecture may form a variety of glandlike structures and may mimic sex cord stromal ovarian tumors. There are Fig. Benign endometrial stromal nodules form single. Microscopically these tumors also are composed of endometrial stromal cells that resemble the stroma of proliferative stage endometrium or that of benign endometrial stromal nodules. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Low-grade ESS. 13-43). The tumor was limited to the endometrium. The myometrium appears infiltrated with irregularly contoured aggregates of tumor cells that resemble endometrial stromal cells. They most often are located in the myometrium.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and high-grade ESS. but some nodules protrude into the endometrial cavity (Fig. High-grade ESS are malignant tumors that form one or more nodules and polypoid masses that protrude into the lumen and invade the myometrium. 66417308 : ¸Ÿ±U 24 ¥°Q . 13-44. In contrast to these benign lesions. Similar his- tologic elements may be found in typical endometrial stromal nodules and ESS. low-grade endometrial stromal sarcomas (ESS).

Mitotic figures are sparse. which may be multiple. usually there are more than 10 mitotic figures per 10 high-power fields (HPFs). and mitotic figures are prominent. Fig. whereas the heterologous elements include cells that resemble chondrosarcoma. light gray nodules distorting the uterus. Histologically they are composed of poorly differentiated. . The histologic appearance of the tumor is. firm nodules that appear gray-white and have a characteristic whorled appearance on cross section. These nodules often are multiple and vary considerably in size and shape (Fig. In sagittal section there are numerous. Mixed mullerian tumors are composed of both epithelial and mesenchymal cells and are classified as carcinosarcomas. Histologically they are composed of smooth muscle cells that have typically elongated "cigar-shaped" nuclei and eosinophilic cytoplasm that has no distinct borders (Fig. Miillerian adenosarcoma is a variant in which the homologous stromal elements form a sarcomatous stroma and the glandular epithelium is benign (Fig. more reliable than its mitotic rate as a predictor of the biologic behavior of ESS. Malignant mixed miillerian tumor. 13-50). A few more aggressive tumors of this type have been reported. 13-49. Several histologic variants are recognized. 13-49). 13-46).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and lack of extensive vascular network provide clues to the leiomyomatous nature of these lesions. It presents in the form of well-circumscribed. Apparently benign glands are surrounded by neoplastic stromal cells. They show low mitotic activity and generally are benign. well. This lesion occurs in premenopausal women and occasionally is associated with exogenous progestin intake. often papillary endometrial adenocarcinoma and homologous or heterologous malignant stromal cells (Fig. Typical lesions protrude into the endometrial cavity as large irregular polypoid masses (Fig. 13-48. fascicular growth pattern. rhabdomyosarcoma. or osteosarcoma cells. solid. 13-47). Lipoleiomyomas contain a sizable adipose tissue component. however. Fig. 13-48). Multiple leiomyomas. 66417308 : ¸Ÿ±U 24 ¥°Q . and the stroma consists of large pleomorphic spindle cells. Tumors of the Myometrium Tumors of the myometrium originate from smooth muscle cells and thus are classified as leiomyomas or leiomyosarcomas. Bizarre (symplastic) leiomyomas have a frightening appearance on microscopy because of many giant cells with very large. Adenosarcoma. cytologically malignant-looking nuclei. 13-47. Cellular leiomyomas are highly cellular and may resemble endometrial stromal nodules.circumscribed. but they contained more numerous mitoses. Leiomyoma is the most common benign tumor of the uterus. By location they may be submucosal. intramural.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Homologous stromal cells resemble endometrial stroma. or subserosal. Nevertheless. These tumors have a poor prognosis. the fusiform nuclei. Carcinomatous component is of the papillary serous type. Fig.271 prominent small blood vessels between the cells. Epithelioid leiomyoma (leiomyoblastoma) is composed of cells that have clear glycogen-rich cytoplasm and resemble leiomyoblastomas of the gastrointestinal tract.

13-54. Leiomyomatosis peritonealis disseminata. solitary mass shows foci of necrosis. Intravascular cast of smooth muscle cells contains prominent blood vessels. 13-50. Mitotic figures are present. B. Intravenous leiomyomatosis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Spindle cells are arranged in a typical interlacing pattern. Omentum contains multiple nodules of smooth muscular tissue.272 A Fig. Leiomyosarcoma. A. B Fig. Leiomyoma. 66417308 : ¸Ÿ±U 24 ¥°Q . Intramural." Fig. 13-5 I . Leiomyosarcoma of the uterus. 13-52. Fig. Elongated nuclei have rounded ends and are described as "cigar-shaped. grossly simulating metastatic leiomyosarcoma. 13-53. Spindle-shaped nuclei show marked hyperchromasia. Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

These lesions are composed of benign smooth muscle cells and have no mitotic activity. Tumors that are mitotically less active may pose diagnostic problems. Borderline malignant tumors more often are multilocular and World Health Organization Classification of Ovarian Tumors 66417308 : ¸Ÿ±U 24 ¥°Q . On cross section they appear yellow or brown and show numerous areas of hemorrhage and necrosis (Fig. usually found in the pelvic veins. 13-56). TUMORS OF THE OVARY Ovarian tumors occur in many forms and generally are classified as originating from the surface epithelium. Intravenous leiomyomatosis is characterized by the presence of grossly visible intravenous proliferation of benign smooth muscle cells. They account for one third of all uterine sarcomas. 13-53). and peritoneal leiomyomatosis. metastasizing leiomyomatosis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Similar epithelium may cover the external surface of the cysts. sex cord stromal cells. which may be ciliated or pseudostratified as in the fallopian tube (Fig. Serous cystadenoma is a benign cystic mass that has one or multiple cavities filled with clear serous fluid (Fig. There typically is focal or diffuse hypercellularity and marked nuclear atypia. It has been recommended that tumors that have more than 5 mitotic figures per 10 HPFs and show nuclear atypia should be designated leiomyosarcoma. 13-54). 13-52).273 Some smooth muscle cell tumors may behave aggressively. and malignant. those that have the same mitotic rate but show no nuclear atypia are designated mitotically active leiomyomas. Histologically they are composed of spindle-shaped cells arranged into fascicles (Fig. Metastasizing leiomyoma is a term used to describe a benign uterine leiomyoma that is associated with secondary nodules in the lymph nodes or the lungs. typically limited to peritoneal cavity. These variants include intravenous leiomyomatosis. Histologically the cavities are lined by cuboidal or low columnar uniform epithelium. Leiomyosarcomas are rare malignant tumors of smooth muscle cells. 13-51). Peritoneal leiomyomatosis refers to extensive proliferation of histologically benign smooth muscle cells. Such intravascular masses usually consist of benign smooth muscle cells and prominent blood vessels (Fig. Papillary processes are common and may be complex. Mitotic figures are found at a rate of more than 10 per 10 HPFs. Such intravascular masses usually consist of benign smooth muscle cells that form microscopic or macroscopic nodules on the peritoneal surfaces (Fig. and germ cells (Table 13-4). soft. Some of them are related to hormonal stimulation or pregnancy and may regress following cessation of hormonal stimulation or termination of pregnancy. These lesions most often occur in pregnancy or under hormonal stimulation and tend to regress after the hormonal stimulus is withdrawn. 13-55).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . On gross examination they usually appear as solitary. belying their benign microscopic appearance. Estimates are that 1 in 800 smooth muscle cell tumors of the uterus is malignant. intramural masses that distort the uterus. Serous Tumors Serous tumors are classified as benign. borderline malignant.

Serous cystadenoma. 13-58. B. a multilocular cystic mass with spaces lined by papillary epithelial masses. It is filled with clear serous fluid and appears translucent. A B Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig.274 Fig. 13-55. There still are several smaller unopened cysts. Serous cystadenoma. 66417308 : ¸Ÿ±U 24 ¥°Q . Cyst is lined by cuboidal cells that have round or elongated regular nuclei with evenly distributed chromatin. Borderline serous tumor of ovary. Prominent papillae lined by cuboidal epithelium project into the lumen of the cystic tumor. Fig. Serous borderline tumor of the ovary. Fluid has flowed out from the main cyst.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . A. 13-56. The cystic mass has a smooth surface. 13-57.

B. interspersed with neuroendocrine and even Paneth cells. 13-58). 13-62). Invasive implant of serous borderline tumor. Mucinous cystadenoma of the intestinal type. 13-57). 13-60. Fig. cystic.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and contain many solid areas (Fig. the former are further divided into epithelial and desmoplastic subtypes (Fig 13-59). invade stroma. mucus-filled masses. Serous carcinoma of the ovary. 13-59. Peritoneal seeding and ascites often are present. The cells of these implants resemble the original tumor and may show mild to moderate atypia. A. and in approximately 30 percent of cases there are peritoneal implants. Fig. but it still shines through the wall of smaller cysts. Papillae fill submesothelial invaginations. 66417308 : ¸Ÿ±U 24 ¥°Q . which on cross section may be classified as unilocular or multilocular (Fig. Malignant serous tumors (serous cystadenocarcinomas) form papillae. and stratification (Fig. 13-61). Papillae are lined by cells that show atypia. mitotic activity. Such cells have basally located nuclei and apical cytoplasm filled with mucus (Fig. 13-63 and Fig. The cavities are lined by tall columnar epithelium that resembles endocervical glands. More often the epithelium may contain goblet cells. Serous borderline tumor of the ovary. Mucus was removed from the main cavity. 13-61. Microinvasion of the stroma may be present.275 form complex papillae on their internal surface (Fig. atypia. 13-60). and resembles intestinal epithelium. Such tumors differ from benign cystadenomas in that they show more nuclear unrest.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Mutinous Tumors Mucinous tumors typically are large. This carcinoma is composed of glands that contain papillary projections lined by cuboidal cells.tumors may arise from the peritoneum without ovarian neoplasia. Borderline mucinous tumors account for 40 percent to 50 percent of all mucinous malignant tumors. and focal invasion (Figs. Similar. Paratubal implant of serous borderline tumor of noninvasive epithelial type. Peritoneal implants are classified as invasive or noninvasive. Tumor nests resemble low-grade serous carcinoma but are composed of cells that show no atypia and are devoid of mitotic figures.

The tumor is a solid mass. Mucinous intestinal cystadenoma of borderline malignancy. Fig. Mucinrich goblet cells line the central cavity of this cystic tumor. Fig. Mucin-rich cells pile up within atypical glands invading the stroma. Fig. Mucin-rich tumor cells line edematous papillae that are infiltrated with neutrophils. 13-64. The tumor appears as a solid mass. 13-66. 13-65. Mucinous cystadenoma of the intestinal type. 13-67. Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Endometrioid adenocarcinoma. Mucinous intestinal cystadenocarcinoma.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Mucinous intestinal cystadenocarcinoma. Irregular glands are lined by relatively uniform mucus-rich cells.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Mucinous endocervical (miillerian) cystadenoma of borderline malignancy. Fig. There is no stromal invasion. FIGO grade II. 13-62. 13-63.276 Fig.

multifocal primaries. There often is a simultaneous mucinous tumor of the appendix. Histologically it is identical with uterine endometrial adenocarcinoma. 13-70. the stroma of the tumor may be luteinized and may resemble ovarian stroma. 13-66). borderline malignant.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Instead of being desmoplastic. and endometrium. Well-differentiated endometrioid adenocarcinoma of the ovary. Empiric criteria have been proposed. These tumors are called adenofibromas and may be classified as benign. 13-68. The similarity is most evident in well-differentiated tumors. Fig. or if the neoplastic glands have a cribriform growth pattern.makes it almost impossible to determine whether there is any true invasion (Fig. a metastasis of the ovarian tumor to the appendix. and carcinoma is diagnosed if the tumor forms layers that are four or more cells thick. Endometrioid tumors that have a malignant stromal component are classified as carcinosarcomas and are equivalent to uterine malignant mixed mullerian tumors. Extraovarian spread of mucinous tumors results in peritoneal seeding and mucinous ascites known as pseudomyxoma peritonei. The distinction between borderline malignant and low-grade malignant mucinous tumors may be difficult. Histologically they resemble endometrioid adenocarcinomas of the uterus and are graded the same way (Fig. Such criteria are most easily applied to endometrioid tumors that have a prominent stromal component. Recently it was proposed that intestinal mucinous borderline tumors may be separated from well-differentiated carcinomas by quantitative nuclear morphologic analysis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . or vice versa. They are so named because of their histologic resemblance to uterine adenocarcinomas. which together with additional foci of squamous differentiation may be the only clue to the true nature of such tumors. Mucinous cystadenocarcinomas are obviously malignant tumors that contain large solid parts or may be composed entirely of solid tissue (Fig. but they are rare. that is. 66417308 : ¸Ÿ±U 24 ¥°Q . Endometrioid Carcinoma Fig. but it is inconsequential from the clinical point of view. Tubulocystic pattern is identical to that found in clear cell carcinomas of the vagina. 13-69. Sarcoma-like stromal reaction occasionally is seen. cervix. which. Less-differentiated lesions may have a typical endometrioid appearance only focally. Histologically such tumors are adenocarcinomas lined by mucus-producing cells. if it forms finger-like projections of solid cellular masses without connective tissue support. The tumor contains glands and squamous morules with central necrosis. Endometrioid adenocarcinomas present as solid or partially cystic ovarian masses (Fig. 13-67). Clear cell adenocarcinoma. 13-68). Borderline tumors of the endocervical type have a better prognosis than those of the intestinal type. In 85 percent of cases cysts are lined by intestinal-like epithelium. The main reason for this diagnostic dilemma lies in the nature of stromal reaction to the tumor. Endometrioid adenofibroma of borderline malignancy. or malignant (Fig. and there is controversy over whether these represent two independent primary tumors. Endometrioid carcinomas account for 20 percent to 30 percent of all ovarian cancers. 13-65). The solid area may contain anaplastic carcinoma or rarely sarcoma. 13-69). Fig.277 13-64). Adenosarcomas and endometrial stromal sarcomas also occur in the ovary. The criteria for borderline malignant endometrioid tumors are not well established.

although 90 percent of patients survive 10 years after surgery. Sex Cord Stromal Tumors Sex cord stromal tumors originate from specialized and nonspecific stroma of the ovary. Other unfavorable signs. fibrotic nodules. The cells lining the central lumen may be filled with mucin. Accordingly. Late recurrences may occur even beyond that period. and no invasion of the stroma is seen.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 13-71). luteinized and nonluteinized fibroblastic stromal cells. usually as adenofibromas. On gross examination they appear as solid or partially cystic masses. Tumors may have a trabecular. but these descriptive terms do not have significant clinical implications. a variant that is found in girls. The epithelial nests may be solid or may have a central lumen that contains dense eosinophilic material or mucus. 13-70). theca cells. The association between clear cell carcinoma and endometriosis is six times greater than that of ovarian carcinomas in general. and transitional cell carcinomas that are of surface epithelial origin and are unrelated to a preexisting Brenner tumor. or gyriform pattern. In malignant Brenner tumors the nests have features of higher grade transitional cell malignancy (Fig. The surrounding stroma often is hyalinized and may contain foci of calcification. transitional cell carcinomas that originate from Brenner tumors (malignant Brenner tumor). which are not consistently reliable predictors Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Tumor cells have oval nuclei with prominent clefts (coffee bean– shaped nuclei) and often are arranged into rosette-like structures.278 Clear Cell Carcinoma Clear cell carcinomas account for approximately 10 percent of all ovarian cancer. Brenner tumor is a benign lesion that accounts for 2 percent to 3 percent of all ovarian tumors. the tumors are composed of cells that resemble granulosa cells. Juvenile granulosa tell tumor. Approximately 75 percent of all granulosa cell tumors are estrogenic. 13-72). The tumor cells are polygonal and have grooved nuclei and clear cytoplasm. Less than 2 percent of all Brenner tumors are classified as borderline malignant or overtly malignant. 13-72. Brenner tumor. but such transitional carcinomas of the ovary are rare. 13-73). Less than 5 percent are bilateral. whereas others are either nonfunctioning or androgenic. has a distinct histologic appearance. The most common pattern is that of small tubules and cysts lined by a single layer of cuboidal hobnailed cells (Fig. Sex cord stromal tumors account for most hormonally active ovarian tumors. Fig. In 25 percent of cases Brenner tumors are found within mutinous ovarian tumors. Transitional Cell Tumors Transitional cell tumors include benign Brenner tumors. Microfollicular and macrofollicular patterns recapitulate the histologic features of graafian follicles. 13-74). which are reminiscent of those found in normal graafian follicles (Fig. 13-71. Microscopically they are characterized by masses of large epithelial cells with clear cytoplasm arranged into glands or solid nests. The epithelial component of borderline malignant Brenner tumors resembles grade I papillary carcinomas of the urinary bladder. Solid tumor nests are enclosed by fibroblastic stroma. All granulosa cell tumors should be considered potentially malignant. and hilar luteinized cells. Diffuse or sarcomtoid tumors may behave more aggressively. Several microscopic patterns are recognized. Cells in the nest to the left show significant atypia. Benign and borderline clear cell tumors rarely occur. Granulosa cell tumors are composed of cells that resemble normal granulosa cells. It consists of cells that often are luteinized and form rudimentary follicles or solid masses (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Granulosa cell tumors usually present as solid masses with some cystic parts. which histologically are composed of nests of transitional epithelium surrounded by dense fibrous stroma (Fig. On cross section solid areas appear brown or grayish-yellow and typically contain blood clots. known as Call-Exner bodies. The most consistent indicator of aggressive behavior is the presence of metastases or invasion of surrounding tissues outside the ovary. Tumors typically appear as small. insular. Similar tumors may originate from the surface epithelium unrelated to Brenner tumors. Malignant Brenner tumor.

tumor rupture.279 A B Fig. Fibromas of the ovary account for 6 percent of all ovarian tumors. Fibromas are benign. 13-74. Tumor cells have clefted. Because of the luteinization of tumor cells. 13-76). Juvenile granulosa cell tumor. theca cell tumors appear yellow on cross section (Fig. B. 13-73. Microfollicular pattern. but they are hormonally active and are composed of luteinized stromal cells. 66417308 : ¸Ÿ±U 24 ¥°Q . and their cytoplasm appears luteinized and clear. Histologically they consist of fibroblast-like tumor cells. Fig. coffee bean—shaped nuclei. Fig. On cross section this lipid-rich tumor appears white and fibrotic. 13-75. A.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . On cross section this lipid-rich tumor appears yellow. Fibrosarcomas are rare and resemble equivalent soft-tissue tumors. Tumors of older patients appear to be more aggressive than those of younger women. Tumor cell nuclei show some atypia. which may have a somewhat more abundant cy - Fig. are large tumor size. Cells form rudimentary follicles. and high mitotic rate. Fibroma. Thecoma. On cross section the masses are white and have a whorled appearance (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . of malignancy. 13-75). Thecomas are similar to fibromas. Granulosa cell tumor. even if they are classified as cellular and mitotically active. 13-76. These hormonally nonfunctioning tumors are composed of fibroblasts that form solid masses.

Fat stain (oil red 0) shows lipid droplets in the cytoplasm of tumor cells. Fig. The tumor is yellow on cross section. Thecoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Sertoli-Leydig cell tumor. A. Sertoli-Leydig cell tumor. Fig. 13-77. Sertoli-Leydig cell tumor. 13-78. The tumor is composed of spindle-shaped cells.28 0 A B Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Spindleshaped and clear cells form nests surrounded by loosely structured stroma and thin-walled vessels. Fig. 13-79. The well-differentiated tumor consists of tubules and groups of Leydig cells. B. and its cells form cords. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Sclerosing stromal tumor of the ovary'. 13-80. 13-81. This tumor shows intermediate differentiation.

nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . These tumors are hormonally active and usually are benign. or skeletal muscle cells (Figs. which may be malignant. Sex cord tumor with annular tubules. yellow. Steroid lipid (cell) tumors are distinctive tumors that appear as yellow or brown nodules or larger masses. Fig. Fig. Fig. which mimic rete ovarii or rete testis 5. hilar cell tumors. abortive tubular structures. Stromal luteoma. Histologically they are composed of tubules lined by spindle-shaped cells arranged around centrally located globules of eosinophilic basement membrane like—material (Fig. and steroid cell tumors not otherwise specified (NOS). but it differs from fibromas and thecomas both clinically and morphologically. Gynandroblastoma is a term that is used to describe Sertoli-Leydig cell tumor cognates that also contain incontrovertible granulosa cells. Thecomas are benign tumors of older women (80 percent are postmenopausal). These tumors typically are solid. and nests of luteinized Leydig cells and spindle-shaped stromal cells 3. Sertoli-Leydig cell tumors occur in all age groups. 13-77). Sarcomatoid variant. Eosinophilic globules are surrounded by spindle-shaped cells. 13-83). They have a favorable prognosis in most instances. lipidrich cytoplasm (Fig. 13-84).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 13-78). The tumor typically contains thin-walled vessels. and occasional tumors may be hormonally active. which are composed of cords. These tumors occur in women under the age of 30 years and are composed of distinct nests of spindle-shaped stromal and clear cells separated from other similar nests by loosely structured stroma (Fig. and malignant variants are extremely rare. Sclerosing stromal tumor of the ovary belongs to the general category of fibroblastic stromal tumors. Almost all Sertoli-Leydig cell tumors are benign. Histologically they are composed of polyhedral luteinized cells with round nuclei and well-developed eosinophilic. sarcomatoid variant. except for steroid cell tumors NOS. I3-84. These tumors occur in patients with Peutz-Jeghers syndrome. Retiform tumors. which is composed of spindleshaped cells with focal formation of vague tubular structures and only sparse Leydig cells. 13-79). They secrete androgenic hormones and cause virilization. such as neoplastic mucous glands. Five histologic patterns are recognized: 1. Tumors of intermediate differentiation. Histologically Sertoli-Leydig cell tumors have features of a developing testis and are composed of cells that resemble Sertoli cells and Leydig cells.281 toplasm than the cells of fibromas. The rare malignant tumors were poorly differentiated and had mesenchymal heterologous elements. Sertoli-Leydig cell tumor. 13-80 to 13-82). 13-83. and often lobulated N(Fig. but their peak incidence is in younger women (average age 25 years). Sex cord stromal tumor with annular tubules (SCTAT) is a unique tumor composed of cells that have intermediate features of granulosa cells and Sertoli cells. which maybe missing altogether 4. The tumor is composed of polyhedral cells that have round centrally located nuclei and welldeveloped eosinophilic cytoplasm. Luteinization of cells occurs at a variable rate. 66417308 : ¸Ÿ±U 24 ¥°Q . They include three entities: stromal luteomas. Intraabdominal spread but not extraabdominal metastases were recorded in such cases. Well-differentiated tumors in which Sertoli cells form tubules surrounded by nests of Leydig cells 2. Sertoli-Leydig cell tumors with heterologous elements. cartilage. The tumor is composed of spindle-shaped cells. Such cells typically contain fat droplets that may be demonstrated by special stains (Fig. 13-82.

Dysgerminoma. diastase-resistant hyaline globules. 13-87 and 13-88). Yolk sac carcinoma. Grossly it appears as a gray-white or yellowish lobulated solid mass (Fig. Glomeruloid Schiller-Duval bodies are typical. Embryonal carcinoma of the ovary is rare. Tumor cells are positive for alpha-fetoprotein. These cells form' solid nests by septa infiltrated with lymphocytes. the five-year survival rate is approximately 95 percent. Dysgerminoma is the most common malignant germ cell tumor of the ovary.282 Germ Cell Tumors Germ cell tumors of the ovary originate from the oocytes and are histologically equivalent to testicular and extragonadal germ cell tumors. but a few sarcomas also have been reported. Fig. Benign cystic teratoma (dermoid) is the most common germ cell tumor of the ovary.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Yolk sac carcinoma is an alpha-fetoprotein–secreting tumor of women under the age of 20 years. including skin. Choriocarcinoma is composed of cytotrophoblastic and human chorionic gonadotropin (hCG)–positive syncytiotrophoblastic cells. It typically occurs after puberty and early reproductive life. 13-90). It occurs in young women and is considered to be an ovarian equivalent of testicular seminoma. 13-86). Fig. nests. including reticular. Dysgerminomas are extremely radiosensitive and have a good prognosis. 13-86. Yolk sac carcinoma. Tumor cells form glomeruloid structures. and so forth (Figs. 13-89). 13-85). Most of these secondary malignancies are squamous cell carcinomas. and teeth (Fig. Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Dysgerminoma. bone. Histologically the tumor is composed of various mature somatic tissues. microcytic. 13-85. This large lobulated tumor was removed from a six-year-old girl. 13-88. tubular.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Histologically the tumor may present in several patterns. Histologically it is composed of polygonal clear cells arranged into nests that are surrounded by stroma infiltrated with lymphocytes (Fig. 13-87. and strands. neural tissue. but in some cases it is diagnosed later in life. Teratomas are benign. On gross examination it presents as a cystic structure that is filled with hair and sebaceous material (Fig. Tumor cells have clear cytoplasm. although they may undergo malignant transformation if they are left inside the body. Tumors also contain periodic acid-Schiff–positive. glandular epithelium. Fig.

nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 13-92. 13-91). Immature teratoma. 66417308 : ¸Ÿ±U 24 ¥°Q . Solid areas appear encephaloid and bulge from the cross section. which may be highlighted with antibodies to thyroglobulin (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig. Neural components of immature teratomas are graded on a scale from Ito III (Fig. Specialized teratomas may represent one-sided differentiation of an overgrowth of a specific tissue or tumor type in a previously benign teratoma. Benign cystic teratoma (dermoid cyst). neural tissue. Struma ovarii is composed of thyroid tissue. 13-95). 13-89. and glands. but those that are composed of neuroblasts are ominous. 13-92 to 13-94). 13-93. Neuroendocrine tumors may resemble carcinoids as in other parts of the body. Benign glial implants are innocuous. grade I . The cavity is filled with sebaceous material and hair. Immature teratoma. Tumors tend to spread throughout the peritoneum. but they also may originate in thyroid tissue (Fig. Fig. 13-91. grade 2. The tumor consists of differentiated neuropil with only occasional immature neural cells. parts of which appear encephaloid (Fig. Fig.283 Immature teratomas are malignant tumors that present as solid masses. Overall five-year survival is in the range of 70 percent. Histologically they may contain many kinds of tissues. mostly because of the efficient use of modern chemotherapy. Fig. but their malignancy derives predominantly from the immature neural tissue. 13-90. and the histologic evaluation of metastases is important for prognostic purposes. Fig. Benign teratoma. The tumor contains mature and immature neural tissue. 13-96). The tumor is composed of squamous epithelium. Immature teratoma.

which appear lobulated and have a smooth surface. 13-95. 13-96. 13-97). It is composed of small undifferentiated cells that form solid compact sheets and nests with areas of necrosis (Fig. Immature teratoma. 13-98.284 Unclassified and Metastatic Tumors of the Ovary Small cell carcinoma with hypercalcemia is a highly malignant tumor of young women.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The tumor consists mostly of immature neuroblastic cells that form rosettes. but they do not show any distinct differentiation. Krukenberg tumor. grade 3. Tumor cells may form abortive rosettes and follicles. focally surrounding spaces filled with proteinaceous fluid. Metastatic carcinoma from the primary tumor in the stomach has symmetrically enlarged the ovaries. 13-97. Fig. The tumor consists of thyroid-like tissue. The tumor is composed of closely compacted small cells. Small cell carcinoma with hypercalcemia. 13-94. Fig. Fig. 66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The tumor consists of small neuroendocrine cells surrounding Fig. Struma ovarii. Fig. Strumal carcinoid.

13-102. Histologically the ovary is permeated with tumor cells. and the tumors often show extensive necrosis (Fig. Burkitt lymphoma. Nevertheless. The ovaries typically are enlarged and have a smooth. 13-101. usually lobulated external surface (Fig.285 Krukenberg tumor represents bilateral metastases of adenocarcinoma of the gastrointestinal tract to the ovaries. which maybe signet ring—like or cuboidal (Figs. Metastasis from colonic adenocarcinoma. Nodular metastases on the surface of the ovary may mimic primary ovarian tumors. and mucinous adenocarcinomas of the large intestine may produce lesions that are indistinguishable from primary ovarian tumors of the same histologic type. usually in the advanced stages of the disease. I3-100. Lymphoma may involve the ovary. Fig. Krukenberg tumor. 66417308 : ¸Ÿ±U 24 ¥°Q . Ovary infiltrated by undifferentiated lymphoid cells has a starry sky appearance. 13-102). Stromal cells of the ovary infiltrated with cancer appear hyperplastic. Krukenberg tumor.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 13-101). 13-98). Fig. Burkitt lymphoma occasionally may present as a primary ovarian mass.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Ovarian stromal cells often are luteinized and hyperplastic. 13-99 and 13-100). metastases tend to be composed of more anaplastic cells. Fig. 13-99. The neoplastic glandlike structures are partially necrotic. Histologically such tumors are indistinguishable from equivalent lymphomas in other sites (Fig. Fig. The ovary is infiltrated with signet-ring cancer cells.

C-F. here they form the chorion frondosum. and the chorion laeve will show persistence of ghostlike atrophic villi seen even at term on the free membranes.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . showing the changing relationship of the fetal membranes to the decidua. Saunders. 1993.) 66417308 : ¸Ÿ±U 24 ¥°Q . the amnion and chorion are closely approximated but never quite fuse with each other and the decidua parietalis. Philadelphia. Persaud TVN: The developing human. clinically oriented embryology. ed 5. B. Drawing of a frontal section of the uterus showing the elevation of the decidua capsularis caused by the expanding chorionic sac of a 4-week embryo. Drawings of sagittal sections of the gravid uterus from the fifth to twenty-second weeks.28 6 Diagram 13-I. Note in D to F that the chorionic villi thrive only where the chorion is associated with the decidua asalis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . In F. (Modified from Moore KL. A. thereby obliterating the uterine cavity.

Dichorionic diamniotic placenta. contain numerous blood vessels filled with fetal blood. In twin pregnancy. succenturiate. or dichorionic diamniotic (Figs. The fetal surface of the placenta shows the thin dividing membrane. 13-103 and 13-104). The fetal surface shows a very thick dividing membrane. which results in gestational trophoblastic disease.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 66417308 : ¸Ÿ±U 24 ¥°Q . 13-104. one from the fetal end and the other from the placental end. or may show abnormal insertion of the umbilical cord and the chorioamniotic membranes (e. such as placenta accreta. The fully functioning placenta.. Such variations are of limited clinical significance in most cases. such as hydatidiform mole and choriocarcinoma.) Fig. develops over a period of weeks and remains in place in utero until the end of pregnancy. (4) abnormal differentiation of trophoblastic cells. which may occur in the uterus (e. the chorioamniotic membranes. Monochorionic diamniotic placenta. (3) abnormal morphology of the placental disk. which results in extrauterine pregnancy.g. which carries nutrients and oxygen to the fetus from the mother. Diagram 13-2. diamniotic. Nau. In pregnancies with multiple fetuses the placenta varies from the normal in that it maybe composed of a single disk or entirely separate disks. which may be multilobated. (2) abnormal separation of the placenta from the pregnant uterus. which occurs at the blastocyst stage. like the entire placenta. Fetal vessels were injected with milk-barium solution to illustrate the vascular anastomoses.g.. Villi. Houston. and the'umbilical cord (Diagrams 13-1 and 13-2). which is the most common multiple pregnancy. Placental abnormalities include (1) abnormal implantation. placenta previa) or outside the uterus. Texas. Finegold.287 DISORDERS OF THE PLACENTA The placenta develops from embryonic trophoblastic cells at the site of implantation of the embryo. including mononuclear cytotrophoblastic and -multinucleated syncytiotrophoblastic cells arranged into chorionic villi. (Courtesy of Dr. which provides the essential support to the developing fetus. 2 to 3 cm from the insertion. circummarginate or circumvallata placenta). There are two sections of umbilical cord. The placental disk consists of trophoblastic cells. Milton J. The mature placenta consists of the placental disk. which included the zone of rupture and a marginal portion of the placental disk for orientation. (Computer-generated diagram by Martin E. Recommended minimum sections include a membrane roll.) Fig. and so forth.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . a single-disk placenta is classified as monochorionic. 13-103.

The Children's Hospital.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . C. The early amnion rupture sequence (TEARS). Fetus shows abnormalities of the head and extremities. 13-106. A B C Fig. MD. Denver. The fetal surface of the placenta shows a dull denuded chorionic surface with thin bands of tissue extending from it. courtesy Sherrie A. Ectopic pregnancy. 13-107. (A and B. A. Placenta accreta. Microscopically the epithelial layer of the amnion is absent and the chorion is thickened and cellular. B. Fetal abnormalities usually are related to placental changes. Caldwell. The fetus was found in the fallopian tube. 13-105. Colo. A hysterectomy was performed because the placenta could not be removed from the pregnant uterus.28 8 A B Fig. A. B.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig.) 66417308 : ¸Ÿ±U 24 ¥°Q . Chorionic villi and blood are found inside the fallopian tube.

without an intervening decidua and Nitabuch fibrinoid layer. and tubule rup. a common cause of preterm labor. including descending infection of the fallopian tubes or the peritoneum. which was impregnated with silver according to the Warthin-Starry method. B.ture may ensue. a feature suggestive of inadequate maternal response. A "bacterial cloud" is seen without much inflammation. D. or chorionic decidua (Figs. 13-108. which occurs in early pregnancy. A.289 Abnormal Implantation and Separation of the Placenta and Rupture of Membranes Extrauterine implantation results in ectopic pregnancy. Abnormal invasion of chorionic villi at an intrauterine site results in placenta accreta. 13-105). usu- ally in the fallopian tubes (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Acute chorioamnionitis. or rupture of the fetal membranes. chorion. results in premature delivery. In the third trimester premature separation of the placenta from the uterus. The early amnion rupture sequence (TEARS). 13-108 and 13-109). Chorionic villi of an abnormally implanted ovum tend to invade the underlying tissue. and (4) iatrogenic infection of the amniotic fluid during amniocentesis or fetal surgery. 13-107). Placenta accreta is firmly anchored in the uterus. and it does not separate normally during delivery. such as abruptio placentae. Histologically placenta accreta shows invasion of chorionic villi into the myometrium. Bacterial polymorphonuclear leukocytes extend from the maternal intervillous space at the subchorionic space into the chorion. The row of membranes sectioned crosswise shows more inflammation at the center nearest the cervical os. is seen "standing on end" in the amnion. Destruction of the muscle layer of the fallopian tube typically is associated with a hematosalpinx. Premature rupture of the membranes also may cause infection. is associated with a variety of fetal malformations that usually affect the head and the extremities (Fig. and until recently many patients with placenta accreta required hysterectomy (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fusobacterium. (2) endometrial infection. The infection may cause inflammation in the umbilical cord (funisitis). fetoplacental infections are classified as secondary to (1) hematogenous spread. Histologically the inflammatory response may include neutrophils. It may be removed with difficulty. C. 66417308 : ¸Ÿ±U 24 ¥°Q . (3) ascending infection of the vagina. which may be sprinkled A B C D Fig. Infections On the basis of the route of entry. amnion (chorioamnionitis). 13-106).

(5) choriocarcinoma. Trophoblastic proliferation. and (6) other trophoblastic lesions. Many cases of chronic inflammation identified histologically and interpreted without additional clinical or microbiological data often are classified as villitis of undetermined etiology ( WE) (Fig. if present at all. which occasionally are arranged into granulomas. or fungi may be demonstrated. is polar.290 at random or may form abscesses. 66417308 : ¸Ÿ±U 24 ¥°Q . Pathogens such as bacteria. Fig. some of which show eosinophilic necrosis. Nearly all villi are enlarged and are interconnected by thin nonedematous cordlike structures. and intermediate trophoblast. The classic features are amphophilia of the villous stroma and atrophy of the trophoblasts. Hydropic abortus must be included in the differential diagnosis of molar gestation. The differential diagnosis of placental site trophoblastic tumor includes the "exaggerated implantation site " and the placental nodule (Fig. Greatly enlarged edematous villus with incompletely formed central cistern. A.extending into the intervillous spaces. Villitis caused by Listeria monocytogenes. 13-117). B. 13-109. 13-111 to 13-115. 13-110). A B Fig. cytotrophoblast. An infiltrate composed of neutrophils involves microvilli. 13-III. Chronic villitis. 13-116). sometimes with the use of special stains. viruses. (2) partial hydatidiform mole. 13-I 10. Representative gross and microscopic aspects of GTD are shown in Figs. (4) placental site trophoblastic tumor. There also is circumferential cellular obliteration of syncytiotrophoblast. Lymphocytes and plasma cells may be found together with macrophages. but it also might represent an immune response. and often one cannot determine whether the inflammatory response was elicited by infective pathogens or by an immune response. representing a normally implanting villus (Fig. (3) invasive mole. The salient features of these lesions are summarized in Table 13-5 and are compared with changes in hydropic abortus. Fig. Complete hydatidiform mole. Gestational Trophoblastic Disease Gestational trophoblastic disease (GTD) has been defined by the World Health Organization and International Society of Gynecological Pathologists as a group of closely related diseases that includes (1) complete hydatidiform mole.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Histologic findings are not reliable indicators for the onset of inflammation. This predominantly intervillous inflammation ("intervillositis") may have been caused by infection.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . but in most cases they are not obvious.

partial hydatidiform mole. intermediate trophoblast. ST. nucleated red blood cells. CHM. not applicable. Gross.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . syncytiotrophoblast. cytotrophoblast. n/r. and Flow Cytometric Features From Popek EJ: ASCP check sample AP 94-7 (AP-241). Microscopic. 1994. I-I A. IT. PHM. n/a. spontaneous abortion. AB. "Partial hydatidiform mole. Abortion. NRBC. complete hydatidiform mole. CT. 66417308 : ¸Ÿ±U 24 ¥°Q . PSTT. placental site trophoblastic tumor. hydropic abortus. none reported." American Society of Clinical Pathologists. Copyright ASCP Chicago.291 Gestational Trophoblastic Disease: Clinical. SAB.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

13-112. Uniform polygonal cells form sheets of intermediate trophoblast. Less than 20 percent of villi are cystic. A. A B Fig. Choriocarcinoma. Cytotrophoblastic and syncytiotrophoblastic cells show foci of necrosis and are admixed with extravasated blood. Enlarged villus shows pronounced scalloping. Invasive CHM showing enlarged villi with trophoblastic proliferation deeply invasive into the myoretrium. "Knuckles" of proliferating syncytiotrophoblast have undergone eosinophilic necrosis. Fig. I3-1 13. islands of trophoblast in the stroma of the villus). B. human chorionic gonadotrophin can be demonstrated in the syncytiotrophoblastic cells. 66417308 : ¸Ÿ±U 24 ¥°Q . A macerated fetus is attached to the placenta..·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Placental site trophoblastic tumor (PSTT).292 A B Fig. which results in pseudoinclusions (i.e. 13-1 14. Immunohistochemically. Fig. B. with only rare multinucleated cells invading the myometrium. A. 13-I 15. Partial hydatidiform mole.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

Am J Surg Pathol 23:617-635. A. Kurman RJ. invasive. few residual blood vessels. B. Manson CM. 1998. Placental nodule is residua from a previous pregnancy.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Hart WR: Primary ovarian mucinous systadenocarcinomas. 1995. Hirsch PJ. Am J Surg Pathol 22:1449-1462. Eichhorn JH. Gordon MD. Lesions easily confused with PSTT. Coyne JD: Post-operative spindle cell nodule of the vulva. The role of infectious and environmental factors. Am J Surg Pathol 22:13791385. Riopel MA. Semin Oncol 21:3-11. Proposed criteria for a discrete morphological entity. 1999. Semin Oncol 21:64-70. A Gynecologic Oncology Group Study.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 66417308 : ¸Ÿ±U 24 ¥°Q . 1993. Kurman RJ: Evaluation of diagnostic criteria and behavior of ovarian intestinal-type mucinous tumors. Am J Surg Pathol 23:69-78. Young RH. Histopathology 26:571-574. 13-1 17. A study of 40 cases and comparison with 44 cases without these patterns. well circumscribed. 1994. 1994. Normal invasion of the uterus by trophoblasts is extensive in early pregnancy and may be underappreciated. Longacre TA. Further Reading Benda JA: Pathology of cervical carcinoma and its prognostic implications. and polar trophoblastic proliferation of anchoring villi. Am J Obstet Gynecol 165:1255-1262. Hydropic abortus (HA) with enlarged edematous villi with amphophilic stroma. Merino MJ: Vaginal cancer. Clement PB: Pathology of the uterine corpus. Exaggerated implantation site with numerous mononuclear cells within the maternal myometrium. Ireland K: Pathology of hyperplasia and carcinoma of the endometrium. An adenoma malignum pattern of microinvasion. Am J Surg Pathol 23:397-409. Hendrickson MR: Diffusely infiltrative endometrial adenocarcinoma. The last documented pregnancy in this case was several years before this curettage. 1995. Scully RE: Ovarian serous borderline tumors with micropapillary and cribriform patterns. Young RH: New and unusual aspects of ovarian germ cell tumors. Am J Surg Pathol 17:1210-1224. 1999. Hum Pathol 22:776-791. 1995. Atypical proliferative (borderline) tumors and intraepithelial. Patel A: Myometrial hyperplasia. 1998. Hoerl HD. A B Fig. Ronnett BM. Brunetto VL et al: Villoglandular adenocarcinoma of the endometrium: a clinioopathologic study of 61 cases. microinvasive. 1991. 1999. Cramer SF. 13-116. Bell DA.293 Fig. it has a central acellular or sclerotic region surrounded by a few viable intermediate trophoblasts. A clinicopathologic study of 49 cases with long-term follow-up. Zaino RJ. and metastatic carcinoma. Mod Pathol 8:71-77.

nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .66417308 : ¸Ÿ±U 24 ¥°Q .

·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .66417308 : ¸Ÿ±U 24 ¥°Q .

(A from Russo J. New York and London. adult.296 FIBROCYSTIC CHANGE The mammary tissue develops from the ingrowth of epithelial strands that differentiate into ducts. and function. In Neville MC. Ductal hyperplasia includes a continuum of changes that range from trivial changes to changes similar to those of ductal carcinoma in situ (CIS). Adult breast illustrating typical variability in size and development of lobules. and the hyperplastic cells may extend into the ductules. fibrosis typically occurs in younger women. Ductal hyperplasia occurs predominantly in terminal ducts and lobular units and is characterized by an increased number of cells inside the lumen of these structures. A B C Diagram 14-I. B. In some cases the lumen is dilated. Occasionally lobular hyperplasia may be more prominent. Once the breasts reach their adult form. but over time microscopic cysts enlarge and transform into fluid-filled macroscopic cysts. (3) radial scar formation. Sclerosing adenosis presents as enlargement of one or more lobular units. lower. Irregular proliferation of ductlike epithelial structures around a centrally located focus of connective tissue is called radial scar formation. whereas small cysts typically develop as multiple dilatations within the same lobule. The normal double cell layer structure of ductules is preserved. whereas multiple cysts are lined by apocrine type of epithelium (apocrine metaplasia). As part of the fibrocystic change. Plenum Press. Occasionally a mass is produced by aggregation of adjacent lobules or less commonly by massive enlargement of a single lobule.) 66417308 : ¸Ÿ±U 24 ¥°Q . if it is quite prominent. If the normal hormonal response of breasts is disrupted or partially altered. middle. the term florid hyperplasia is used (Fig. ductules.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . they remain sensitive to hormonal stimulation and undergo typical cyclic changes during each menstrual cycle. Upper. The breasts involute after menopause. which is termed atypical ductal hyperplasia. The breasts involute to some extent after the cessation of lactation. early adolescence. a complex set of changes characterized by fibrosis. Daniel CW. Cystic dilatation begins at the level of terminal ducts and lobules. 1987. editors: The mammary gland: development. If there are more cells layers. Russo IH: Development of the human mammary gland. The largest cysts are associated with atrophy of the remaining lobular elements. Fibrosis leads to the expansion of the dense perilobular connective tissue.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . A. and this change is termed blunt duct adenosis or microglandular adenosis. Cysts are the most common feature of fibrocystic disease. 14-1 and 14-2). Development of mammary ducts and lobules. female breasts reach their full differentiation only under proper hormonal stimulation during pregnancy and lactation. the breast tissue undergoes fibrocystic change. and fibrotic nodules are the sole lesions in approximately 5 percent of benign breast biopsy specimens. but they remain capable of assuming their full functional potential again. regulation. including (1) sclerosing adenosis. but their lumina may be compressed or narrowed. and (4) lobular hyperplasia. Solitary cysts are lined by simple cuboidal or flattened epithelium. hyperplasia is considered to be moderate. Ductal hyperplasia may be associated with lobular hyperplasia. and acini arranged into lobules (Diagram 14-1). birth. which encroaches on the lobules and ultimately replaces the loose interlobular stroma. In mild hyperplasia the ducts are lined by one or two additional cell layers. 14-2). which is caused by an increased number of alveolar ducts along with an increase in the density of interlobular fibrous tissue. Epithelial proliferative lesions occur in several histologic forms. epithelial proliferation. However. (2) ductal hyperplasia. and cyst formation (Figs.

The epithelial nests inside the ducts are partially solid and partially cystic but lack fibrovascular stalks. Focal adenosis shows similarity of proliferated ductules to those in the adjacent uninvolved normal lobule. Fibrocystic change. D. A B Fig. 14-2. Fibrocystic changes.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 14-I. Fibrosis leads to merging of perilobular and intralobular connective tissue. C.297 A B C D Fig. B. A. A. B. The overall lobular structure is preserved. Florid duct hyperplasia. along with an increase in the density of intralobular fibrous tissue. Radial scar. Dilated terminal duct and lobules are lined by epithelium that either is flattened or shows apocrine metaplasia (evidenced as cuboidal cells with eosinophilic cytoplasm). 66417308 : ¸Ÿ±U 24 ¥°Q . Central fibrosis is surrounded in a radiating manner by ductlike structures. Sclerosing adenosis involves hyperplasia of alveolar ductules. Ductules show swirling and collapse of their lumina.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

14-4. Cellular fibrous stroma shows periductal layering. Adenomas are benign circumscribed tumors (Fig. Fibroadenoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Breast tumors represent the most common malignancy in women. Most breast lesions show both of these growth patterns. are recognized (Fig. They may range in size from less than 1 mm to several centimeters in diameter. Fibroadenoma Fibroadenoma is the most common breast mass encountered Fig. Lactating adenoma. or adenomas. B. 14-5. Fibroadenoma. Its margins are less distinct than those of typical fibroadenoma or juvenile fibroadenoma. 14-4). A.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 14-5). rubbery nodules that are distinct from the surrounding tissue (Fig. In lactating adenomas the ductlike structures are dilated and show cytoplasmic vacuolization and enlargement that is typical of lactation. it is surprising that pure epithelial tumors . On gross examination fibroadenomas are sharply circumscribed. Myxoid stroma distorts the elongated ducts. and lobulated on cross section. Intracanalicular type. Two patterns of growth. Adenoma Considering the relative frequency of fibroadenomas and mammary carcinoma. intracanalicular and pericanalicular. Fig. 14-3. they are as tubular or lactating (Fig. are so infrequent. constituting the majority of lesions found at biopsy or in surgically removed specimens in women under the age of 25 years. grayish white. Most malignant tumors originate from the mammary epithelium and accordingly are called carcinomas. Histologically classified. Histologically they are composed of proliferating ducts and stroma. Adenomas are benign epithelial tumors. Pericanalicular type.298 TUMORS Tumors of the breast may be benign or malignant. A B Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . This spherical tumor surgically shelled out from the breast of a young women appears myxoid. translucent. 14-3). The lobulated tumor appears fleshy brown on cross section. most of them are classified as fibroadenomas. accounting for 30 percent of all newly diagnosed cancers in 1998. Myoepithelial cells surround the cuboidal ductal epithelium. because they also entail proliferation of stromal cells. in young women. Breast cancer is responsible for 16 percent of cancer-related deaths in women. Both of these tumor types are composed of closely packed terminal ducts with little surrounding stroma. 14-6). However.

On gross examination low-grade tumors tend to have a variegated pale appearance. A. and the nuclei of these tumor cells show atypia. Phyllodes tumor.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Adenoma. Phyllodes Tumor Phyllodes tumors are composed of proliferating epithelial and stromal cells. The excised specimen is firm and rubbery and may separate into leaflike structures. 14-8). High-grade tumor has a fleshy appearance. Phyllodes tumors are classified clinically as low-grade or high-grade neoplasms. Tubular adenoma consists of tubules surrounded by stroma similar to that of normal breast. 14-6. hyperchromasia. A B Fig. 14-7. which account for its name (Greek phyllon. High-grade tumors have a more cellular stroma. 66417308 : ¸Ÿ±U 24 ¥°Q . B. Stroma of low-grade tumors is composed of loosely arranged cells that have bland nuclei. The presence of interlobular duct suggests focal hyperplasia rather than neoplasia. Low-grade tumor lacks encapsulation and shows a variegated redtan and white cut surface. meaning leaf). B.299 A B Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and highgrade tumors appear more fleshlike (Fig. 14-7). Lactating adenoma is composed of tubules that show lactational changes. At presentation phyllodes tumors are on average larger than fibroadenomas or adenomas. A. and mitotic figures (Fig. and a history of rapid tumor growth is a common presenting symptom.

A B Fig. 14-9). nuclear anaplasia. Phyllodes tumor. 14-10).300 Intraductal Papilloma Papillomas are benign intraductal tumors that usually reach clinical attention primarily because of nipple discharge or bleeding. Epithelial elements trapped in the fibrous scar may be mistaken for invasive carcinoma. but 20 percent to 25 percent occur more peripherally and appear to be multiple. Papillomas must be differentiated from papillary carcinoma. which is more pronounced around the elongated ducts. Multiple lesions more commonly are associated with atypical patterns of epithelial proliferative disease. 14-10. Some authors believe that the risk is largely confined to patients who have multiple papillomas. Ductal papilloma. Most papillomas measure 0. Papillomas as a group confer a slightly elevated risk for the subsequent development of invasive mammary carcinoma. although a few may present as a palpable mass. Fig. Fig. Low-grade tumor shows low cellularity. and intraductal papillary proliferation without fibrovascular cores. subareolar type. including a cribriform pattern of epithelial growth. which may obscure their papillary nature.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Ductal papilloma. The presence of papillary carcinoma in an intraductal papilloma may present a difficult diagnostic problem. and their biologic behavior and tendency to progress to invasive cancer should be predicted more accurately by evaluating the degree of cellular atypia rather than their architectural features. Papillomas display a propensity for degeneration and necrosis and often are accompanied by periductal fibrosis and sclerosis. 14-8.5 to 2 cm in diameter and are located in the main collecting ducts.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . an indolent malignancy of older women that also is largely intraductal but displays definitive signs of malignancy. Large subareolar lesions may be quite cellular and are composed predominantly of glandlike structures (Fig. Microscopically the hallmark of papillomas is intraductal proliferation of epithelial cells arranged into fronds that have a fibrovascular core (Fig. A. Epithelial cells are arranged on fibrovascular stalks that project into the ductal lumen. but the absence of intraductal carcinoma in adjacent ducts is a clue to their benign nature. The lesion shows florid proliferation of epithelial cells with focal nuclear atypia. B. 66417308 : ¸Ÿ±U 24 ¥°Q . High-grade tumor consists of densely arranged stromal cells showing nuclear atypia. 14-9.

Partial cribriform intraductal pattern. Atypical hyperplasia is the only finding in approximately 3 percent of breast biopsy specimens. it must be recognized and treated appropriately. fenestrated. ADH may mimic noncomedo type ductal CIS growing in a cribriform. nevertheless. Atypical ductal and lobular hyperplasia. or mixed pattern (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 14-11). and D. There also is controversy over whether atypical hyperplasia is only a risk factor or a definitive precursor to invasive carcinoma. E. but their reproducibility has been a matter of discussion. B. Micropapillary intraductal pattern. ALH appears as distention of lobules filled with atypical cells. 14-I I. ADH usually is an incidental finding in biopsy specimens that show mostly benign changes. regardless of the specific cellular ar- A B C D E Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . solid. The most common patterns of ADH include A. Regularity of the pattern. C. but neither in a fully developed form. partially cribriform. micropapillary. Several studies have shown that atypical hyperplasia is associ - ated with a four. Microscopically ADH is characterized by intraductal proliferation of cells showing either the growth pattern or the cytologic features that are characteristic of noninvasive carcinoma. Diagnostic criteria for ADH and ALH have been defined. Fenestrated intraductal pattern.to fivefold higher risk for carcinoma than that for age-matched controls. Cribriform intraductal pattern.301 Atypical Hyperplasia Atypical hyperplasia occurs in two forms: atypical intraductal hyperplasia (ADH) and atypical intralobular hyperplasia (ALH).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

The microscopic features are distinctive and include intralobular proliferation of cells distending the lobules. B. these tumors are subtyped as (1) cribriform. Comedo type DCIS accounts for 3 percent to 5 percent of all breast carcinomas and 35 percent to 50 percent of solitary noninvasive carcinomas. Several histologic subtypes are found. and uniform.302 rangements. ALH often is multicentric. It usually is not detected by palpation but rather incidentally in breast biopsy tissue of premenopausal women. It is not always possible to distinguish ALH from intralobular carcinoma. It is considered to be less aggressive than comedo type DCIS. The cytoplasm of most tumors is well developed. such as the presence of hormone receptors. The cells have moderate to scant cytoplasm. The risk of developing invasive carcinoma of A B Fig. (2) cribriform. round-to-oval nuclei with delicate chromatin and small nucleoli. It also carries a four. (4) solid. round cells with distinct borders. and round to polygonal. (2) micropapillary. Cancerization of the lobule presents as extension of the malignant cells into the acini. Nuclear features are those of highgrade tumors. these lesions represent a diagnostic problem and there is no consensus regarding therapy. and a cheesy "comedo-like " necrotic material may be expressed from the dilated ducts. Such an extension of tumor should not be confused with invasion. The cells are uniform. distending them to as much as 10 times their normal diameter. delicate chromatin. On gross examination they are well circumscribed. On the basis of histologic growth patterns.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . moderate to scant cytoplasm. and (4) papillary (Fig. Other favorable biologic features. The cytologic features also resemble those of noncomedo type intraductal carcinoma and include relatively small. the unequivocal malignant potential of these lesions is underscored by a 30 percent recurrence rate after incomplete surgical excision and the invasiveness of cancer found in 50 percent of these recurrences.to fivefold higher risk for invasive cancer. and diploid DNA content. ALH is found in 1 percent of breast biopsy specimens. 66417308 : ¸Ÿ±U 24 ¥°Q . 14-13). Histologically it presents as multifocal interlobular proliferation of atypical neoplastic cells (Fig. Pagetoid spread beneath the epithelium of larger ducts is common. Mitotic figures are rare. Noninvasive Carcinoma Noninvasive carcinoma of the breast is diagnosed in approximately 10 percent of breast biopsy specimens. Tumor cells typically have round or oval nuclei with homogeneous chromatin and inconspicuous nucleoli. DCIS is further divided into (1) comedo. Retrograde extension of the tumor cells into the acini (cancerization of the lobules) is common. also are also usually found. low proliferation rates. Microscopically comedo DCIS grows inside the ducts. The atypical neoplastic cells form solid masses that typically show central necrosis (Fig. (3) solid. is an important theme of ADH. The majority of comedo DCIS present as palpable masses that are 2 to 3 cm in diameter. and (5) papillary subtypes. and small nucleoli.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Two major categories are recognized: ductal carcinoma in situ ( DCIS) and lobular carcinoma in situ (LCIS). which should be diagnosed only if the neoplastic cells extend across the borders of the loose intralobular connective tissue. comedo type. occasionally hyperchromatic. mostly in premenopausal women. Noncomedo DCIS accounts for 5 percent to 8 percent of all breast carcinomas and 50 percent to 70 percent of solitary noninvasive carcinomas. ALH has no distinguishing clinical or mammographic features and usually is an incidental finding on histologic examination. However. small. with a lower short-term recurrence rate (less than 5 percent) after local excision. A. but the patterns often are intermixed and usually are present in the same lesion. 14-12. The distended ducts are lined by atypical cells that have undergone necrosis in the central portion. and mitoses are common. DCIS. Lobular carcinoma in situ (LCIS) accounts for 1 percent to 3 percent of all breast carcinomas and 10 percent to 30 percent of solitary noninvasive carcinomas. but some may be as large as 5 cm or more. 14-12). Because of their perplexing similarity to intraductal carcinoma. round regular nuclei. Noncomedo DCIS rarely produces palpable masses and usually is diagnosed by biopsy of microcalcific breast lesions recognized by mammography. 14-13). (3) micropapillary.

Not otherwise specified.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . D. a rate that translates to a greater than tenfold relative risk and a 20 percent absolute risk over 20 years. and C. Lobular carcinoma in situ presents in the form of distended acini filled with atypical cells. The lobular pattern is preserved. Solid ductal. and in this sense it is a diagnosis of exclusion. 14-13. DCIS. and LCIS. Modern taxonomic attempts to subdivide these lesions into categories with distinct morphologic.303 A B C D Fig. and most invasive carcinomas that develop are ductal rather than lobular. Typical growth patterns of ductal carcinoma in situ include A. It accounts for approximately 60 percent of all breast carcinomas and 70 percent of invasive breast can - NOS. 66417308 : ¸Ÿ±U 24 ¥°Q . B. biologic. Cribriform ductal. This indicates that LCIS may be a marker for the development of invasive breast cancer rather than its precursor. The system of nomenclature used here is a compromise derived from several studies and proposed classifications (Table 14-1). Infiltrating ductal carcinoma not otherwise specified (IDCNOS) is a heterogeneous group of lesions characterized by a relative absence of histologic features that define other special forms of breast carcinoma. noncomedo type. and clinical features have not produced definitive results because breast carcinomas are a heterogeneous group of tumors. Major Histologic Types of Breast Carcinoma and Their Relative Incidence for All Stages Combined Invasive Breast Carcinoma Invasive breast carcinoma accounts for approximately 90 percent of all breast cancers. the breast after excision of LCIS increases by approximately 1 percent per year. The risk is bilateral.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Papillary ductal pattern.

nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . B. Acinar and tubular. Common growth patterns include A. C. and D. NOS. Infiltrating ductal carcinoma.304 A B Fig. The foci of hemorrhage are due to previous biopsy. 14-14. Irregularly shaped fibrotic tumor does not have definite borders even though it seems to have been removed in toto. A B C D Fig. Infiltrating ductal carcinoma. Solid hypercellular. NOS. Typical scirrhous tumor presents as a stellate scar in the fat tissue of the breast. Acinar and solid. 66417308 : ¸Ÿ±U 24 ¥°Q . 14-15. B.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . A. with adequate normal peritumoral breast tissue. Solid desmoplastic.

chromatin pattern. The cytologic features of these subtypes are the same as those of classic ILC. Grade I. Grade III. median 10-year survival rates of 90 percent.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Histologically IDC-NOS is ap adenocarcinoma that has no distinctive features. (3) mixed. IDC-NOS usually presents as a firm mass that is gritty on cross section. or it may consist of solid strands or acini (Fig. and nucleoli (Fig. High power field. Infiltrating lobular carcinoma (ILC) accounts for approximately 15 percent of all invasive breast carcinomas. 14-17). It is clinically and biologically more aggressive than the special types of cancer separated from it. the tumor may present in several histologic variants. C. It may vary in size and shape and may present as a small stellate mass with indistinct borders or as larger fibrotic masses that are relatively distinct from the remainder of the breast (Fig. severe atypia. 14-15). 60 percent. However. such as (1) solid.305 cers. nuclear pleomorphism is assessed in the worst area. or desmoplastic. Using this grading system in prospective studies. In addition to the classic type. (2) alveolar. 66417308 : ¸Ÿ±U 24 ¥°Q . Nuclear grading is based on assessing the lesionis size and shape. Nuclear atypia in infiltrating ductal breast carcinoma. Grade II. the degree of nuclear pleomorphism. paucicellular. which shows single file ( " Indian file " ) cell arrangement. grade II. It may be cellular. 14-14). The median fiveyear survival rate for IDC-NOS is only approximately 60 percent. compared with 80 percent to 95 percent for the special types of cancer. and grade III lesions. B. respectively. moderate atypia. A B Histologic Grading of Breast Carcinoma *The percentage of tubule formation is based on assessment of the entire tumor. and 40 percent were associated with grade I. Table 14-2 shows the widely used Elston modification in which numeric scores are assigned to each of three major histologic features: the percentage of tubule formation. and mitotic counts are assessed at the leading edge of tumor growth. 14-16. 14-16). mild atypia. Several grading systems for IDC-NOS have been developed over the years. A.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . or (4) pleomorphic (Fig. C Fig. and the number of mitoses per 10 high-power fields based on microscopic evaluation of the entire lesion. HPF.

the tumor should be classified as IDC-NOS.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . For the most part these variants occur in a typical form. The lesions appear firm. Microscopically the tumor has blunt. with a 10-year survival rate of 80 percent to 90 percent. On cross section it appears lobulated. (5) Paget disease. Histologically the tumors are composed of small islands of malignant cells in a contiguous pool of extracellular mucinous material (Fig. (2) mucinous carcinoma. 14-18). 14-17. and the cells are arranged into solid nests that have a syncytium-like appearance (Fig. and D. Typical medullary carcinoma has a better prognosis than IDC-NOS. If the mucinous parts account for only 75 percent or less. Bizarre tumor giant cells and foci of squamous metaplasia may be seen in some tumors. and gelatinous. The mucinous part must constitute 90 percent of the total lesion if the tumor is to be classified as mucinous. with a fiveyear survival rate of 95 percent to 100 percent. Cytologic and nuclear features are those of a low. concurrent or subsequent contralateral breast cancer maybe present in up to 20 percent of patients.30 6 A B C D Fig. 1 cm in diameter or smaller. There may be a minor intratubular component. which is most prominent in the loose connective tissue stroma and at the margins of nests of neoplastic cells. The tumors contain a lymphocytic infiltrate. and (6) metaplastic carcinoma.to intermediate-grade malignant tumor. relatively soft. B. pushing borders.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Classic ("Indian file"). tan. and homogeneous in consistency. It has a favorable prognosis. 14-19). and stellate. Typical mucinous carcinomas have a very good prognosis with a 10-year survival rate in the range of 85 percent to 90 percent. which usually is circumscribed and measures 2 to 3 cm in diameter. However. Mucinous carcinoma. Tubular carcinoma accounts for approximately 5 percent of all breast cancers. Medullary carcinoma accounts for approximately 7 percent of all breast cancers. (4) cribriform carcinoma. Microscopically these tumors 66417308 : ¸Ÿ±U 24 ¥°Q . Infiltrating lobular carcinoma. Common growth patterns include A. Pleomorphic. Variants of Invasive Carcinoma Several variants of breast carcinoma that differ biologically from IDC-NOS and ILC have been described. wellcircumscribed. Alveolar.An in situ component is rare. white. (3) tubular carcinoma. Tumors present as soft palpable masses that produce vague. the most important of which are (1) medullary carcinoma. Solid. also known as colloid carcinoma. and usually is detected by mammography. C. accounts for approximately 2 percent to 3 percent of all breast cancers. Tubular carcinoma usually presents as a small mass. tan-white. soft. which usually is of the comedo type. glistening. It presents as a palpable mass. On cross section they appear circumscribed. nonspecific findings on mammography. but they also may have subtypes.

Cribriform invasive carcinoma is a recently described histologic entity that has biologic properties similar to those of tubular carcinoma (Fig. Medullary carcinoma. Mucinous carcinoma. Groups of tumor cells with clear cytoplasm form nests in the epidermis of the nipple. 14-22). Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The glands are uniformly distributed in centrally dense fibrous stroma with prominent elastosis. Tumor cells form small angular glands evenly distributed in the dense fibrous stroma. 14-21). Low-grade tumor cells form islands that contain round lumina. 14-21. Paget disease of the nipple.307 Fig. Clusters of well-differentiated cells appear suspended in pools of mucin-filled spaces between thin strands of fibrovascular stroma. The peripheral stroma is less dense. or angular ( " teardrop" ) shapes (Fig. Tubular carcinoma. are composed of small glands or tubules that have round. Cribriform carcinoma. Tumor cells form syncytia-like solid nests with pushing circumscribed margins surrounded by lymphocytes. Cribriform or micropapillary DCIS may be present in up to 65 percent of tubular carcinomas. oval. 14-20). and in these places the glands may invade the adjacent tissue. 14-18. Fig. 14-20. Fig. 14-22. 66417308 : ¸Ÿ±U 24 ¥°Q . Paget disease of the nipple presents as an eczematous rash or as a red oozing lesion of the nipple.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 14-19. Fig. It represents the intraepidermal spread of malignant cells that reach the skin through ducts that are involved with DCIS or high-grade ductal carcinoma (Fig.

Fig. Metaplastic bone is formed between sheets of carcinoma cells. PgR).308 Figure 14-23. and clear cell carcinoma (Figs. and p53 (Fig. or osteogenic sarcoma (Figs. chondrosarcoma. Rare forms of breast carcinoma account for less than 1 percent of all breast cancers. Figure 14-26. Ki-67. Pseudosarcomatous metaplastic carcinomas contain at least 20 percent of metaplastic elements. I mmunohistochemistry of Breast Carcinoma Immunohistochemical analysis is being increasingly employed by pathologists to measure unreported prognostic factors. Figure 14-27. Although these tests will undoubtedly play an important role in the future. salivary gland—like carcinoma. they have yet to be technically and clinically validated before they become part of routine practice. HER-2/neu. Metaplastic carcinoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . such as areas that resemble fibrosarcoma. invasive papillary carcinoma.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . including estrogen and progesterone receptors (ER. Metaplastic carcinoma. secretory carcinoma. Such tumors grow fast and have a poor prognosis. Included among these cancers are signet-ring carcinoma. 66417308 : ¸Ÿ±U 24 ¥°Q . This breast tumor is indistinguishable from equivalent carcinoma in the salivary glands. . Tumor has features of fibrosarcoma. Adenocystic carcinoma. 14-25. pS2. Tumor shows chondroid differentiation. 14-28). Invasive papillary carcinoma. 14-25 to 14-27). The tumor grows in a micropapillary pattern. Metaplastic carcinoma is a rare cancer that may present as squamous cell carcinoma and pseudosarcomatous carcinoma. Figure 14-24. Metaplastic carcinoma. 14-23 to 14-25).

Am J Surg Pathol 10:87-101. Hum Pathol 25:802-809. progesterone receptors. Am J Surg Pathol 14:12-23. Am J Surg Pathol 7:53-60. Berman M: Angiosarcoma of the breast. Lefkowitz M. Immunohistochemistry of breast cancer. Hertzel BF. Sheils LA: The cytopathology of proliferative breast disease. Semin Diagn Pathol 11:199-207. Tavassoli FA: Ductal carcinoma in situ: introduction of the concept of ductal intraepithelial neoplasia. Oberman HA: Hamartomas and hamartoma variants of the breast.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Love SM. Semin Diagn Pathol6:135-145. 1984. estrogen-induced protein pS2. Merino MJ. Anthony PP: Primary lymphoma of the breast. C. Proliferation-associated marker Ki-67. Hutter RVP et al: Practice protocol of the examination of specimens removed from patients with cancer of the breast. Histopathology 27:205-218. 1983. and F. Fechner RE: Frozen section examination of breast biopsies. Am J Clin Pathol 54:431-437. Interobserver variability in histopathologic diagnosis. Andersen JA. 1991. A nondisease? N Engl J Med 307:1010-1014. A study of 51 patients. Clinicopathologic study of 351 cases. Franklin S. 66417308 : ¸Ÿ±U 24 ¥°Q . Cancer 53:2557-2560. Gareen I. 1995. Bannayan GA. Dawson AE. Ellis I0: Phyllodes tumours of the breast: a clinicopathological review of thirty-two cases. 1995. Lesser M: Prognosis in infiltrating lobular carcinoma. 1985. A. 1982. Cancer 37:2891-2905. Lefkowitz W. Further Reading Andersen JA: Lobular carcinoma in situ. Semin Diagn Pathol 11:223-235. A long-term follow-up study of 32 cases. 1972. Am J Clin Pathol 103:6-7. Arch Pathol Lab Med 121:27-33. Happerfield LC. Carter D. Hajdu SI: Gynecomastia. Foschini MP et al: Long-term follow-up of in situ carcinoma of the breast. Rosen PP. Estrogen receptors. 1994. Histopathology 9:297-307. 1994. 1994. Telesinghe PU. A histological study of 52 cases. 1989. Gaffey MJ. Mod Pathol 11:140-154. Am J Clin Pathol 103:438-442. Frierson HR Jr et al: Medullary carcinoma of the breast. Caicco JA: Florid papillomatosis of the nipple. Oberman HA. 1974. p53 tumor-suppressor gene product. 1998. Elston CW. A clinicopathological study of 77 cases. Hensen DE. Gregory WM et al: The classification of ductal carcinoma in situ and its associations with biological markers. Feudale E. Blamey RW. An analysis of "classical" and variant tumors. 1976. 1995. HER-2/neu oncoprotein. Practice parameter. Wargotz ES: Intraductal (intracystic) papillary carcinoma of the breast and its variants. Moffat CJC. including nine with mammary carcinoma. Elston CW: Pathological prognostic factors in breast cancer. 1990. B. Gram JB: Radial scar in the female breast. Gelman RS. Kempson RL: Breast adenomas. Pinder SE. Histopathology 19:403-411. Mod Pathol 8:31-38. Mulford DK. Rosen PP. Mills SE.309 A B C D E F Figure 14-28. Bobrow LG. College of American Pathologists. 1997. Zaloudek C. 1986. Dixon AR. E. A publication of the Cancer Committee. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Eusebi V. Acta Pathol Microbiol Scand (A) 82:735-741.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Silen W: Fibrocystic "disease" of the breast. Di Costanzo D. D. 1995.

nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .66417308 : ¸Ÿ±U 24 ¥°Q .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

suprabasal acantholysis. and other pathogens. bacteria. Darier disease.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Hailey-Hailey disease. X-linked ichthyosis) but there also is an acquired form. ichthyosis vulgaris. Histologically the lesions show prominent partial acantholysis of the lower stratum spinosum (Fig. 15-1). neck. Porokeratosis. It affects men more often than women. The diseases usually are hereditary (e. is an autosomal dominant disease whose presenting symptoms include lesions of the scalp. 15-I. known as cornoid lamella (Fig. 15-4).g. which become crusted and fissured. individually keratinized cells (grains) (Fig. 15-2. The basic lesion is a papule that is 1 to 3 mm in diameter. Plaques often are found in the axillae. often with an atrophic center. lamellar ichthyosis. or familial benign pemphigus. 15-2). A suprabasal cleft is formed. These lesions become confluent. 15-3. or diffuse or localized keratoses. forming scales. and formation of rounded cells (corps ronds) and oval. Histologically the basic lesion consists of a broad zone of hyperkeratosis with parakeratosis. Secondary infection is common. 15-5). Ichthyosis vulgaris. such as recurrent bullae in epidermolysis. which are found floating in the cavity. bullosa. In well-developed lesions. Ichthyosis is a term used to describe a complex group of disorders of keratinization characterized by formation of scales on the skin surface. neck. is an autosomal dominant disease that presents with small vesicles on an erythematous base. These papules become confluent. Fig. 15-3). Brown scaly papules form aggregates on the lateral surface of the shoulder. fungi.312 HEREDITARY SKIN DISEASES Hereditary skin diseases (genodermatoses) present in many forms. or keratosis follicularis. I NFECTIONS Fig. and upper chest in a distribution resembling that of seborrheic keratosis. or intertriginous zones that are predisposed to friction and excessive moisture. here from right to left. Porokeratosis is a disease that is characterized by the formation of small papules with surface scale that progressively enlarge to form a sharply demarcated ring of hyperkeratosis. It may be more widespread and also may involve mucosal surfaces and nails. The skin often is infected by viruses. Darier disease. Cornoid lamella is formed by a column of parakeratosis overlying slightly vacuolated keratinocytes that have migrated centrifugally. the basal layer forms villi that project into the clefts. Histologically all forms of ichthyosis are characterized by hyperkeratosis..·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Ichthyosis vulgaris. a common autosomal dominant disease. Autosomal dominant transmission has been suggested for the variant known as porokeratosis of Mibelli. The extensor surface of the arm is covered with polygonal scales. involves in a symmetric manner the exterior surfaces of the limbs and the trunk (Fig. leading to detachment of groups of cells and a few individual cells. protozoa. The dermis beneath the cornoid lamella contains a lymphocytic infiltrate. Histologically the ring of hyperkeratosis is represented by a discrete parakeratotic column of hyperkeratosis. 15-6). Fig. Dermal inflammation is minimal. forming erythematous plaques (Fig. keratotic surface (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Superficial bacterial infections exacerbate or trigger the development of these lesions. with a dirty gray-tan.

The bulbous form is caused by Staphylococcus aureus. 15-7).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 66417308 : ¸Ÿ±U 24 ¥°Q . Fig. 15-4. A cleft is formed as a result of acantholysis of the lower strata of epidermis. Impetigo contagiosa (nonbullous type) most often is caused by streptococci. 15-8. In this bullous lesion a blister containing pus has formed below the stratum granulosum.313 Fig. Hailey-Hailey disease. The papules and vesicles have fused to form a fissured plaque with a scaly surface. A suprabasal cleft is formed as a result of acantholysis of deeper parts of the epidermis. Impetigo. Hailey-Hailey disease. Vesicles rupture to produce a yellow or honeycolored surface crust (Fig. Bacterial Infections Impetigo is a clinical diagnosis that denotes superficial bac- terial infection of the epidermis. Fig. which results Fig. Fig. The infection begins in the form of small papules that become thin-roofed vesicles. The lesions are erythematous and covered with yellow-white purulent crusts.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Darier disease. Impetigo. 15-5. 15-7. Staphylococci cause extensive cleavage of epidermis in the upper layers. 15-6. The clefts contain rounded cells (corps ronds) and oval individually keratinized cells (grains).

Clinically HSV and VZV present in the form of a vesicular exanthema on erythematous skin (Fig. Fig. often multiple papules or larger excrescences. and less commonly cytomegalovirus (CMV). 15-9). except for verruca plana. These chronic skin lesions present as localized. 15-17). Secondary bacterial infections are common. or Malassezia.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Viruses grow in keratinocytes. Keratinocytes infected with herpesviruses show ballooning degeneration and often become multinucleated (Fig. Fungal hyphae and spores are evident in the stratum corneum. causing widespread cellulitis. Fungal infection of hair follicles may cause deep folliculitis and abscesses. 15-13 and 5-14). or blisters. As the viral aggregates are extruded into the stratum corneum. 15-16).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Tinea. varicella-zoster virus (VZV). Majocchi granuloma. Tinea versicolor. This skin lesion in part is caused by the uptake of HIV into the Langerhans cells and Fig. In ruptured lesions the dermis shows a strong inflammatory response. Histologically the papule shows striking acanthosis of the epidermis with some extension into the dermis (Fig. 15-10. Vesicles formed as the result of acantholysis of epidermis are associated with a variable inflammatory response in the dermis. bowenoid papulosis. 15-9. which leads to minimal elevation of the skin (Figs. Lesions often are annular and show scaling with central clearing (Fig. Deeper bacterial infections may involve both the epidermis and the dermis (pyoderma) and may extend into the subcutis. Fungal Infections Tinea is the name for epidermal infections caused by fungi. type I and type II. This superficial fungal infection (ringworm) appears as a round scaly erythema with central clearing. or epidermodysplasia verruciformis. Histologically impetigo contagiosa shows collections of neutrophils in the epidermis beneath the stratum corneum. The lesions vary in appearance and may present as papules. herpes zoster virus (HZV). known as dermatophytes. Fig. which have been named kerion or Majocchi granuloma (Fig. This fungal infection of the hair follicles presented as a dermal abscess. Histologically the skin shows acute and chronic inflammation surrounding cellular debris and fragments of hair and fungi (Fig. The skin infection may present as a solitary lesion or as umbilicated papular lesions. Herpes simplex virus (HSV) infections of the skin may be caused by any of the several HSV viruses. Histologically there usually is a superficial infestation with fungal yeast and hyphae with variable inflammation in the dermis (Fig. some of which are surrounded by an erythematous ring. but they most often are caused by HSV.314 in the formation of bullae or extensive exfoliation. condyloma acuminatum. Trichophyton. 15-11). plaques. filling their cytoplasm in the form of eosinophilic inclusions. In bullous impetigo the blister is below the level of the granular layer (Fig. Viral Infections Human papillomaviruses ( HPV) of several types may infect the skin and cause warts (verruca vulgaris or verruca plana). Intranuclear viral particles account for their " ground glass " appearance. 15-10). 66417308 : ¸Ÿ±U 24 ¥°Q . may cause a psoriasiform dermatitis. which usually belong to the genera Microsporum. 15-11. Human immunodeficiency virus ( HIV). Molluscum contagiosum is a DNA virus (deoxyribovirus) of the pox family. Epidermophyton. 15-12). 15-8). they become basophilic.1 and HSV-2. 15-15).

Neutrophils surround a centrally located hair covered with fungal spores and hyphae. Human papillomavirus type 3 has caused hyperpigmented. Herpes simplex virus infection. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Molluscum contagiosum. Fig. 15-15. multiple skin lesions. I 5-12. 15-17. Majocchi granuloma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Perioral skin shows grouped vesicles. which have pale nuclei and multinucleation. Fig. Fig. only slightly elevated. The keratinocytes in the upper spinous layer show typical vacuolization. Fig. Acanthotic invaginations of the epidermis contain cytoplasmic inclusions of viral particles. 15-16. Verruca plana. 15-14.315 Fig. Early changes include ballooning degeneration of midepidermal keratinocytes. 66417308 : ¸Ÿ±U 24 ¥°Q . Verruca plana. 15-13. Herpes zoster.

which results in the formation of subepidermal bullae. Necrotic keratinocytes and fragments of lymphocytes are seen focally. 15-18. I NFLAMMATORY DERMATOSES Acute and chronic dermatoses may be related to an immune or metabolic injury. The initial erythematous lesions show spongiosis and an infiltrate in the epidermis that contains many eosinophils as well as lymphocytes and neutrophils. leaving behind reddened. preferentially affecting the legs. thighs. and leukocytoclasis of lymphocytes but lack suprapapillary thinning (Fig. 15-22). Erythema multiforme is a common immune-mediated disease that represents a hypersensitivity response to a variety of antigens. 15-19). The blister cavity contains Fig. 15-20). It is the most common blistering disease of the elderly. Bullous pemphigoid is a chronic blistering disease that occurs in several forms. flaccid blisters form and rupture. An acantholytic cleft separates the basal cell layer. In the most common form. 15-19. 15-18). The dermal inflammatory infiltrate contains neutrophils and scattered eosinophils (Fig. Immunoglobulin G (IgG) may be demonstrated by immunofluorescence (IF) microscopy on the surface of keratinocytes in the lower layers of the epidermis (Fig. HIV infection. The dermal infiltrate usually is superficial and is located around the blood vessels and diffusely in the papillary dermis. and other changes in the body. IgAmediated. Fig. Pemphigus vulgaris. and lower trunk. Granular deposits of IgA may be seen by IF microscopy in the tips of dermal papillae.herpetic lesions appear on the extensor aspects of the legs and arms. forming larger bullae. Histologically the blisters start at the tips of dermal papillae and then become confluent. Pemphigus vulgaris.316 Fig. pemphigus vulgaris. IF microscopy shows linear deposits of IgG along the cell membrane of basal keratinocytes. Histologically the lesions differ from classic seborrheic dermatitis or psoriasis in that they show necrosis of keratinocytes. but most often they have a complex pathogenesis. 15-20. The disease occurs at any age. although it is more common in children and young adults.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . metabolic.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . from the superficial layers of the epidermis. blistering disease that often is accompanied by a sensitivity to gluten in the diet. IgG deposits may be demonstrated along the dermoepidermal basement membrane by IF microscopy (Fig. 15-23). eosinophils and neutrophils. eroded skin. Histologically the blisters present as clefts just above the basal row of keratinocytes with minimal necrosis (Fig. It is characterized by a split in the lamina lucida portion of the basement membrane. This psoriasiform dermatitis of AIDS shows acanthosis of the epidermis and a scant dermal lymphocytic infiltrate. 15-21). In many cases the pathogenesis of such dermatoses is not known. There are two 66417308 : ¸Ÿ±U 24 ¥°Q . Small pruritic vesicles that resembl. Immune-mediated Dermatoses Pemphigus is a term that encompasses several diseases that are characterized by the formation of intraepidermal blisters caused by the binding of antibodies to the cell membrane of keratinocytes. Vesicles and bullae form at the dermoepidermal junction (Fig. which is still attached to the basement membrane. Dermatitis herpetiformis ( Duhring disease) is a rare. in part is a reflection of immune.

this disease is characterized by a rather sparse lymphocytic dermal infiltrate. 15-23. The same type of immune reaction may result from hypersensitivity to microbes or from malignant tumors. 15-21. Fig. The blister is subepidermal and its cavity contains proteinaceous fluid and inflammatory cells. 15-24. Secondary infection is common. The early blisters contain fragmented lymphocytes and necrotic keratinocytes. Dermatitis herpetiformis. It also may be part of a systemic autoimmune disease. In all forms of lupus erythematosus there are autoantibodies to DNA virus and a variety of other antigens. Erythema multiforme. which show a tendency to aggregate at the tips of dermal papillae. Fig. 15-24).317 Fig. often mild form that is intermediate between SLE and DLE is called subacute lupus erythematosus. but ulti - mately the entire epidermis becomes necrotic. dusky gray. Bullous pemphigoid. In contrast to classic erythema multiforme. SLE is associated with arthritis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and the underlying dermis usually shows a lymphocytic infiltrate. such as systemic lupus erythematosus. Fig. A third. which are called iris lesions or target lesions. Both forms present with distinctive skin lesions. Stevens-Johnson syndrome presents as a generalized blistering disease that involves the entire body and the oral and ocular mucosae. The targetoid lesions on the palms have a central. forms: erythema multiforme minor and Stevens-Johnson syndrome. especially in the most severe systemic form of the disease. In the minor form erythema multiforme tends to occur on the extremities or on the trunk. which is known as toxic epidermal necrolysis. Skin lesions appear atrophic and 66417308 : ¸Ÿ±U 24 ¥°Q . and many other disorders. By definition more than 30 percent of the skin surface is involved. Histologically the disease is characterized by perivascular dermal infiltrates of lymphocytes. During the first 24 hours deposits of IgM are found in the walls of small blood vessels of dermal papillae by IF microscopy.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . kidney disease. Lupus erythematosus is an autoimmune disorder that may present as a systemic disease (SLE) or in a localized form as discoid lupus erythematosus (DLE). Blisters form as a result of necrosis of basal keratinocytes. The subepidermal blister contains neutrophils. 15-22. which is related to hypersensitivity to drugs. Bullous pemphigoid. necrotic center. These skin lesions consist of a zone of erythema with a pale center or a central vesicle (Fig. A band of IgG is found along the dermoepidermal junction.

15-25. Malar erythema ( " butterfly rash") is common in SLE (Fig. Atrophic epidermis covers sclerotic dermis. 66417308 : ¸Ÿ±U 24 ¥°Q . Appendages often are destroyed. DLE. although in the beginning both diseases have many common features. necrotizing vasculitis. Infiltrates of lymphocytes center around blood vessels and skin appendages. and if this destruction extends into the subcutis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Epidermal atrophy is common. Lymphocytic infiltrates are found at the dermoepidermal junction. DLE. which contains superficial and deep perivascular appendages and infiltrates of lymphocytes around blood vessels and skin appendages. telangiectasia. 15-26. Histologically DLE differs from SLE. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Periodic acid—Schiff method stains a thickened basement membrane. acute systemic disease. Nonspecific but disease-related manifestations include urticaria. and bullous eruptions. If the lesions are concentrated in the subcutis. 15-28.318 tend to occur on sun-exposed skin. Lupus erythematosus. Hydropic changes of the basal layer are accompanied by necrosis of keratinocytes. Raynaud phenomenon. This patient with acute lupus erythematosus has a classic red "butterfly rash" over her malar areas. Hyperkeratosis of patulous hair follicles is prominent. SLE. Advanced lesions have thick basement membranes and a dermis that is sclerotic. Fig. 15-26). the term lupus Fig. Chronic discoid lupus is characterized by prominent epidermal atrophy and prominent infiltrates of lymphocytes in the superficial and deep dermis (Fig. 15-27. The reticular dermis appears edematous and contains increased amounts of hyaluronic acid. 15-25). the disease is called lupus erythematosus profundus. The eroded erythematous surfaces weep fluid. Early changes include infiltrates of lymphocytes at the dermoepidermal junction with foci of necrosis of ker- atinocytes and surface parakeratosis (Fig. 15-27). Infiltrates of lymphocytes in the deeper dermis are found around the skin appendages and blood vessels. and hypocellular (Fig. 15-28). The dermis contains scattered lymphocytes and melanophages. Fig. eosinophilic.

Skin lesions are most prominent on the upper eyelids and cheeks. Early lesions contain IgM and complement. 15-32). Skin atrophy develops over time. nail folds. and dorsal surface of the knuckles. Deposits of immunoglobulins without complement are found in the sunprotected skin in approximately 50 percent of patients with SLE. IgA. telangiectasia. Granulomas also typically form in the skin as part of a type IV. (3) granuloma annulare. Granulomatous Diseases Granulomatous reactions in the dermis may be elicited by mycobacteria. panniculitis is applied. cell-mediated hypersensitivity reaction. 15-31).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Mixed connective tissue disease is an autoimmune disorder that has some features in common with SLE. and giant cell arteritis.319 Fig. as typically found in Wegener granulomatosis. (2) granulomatous vasculitis. and sun-exposed skin shows deposits in 70 percent of these patients. and fibrin. Granuloma annulare. but later there also are deposits of IgG. Papules are distributed on the extremities in an annular manner. (5) erythema nodosum. and (7) rheumatoid nodules. Lesions also appear on the elbows and knees. 15-3I. Granuloma annulare presents in the form of papules arranged in an annular manner (Fig. Histologically the lesions show foci of mucin and fibrin deposition in the superficial dermis surrounded by macrophages (Fig. Histologically the skin lesions are subtle. are typical (Fig. and occasional hypopigmentation. (6) erythema induratum. such as M. 15-30. granulomatous diseases according to their clinical and histopathologic features. It is characterized by antibodies to nuclear riboproteins and a lack of antibodies to native DNA. tuberculosis or M. patients develop symmetric erythematous skin lesions on the face (Fig. which form gran- ular deposits along the epidermal basement membrane. Fig. in many instances it is not possible to identify an inciting antigen. Dermatomyositis. there are no deposits of immunoglobulin along the dermoepidermal junction. edema. Dermatomyositis is an autoimmune disease in which the primary target organs are the skin and skeletal muscle. on the hair follicles. Immune complexes. 66417308 : ¸Ÿ±U 24 ¥°Q . (4) necrobiosis lipoidica. Diffuse erythema symmetrically involves the cheeks and upper eyelids. and polymyositis. and thus it is more convenient to classify various Fig. Granular deposits of immunoglobulin and complement are seen along the dermoepidermal junction. The cause of this disease is not known. Churg-Strauss syndrome. or by fungi. 15-30). with some similarity to those of acute SLE.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . SLE. In contrast to SLE. There is slight hyperkeratosis. Skin lesions resemble those of SLE and scleroderma. scleroderma. and occasionally diffusely spread in the papillary dermis and in the blood vessels. The causative pathogen may be demonstrated by special stains. leprae. In both the childhood and the adult forms of dermatomyositis. The most important noninfectious granulomatous diseases are (1) sarcoidosis. 15-29). However. 15-29.

most often on the posterior calf (Fig. but most often it is a reaction to streptococcal or other infection. They respond favorably to tuberculostatic therapy. Depressed areas reflect tissue necrosis caused by the underlying vasculitis. The lesions may ulcerate and heal by scarring. and in such cases it is considered to be a type IV hypersensitivity reaction. 15-36). show erythematous deep subcutaneous nodules. and the amount of collagen increases (Fig. It may be part of generalized sarcoidosis. 15-34. it represents a hypersensitivity reaction to mycobacterial infection in some other part of the body. Erythema nodosum. Erythema nodosum is an inflammatory lesion of the subcutis that typically presents in the form of erythematous painful nodules on the anterior shin (Fig. Histologically it involves the connective tissue septa of the subcutis. 15-34). The lesions may spread to other parts of the legs. Erythema induratum. firm. Lesions of this type that develop in patients who are not infected with M. that is. Deposits of fibrin and mucin in the upper dermis are surrounded by macrophages penetrating between the collagen bundles. which-is the favored site for these lesions.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Initially the septa are widened by infiltrates of lymphocytes. 15-32. Erythema induratum is one of the classic tuberculoids. 15-35.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . erythematous nodules. Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . 15-35). Granuloma annulare. Histologically there are signs of necrotizing vasculitis with neutrophilic infiltrates affecting arteries and veins in the fat lobules of the subcutis (Fig. Lymphocytic infiltrates extend into the fat lobules. Fig. as the lesions evolve. Erythema nodosum. Deep erythematous nodules are typically found on the legs.. and the infiltrates may extend into the fat tissue. Later. Small compact granulomas often are present. The connective tissue septa of the subcutis are widened. and even the face. and eosinophils. tuberculosis are called nodular vasculitis. The skin lesions present as painful. Erythema nodosum may have many causes. 15-33.320 Fig. The shin. neutrophils. Fig. 15-33). the-septa become infiltrated with lymphocytes and macrophages. Multinucleated giant cells and eosinophils may be present. fibrotic. the hands. and infiltrated at their edges with lymphocytes. Focal hemorrhages are common.

The intervening dermal papillae are edematous and contain dilated capillaries surrounded by scattered lymphocytes. Fig. Psoriasis. intergluteal groove. face. 15-37). Lymphocytic infiltrates extend into the fat tissue. knees. Parakeratotic layers may contain nuclear debris (Munro microabscesses). The early skin lesions present histologically with spongiosis with neutrophils and lymphocytes at the orifices of hair follicles (Fig. such as the scalp. The epidermis overlying the dermal papillae is thin. 15-38. 15-36. It is covered with a crust of parakeratosis and many neutrophils.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Psoriasis is considered to be a disorder of proliferation and differentiation of keratinocytes that results in irregular acanthosis of the epidermis. Nodular vasculitis. 15-38). The skin shows deep erythema and is covered with silvery scales. scalp. Idiopathic Skin Disease Psoriasis is a common skin disease of unknown etiology. Pityriasis rosea is a rather common transient papulosquamous disease that presents in the form of erythematous papules or small plaques. Histologically the lesions show a surface scale of parakeratosis with slight spongiosis but without microvesicula- 66417308 : ¸Ÿ±U 24 ¥°Q . Seborrheic dermatitis is a chronic scaling spongiotic and psoriasiform dermatitis of unknown etiology that affects approximately 3 percent of the total population in the United States. The acanthotic epidermis shows bridging of thickened rete ridges. Pityrosporum yeasts may be seen in the parakeratotic surface crusts. The inflammation is centered around medium-sized arteries in the fat lobules of the subcutis. The disease affects skin that has prominent sebaceous follicles. The epidermis lacks stratum granulosum and typically is covered with alternating zones of keratotic and parakeratotic scales. Foci of spongiosis of the upper epidermal layers infiltrated with neutrophils and occasional lymphocytes are known as spongiform pustules of Kogoj. 15-39). It ranges in severity from common minimal dandruff of the scalp to the severe but rare Leiner disease (erythroFig. and central chest. The skin lesions appear as relapsing and remitting papulosquamous plaques and silvery scales (Fig. The dermal papillae are edematous and contain dilated vessels surrounded by scattered lymphocytes and some extravasated red blood cells. Psoriasis. It affects 1 percent to 2 percent of the entire population in the United States.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . With the progression of the disease the interfollicular epidermis becomes involved. often arranged in the axes of skin lines. 15-37. and the lesions may resemble psoriasis. derma desquamativum) of neonates. supraorbital region. and the nails.321 Fig. The epidermis typically has thickened rete ridges that extend into the dermis (Fig. although they typically show much more spongiosis. The skin lesions most often are found over the elbows.

and early fibrosis of the papillary dermis. or Mucha-Habermann disease. 66417308 : ¸Ÿ±U 24 ¥°Q . 15-40. and the amount of acanthosis may be variable. Fig. Lymphocytic infiltrates and hemorrhages may be seen in the dermis extending into the epidermis. or chronic superficial dermatitis. and the epidermis is spongiotic and covered with thin parakeratotic scales (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . slight spongiosis. The unit lesion is a papule with slight spongiosis. Fig. typically affects children and young adults.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . This disorder may include several disease entities that present with slightly scaly. 15-42. xanthoerythroderma perstans.322 tion or neutrophilic infiltration (Fig. Seborrheic dermatitis. 15-41. Parapsoriasis. Foci of hemorrhage and lymphocytic infiltrates in the upper dermis extend into the epidermis. The scale is focal and loosely attached. erythematous macules and plaques that have a fine scale and orange-red color. Small plaque parapsoriasis is a chronic macular to papular scaling disorder of unknown etiology. The histologic changes are very subtle and often do not allow for a definitive diagnosis. 15-40). Pityriasis lichenoides and varioliformis acuta (PLEVA). The dermis shows sparse lymphocytic infiltrates around the vessels of the superficial plexus. and a lymphocytic infiltrate with a few small hemorrhages extending from the papillary dermis into the epidermis. It is more common in males than in females. Fig. Spongiosis and parakeratosis of the epidermis of the orifice of the hair follicle is associated with mild inflammatory infiltrates. Fig. which shows hyperkeratosis and necrosis of individual keratinocytes. It is also known as digitate dermatosis. Pityriasis lichenoides et varioliformis acuta (PLEVA). Pityriasis rosea. 15-41). 15-39. surface parakeratosis. A superficial perivascular lymphocytic infiltrate is accompanied by slight hyperkeratosis.

Histologically the lesions show a superficial and deep perivascular lymphocytic infiltrate that extends into the epidermis (Fig. and nevus. Lentigo. 15-42). I Regression of the dermal portion of a lesion can lead to fibrosis. The epidermis shows slight acanthosis and parakeratosis. or subcutaneous. 66417308 : ¸Ÿ±U 24 ¥°Q . Lamellar fibroplasia at the tips of rete ridges can be a residual component in melanomas that arise in disordered nevi. slightly scaly macules or papules. pigmented macule that is less than 5 mm in diameter and has a uniform brown color.323 with a 3:1 ratio. and metastatic melanomas may have symmetry. Freckles appear on sun-exposed skin. and occasionally small plaques. ically it is characterized by elongation of rete ridges. Lentigo may be associated with sun damage (solar lentigo). These lesions typically are found on the arms. or with polyps of the gastrointestinal tract NEOPLASMS AND RELATED DISORDERS Tumors of the skin are classified according to their site of origin as epidermal. lentigo. *. Melanoma in situ does not have a dermal component. t . +++ =very striking feature in almost all lesions. + = common. malignant pigmented lesions are called malignant melanomas (Table 15-1). discrete. buttocks. Hemorrhages in the papillary dermis extend into the dermis. +/—=rare or uncommon. ++ = present in almost all lesions. nearly round.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . At birth. Meaning of scale: —=absent. I. HistologComparison of Melanocytic Lesions* Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . but it also occurs in association with hypertrichosis on the shoulders of young men (Becker nevus). The palms show multiple pigmented lesions. Ephelis or freckle is a small. Ulceration may result from extensive epidermal necrosis. 15-43). increased pigmentation of basal keratinocytes. small melanomas. hyperpigmented lesion that is not limited to sun-exposed skin (Fig. and in some recurrent junctional components of nevi after surgery or trauma. 15-44). §. dermal. It presents with small round to oval. occasionally in acral nevi in young patients. 15-43. legs. Melanocytes are not increased in number. which appear in crops and disappear spontaneously. The tendency to form freckles is transmitted in an autosomal dominant manner. round to oval. Pigmentary Lesions Benign pigmentary lesions include ephelis. Histologically freckles are characterized by an increased amount of melanin in the basal keratinocytes. t . and according to their biologic characteristics as benign or malignant. as well as single cell necrosis associated with invading lymphocytes. and an increased number of melanocytes (Fig. Nodular melanomas. or trunk. Lentigo is a discrete.

Nevertheless. which do not show proliferation of keratinocytes. The epidermis shows slight thickening of rete ridges. 15-44. in contrast to malignant melanomas. Melanocytes show atypia that may be mild. In some enlarged nevi there is grossly visible irregular pigmentation (Fig. These lesions. which form elongated rete ridges. 15-46. Melanomas also show upward proliferation of melanocytes. as are individual melanocytes on slightly distorted rete ridges. Lentiginous junctional nevus with minimal architectural disorder and cytologic atypia (MIN-I).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and hyperpigmentation of basal keratinocytes at the rete ridges. However. Numeric grades may be applied. 15-47. and nucleoli are not visible. This lesion is larger than 6 mm in diameter. II. or III (see Figs. grade I. Lentiginous lesion may be static and unchanging or they may progress from simple lentigo to lentiginous nevi.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . all of these lesions involve keratinocytes. formerly called dysplastic junctional melanocytic nevi. moderate. It is irregularly pigmented and shows inflammatory erythema at its borders. Lentigo. or severe. When the melanocytes form rounded nests of nevus cells on the elongated rete ridges. Fig. histologic distinction between atypical lentiginous lesions and melanoma may be difficult. 15-46 to 15-48). The nests of nevus cells distort the rete ridges more than those in MIN-I. followed by the exten - 66417308 : ¸Ÿ±U 24 ¥°Q . The nuclei are larger. 15-45. The nevus cell nuclei are small. Histologically such lesions show architectural disorder such as elongation and distortion of rete ridges and fibrosis of the papillary dermis (Fig. Compound melanocytic nevus is formed by the proliferation of nevus cells in the epidermis. and a few cells have visible nucleoli. Junctional nevus with architectural disorder (dysplastic nevus). increased prominence of a few melanocytes. and are graded from mild to severe. and the lesions are designated melanocytic intraepidermal neoplasm ( MIN). 15-46). and pigmentation of mucosae of the mouth and other body ostia (Peutz-Jeghers syndrome). Nests of nevus cells are present. the preferred term is lentiginous junctional melanocytic nevus.324 Fig. Fig. now are called junctional melanocytic nevus with architectural disorder and atypism of melanocytes. The papillary dermis is fibrotic. Lentiginous junctional nevus with moderate architectural disorder and cytologic atypia (MIN-II). Fig. 15-45).

15-46 to 15-48) are accompanied by dermal changes. The epidermal changes of such lesions (see Fig. Congenital compound melanocytic nevus. 15-51. Proliferated melanocytes (nevomelanocytes) form nests at the dermoepidermal junction (Fig. There is no intraepidermal upward migration of individual atypical melanocytes. Compound melanocytic nevus with architectural disorder. with rather uniform brown pigmentation. symmetric. Fig. sion of these cells. 15-51). Compound melanocytic nevus. Junctional melanocytic nevus with severe architectural disorder and cytologic atypia (MIN-III). Dermal 66417308 : ¸Ÿ±U 24 ¥°Q . Compound melanocytic nevi are slightly raised. 15-50. The size of nevus cell nests also decreases in size. their nuclei and cytoplasm diminish in size. Compound melanocytic nevus with architectural disorder differs from the typical compound melanocytic nevus in that the junctional component extends for many rete ridges beyond the region that contains the dermal component (Fig. with certain cytologic modifications. and are round-to-oval. and nucleoli are prominent. into the dermis. have a smooth outline. and only 1 percent of whites are born with a congenital compound melanocytic nevus. Congenital compound melanocytic nevi often have a slightly irregular outline with peripheral speckling of the pigmentation. Fig. They remain less that 6 mm in diameter. Most compound nevi are acquired after birth. Each nest of melanocytic nevus cells is surrounded by a fibrillar basement membrane. The nuclei are enlarged. They vary in size and occasionally may cover segments of the skin as so-called giant congenital nevi (Fig 15-49). This intermediate-sized lesion shows peripheral speckling of pigmentation. The nests of nevus cells are almost confluent on the distorted rete ridges. The nests of nevus cells appear irregular and distort the rete ridges. 15-50).325 Fig. The epidermal component extends several rete ridges beyond the dermal component. Histologically compound melanocytic nevi have sharply circumscribed lateral borders. Some compound melanocytic nevi have prominent individual melanocytes on elongated rete ridges. The cells in the deeper reticular dermis are dispersed and smaller than those at the dermoepidermal junction. and the cells tend to become dispersed in a fine collagenous matrix. as in lentiginous nevi. Fig. As the nevus cells extend into deeper reticular dermis. 15-49. 15-48.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

but they tend to be more common in the older age groups. The junctional lesion is accompanied by dermal lamellar fibroplasia in the form of collagen layers parallel to the surface of the skin. Lentigo maligna melanoma (LMM) most often occurs on the face of elderly persons with very sun-damaged skin and accounts for approximately 15 percent of cases of malignant melanoma (Fig. It characteristically has a long intraepidermal growth phase. Fig. 15-53. Spitz nevus is a variant of compound nevi that is found in children and young adults. 15-52. Smaller groups of cells have descended into the dermis. estimated to affect 1 in every 70 whites in the United States. There usually is a mixture of spindle-shaped and epithelioid melanocytes. 15-52). 15-55). 15-55. Spitz nevus. and a single large round nucleolus (Figs. 15-54. Fig. Spitz nevus and its variants occasionally may be difficult to distinguish from malignant melanoma. but in addition it contains large cells with large nuclei and finely dispersed delicate chromatin. malignant melanoma.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and it forms a spindle cell nodule Fig. Malignant melanoma is a malignant tumor of melanocytes. Mitoses are common in the upper part of the lesion but not in the deeper dermal parts. sharp nuclear envelope.326 changes include fibrosis at the tips of rete ridges. become dispersed between the collagen bundles. or condensation of eosinophilic collagen bundles around the tips of rete ridges (concentric eosinophilic fibrosis) (Fig. Spitz nevus. Epidermal hyperplasia is associated with a proliferation of large epithelioid and spindle-shaped melanocytic nevus cells that form nests at the dermoepidemal junction. is called pigmented spindle cell nevus of Reed. which shows pigmentation and is restricted to the epidermis and papillary dermis. Malignant melanomas may occur in any age group. and cease mitotic activity. It has all the features of compound nevi. 66417308 : ¸Ÿ±U 24 ¥°Q . arranged parallel to the skin surface (lamellar fibroplasia). the cells decrease in size. The cells become smaller as they descend into the dermis and are less cohesive. Fig. 15-53 and 15-54).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Certain patterns of clinical presentation have been defined. At the base of the lesion. Variant Spitz nevus. Lentigo maligna. Compound melanocytic nevus with architectural disorder.

the term neurotropic melanoma is applied. Acral lentiginous melanoma accounts for approximately 5 percent of all cases of malignant melanoma. It originates in the skin of distal extremities that often are protected from the sun. 15-58). Fig. The nuclei usually contain prominent nucleoli. A B Fig. Desmoplastic melanoma. 15-59. Fig. 15-57). The invasive nodule is composed of spindle-shaped atypical melanocytes. 15-56. Desmoplastic melanoma. Malignant melanoma. but characteristically it contains highly dendritic cells and often small melanoma cells (Fig. 15-59).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 15-56). Histologically it has an intraepidermal and a dermal component (Fig. Fig. A. 15-58. Malignant melanoma.327 in the dermis (Fig. 15-60). It has mostly a dermal neoplastic component with relative sparing of the adjacent epidermis. a distinctive histologic variant that is associated with minimal lentiginous proliferation of atypical melanocytes in the epidermis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 15-57. A well-circumscribed nodule is protruding above the skin surface. Malignant melanoma cells vary in size and shape and may proliferate as individual cells or in small groups. It presents as an irregularly shaped maculopapular lesion with varied pigmentation (Fig. When desmoplastic melanomas form structures that resemble nerves or invade nerves in the dermis. Lentigo maligna melanoma. Spindle-shaped cells showing nuclear atypia are intermixed with fibroblasts and bundles of collagen. Superficial spreading melanoma accounts for 60 percent of cases of malignant melanoma. It may have a prolonged epidermal phase. There is no pigment. Acral lentiginous melanoma has the growth pattern of lentigo maligna melanoma or a superficial spreading melanoma. Superficial spreading malignant melanoma with invasion. Atypical melanocytes may be seen in the superficial stratum corneum and the granular layer of the epidermis. This superficial spreading melanoma has invaded the dermis. B. 66417308 : ¸Ÿ±U 24 ¥°Q . Nodular melanoma accounts for 15 percent of all cases of malignant melanoma and presents as a well-circumscribed hyperpigmented nodule. The lesion appears multinodular and shows pale gray scaly foci of atrophy or regression. Nodular melanoma. typically presents in the form of spindle-shaped amelanotic cells in a fibrous and myxoid stroma (Fig. The cytoplasm may be well developed and pigmented or scant and nonpigmented. It may be difficult to distinguish it from scar.

respectively. Histologically it is composed of nests and strands of squamous cells. Several histologic variants are recognized. 15-62. The epidermis is acanthotic. The dermis shows signs of solar injury. Seborrheic keratosis. Seborrheic keratosis. It occurs in several histologic patterns. Squamous cell carcinoma most often occurs on sunexposed skin and presents as a nodular or ulcerated lesion (Fig. Actinic keratosis. all of which show acanthosis of the epidermis without cytologic atypia (Fig. hyperplastic actinic ker - Fig. B. It may be hyperpigmented and confluent and tends to bleed or ulcerate (Fig. is one of the most common neoplasms in whites. Squamous carcinoma in situ of sun-protected skin is known by several names. these lesions are called squamous intraepithelial neoplasia (SIN). also known as solar keratosis or senile keratosis. 15-62). 15-6I I. Fig. The prognosis of melanomas depends on the extent of tumor spread. The surface of the epidermis usually is keratinized. 15-63). Exophytic slightly yellowish skin lesion. invasive. The important histologic features that are useful in distinguishing malignant melanomas from other pigmented lesions are listed in Table 15-1. Bowen disease also is graded SIN-I. Acral lentiginous melanoma. The histologic diagnosis of malignant melanoma may be fraught with difficulties. In SIN I cytologic atypia is restricted to the basal layer. 15-61). According to the degree of atypia. or it is designated by levels Ito IV according to the systems developed by Breslow and Clark. It presents as a scaly. and the dermal papillae are fibrotic. As in typical Bowen disease. including Bowen disease or erythroplasia of Queyrat if it is found on the penis. It occurs mostly in the elderly as a well-demarcated. This slide was stained with the antibody HMB45 to show the dendritic melanocytes in the epidermis and the nodule of tumor cells in the dermis. SIN-II. Epidermal Tumors Seborrheic keratosis is a very common benign epidermal lesion that is known as verruca seborrheica.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 15-68). and large cell acanthoma. or III (Figs. 15-64 and 15-65). erythematous patch on sun-exposed skin. 15-66). which appear in the basal layer but spread through all layers of the epidermis (Fig. Pigmented lesion with a corrugated surface. grade I. Such lesions may be mistaken for malignant melanoma. 15-67). and SIN-III. Histologically the affected skin contains atypical keratinocytes with enlarged hyperchromatic nuclei arranged in an irregular pattern. 66417308 : ¸Ÿ±U 24 ¥°Q . this neoplasia is characterized by cytologic atypia of cells. mimicking acantholytic bullous disorders.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Histologically the extent of invasion maybe expressed in millimeters. and the suprabasal region may show acantholysis. and in SIN III the entire thickness of the epidermis is involved. flat to raised papule or plaque that is flesh-colored or yellow-pigmented with a rugose surface (Fig. Actinic keratosis is a precursor of invasive squamous carcinoma. Tumors may differ with regard to the level of differentiation and keratinization (Fig. including pigmented actinic keratosis. with interconnected rete ridges." atosis. A.328 A B Fig. lichenoid actinic keratosis. Small collections of keratin form "horn pseudocysts. 15-60. in SIN II the entire lower half of the epidermis contains atypical cells. II.

15-63. Fig. 15-67. Fig. Atypical keratinocytes replace almost the entire basal layer. Actinic keratosis (SIN-II). The tumor is composed of invasive nests of keratinizing squamous cells. The surface shows extensive keratosis and parakeratosis. Actinic keratosis (SIN-I). Foci of ulceration and hemorrhage occur because of the increased fragility of the skin. Fig. Bowen disease (SIN-III). Atypical keratinocytes are found in all layers of the epidermis. Confluent lesions on sun-damaged skin. Actinic keratosis. The irregularly shaped plaque on the forehead has a hyperkeratotic and hemorrhagic crust. The lower half of the epidermis has been replaced by atypical keratinocytes. Decreased cohesiveness of the cells cause suprabasal cleavage.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 15-65. I5-66. Squamous cell carcinoma. 15-68. 66417308 : ¸Ÿ±U 24 ¥°Q . 15-64. Squamous cell carcinoma. Fig.329 Fig. Fig.

330 Histologically this tumor resembles squamous cell carcinoma from other sites. Fig. 15-69. Intraepidermal neutrophils are present and may form abscesses. Keratoacanthoma is a solitary. It typically grows rapidly.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Histologically keratoacanthomas are symmetric. The intradermal portion of the tumor is sharply demarcated. Mitoses are prominent. Keratoacanthoma. Fig. Peripheral cells show palisading. Fig. Basal cell carcinoma. especially because the metastatic tumors also may establish contact with the epidermis. The lesion has a spherical contour compressing the lateral epidermis and the dermis. Clefts are seen between the tumor nests and the stroma. and most lesions fully develop over several weeks or months. 66417308 : ¸Ÿ±U 24 ¥°Q . There also are scattered apoptotic cells. The tumor is composed of basaloid cells that form compact nests. Basal cell carcinoma. Keratoacanthoma. Central area consists of a keratotic plug with papillary projections of keratinized epithelium. in contrast to acantholysis in squamous cell carcinoma. symmetric. Metastases of squamous cell carcinoma of the internal organs to the skin may be difficult to distinguish from primary tumors. 15-72. 15-70. it compresses the adjacent epidermis. crater-like lesions that have a central keratotic plug and folds of keratinized epithelium (Fig. The keratinocytes are large and pale and remain closely adherent to one another. The tumor is round and symmetric and has a visible central keratotic plug. 15-70). and thus mimic a primary skin neoplasm. 15-71. The adjacent epidermis shows no signs of atypia. which forms a collarette around the central craterlike tumor. round.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Because of the expansile growth of the lesion. and there is no invasion or extension beyond its margins. Fig. 15-69). nodular lesion with a central keratotic plug (Fig. This nodular tumor has a depressed center and is surrounded by telangiectatic blood vessels.

15-76). Extensive keratinization makes basal cell carcinomas resemble squamous cell carcinoma. Pigmentation most often is seen in superficial basal cell carcinomas. and (6) cleft formation that separates nests of neoplastic cells from the stroma (Fig. Adnexal Tumors Many histologically distinct tumors are found in the dermis and subcutis. (3) mitotic figures. balancing the proliferation. apocrine glands. which are called keratotic basal cell carcinomas. which have been chosen to illustrate this heterogeneity. exophytic. but metastases are extremely rare. The tumor is composed of groups of basaloid cells in a cellular stroma. these tumors may show foci of keratinization. Pigmentation of tumor cells may be found. someti mes depressed. basal cell carcinoma presents in several forms. Each of these types of tumor grows slowly. erythematous. Clinically there are three types of tumors: (1) nodular type. Histologically. (4) individual cell apoptosis. Fig. (2) peripheral palisading at the margins of cell nests. which is an opalescent gray nodule that often is associated with telangiectasia. 15-72). Fig. Basal cell carcinoma—like changes occur in the epidermis overlying dermatofibromas. they also may enlarge quickly and ulcerate. but. sebaceous glands. heavily pigmented melanocytes. 66417308 : ¸Ÿ±U 24 ¥°Q . Trichoepithelioma. which is a flat. Fig. and (3) morpheic type. but most of them have at least four of the following six features: (1) basaloid cells that resemble the basal layer of the epidermis. which is a scaly. 15-75). Histologically this tumor varies with regard to the degree of its differentiation. Only some tumors. 15-71). The only exception is the morpheic basal cell carcinoma. Multiple small papular lesions appear flesh-colored.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .331 Basal cell carcinoma is the most common malignant tumor in whites. 15-75. Inexorable local lesions are common. Syringocystadenoma papilliferum. sometimes pearly borders. These tumors usually are solitary and benign. papillary lesion (Fig. and this is attributed to the proliferation of dendritic. There also may be focal sebaceous differentiation and even formation of ducts that resemble sweat ducts. Keratinization maybe seen in the typical basal cell carcinomas. and many others. white plaque with adjacent erythema (Fig. These tumors originate from cells that form hair follicles. Trichoepithelioma is a tumor of the hair follicles that presents in the form of solitary or multiple skin nodules (Fig. which often lacks peripheral palisading and shows very little cleft formation. (2) superficial type.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 15-74). 15-73. It typically occurs on the sun-exposed skin of the elderly and is directly related to excessive ultraviolet light exposure. Histologically the tumor cells line connective tissue papillae that project into the lumen of a cystic cavity (Fig. have low mitotic count. but most tumors contain both keratotic and basaloid areas (Fig. which transfer the pigment to tumor cells. flat lesion with distinct. They differ from basal cell carcinoma in that they lack clefts between nests of tumor cells and stroma. Syringocystadenoma papilliferum is a tumor that typically occurs on the face or the scalp as a crusty. and those tumors are termed basosquamous carcinoma. but they may be multiple and malignant. 15-73). (5) cellular stroma composed of spindleshaped cells in a mucinous matrix with fine collagen fibrils and scattered mast cells. The tumor presented as a solitary crusted papillary lesion. The stroma of morpheic basal cell carcinoma is dense and collagenous. 15-74. Trichoepithelioma. and show no areas of confluent necrosis. Furthermore. are presented here.

Juvenile xanthogranuloma. 15-80. 15-79. Cellular blue nevus is larger and may resemble malignant melanoma. 15-78. 15-81. Papillary fronds lined by epithelial layers project into a cystic cavity. 66417308 : ¸Ÿ±U 24 ¥°Q . Tumor cells that have round nuclei of uniform size and very little cytoplasm form compact nests in the dermis. 15-77. Fig. Common blue nevus appears as a black.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Sebaceous carcinoma.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . B. Merkel cell carcinoma. Blue nevus. A B Fig. sebaceous cells that have clear cytoplasm.332 Fig. The dermis is replaced by densely packed spindle cells that contain variable amounts of brown melanin pigment. slightly raised papule. Fig. Fig. 15-76. A. Typical lesions present as slightly orange-colored papules or nodules. Cellular blue nevus. Fig. The tumor is composed of epithelial cells that differentiate focally into lipid-laden. Syringocystadenoma papilliferum.

Mihm MC Jr. Mod Pathol 11:79-92. It presents in the form of solitary or multiple skin nodules (Fig. 15-84. ]AMA 278:1914-1923. Histologically this tumor is composed of spindleshaped cells lining clefts that contain red blood cells (Fig. Mihm MC Jr: Recognition and evaluation of cytological dysplasia in acquired melanocytc nevi. Sem Diagn Pathol 13:72-90. Smoller BR: The differential diagnosis of pagetoid cells in the epidermis. Kohler S. many of which have ulcerated. They correspond histologically to equivalent tumors of soft tissues. and a proposed classification. 1998. 15-79 and 15-80). Infiltrates of macrophages are found in the dermis (Fig. Rouse RV. 15-82). 1999. In addition to the common type. Fig.333 Fig. Between the larger lesions there still are many smaller ones that resemble bruises. 1996. DeLeo V. which may show atypia. Patients present with purplish macules of the skin. but mitoses are present. Purplish nodules. 15-78). Hum Pathol 30:506-512. cover large parts of the body. Leung DYM. This well-developed lesion consists of Iipidized macrophages and scattered multinucleated Touton giant cells. Mesenchymal Tumors Mesenchymal tumors of the dermis and epidermis most often are benign but may be malignant. 15-77). and the clefts between the tumor cells contain red blood cells.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . a review. often multifocal malignant vascular tumor that involves the skin and the internal organs. Juvenile xanthogranuloma is a nodular lesion composed of macrophages. 15-83). It occurs both in a sporadic form and epidemically in patients who are infected with HIV. In fully developed lesions these macrophages have lipid-rich cytoplasm. Further Reading Carlson AJ. 1998. Kaposi sarcoma. 15-82. 15-84). Kaposi sarcoma is a low-grade. Merkel cell carcinoma is a malignant skin tumor that is composed of neuroendocrine cells. Sebaceous carcinoma is a rare form of malignancy that originates from the sebaceous glands. 1998. 1997. It has been linked to infection with herpesvirus type 8. Rippey JJ: Review: Why classify basal carcinomas? Histopathology 32:393-398. The epithelial cells of this tumor differentiate into fat-laden sebaceous cells (Fig. The tumor is composed of spindleshaped cells. This lesion typically is found in children. The tumor is composed of dense aggregates of uniform cells that have round nuclei and little cytoplasm (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . which evolve over time `ipto hemorrhagic nodules (Fig. there is a cellular blue nevus.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Only some of these tumors are illustrated here. Soter NA: Allergic and immunologic skin disorders. Fig. Blue nevus is a dermal lesion composed of dendritic and spindle-shaped highly pigmented cells that produce blueblack skin nodules (Figs. Diaz LA. LeBoit PE: Cutaneous lymphocytic vasculitis: a definition. Murphy GF. LeBoit PE: Minimal deviation melanoma: concept or quagmire? Adv Dermatol 13:289-304. 15-81). Scattered multinucleated cells with a wealth of nuclei also are present. 15-83. Kaposi sarcoma. Juvenile xanthogranuloma. Nuclear atypia is minimal.

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16-3). In addition to spindle-shaped cells. subcutaneous nodule in the upper extremity. 16-1). and large amounts of coarse.336 FIBROBLASTIC LESIONS Benign Fibroblastic Tumors and Tumor-Like Lesions Fibroblastic tumors encompass a variety of lesions ranging from purely reactive conditions secondary to injury and benign fibromas to fibrosarcomas that have the ability to both recur and metastasize. the latter within the muscles. 16-I. Proliferative fasciitis and proliferative myositis are reactive fibrous lesions that have similar histologic features. The cells resemble tissue culture fibroblasts in that they have enlarged but regular nuclei with prominent nucleoli. especially the forearm. whereas older lesions contain more collagen and may be hyalinized or cystic. These lesions resemble nodular fasciitis in their proliferative spindle cell component and myxoid background. The lesion is seen in adults. Mitotic figures may be numerous. Nodular fasciitis is a tumor-like spindle cell proliferation that may be confused with sarcoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fibrous hamartoma of infancy usually occurs in the axillary soft tissue or in the proximal parts of the extremities Fibrous Tissue Tumors Fig. fat cells. It is more common in young adults. variable lymphocytic infiltration. Histologically it consists of scattered fibroblasts. It typically and almost exclusively occurs on the thoracic wall at the lower end of the scapula. 16-2. Typically it first appears as a small (1 to 2 cm in diameter). 16-2). but they also contain ganglion cell–like cells with large nuclei and prominent nucleoli (Fig. but atypical forms seldom are present. The histologic appearance changes as the lesion ages. and newly formed collagen fibers (Fig. The former arises at the fascial level. Elastofibroma is a nonneoplastic condition that probably is degenerative. Histologically. Fibromatoses fall midway in the spectrum in that they have the ability to recur locally but do not metastasize (Table 16-1). there are polygonal ganglion cell—like cells that have more cytoplasm. they may extend to the fascia and form an intramuscular mass that may be confused with soft-tissue sarcoma. 66417308 : ¸Ÿ±U 24 ¥°Q . typically in middle-aged persons. nodular fasciitis is composed of enlarged spindle-shaped to round cells in a richly vascular myxoid background that contains extravasated erythrocytes.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Multinucleated giant cells may be present. most of whom are elderly women. Although most lesions are superficial. mildly painful. Younger lesions are cellular. collagen fibers. serrated elastic fibers of variable sizes that maybe highlighted with elastin stains (Fig. Fig. rapidly enlarging. Nodular fasciitis. but it also occurs in older adults. Proliferative fasciitis. The lesion is composed of spindleshaped cells in a myxoid background.

The most common locations include the shoulder girdles. The microscopic tumor infiltration beyond the margins explains the common recurrence of locally excised desmoids. Fibrofatty tissue contains fragmented elastic fibers. B. 16-4. A. delicately staining nucleoli. Histologically it consists of collections of cellular fibrous tissue traversing fibroadipose tissue and of nodules of immature-appearing fibroblasts in a myxoid stroma (Fig. Broad bands of collagen. Elastofibroma. most commonly between 30 and 40 years of age. Fibrofatty tissue contains groups of loosely arranged immature-appearing fibroblasts. 16-3. The periphery may have an infiltrating or sharply demarcated appearance (Fig. Fibrous hamartoma of infancy. It is more common in boys. chest wall. Histologically all desmoids are composed of long. 16-5. Abdominal wall desmoid appears as a gray-white mass measuring 4 cm in diameter. Desmoids typically arise within muscles but extend into fat tissue and the subcutis. 66417308 : ¸Ÿ±U 24 ¥°Q . and thigh. Fibromatoses Fibromatosis is the term given to a group of differentiated fi- broblastic lesions with locally infiltrative features. may be present. A B Fig. sweeping fascicles of differentiated fibroblastic cells with ill-defined cytoplasmic borders.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The lesion is poorly circumscribed and usually measures 3 to 5 cm in diameter. similar to those seen in keloids. the two forms vary in their clinical presentation and biologic behavior. Fig. 16-5). Fi gromatoses in adults are divided into two types: a deep form (desmoid tumor) and a superficial form (palmar and plantar fibromatoses). Fig. Extraabdominal desmoids occur in both women and men. Broad bands of fibroblastic collagenous tissue infiltrate the space between muscle cells. Desmoid tumor. Approximately half of all cases are abdominal desmoids. 16-4).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . On sectioning they are firm graywhite masses that have a rubbery consistency and a trabeculated surface.337 during the first year of life. and only rare mitoses. Desmoid tumor (aggressive or musculoaponeurotic fibromatosis) previously was commonly classified as low-grade fibrosarcoma. which typically occur in the rectus abdominis muscles of young women.

The term MFH is retained for historical reasons. There are four histologically distinct subtypes of MFH: (1) storiformpleomorphic. MFH occurs in soft tissues of extremities. (2) myxoid.338 FIBROHISTIOCYTIC TUMORS The generally accepted category of fibrohistiocytic tumors has been retained for historic reasons to facilitate the communication between clinicians and pathologists who have been using this term for more than 30 years. such as malignant fibrous histiocytoma (Table 16-2). and (4) inflammatory. Fibrohistiocytic Tumors B A Fig. ulcerate. This category includes benign tumors. On gross examination the tumor appears as a fibrotic. Dermatofibrosarcoma protuberans. however. 16-7). Fibroblasts arranged in whorls infiltrate the subcutaneous fat. The tumors show an infiltrative pattern of growth into subcutaneous fat. Malignant fibrous histiocytoma ( MFH) is a malignant tumor composed of cells that resemble fibroblasts and histiocytes. Dermatofibrosarcoma protuberans ( DFSP) is a superficial tumor of intermediate (low-grade) malignancy. white mass with areas of necrosis and hemorrhage (Fig. Immunohistochemical data indicate that these cells are fibroblasts and that there is no evidence of differentiation into histiocytes (macrophages). 16-6). Myxoid MFH is the second most common subtype. such as dermatofibrosarcoma protuberans. Storiform-pleomorphic MFH is the most common subtype. (3) giant cell. and in other sites.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 16-6. The cells typically are pleomorphic. in the retroperitoneum. Immunohistochemical data indicate. A. which often transform into xanthoma cells. It consists of parts that resemble the conventional MFH and parts that show poor cellular cohesion and infiltrates of inflammatory cells. This 3 cm mass located in the dermis and subcutis appears grayish-white on cross section. Although most of the lesions are quite cellular.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and malignant tumors. As its name implies. Histologically this tumor consists of large spindleshaped or polygonal cells arranged into sheets or short intersecting fascicles. most commonly on the chest wall or trunk (Fig. Initially developing as a plaque or small nodule. a feature that accounts for the high frequency of recurrences after conservative local excision. it has a myxoid component. which show no evidence of histiocytic differentiation. with an abundant infiltrate of osteoclast-like multinucleated giant cells. Inflammatory MFH is the least common subtype and usually is found in the retroperitoneum. 66417308 : ¸Ÿ±U 24 ¥°Q . Mitoses are prominent and often atypical. such as benign fibrous histiocytoma. hyalinization or a myxoid change of the stroma may supervene to obscure the typical appearance. Histologically DFSP is composed of slender fibroblastic cells that often are arranged in a repetitive storiform pattern. Giant cell MFH is composed of spindle and round cells. The cells seldom display significant mitotic activity. that these tumors are composed of fibroblastic cells. B. This tumor occurs primarily in young adults and develops as a cutaneous mass. which occupies more than 50 percent of the entire mass. including neutrophils and macrophages. tumors of intermediate malignancy. it may become large. and give rise to satellite nodules. often multinodular.

Malignant fibrous histiocytoma (MFH). Lipoma probably is the most common soft-tissue tumor. Giant cell MFH consists of fibroblastic and multinucleated giant cells. C. 16-8).33 9 A B C D Fig. This benign tumor typically occurs in subcutaneous tissue but may be found elsewhere.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and (7) myelolipoma. It is composed of mature fat cells that may be admixed with connective tissue. including (1) angiolipoma. 16-7. Lipomatous Tumors 66417308 : ¸Ÿ±U 24 ¥°Q . (3) spindle cell lipoma. (4) pleomorphic lipoma. blood vessels. and other elements (Fig. (6) perineural fibrolipoma. D. Myxoid MFH consists of myxoid tissue surrounding prominent blood vessels. This large fleshy mass was removed from the deep soft tissue of the calf. B. (5) intramuscular lipoma. Storiform-pleomorphic MFH consists of spindle-shaped and larger pleomorphic cells. Several subtypes are recognized.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . (2) angiomyolipoma. A. LIPOMATOUS TUMORS Lipomatous tumors are composed of fat cells and their precursors (Table 16-3).

20 percent are intraabdominal. primitive round cells with a high nuclear-cytoplasmic ratio (Fig. Varying numbers of lipoblasts are present. In addition to fat cells. 16-10. The first two forms are low-grade sarcomas. 16-9). Spindle cell lipoma. many of which have multiple cytoplasmic vacuoles (Fig. This tumor most often develops on the back or the shoulder and less often appears on the thigh. Hibernoma. Fig. Immature. 16-9. 16-8. Several histologic subtypes are recognized: (1) well-differentiated (lipoma-like and sclerosing). The latter are immature fat cells that contain one or more fat vacuoles.. whereas the latter three are high-grade sarcomas that have a tendency to metastasize. Well-differentiated liposarcomas resemble mature fat tissue or lipomas. 66417308 : ¸Ÿ±U 24 ¥°Q . Myxoid liposarcoma is the most common type. 16-11. Hibernoma is a benign tumor of brown fat (Fig. Lipoblastoma. B). It may coexist as a minor component of otherwise typical myxoid liposarcoma. (3) round cell.16-11). Histologically it has a typical pattern with abundant branching fine capillaries surrounded by uniform small tumors cells suspended in hyaluronic acid—rich matrix (Fig. C). Lipoblasts vary in size and shape and typically contain vacuoles of lipid in their cytoplasm. Histologically it is composed of pleomorphic tumor cells.340 Fig. the tumor contains spindle-shaped fibroblastic cells. (2) myxoid. in such cases the tumor shows more pronounced aggressiveness. 16-10). especially in abdominal liposarcomas of this type. On gross examination liposarcoma appears as a yellow mass that may be relatively circumscribed or invasive (Fig. Histologically it consists of uniform. Approximately 50 percent of liposarcomas occur on the lower extremities. Round cell liposarcoma represents the cellular or poorly differentiated variant of myxoid liposarcoma. and (5) dedifferentiated.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . There often is a hemangiopericytomatous pattern in which the cells surround branching blood vessels. including highly atypical multinucleated giant cells. 16-11. Lymphocytic infiltrates are common. richly vascular fat tissue has a lobular appearance. Dedifferentiated liposarcoma consists of areas that resemble well-differentiated liposarcoma and areas that resemble high-grade MFH. and the only indication that the tumor is malignant stems from the hyperchromatic atypical cells in the widened connective tissue septa and the presence of scattered lipoblasts.D). Lipoblastoma is a benign tumor of infancy and childhood that is composed of lobules of immature fat cells (Fig. Liposarcoma is a common soft-tissue malignancy that almost exclusively occurs in adults.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. 16-11. Pleomorphic liposarcoma is a relatively rare tumor that typically is found in the elderly. (4) pleomorphic. The tumor is composed of multivacuolated cells that resemble normal brown fat cells. which indent or scallop the nucleus.

whereas others.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .341 A B C D Fig. many of which contain lipid vacuoles in their cytoplasm. On the basis of histology it is difficult and often impossible to determine the true nature of such vascular lesions. On gross examination this liposarcoma appears as a yellow. D. deepseated circumscribed mass. such as bacillary angiomatosis or pyogenic granuloma. maybe reactive lesions (Fig. A. Low-grade malignant tumors such as hemangioendothelioma and highly malignant angiosarcomas are less common (Table 16-4). B. Liposarcoma. Some congenital hemangiomas actually are hamartomas. 66417308 : ¸Ÿ±U 24 ¥°Q . 16-1 I. Benign tumors of endothelial cells occur in all age groups and may present in many clinical and pathologic forms. Round cell liposarcoma consists of compact sheets of round cells. Most vascular tumors are benign. C. some with fat vacuoles. 16-12). Pleomorphic liposarcoma consists of large pleomorphic and multinucleated cells. Myxoid liposarcoma consists of small lipoblasts in a loose myxoid stroma arranged around prominent branching blood vessels. Endothelial Tumors of Blood and Lymph Vessels VASCULAR TUMORS Vascular tumors composed of endothelial cells of blood and lymph vessels are very common lesions of the skin and subcutaneous tissue. but they also occur in many other tissues and in internal organs.

B. Hajdu. 16-12. The tumor is composed of endothelial cells lining irregular channels. some of which contain blood. Manhasset. The lesion is composed of thin-walled vessels with edematous stroma that is rich in inflammatory cells and capillaries that have collapsed lumina. 16-15. The dilated vascular spaces lined by flattened endothelial cells contain proteinaceous lymph and a few lymphocytes. A.342 A B Fig. red nodule that bleeds easily on trauma. B. A. The vacuoles represent microlumina. It forms fast and tends to recur rapidly if it is incompletely excised. Pyogenic granuloma. The lesion is a well-circumscribed. Epithelioid hemangioendothelioma.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . (Gross specimen photograph courtesy of Dr.) 66417308 : ¸Ÿ±U 24 ¥°Q . New York. 16-13. Steven I.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Angiosarcoma. The tumor consists of endothelial cells arranged into cords and clusters. Lymphangioma. Fig. Fig. A B Fig. 16-14. The tumor forms a hemorrhagic mass in the deep soft tissue.

and (11) lymphangiomyomatosis. (3) intramuscular hemangioma. and (3) Kaposiform hemangioendothelioma. palms. 16-15. specialized arteriovenous anastomoses regulating the blood flow in distal parts of the body. Most often they arise from the nailbeds or from the fingers. Tumor cells are arranged around thin-walled blood vessels. Hemangioendothelioma is an endothelial cell neoplasm of intermediate (borderline) malignancy that occurs in several forms. feet. which often show papillary intraluminal tufting. including (1) capillary hemangioma. Immunohistochemically the cells express endothelial markers such as von Willebrand factor. 16-13). (2) cutaneous tumors that arise in lymphedematous extremities. and although they resemble pericytes. Simple excision is curative in most instances. (3) angiosarcomas of the breast. Glomus tumors are small painful nodules in superficial soft tissues of adults. glomangiomyoma. B). Several clinical and pathologic variants are recognized. The less differentiated tumors may show solid strands and sheets. (5) angiomatosis.343 Benign tumors of blood vessels are called hemangiomas. which may show some nuclear unrest when irritated. which usually are thrombosed. Hemangiopericytoma is a rare borderline malignant tumor that occurs in deep soft tissues of the extremities and the retroperitoneum of adults. and rare malignant glomus tumors have been described. legs. 66417308 : ¸Ÿ±U 24 ¥°Q . reminiscent of Kaposi sarcoma. Because angiosarcoma-like areas occur in many hypervascular soft tissues and bone tumors. These cells are arranged into cords and clusters in a loose fibromyxoid stroma. On gross examination tumors often are hemorrhagic and poorly demarcated from normal tissue (Fig. They recapitulate the basic features of glomus bodies. Histologically hemangiopericytomas are composed of spindle-shaped or round cells embedded in a moderately dense stroma matrix arranged around dilated vas- Perivascular Tumors Fig. blood-filled vascular channels. Kaposiform hemangioendothelioma is a rare childhood tumor of superficial or deep soft tissues. Neoplastic endothelial cells have cytoplasmic vacuoles. 16-16). round to polygonal cells arranged into sheets and cords surrounding thin-walled dilated blood vessels (Fig. Histologically it is composed of cavernous blood spaces juxtaposed with bland spindle cells.A). 16-14). Histologically it resembles Kaposi sarcoma. that is. which may contain erythrocytes. lined by variably atypical endothelial cells. (8) intravascular papillary endothelial cell hyperplasia (Masson hemangioma). and (4) angiosarcomas of deep soft tissues. Spindle cell hemangioendothelioma is a rare vascular tumor of the subcutis of young adults. 16-15. WeibelPalade bodies are the electron microscopy (EM) markers of endothelial cells. usually located on the hands.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and receptors for the lectin Ulex europaeus. I6-16. (7) pyogenic granuloma. Angiosarcoma also must be distinguished from Kaposi sarcoma and benign vascular tumors. Round and polygonal cells surround thin walled blood vessels in a collar-like manner. and forearms. Glomus tumor. Histologically the tumors show a wide spectrum of differentiation. it is important not to diagnose such tumors as angiosarcomas. Epithelioid hemangioendothelioma is composed of endothelial cells that have abundant eosinophilic cytoplasm and thus resemble histiocytes (Fig. (9) cystic lymphangioma. and those that originate from endothelial cells of lymphatics are called lymphangiomas (Fig. PERIVASCULAR TUMORS The new World Health Organization (WHO) classification of soft-tissue tumors assigns glomus tumors and hemangiopericytomas to a separate category of perivascular tumors (Table 16-5). Histologically the tumors are composed of uniform. (10) lymphangiomyoma. representing miniature vascular lumens. it has not been proved that they truly are derived from normal pericytes. (4) epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia or Kimura disease). their true nature is subject to controversy. albeit 10 percent of glomus tumors recur locally. 6) bacillary angiomatosis.Variants such as glomangioma. The same rule applies to hemangiopericytomas. The well-differentiated tumors show irregular anastomosing. resembling carcinoma or lymphoma (Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Angiosarcoma is a term that encompasses four clinical entities: (1) cutaneous tumors that occur without preexisting lymphedema. (2) spindle cell hemangioendothelioma. such as (1) epithelioid hemangioendothelioma. (2) cavernous hemangioma. More than one half of all soft-tissue tumors of this type arise from the wall of identifiable vessels. CD31 and CD34.

SMOOTH MUSCLE CELL TUMORS Smooth muscle cell tumors include leiomyomas and leiomyosarcomas. Thin-walled blood vessels in a "staghorn"pattern are surrounded by spindle-shaped cells in a collagenous matrix. Smooth Muscle Tumors 66417308 : ¸Ÿ±U 24 ¥°Q . some tumors of the same histologic appearance react with antibodies to smooth muscle actin. Leiomyosarcomas are malignant tumors composed of atypical smooth muscle cells. especially the legs and ankles. Fig. 16-19). 16-17. Leiomyomas are benign soft-tissue tumors that are grouped into four clinicopathologic categories: (1) piloleiomyoma arising from arrectores pilorum and presenting as small 1 to 2 cm nodules. depending on the extent of vascularization (Fig. However. Reticulin fibers surrounding each tumor cell and arranged radially perpendicular to the lumen of the vessel may be demonstrated with special stains. and (4) leiomyomas of deep soft tissue. most notably MFH and liposarcomas. and desmin. which histologically resemble the more common uterine and gastrointestinal tumors (Table 16-6). arranged into fascicles that in - Fig. which on cross section appear grayish-tan or brown and red. Leiomyomas usually are well-demarcated nodules.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 16-19. This spherical nodule was shelled out from subcutaneous soft tissue.344 Fig. The tumor is composed of smooth muscle cells that have uniform elongated nuclei and welldeveloped cytoplasm. There are no immunohistochemical stains that would be typical of hemangiopericytoma. smooth muscle cell actin. Histologically the tumors are composed of smooth muscle cells that have uniform elongated nuclei with blunt tips and a welldeveloped eosinophilic cytoplasm (Fig. (3) angiomyoma presenting as vascular subcutaneous nodules with a predilection for the lower extremities. 16-17). Hemangiopericytoma. Hemangiopericytomatous patterns of growth may be seen in other soft-tissue sarcomas. Leiomyoma. 16-18. 16-18).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . cular lumina (Fig. Most tumors react positively with antibodies to CD34 and are negative for endothelial cell markers. Mitotic activity usually is low. which are rare tumors that show considerable regressive changes. (2) genital leiomyoma commonly found in the vulva or the scrotum. which suggests that some "hemangiopericytomas" are not of pericytic origin but are leiomyosarcomas. except in highly malignant tumors. It is brownish-red on cross section because of an abundance of blood vessels in its stroma. such as hyalinization. Leiomyoma.

nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Histologically the tumors are composed of polygonal cells arranged into sheets (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . and often are pleomorphic (Fig. A B Fig. its location. 16-21. rhabdomyoma cells are larger and show cytoplasmic vacuolization (Fig. bizarre leiomyoblastoma) more often is found in the gastrointestinal tract but also may occur in soft tissues. The most common sites are the peritoneum. Adult rhabdomyoma is a rare tumor of adults that typically presents as a slow-growing mass in the oral cavity or nasopharynx. B. and some cells even have a signet ring—like appearance. 16-21. A). A. Leiomyosarcoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Tumor presented as a lobulated pharyngeal mass. Grossly the tumor is a brown or red multilobular mass that measures 1 to 5 cm in diameter (Fig. TUMORS OF STRIATED MUSCLE Tumors of striated muscle include rhabdomyomas and rhabdomyosarcomas. Tumor is composed of large polygonal cells that have ample eosinophilic cytoplasm and small nuclei. but there are mitotic figures. and the prognosis is determined by taking into account the size of the tumor.345 A B Fig.) tersect obliquely or perpendicularly with one another. Four clinicopathologic entities are recognized: (1) adult rhabdomyoma. 16-20. and mesentery. Antonio Racela. B. Neoplastic cells have elongated nuclei that show hyperchromasia.A). Strictly speaking. Areas of necrosis are prominent in larger tumors. Adult rhabdomyoma. only adult rhabdomyoma and fetal rhabdomyoma are soft-tissue tumors. A. Histologically it is composed of large polygonal cells that resemble skeletal muscle cells. Pleomorphic leiomyosarcoma is composed of atypical spindle- shaped cells that vary in size and shape and often show considerable nuclear pleomorphism. Nuclei appear more uniform. (2) rhabdomyoma of female genital organs. The number of mitoses varies. B). B). Compared with normal or hyperplastic muscle cells. and the histologic findings. have irregular distribution of chromatin. (3) fetal rhabdomyoma. Rhabdomyoma is a benign tumor that shows striated muscle differentiation. and (4) cardiac rhabdomyoma. These cells have welldeveloped cytoplasm that may be clear or eosinophilic. Epithelioid leiomyosarcoma (leiomyoblastoma. (Gross specimen photograph courtesy of Dr. which indicate that this is a malignancy. 16-21. Tumors that measure more than 6 cm in diameter and have more than 3 to 5 mitoses per 10 high-power fields are malignant. 16-20. Epithelioid leiomyosarcoma consists of polygonal cells that often have clear cytoplasm. Overland Park. omentum. 16-20. Kansas.

E). and vagina of preschool-age girls (see Figs. 16-22.346 Rhabdomyosarcoma is a malignant tumor that shows striated muscle differentiation and primarily affects children. and (5) pleomorphic. Spindle cell rhabdomyosarcoma is a rare childhood tumor that is composed of spindle-shaped rhabdomyoblasts. which previously was considered to be a common soft-tissue sarcoma of the extremities in adults. On gross examination the tumor appears as a myxoid mass. Desmin. Five clinicopathologically distinct types are recognized: (1) embryonal. Pleomorphic rhabdomyosarcoma. It has a peak incidence in the first year of life. the tumor may contain larger multinucleated cells with abundant eosinophilic cytoplasm. Embryonal rhabdomyosarcoma consists of small and large rhabdomyoblasts. cervix. Most of these tumors actually are desmin negative and represent pleomorphic MFH. 66417308 : ¸Ÿ±U 24 ¥°Q . although some overlap exists among these types. E. Embryonal rhabdomyosarcoma are composed of a mixture of small and large rhabdomyoblasts. B. Alveolar spaces are formed between discohesive cells. Rhabdomyosarcoma."exophytic tumors of the urinary bladder. (2) botryoid. D. 13-29 and 13-30). which show Zband–like condensations (Fig. C. A. 16-22. EM is useful for demonstrating myofibrils. 16-22. " grapelike. Alveolar rhabdomyosarcoma accounts for 10 percent to 20 percent of all cases of rhabdomyosarcoma. which is the best marker of striated differentiation. The degree of rhabdomyoblastic differentiation correlates positively with the prognosis. EM shows thick and thin filaments and Z-band—like densities. A B C D E Fig. 16-22. Urogenital and head and neck areas most often are involved. now is considered to be rare. which have prominent eosinophilic cytoplasm (Fig. B). Because of poor cohesiveness of the cells and areas of necrosis. Rhabdomyosarcoma stains positively with antibodies to desmin. Histologically. In some cases loose myxoid areas alternate with cellular areas in a trabecular pattern. D). Histologically the tumor is composed of small cells that are separated into groups by fibrovascular septa. C). (4) alveolar. Botryoid rhabdomyosarcomas are myxoid. On gross examination rhabdomyosarcoma usually appears as a gray-white myxoid mass (Fig. central parts of tumor nests transform into " alveolar spaces " (Fig. In addition to the round undifferentiated cells. embryonal rhabdomyosarcoma accounts for 75 percent of all cases. Similar tumors occasionally are found in the liver and upper respiratory tract. 16-22.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Alveolar rhabdomyosarcoma is composed of undifferentiated small round cells attached to fibrous septa. (3) spindle cell. may be demonstrated even in the smaller cells (Fig. 16-22.A). It occurs predominantly in adolescents and preferentially involves the distal parts of the extremities and the head and neck area.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

Neurofibroma is a common benign nerve sheath tumor that most often appears as an unencapsulated subcutaneous nodule. Spindle-shaped cells are surrounded by wavy matrix. Nerve sheath myxoma (neurothekeoma) is a benign nerve sheath tumor of the subcutis that most often is found in children and young adults. perineurial cells. Cellular myxoid lobules are found enclosed in dense connective tissue septa. B Fig. Neurofibroma. The spindleshaped tumor cells are intermixed with wavy collagen bundles. and Schwann cells (Fig. 16-23. Histologically it is composed of multiple lobules of spindle cells suspended in myxoid material surrounded by dense fibrous bands (Fig. The cellular areas consist of sheets of spindle cells with palisaded nuclei that form columns around an amorphous matrix (Verocay bodies) (Fig. Spindle-shaped cells show palisading.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and many of them are quite common. and those that display neuronal feature ganglioneuroma. Schwannoma. 16-23. Most of these neural tumors are benign. It typically originates from peripheral nerves and often is recognized as a fusiform mass that focally expands the nerve or is attached to it (Fig. B). A. Tumor has produced a bulging mass in the peripheral nerve. 66417308 : ¸Ÿ±U 24 ¥°Q . 16-24). A Fig. 16-25). Malignant nerve sheath tumors are rare. 16-23. perineurial cells. 16-24. It consists of haphazardly arranged fibroblasts. Nerve sheath myxoma. and perineurial fibroblasts. which is evidenced by the alignment of nuclei at the margins of eosinophilic areas composed of cytoplasmic processes. The stroma may be myxoid or densely collagenous. Schwannoma is a benign tumor that is composed of Schwann cells. 16-25. Histologically it is characterized by cellular Antoni A areas alternating with myxoid Antoni B areas. Benign Neural Tumors Benign Neural Tumors Benign neural tumors are listed in Table 16-7.347 NEURAL TUMORS Neural tumors include neoplasms that show nerve sheath differentiation and are composed of Schwann cells.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. B. A).

B. Some tumors may be pleomorphic and resemble MFH. Schwannomas almost never Malignant Neural Tumors undergo malignant transformation. account for less than 10 percent of all soft-tissue sarcomas. B).348 Malignant Neural Tumors Malignant neural tumors are listed in Table 16-8. Malignant peripheral nerve sheath tumor (MPNST). Approximately 50 percent of these tumors arise in patients with neurofibromatosis type I through malignant transformation of nerve trunk fibromas. Multiple malignancies occasionally are found. Well-differentiated malignant neural tumors stain with antibodies to S-100 protein (Fig. Precise diagnosis of such tumors often is uncertain unless the tumor arose in the context of neurofibromatosis type I or the mass was obviously attached to a peripheral nerve. 16-26. Some tumor cells in the MPNST stain with the antibody to S-100 protein. 16-26. A. Glandular malignant schwannoma is the term used for those that contain glandular elements. MPNST originating from nerves or from preexisting neurofibromas within a nerve expand the nerve in an irregular manner and extend into the adjacent soft tissues (Fig. whereas the remainder arise sporadically. Clear cell sarcoma shows melanocytic differentiation. These ancillary tests are of no value in undifferentiated tumors. Differentiation into Schwann cells may be detected by EM in better differentiated tumors. Tumor is arising from the ulnar nerve. A B C Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Malignant triton tumor is the designation used to describe tumors that contain rhabdomyoblasts. 16-26. again mostly in the context of neurofibromatosis. 66417308 : ¸Ÿ±U 24 ¥°Q . C. Histologically MPNST resembles fibrosarcoma except for the fact that spindle cells tend to have an irregular buckled shape that is reminiscent of normal Schwann cells (Fig. Histologically MPNST is composed of nondescript spindle-shaped cells. 16-26. A). Malignant peripheral nerve sheath tumors (MPNST). C). which include malignant schwannoma and neurofibrosarcoma. Most patients are middle-aged but some are young.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Heterologous elements such as cartilage and bone may be present. like normal Schwann cells. especially those with neurofibromatosis. but many highly malignant ones do not.

The peripheral part consists of trabeculae of newly formed bone. B. 16-27. 16-27. C. Sharply demarcated intramuscular lesion shows a distinct difference between the peripheral rim of bone and the central part. 16-28). Myositis ossificans is a pseudoneoplastic condition that is marked by the formation of reactive bone inside the muscle. and most patients are older than 40 years. A). and osteoclasts. or the buttocks (Fig. is rimmed by mature bone at the periphery (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Cartilage and Bone-Forming Tumors of Soft Tissue A B C Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . A.349 CARTILAGE AND BONE-FORMING TUMORS Cartilage and bone-forming tumors are listed in Table 16-9. Myositis ossificans. 16-2 7. Deep muscle compartments of the extremities and the retroperitoneum are the most common sites. Histologically most tumors are highgrade sarcoma and may be indistinguishable from those in MFH except that focally they show osteoblastic differentiation and produce trabecular osteoid (Fig. The central part consists of osteoblasts surrounding osteoid and osteoclast-like giant cells. most often in the anterior muscle of the thigh. osteoid. The central part. The mature lesion is sharply demar- cated from the surrounding muscle.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . which consists of osteoblasts. Histologically these tumors have the same features as their more common equivalents in the bones. Osteosarcoma of soft tissues is a tumor of adulthood. It typically occurs in young adults and presents as a painful mass. B and C).

Vascularity of the tumor imparts to it a hemangiopericytomatous pattern.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 16-29. which may be found in the lungs at the time of diagnosis. Askin tumor. Chondrosarcomas of soft tissues may present as extraskeletal myxoid chondrosarcoma or mesenchymal chondrosarcoma. Tumor is composed of high-grade malignant spindle-shaped cells surrounded by osteoid. The tumor consists of primitive round cells in a collagenous stroma demarcating islands of differentiated cartilage (Fig. Histologically it consists of spindle-shaped cells sus - 66417308 : ¸Ÿ±U 24 ¥°Q . a typical finding in skeletal chondrosarcoma. MISCELLANEOUS SOFT TISSUE TUMORS Soft tissues may give rise to a variety of tumors of unknown or incompletely known histogenesis (Table 16-10). This group of tumors includes extraskeletal Ewing sarcoma. It presents as a gray gelatinous tumor of the extremities and the retroperitoneum.350 Fig. Mesenchymal chondrosarcoma of soft tissues is a rare malignancy that is similar to its osseous counterpart. It occurs in young patients in the thigh and the meninges and is prone to metastasis. Osteosarcoma of soft tissue. Extraskeletal myxoid chondrosarcoma is a highly malignant tumor of middle-aged persons. 16-28. Hyaline cartilage. Mesenchymal chondrosarcoma of soft tissue. even though there is no doubt that they may not be related one to another histogenetically. Extraskeletal myxoid chondrosarcoma. it also is known as chordoid sarcoma. Small round cell tumors of soft tissues are grouped together because of similar morphology. Some of these tumors are benign. others are malignant. Trabeculae of spindle cells are suspended in myxoid matrix. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and intraabdominal desmoplastic small round cell tumors (Figs. Primitive-appearing round cells in fibrous stroma are focally juxtaposed to differentiated cartilage. 16-29). Neuroblastomas and metastatic tumors such as nephroblastoma or hepatoblastoma and lymphomas might have the same morphology. is seen only occasionally. pended in a myxoid matrix (Fig. These tumors usually are highly vascular and may have a hemangiopericytomatous appearance. peripheral neuroepithelial tumors (PNET. Because of its resemblance to chordoma. 16-31 and 16-32). or peripheral neuroepithelioma). Fig. 16-30). 16-30. and in all likelihood still others are not even neoplastic.

Tumor is composed of nests of small cells arranged focally into rosettes. Biphasic tumor consists of glandlike structures surrounded by uniform spindle-shaped cells. 66417308 : ¸Ÿ±U 24 ¥°Q .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig. A B Fig. Monophasic tumor is composed of nearly uniform spindle-shaped cells with some whorling focally. Peripheral neuroepithelioma (PNET). Synovial sarcoma. 16-33.351 Miscellaneous Soft-Tissue Tumors Fig. 16-3I. Nests of small blue cells are surrounded by dense collagenous stroma.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Intraabdominal desmoplastic small round cell tumor. B. 16-32. A.

A.352 A A B B Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Alveolar soft-part sarcoma. C. Electron microscopy shows rhomboid crystals with a latticelike pattern and regular periodicity. The epitheliod sarcoma cells are uniformly positive for cytokeratin. B. The central space gives the tumor an alveolar appearance. B.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 16-35. 16-34. Epithelioid sarcoma. Polygonal cells are arranged into nests surrounded by connective tissue septa. A. Polygonal cells form compact nests surrounded by spindle-shaped cells. Fig. The cells show membrane staining for CD34.

Kuramochi S: Glomangiosarcoma in a glomus tumor. Enzinger FM. Middleton LP. prognostic indicators.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Hirayama A. Allen PW: The fibromatoses. Bernstein KE. Arch Pathol Lab Med 113:1363-1366. Erlandson RA. 1995. Pieterse AS. Hum Pathol 17:778-795. Am J Clin Pathol 102:677-683. 1993. Sanjay BK. which previously was believed to reflect differentiation into synovium. Smith PS. An analysis of 89 cases. 16-35). 1977. The biphasic form of synovial sarcoma consists of glandlike epithelial structures and mesenchymal spindle cells (Fig. Sem Oncol 24:515-525. Enzinger FM: Malignant fibrous histiocytoma 20 years after Stout. Am J Surg Pathol 22:588-594. Jesen OM et al: Extraskeletal osteosarcomas. 1994. Am J Surg Pathol 3:507-523. Fletcher CDM: Benign fibrous histiocytoma of subcutaneous and deep soft tissue. Miettinen M. Jensen B. Histopathology 27:103-120. The cytoplasm contain PAS-positive crystals. Histologically the tumor is composed of epithelial-like cells arranged into sheets or groups surrounded by connective tissue stroma (Fig. A clinicopathologic classification based on 140 cases. Hollowood K. An immunohistochemical and ultrastructural study. Allen PW. Central necrosis is common in larger clusters.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 1962. A reappraisal of its morphologic spectrum and prognostic factors based on 177 cases. but they also are positive for CD34. Hollowood K. Lattes R: Nodular (pseudosarcomatous) fasciitis. Enzinger FM: Epithelioid sarcoma. 1:255-270. rare soft-tissue sarcoma of unknown histogenesis. Chu YC. Chase DR. 66417308 : ¸Ÿ±U 24 ¥°Q . Central areas of tumor nests tend to necrotize. A clinicopathologic study of 228 tumors in 222 patients. 16-33. A clinicopathologic study of 25 cases. Alveolar soft-part sarcoma is an architecturally distinct. 16-33. Bergh P. Soini Y: Malignant fibrous histiocytoma. which have a lattice-like appearance on EM. J Clin Pathol 35:842-848. Histopathology 7:511-523. 1988. Most often it is located in the deep soft tissue of the thigh. Cancer 29:8-22. Am JSurg Pathol 23:636-650. Nascimento AG. but it may occur anywhere. Helwig EB: Leiomyosarcoma of the skin and subcutaneous tissue. Sem Diag Pathol 12:87-97. B). Dasu S. Coffin CM. Cancer 47:156-169. The tumor does not contain keratin and is not epithelial. Fields JP. Hum Pathol 29:1372-1381. The nuclei of tumor cells have complex outlines. Azzopardi JG. Hum Pathol 7:61-82. Kahn LB: Myofibroblasts and related cells in malignant fibrous and fibrohistiocytic tumors. Salm R: Pleomorphic lipoma. Gunterberg B. Epithelioid sarcoma is a rare soft-tissue sarcoma that affects young adults (average age 30 to 35 years). 1997. 1981. The tumor cells typically stain with antibodies to vimentin. 1989. Henricks WH. Fletcher CDM: Soft tissue sarcomas that mimic benign lesions.353 Synovial sarcoma is a distinctive malignant tumor of soft tissues that often shows a dual epithelial and spindle cell mesenchymal differentiation. Rock MG: Well differentiated liposarcoma. McClure J: Fibroma of tendon sheath. giving the nests an alveolar appearance. Schumacher B. Even though there is no evidence that the tumor is related to the synovium. Goodlad JR. 1986. Evans HL: Liposarcoma. Lehto V-P. Hum Pathol 28:205-218. Dehner LP: Vascular tumors in children and adolescents. Iocco J. Am J Surg Pathol 10(suppl 1):43-53. with emphasis on spindle and pleomorphic tumors. its name was retained for historical reasons. 1998. Fletcher CDM: Malignant fibrous histiocytoma: morphologic pattern or pathologic entity? Sem Diag Pathol 12:210-220. Aiba M. Histologically it occurs in both biphasic and monophasic forms. Miettinen M. 1995. 1982. Smith BH: Hemangiopericytoma. 1998. Epithelial cells and some spindle-shaped cells react immunohistochemically with antibodies to keratins and epithelial membrane antigen (EMA). 1982. Hum Pathol 29:636-640. there is no evidence of neuroendocrine or neural differentiation. 1983. Am J Surg Pathol 1977. An analysis of 106 cases. Churg AM. Enzinger FM: Hemangioma of skeletal muscle. 1997. 1997. Weiss SW: Dedifferentiated liposarcoma: a clinicopathologic analysis of 155 cases with a proposal for an expanded definition of dedifferentiation. Pathol Annu 28(pt 1):97-120. 1976. It accounts for 10 percent of softtissue sarcomas. Am J Surg Pathol21:271-281. Cancer61:1467-471. Histologically the tumor has a distinctive organoid appearance (Fig. and EMA. Hum Pathol 30:430-435. 1979. The Mayo Clinic experience with 58 cases. It tends to arise from distal parts of the extremities and usually presents as a superficial nodule. The monophasic synovial cell sarcoma is composed only of spindle cells (Fig. and treatment. 16-34). Tumor cells are polygonal and have an abundant granular eosinophilic cytoplasm. 1985. Cancer 49:1668-1678. A tumour simulating liposarcoma. 1999. Stout AP: Elastofibroma dorsi. but during histologic examination tumor cells usually extend beyond the area that is assumed to be involved on the basis of gross impression. Heterogeneous patterns of intermediate filament proteins by immunohistochemistry. Virchows Arch [A] 44:187-199. A). A study of 55 cases with a reassessment of its classification. Meis-Kindblom JM. Although it resembles paraganglioma. Fletcher CDM: Recent developments in soft tissue tumours. Kindblom L-G: Extraskeletal myxoid chondrosarcoma. 1995. Paull G et al: The expanding clinical spectrum of desmoplastic small round-cell tumor: a report of two cases with molecular confirmation. 1999. Diagnosis. 1972. Goldblum JR. 1998. 1990. Duray PH. and the cytoplasm of most cells is well developed and eosinophilic. Wolf AN. Hibshoosh H. Woodruff JM: Role of electron microscopy in the evaluation of soft tissue neoplasms. Am JSurgPathol 14:801-809. Merino JM: The histological spectrum of hemangiopericytoma: application of immunohistochemical analysis including proliferative markers to facilitate diagnosis and predict prognosis. Ladany M. A clinicopathologic analysis of 21 cases. Synovial sarcoma occurs in young adults (25 to 35 years) and predominantly involves the extremities. keratin. Lucas DR. Am J Clin Pathol 37:490-506. Stemmermann GN. Krill CE: Tumors of skeletal muscle. Am J Surg Pathol 9:241-263. 1986. Most patients are young. Virtanen I: Monophasic synovial sarcoma of spindle-cell type. Lattes R: Immunohistochemical and molecular genetic approach to soft tissue tumor diagnosis: a primer. Further Reading Agamanolis DP. 1983. The neoplastic nature of the lesion may elude the clinician and the pathologist alike. a nonrecurrent lesion.

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·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .66417308 : ¸Ÿ±U 24 ¥°Q .

Bones of the extremities are short and have a disproportionately large cartilaginous epimetaphyseal part. The growth of the long bones of the extremities has been stunted.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Many of the genes responsible for these developmental defects have already been cloned. which typically are blue. 66417308 : ¸Ÿ±U 24 ¥°Q . The clinical and pathologic findings vary from mild to severe. Histologically bones show irregular and inefficient osteogenesis and are composed of incompletely calcified. Osteogenesis imperfecta type II. Achondroplasia. 17-3). ligaments. 17-2). all of which are caused by mutations in the genes encoding collagen type I. 17-2.356 DEVELOPMENTAL AND GENETIC DISORDERS Developmental disorders that affect the bones most often are based on a genetic defect that prevents the normal formation of the osteon. the basic anatomic and functional unit of the bone. which is also called marble bone disease or Albers-Schonberg disease. all of which except the rare type III are transmitted in an autosomal dominant manner. which accounts for dwarfism. Nevertheless. The basic nature of others remains obscure. Fig.000 newborns. 80 percent of cases are sporadic. and sclerae. 17-1). 17-4). and irregular trabeculae (Fig. Type II osteogenesis imperfecta is lethal in infancy.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . small thorax. had a large. Four main forms of osteogenesis imperfecta have been identified. depending on the type of the disease and the nature of the genetic defect. Achondroplasia is the most common cause of disproportionately short stature. the most prominent feature of this disease (Fig. and it may be associated with dental defects and abnormalities of the skin. soft head. 17-3. Osteopetrosis. Achondroplasia. and short extremities. Affected infants show minimal calvarial mineralization ( "rubber head " ) and short compressed and fractured bones of the extremities (Fig. Osteogenesis imperfecta is a name given to several clinical syndromes. is a term used to describe four clinical syndromes that are characterized by excessive thickness of bones. which is transmitted from one generation to another in an autosomal dominant manner. Despite this variability the pathogenesis of all types involves defective osteoclast function that impairs bone Fig. affecting 1 in 40. Epiphyseal growth plate is broad and disorganized. Fig. The infant. It is based on the mutation of the gene encoding the receptor for the fibroblast growth factor. Histologically the long bones show abnormalities of endochondral ossification at the epiphyseal growth plate (Fig. Osteopenia is the main feature. as compared with short diaphysis. who died shortly after birth. which by radiograph showed numerous fractures. 17-I. thin. and the pathogenesis of many developmental bone disorders has been elucidated.

the basic anatomic unit of bone. the rate of Fig. in other cases bone disease is secondary to a primary disease of the kidneys. Sporadic nongenetic developmental anomalies of the skeleton occur without obvious causes. Cortex is incompletely mineralized and the trabeculae are irregular. In some instances a genetic defect is found to be the cause of bone disease. The bones remain sclerotic forever (Fig. In severe forms of the disease there is anemia because the thick bones do not contain enough space for hematopoiesis. primary spongiosa of growing bones is not removed but persists into adult life. Fig. The medullary spaces of the bone do not contain fibrous tissue or hematopoietic marrow cells but are filled with bone corresponding to primary spongiosa. incompletely understood. Carbonic anhydrase II deficiency has been identified in some cases. Bones are structurally weak because of a loss of trabecular bone. or gastrointestinal tract. however.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . METABOLIC AND DEGENERATIVE DISEASES Metabolic Bone Diseases In adults metabolic bone diseases are disorders of the bone remodeling system. which is responsible for the maintenance of the anatomic and functional integrity of the osteon. Osteopetrosis. Amelia. endocrine glands. 17-6. 66417308 : ¸Ÿ±U 24 ¥°Q . The pathogenesis of many bone diseases such as osteoporosis remains. Osteoporosis is defined as a loss of normally mineralized bone. Fig. Extremities have not formed. Osteogenesis imperfecta type II. Sclerotic bones tend to fracture easily despite their thickness. In most severe cases such as amelia. Cortical bone and trabeculae are thin. 17-7. Osteoporosis. In states of low bone turnover. and they present as abnormalities of fingers and toes (syndactyly). and reduced thickness of cortical bone (Fig. As a result. 17-6). Neonatal long bones show irregular osteogenesis. Fig. li mbs are not formed at all (Fig. 17-4. as in hypophosphatasia or Marfan syndrome. 17-7). cortical porosity.357 resorption.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Parts of extremities or the entire limb may be defective or missing. 17-5. 17-5).

Inadequate mineralization of the osteoid. Osteomalacia and rickets are diseases that result from defective mineralization of the trabecular and cortical bone matrix. pigeon breast. The surface of the bone trabeculae is smooth and covered with flattened inactive cells. Osteoporosis. which typically contain more osteoid than normal (Fig. active. and lumbar lordosis. 17-8. Bone resorption indices point to an increased bone resorption. 66417308 : ¸Ÿ±U 24 ¥°Q . 17-9. and the surface of the bone trabeculae appears smooth and " inactive" (Fig. Affected bones are weak and tend to become deformed (bowlegs). Other features of rickets. accompanied by inadequate reabsorption and remodeling of the peripheral rim of the trabeculae.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Very little or no osteoid may be found. rachitic rosary (thickening of the costochondral junction). It usually is related to vitamin D defi- ciency. Osteoporosis. thus inhibiting normal bone growth. the osteoid surface areas covered with osteoblasts are increased but the width of the osteoid is normal (Fig. such as craniotabes.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The trabeculae are rimmed with osteoid. lined by osteoblasts. which typically is found in patients with end-stage kidney disease. Osteomalacia. Rickets is a disease of childhood in which defective mineralization occurs at the growth plate. In high-turnover osteoporosis. also are related to basic defects in bone mineralization and growth. The affected bones show decreased mineralization of the os- Fig. Epiphyseal growth plate is disorganized and widened. Fig. results in their widening and structural weakness. Bone resorption studies indicate decreased resorption surface areas and number of osteoclasts. Osteomalacia is characterized by softening of bones. Osteoid surface areas are decreased. Typically the epiphyseal growth plate is disorganized and widened (Fig. 17-10. Rickets. 17-8). 17-9). inactive. 17-I I. Such bones tend to be less resistant to stress and are prone to deformities and fractures. Osteomalacia is a major component of renal osteodystrophy. 17-11). 17-10). Fig.358 bone formation is normal to reduced and small amounts of osteoid are present. Thick seams of osteoid cover the calcified core of bone trabeculae. Fig.

66417308 : ¸Ÿ±U 24 ¥°Q . Osteoblasts form an almost continuous line along the thick seams of osteoid rimming the bone trabeculae. 17. often encountered. There also is marrow fibrosis. also known as osteitis deformans. progressive deformities. Hyperparathyroidism. 17-I5. which also tends to involve the hematopoietically active flat bones. Paget Disease of Bone Paget disease of bone. Deformities of weight-carrying bones of the extremities are the most common feature of polyostotic Paget disease. Fig. and groups of osteoclasts are seen in lacunae of bone. Trabeculae are rimmed with prominent osteoid. The bone marrow shows fibrosis. 17-13). These lesions may resemble giant cell tumors of bones (Fig. Renal osteodystrophy. and brown tumors of hyperparathyroidism rarely are seen today. 17-12). Fig. fractures. 17-14. and the medullary spaces contain increased amounts of dense fibrous tissue and scattered osteoclasts. Weakened bones tend to fracture or bleed.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Focal aggregates of„multinucleated osteoclasts may result in lytic lesions (osteitis fibrosa cystica) or tumors ( " brown tumors of hyperparathyroidism"). It may involve one or more bones. Paget disease of bone. Hyperparathyroidism Hyperparathyroidism is an important cause of metabolic bone changes. causing pain. Such changes respond well to treatment of the primary disease.12. For unknown reasons hyperparathyroidism affects the cortical and subperiosteal bone more than the trabeculae of the cancellous bone. Early diagnosis of primary hyperparathyroidism and successful treatment of chronic renal diseases have reduced the occurrence of severe forms of renal osteodystrophy and osteitis fibrosa cystica. which leads to accelerated remodeling of the bone and loss of minerals from the osteon (Fig. 17-14). Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Minor bone changes similar to those seen in other forms of osteomalacia are. Fig. 17-15). It is a common disease that affects 3 percent of the white population over 40 years of age. The incidence of Paget disease increases with age. Brown tumor of hyperparathyroidism is composed of numerous multinucleated osteoclasts. is a chronic osteolytic and osteosclerotic bone disease of uncertain cause. The bone appears sclerotic and dense. and these secondary changes are accompanied by additional histologic changes that reflect replacement of damaged bone and new bone formation. Hyperparathyroidism. and arthritis. Parathyroid hormone stimulates both osteoblasts and osteoclasts. Most patients (80 percent to 90 percent) are asymptomatic. nevertheless. Involvement of the skull is especially common in monostotic Paget disease. 17-13. Involved bones appear sclerotic and dense (Fig.359 teoid but increased osteoclastic bone resorption and fibrosis of the medullary spaces (Fig.

17-17). and new bone formation finally result in a jigsaw mosaic pattern. (2) active osteogenic phase. B. is the most important and most common of these diseases. particularly cartilage. which is caused by deposition of calcium pyrophosphate crystals in articular cartilage.5 percent of the population. Histologically tophi are characterized by deposits of uric acid crystals with a central core of proteinaceous material (Fig. ligaments. also known as alkaptonuria. which 66417308 : ¸Ÿ±U 24 ¥°Q . Crystal deposits are surrounded by granulation tissue that often contains foreign body multinucleated giant cells (Fig. A. and (3) quiescent sclerotic phase (Fig. containing up to 100 nuclei. affecting approximately 0. The osteoclasts are morphologically abnormal and many are very large. and intervertebral discs. 17-16). and basic calcium phosphate (hydroxyapatite) and calcium oxalate. Urate crystals accumulate in the synovial fluid. Homogentisic acid interferes with the normal metabolism of cartilage. In the active resorptive phase the bone marrow is replaced by richly vascular. Pseudogout. Active osteogenic phase is characterized by new bone formation. In chronic tophaceous gout. However. is an inborn error of metabolism that is marked by a deficiency of homogentisic acid oxidase. Active resorptive phase is characterized by increased osteoclastic activity. During an acute attack uric acid crystals typically are seen in the cytoplasm of polymorphonuclear leukocytes obtained from the inflamed joint. 17-16. and even in some internal organs such as the kidneys. In the second phase osteoblastic activity is triggered. Paget disease of bones. which is caused by deposition of urate crystals. Repeated episodes of bone removal.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and cause grossly visible blue-black discoloration. earlobes. menisci. synovium. tophi may be seen not only around the joints but also in the subcutaneous tissue. These deposits are composed of typical biaxial crystals. Arthritis may result from the deposition of monosodium urate. which becomes brittle and easily abraded from the joint surface. eliciting an intraarticular inflammation. in tissues fixed in absolute alcohol. C. calcium pyrophosphate. 17-18). Crystal-induced Arthritis Crystal-induced arthritis refers to a group of metabolic disorders that are characterized by deposition of crystals in and around the joints. most patients have a short history. 17-19). Polymers of homogentisic acid accumulate in connective tissue. remodeling.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . In sclerotic phase the bone has prominent seams that impart to it a jigsaw mosaic pattern. Gout. uric acid crystals appear birefringent when examined under polarized light. In histologic slides these deposits appear brown (Fig. Ochronosis. In contrast to gout. As the disease progresses deposits of urates form masses ( " tophi " ) that erode the adjacent bone and extend into the soft tissues. loose connective tissue and congregations of osteoclasts along the existing trabeculae and within the cortex.360 A B C Fig. Paget disease may be divided into three phases: (1) active resorptive phase. In acute phases the disease evokes an acute inflammatory response followed by a chronic inflammation. Challdike deposits are seen in chronic stages of the disease. it is washed out during tissue processing. which is the hallmark of sclerotic Paget disease. tendons. resembles gout. Because uric acid is soluble in water that contains fixatives.

66417308 : ¸Ÿ±U 24 ¥°Q . and hormones. sparing the cortex that receives blood from periosteal Degenerative Joint Disease Degenerative joint disease. and reparatory changes (Diagram 17-1). is a common noninflammatory disease of movable joints that is characterized by degeneration of articular cartilage and adjacent bone and new bone formation. with a broad subchondral base and the apex pointing inside (Fig. or as idiopathic and secondary when it is related to identifiable causes.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and focal necrosis of subchondral bone and osteophytes (Fig. 17-18. is blood vessels. The articular cartilage may be intact because it receives nutrients from the synovial fluid. Many predisposing factors have been identified. 17-17. including systemic. Fig. also known as aseptic or avascular necrosis. also known as osteoarthritis. a term used to describe bone necrosis that occurs in many sites but which most often is found in the femoral head of the elderly. remodeling of tidemark. drugs. These changes typically include fragmentation of cartilage. Gout. Corticosteroids are the most common identifiable cause of osteonecrosis in younger persons. Osteonecrosis of the head of femur. Fig. subchondral pseudocysts. 17-21). leads to joint dysfunction. The necrotic bone appears discolored and is demarcated from surrounding normal bone. The infarct usually involves the medulla and the bone marrow. Severe spondylosis with chondrocalcinosis of intervertebral disks and degenerative arthropathy of weight-carrying joints develops at an early age. In most instances the exact cause cannot be found and the condition is considered to be idiopathic. eburnation. proliferation of chondrocytes.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . associated with destruction of the bone and joint. Tophus appears as a soft-tissue mass. The medullary bone and the bone marrow often are affected. Polymers of homogentisic acid appear as brown material in the connective tissue. metabolic. and autoimmune diseases. Osteonecrosis Osteonecrosis. 17-20. Treatment of endstage kidney disease by xenotransplantation and trauma is another common cause. In the head of the femur the necrotic area usually appears triangular. subchondral bone sclerosis. Ochronosis. Fig. Morphologically the bone shows typical signs of ischemic necrosis. Osteoarthritis may be classified as primary.361 Fig. 17-20). Gout. Tophus consists of deposits of uric acid surrounded by granulation tissue that contain foreign body giant cells. The pathologic changes include a variety of degenerative changes. 17-19.

66417308 : ¸Ÿ±U 24 ¥°Q . Possible insults to joint structure and function are numerous and result in a high cumulative prevalence of joint disorders. 17-21.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . B. Degenerative joint disease. A. Degeneration of cartilage leads to denuded articular surface areas. B A Fig.36 2 Diagram I7-I. Fragmentation of cartilage with proliferation of chondrocytes leads to remodeling of the tidemark.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

chronic infiltrates of lymphocytes. and the primary infection of the joint may spread into the underlying bone. The bone fragments generated in this process remain inside the cavity of the abscess and are known as "sequestrum:" Reactive bone sclerosis forms around the abscess. which may be medullary or subperiosteal (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and mycobacteria such as Mycobacterium tuberculosis. 66417308 : ¸Ÿ±U 24 ¥°Q . Osteomyelitis typically results from bacterial infections that may reach the bone by blood-borne means. Pannus infiltrated with mononuclear cells covers the articular cartilage. known as pannus. Infection has caused massive destruction of the bone shaft and has extended into the surrounding soft tissue. including Streptococcus and Staphylococcus species. 17-23. Destructive lesions lead to ankylosis and deformities of the joint. 17-24). Infectious arthritis may be caused by viruses. which also leads to destruction of the cartilage and adjacent bone and formation of intraarticular free bodies ( " mice" ) (Fig. spirochetes such as Treponema pallidum and Borrelia burgdorferi. Viral arthritis usually is a short-lived acute infection that heals spontaneously and leaves no consequences. Mixed infections are especially common in posttraumatic osteomyelitis complicating open fractures or bullet wound. Staphylococcus aureus tends to produce abscesses and cavitary lesions. Fig. corresponding to the pseudocapsule of a chronic ab- Fig. or fungi. Osteomyelitis. the inflammatory response may be mediated by neutrophils or macrophages and lymphocytes. Neisseria gonorrhoeae. Arthritis is a common feature of human immunodeficiency virus (HIV) infection. and immune-mediated inflammatory diseases of the joints. The pathologic findings are nonspecific and include synovial edema. Chronic granulation tissue forms a layer. from adjacent infected joints or soft tissues. and mild hyperplasia of synovial cells. Morphologic changes in bones affected by osteomyelitis reflect its etiology and pathogenesis. such as rheumatoid arthritis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and the HIV virus may be isolated readily from the affected joints. 17-25). accounting for more than 80 percent of all cases that are unrelated to bone fracture. which may form granulomas (Fig. 17-24. Tuberculous arthritis. Articular surface is covered with grapelike bodies ("rice bodies"). 17-23). Bacterial arthritis maybe caused by a variety of pathogens. Staphylococcus aureus is the most common pathogen. Fig. 17-22). 17-22. Epstein-Barr virus infection typically is associated with arthritis. bacteria. infections of the joints (infectious arthritis). or as a result of a bone fracture or bullet wound. Depending on the causative agent. Tuberculous synovitis. Infections of Bones and Joints Infections of bone and joints may occur in an isolated form or together. Osteomyelitis may spread into the joint and cause arthritis. Deep-seated abscesses form sinus tracts lined by granulation tissue that does not heal (Fig.363 I NFLAMMATORY DISEASES Inflammatory diseases of bones and joints include infections of the bone (osteomyelitis).

Such a walled-off abscess is called a Brodie abscess. Fig. that result from tuberculosis of the spine are rare (Fig. The groups of chronic arthritides that do not have positive immunologic test results are. Chronic osteomyelitis. 17-28). Hypertrophic synovitis typical of advanced rheumatoid arthritis leads to erosion of the joint surfaces. The most important among these diseases is rheumatoid arthritis. such as severe gibbous kyphoscoliosis (Pott disease). These nodules consist of a central area of fibrinoid Fig. Rheumatoid arthritis. Rheumatoid arthritis is a systemic disease that may affect many internal organs. 17-28. Fig. and some less common diseases.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . With time the synovium forms a cover over the joint surfaces ( " pannus " ). Fig. Hyperplastic synovium forms hypervascular fronds that are infiltrated with lymphocytes. It may obliterate the entire cavity and cause ankylosis ( Diagram 17-2). 17-30). enteropathic arthritis." Extensive new bone formation results in complete obliteration of medullary spaces and high-density osteosclerotic lesions (Fig. Osteomyelitis. deformities. termed seronegative. reduced mobility. The inflamed synovium is edematous and is infiltrated with lymphocytes and plasma cells (Fig. which is a systemic. 17-27. and lungs. presumably autoimmune. which are increased in number and often show signs of endothelial proliferation and fibrinoid necrosis. Reiter syndrome. Nodules form in the subcutaneous tissue. and often complete loss of joint function and ankylosis. chronic disease that also involves the soft tissues. 17-27). pannus tends to fragment and form loose intraarticular bodies ( " rice bodies") (Fig. Since the advent of modern chemotherapy. plasma cells. 17-26). 66417308 : ¸Ÿ±U 24 ¥°Q . The bone appears sclerotic.364 scess of soft tissues or parenchymal internal organs. Noninfectious Arthropathies Noninfectious arthritis and spondylitis are common diseases that often are accompanied by other systemic symptoms. Rheumatoid arthritis begins as a slowly evolving but persistent chronic inflammation that may lead to significant deformities of joints (Fig. heart. Tuberculosis of spine (Pott disease). This group includes diseases such as ankylosing spondylarthritis. and macrophages.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Destructive lesion of vertebral bodies may result in kyphoscoliosis. psoriatic arthritis. Granulation tissue forms between the bone trabeculae in response to persistent infection. 17-29). 17-25. Chronic osteomyelitis leads to deformities of the skeleton. As a result of foci of necrosis and mechanical trauma. All of these changes are associated with joint deformities. muscles. Prominent deformities of hands are features of long-lasting disease. in contradistinction to rheumatoid arthritis. 17-26. The disease is accompanied by a set of immunologic disturbances reflected in positive serologic tests such as the test for rheumatoid factor. Sclerotic bone surrounding a sequestrum-containing abscess cavity is referred to as " involucrum. The infiltrates are most prominent around the blood vessels.

A. 17-29.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Synovium is cellular and covered with fibrin. Diagram 17-2. 66417308 : ¸Ÿ±U 24 ¥°Q . Prominent synovial vessels are surrounded by plasma cells and lymphocyte.365 A B Fig. B.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Complex multifactorial pathogenesis of rheumatoid arthritis involves genetic susceptibility and environmental influences. Rheumatoid arthritis.

·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . A. 66417308 : ¸Ÿ±U 24 ¥°Q . Chronic synovitis results in the formation of fibrovascular structures lined on their surface by synovial cells. 17-30. The subcutaneous nodule is composed of a central zone of fibrinoid necrosis surrounded by palisaded histiocytes. Pannus invading the subchondral bone.366 A B C Fig. Rheumatoid nodule. Rheumatoid arthritis. 17-31. Hyperplastic synovium and a rheumatoid nodule removed from joint. C. Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . B.

which should never be based on microscopic findings alone. Neoplasms of bones are rare. Primary tumors of joints are even less common than bone tumors. Right. Diagram 17-3. (Modified from Madewell JE. 17-33). 17-32). Sweet DE: Radio) Clin North Am 19:715. Clinical symptoms are rare except in tumors that compress nerves or cause facial deformities.2 percent of all tumors of internal sites. Typical anatomic locations of the most common bone tumors and their radiographic features are shown in Diagram 17-3. Clinical and radiologic data are essential for proper pathologic diagnosis. Osteoma. and a pathologist.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Ragsdale ED. distal end of femur. This tumor most often is located within the cortex of long bones or immediately beneath it (Fig. most notably in the lungs of coal workers (Caplan lesion). Although neoplasms of bone are quite heterogeneous. 1981. Osteoid osteoma is a benign bone-producing tumor that may occur at any age but most often is seen in the second and third decades.) 66417308 : ¸Ÿ±U 24 ¥°Q . accounting for only 0. proximal end of tibia. Rheumatoid nodules. especially in children and young adults. Anatomic locations of common benign and malignant bone neoplasms. overall they tend to affect younger persons. The tumor is composed of mature bone. which show signs of infarction. Benign Bone-forming Tumors Osteoma is a benign slow-growing tumor that is composed NEOPLASMS - of mature bone (Fig. and the long bones of legs are the most common site. a radiologist. Malignant neoplasms are distinctly rare in short bones. with a peak incidence under the age of 20 years. and chronic inflammation also may occur in internal organs. 17-31). Left.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Large vessel disease is even less common but may involve internal organs. Fig. Males are affected significantly more often than females. Vasculitis that involves small vessels occasionally is seen in patients with a high titer of immunoglobulin M (IgM). 17-32. Long bones more often are involved than short bones. they are an important cause of morbidity and mortality. fibrosis. The evaluation of patients with bone tumors is based on an interdisciplinary approach that includes a clinicianorthopedic surgeon. Nevertheless.367 necrosis surrounded by palisaded macrophages and lymphocyte or plasma cells (Fig.

368

It consists of a small nidus of bone-forming cells surrounded by sclerotic bone. The nidus, which by definition measures only 1 to 2 cm in diameter, is composed of osteoblasts, interlacing trabeculae of woven bone and osteoid, blood vessels, and occasional osteoclasts. Osteoblastoma is a benign bone-producing tumor that accounts for 1 percent of all bone neoplasms. It more often is found in males than in females and most often is located in

the posterior parts (transverse and spinous processes) of the vertebrae. Radiologically it is a mixed osteolytic and osteoblastic lesion that may cause cortical thinning and eventually cortical expansion (Fig. 17-34). On gross examination osteoblastoma appears as a granular, hemorrhagic, gritty mass that is sharply demarcated from the normal bone. Histologically it is indistinguishable from osteoid osteoma. The tumor contains numerous interlacing trabeculae of osteoid

A

B

C

Fig. 17-33. Osteoid osteoma.A, Radiograph shows a dense blastic reaction of cortex with a small lucent area. B, Nidus of osteoid osteoma measures approximately I cm in diameter and has a finely granular lattice-like appearance. C, Bone spicules lined by osteoblasts are formed within fibrovascular stroma.

A

B

Fig. 17-34. Osteoblastoma. A, Radiograph show an osteolytic lesion with foci of calcification. B, Osteoblasts line newly formed spicules of osteoid and bone.

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369

and woven bone that are lined by a nearly continuous population of osteoblasts, which may be likened to soldiers in a row or crows on a fence. The stroma is highly vascular and there are scattered osteoclasts. No other elements are seen, although recently there have been reports that small foci of cartilage occasionally are found. Osteoblastomas are benign tumors but a rare aggressive variant may appear occasionally. These tumors are considered to be low-grade osteosarcomas and are treated accordingly. .

Malignant Bone-forming Tumors
Osteosarcoma is a complex family of biologically diverse

pathologic entities that share a single histologic finding: the production of bone or osteoid by malignant cells. On the basis of clinical and pathologic features, conventional ( "classic" ) osteosarcomas may be separated from several variant forms. Variant forms of osteosarcoma have a different prognosis from that of conventional osteosarcoma and need to be recognized. Conventional osteosarcomas account for 65 percent to 75 percent of all osteosarcomas. Although they may occur in any age group, most tumors are diagnosed in persons between 10 and 30 years of age. Males are affected twice as often as females. Fewer than 1000 cases of conventional osteosarcoma are diagnosed yearly. Although any bone may be involved, most tumors arise in the distal part of the femur and in the proximal parts of the tibia, fibula, femur, and radius. Approximately 90 percent of tumors arise in the metaphysis, and 10 percent arise in the diaphysis. Epiphyseal involvement

almost always represents secondary extension or metastasis from a metaphyseal primary tumor. Radiologically osteosarcoma presents as a highly aggressive and destructive lesion that has a variegated appearance on radiograph (Fig. 17-35). Most lesions contain both radiolucent and radiopaque areas, and extension into the soft tissues is common. There are, however, no specific diagnostic radiologic features or features that would have special prognostic significance. The gross and microscopic appearance of conventional osteosarcoma is highly variable and depends on its histologic composition. Lesions that are rich in osteoid and bone appear dense, granular, and sclerotic, and their color varies from yellow-brown to ivory-white. Tumors that contain significant amounts of cartilage have an overall gray-blue, lobulated, chondroid appearance. If little matrix is present, the tumors appear gray-tan; hemorrhage may account for the brownish-red mottling of some lesions. Microscopically osteosarcoma is composed of atypical spindle-shaped cells (Fig. 17-36). The production of osteoid or bone by malignant cells represents the single diagnostic criterion of conventional osteosarcoma. Osseous matrix may be the dominant histologic finding or it may be quite inconspicuous. Cartilage and collagenous stroma also may be present, and accordingly tumors may be further subclassified as osteoblastic, chondroblastic, or fibroblastic. Most osteosarcomas represent a mixture of these three patterns. Histologic subclassifications are impractical and have no clinical value. Multidisciplinary protocols used in the treatment of osteosarcoma have dramatically improved the long-term survival

B A

Fig. 17-35. Osteosarcoma, conventional. A, MRI shows a predominantly blastic lesion extending into soft tissue. B, The mass in the distal femur has destroyed the cortex, extending into the soft tissue. Whitish areas represent the sclerotic part of the tumor. Medullary cavity contains a "skip" metastasis that appears as a whitish nodule.

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Fig. 17-36. Osteosarcoma. conventional. Tumors may show several histologic patterns. A, Hypercellular tumor forms only a few bone spicules. B, Osteoblastic tumor shows extensive new bone formation. C, Chondroblastic tumor contains abundant cartilage. D, Fibroblastic osteosarcoma consists of heterogeneous spindle-shaped cells with focal bone formation.

of patients with conventional osteosarcoma from less than 20 percent in the past to approximately 80 percent as reported in most recent studies.

Osteosarcoma Variants
Parosteal osteosarcoma is a low-grade malignant tumor that arises from the surface of bones. It most often occurs in the third to fifth decade of life, and women are affected twice as often as men. It is almost exclusively a disease of long bones and most often affects the posterior aspect of the distal femur (Fig. 17-37). Radiologically it appears as a radiopaque, lobulated mass that seemingly is applied to the surface of the involved bone. The tumor generally grows along the surface of the bone without involving the medullary cavity. On gross examination the tumor arises from the bone surface and tends to be large. Microscopically, parosteal osteosarcoma is composed of relatively innocuous spindle-shaped fibroblastic cells that produce well-formed lamellar bone spicules. With appropriate treatment, the long-term survival rate is over 90 percent. Periosteal osteosarcoma has a peak incidence in the second and third decades of life. Men are affected more often than women. This tumor most often arises in the diaphysis and

metadiaphysis of long bones, especially the femur and the tibia. Radiologically it may involve part of the surface or may extend into the soft tissues in a spiculated "sunburst " pattern (Fig. 17-38). Like parosteal osteosarcoma, this tumor also may circumferentially envelop tubular bones from which they have arisen. On gross examination the tumor is located in the metaphysis or metadiaphysis; it has a broad base, with fusiform elevation of the periosteum. Microscopically it has the features of high-grade chondroblastic osteosarcoma. The five-year survival rate is 50 percent. Intraosseous well-differentiated osteosarcoma is a rare variant that has a peak incidence in the third decade and affects women more often than men. The tumor has a strong predilection for the long bones of the extremities, especially the metaphysis, but it also may occur in the diaphysis. Radiologically it has no distinct features and may simulate fibrous dysplasia or desmoplastic fibroma. Grossly it contains both osteoblastic and osteolytic areas and often is confined to the medullary cavity (Fig. 17-39), although older lesions may extend beyond the cortex. The tumor shares the innocuous histologic features of parosteal osteosarcoma. Microscopically it is composed of relatively bland fibroblastic cells that form mature bone spicules, resembling parosteal osteosarcoma. It has a favorable prognosis.

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Fig. 17-37. Parosteal osteosarcoma. A, Radiopaque lobulated masses are found on the surface encircling the long bone. B, Longitudinal section of the femur shows a superficial tumor attached to the posterior side of the bone. C, Bland spindleshaped cells surround lamellar bone spicules.

Fig. 17-38. Periosteal osteosarcoma. A, Radiograph shows a spiculated surface mass that has a "sunburst" appearance. B, Surface tumor arising from the shaft of the femur has a broad base. The medullary cavity is intact. C, Tumor cells form cartilage. Nuclei show high degree of atypia.

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Fig. I7-39. Intraosseous well-differentiated osteosarcoma. A, The medullary cavity contains tumor tissue that is partially sclerotic. B, Bone spicules are associated with innocuous fibroblastic cells.

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Fig. 17-40. Telangiectatic osteosarcoma. A, Radiograph shows an invasive tumor with prominent cystic areas. B, Multiple cystic areas involving the proximal metaphysis of the bone resected after chemotherapy. C, Large hemorrhagic mass in the distal epimetaphysis of the femur has destroyed the cortex and extended beyond the confines of the bone. D, High-grade osteoblastic cells are surrounded by cystic dilated vascular spaces and extravasated blood.

Telangiectatic osteosarcoma has the same clinical features as conventional osteosarcoma but differs in that it is cystic and hemorrhagic and may resemble aneurysmal bone cyst (Fig. 17-40). Microscopically the tumor is composed of highgrade osteoblastic cells that produce little osteoid and are surrounded by prominent dilated blood vessels.

Benign Cartilage-forming Tumors
Osteochondroma is the most common benign cartilaginous tumor of bones, accounting for approximately one third of all benign bone neoplasms. Most often it is found in children and adolescents. It usually is located in the metaphysis of long bones, growing away from the nearest joint. On gross examination the tumor apparently arises from the cortex and may be sessile or pedunculated. The lesion consists predominantly of cancellous bone that is covered with a cartilaginous cap (Fig. 17-41). Histologically the lesion is composed of ma -

ture bone and cartilage and is not resected unless it causes compression, fracture, or other complications. Enchondroma is a benign cartilaginous tumor of short bones of the hand and foot of adults. When tumors are multiple and unilateral, the disorder is referred to as Oilier disease. If tumors are multiple and are associated with angiomas of soft tissues, the condition is called Maffucci syndrome. Solitary enchondroma is the most common of all tumors that occur in the short tubular bones of hands. Enchondromas typically are located, in order of decreasing frequency, in bones of the fingers, metacarpal bones, phalanges of toes, and metatarsal bones. Tumors arise from the medullary cavity, extending the bone longitudinally, expanding it, and causing cortical thinning. Histologically the tumors consist of hyaline cartilage of variable cellularity. There often are numerous binucleated chondrocytes with nuclei larger than the nuclei of mature lymphocytes (Fig. 17-42). Finely dispersed chro-

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Fig. 17-41. Osteochondroma. A, The lesion is composed of cancellous bone covered with a cartilaginous cap. B, A cartilaginous cap covers the cancellous bone. .

matin and nucleoli are seen, but mitoses are not apparent. These tumors do not metastasize but may recur after curettage. Conservative treatment is recommended because only a few tumors that have metastasized have been reported. Periosteal chondroma is a rare, benign, slow-growing, cartilaginous tumor that arises from the surface of a bone under the periosteum. Like enchondromas of the hand and feet, its histologic features may be alarming, but its behavior is benign. The most common location is the metaphyseal region of long tubular bones, such as the humerus and femur, proxi mal tibia, and phalanges of fingers (Fig. 17-43). Radiologically the lesion typically is small (1 to 3 cm in diameter) and saucer-shaped on the surface of the bone with a dense rim of reactive bone tissue. The lesion usually protrudes into the soft tissue but is well delimited by the periosteum, which may form a thin eggshell ossification around it. On gross examination periosteal chondroma is a lobulated cartilaginous nodule surrounded by a rim of bone. Histologically it may appear as an innocuous proliferation of hyaline cartilage, but it is common to find binucleated cells and enlarged nuclei with finely dispersed chromatin. This histologic pattern is similar to that of a low-grade chondrosarcoma. The diagnosis is based on typical radiologic findings, and the histologic findings should not be a cause for alarm because the tumor is invariably benign. Nevertheless, it should be distinguished from periosteal chondrosarcoma and periosteal osteosarcoma, both of which show much more pronounced nuclear atypia. Chondromyxoid fibroma is a rare, locally aggressive but benign tumor of bone that accounts for less than 0.5 percent of benign bone tumors. It may occur in any age group but is more common in the second and third decades of life. The most common sites of involvement are the metaphyses of long bones, proximal tibia and fibula, and distal femur, which

Fig. 17-42. Enchondroma. The tumor is composed of cartilaginous cells that show mild nuclear variation.

is the site of origin of approximately one half of all cases. Radiographically the lesion has an eccentric radiolucent area surrounded by a sclerotic rim of dense bone, which imparts a geographic appearance (Fig. 17-44). In contrast to other cartilaginous tumors, chondromyxoid fibromas rarely contain calcifications. Tumor may destroy the cortex, but generally it is well delimited by the periosteum. On gross examination the tumor is glistening, myxoid, lobulated, and cartilage-like, and in resected specimens it is surrounded by a rim of dense bone. Microscopically the tumor contains lobules of myxoid tissue surrounded by condensation of cells at the periphery of the lobulated areas. The myxoid areas are poorly cellular, containing stellate, triangular-shaped, spindle-shaped, or round cells Hyaline cartilage differentiation is not seen even though some cells resemble chondroblasts. At the periphery of lobules there is condensation of

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Fig. 17-43. Periosteal chondroma. A, Radiograph of the posterior surface of distal femur shows a well-delineated nodule that has a saucer-like shape at the base and a rim of peripheral calcified material. B, The tumor is composed of cartilage, which focally has lacunae with two nuclei. C, Cartilage cells show signs of atypia.

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Fig. 17-44. Chondromyxoid fibroma of bone. A, Tomogram of the elbow shows a lytic lesion surrounded by a sclerotic border. B, The tumor consists of lobulated cartilaginous tissue enclosed by thick sclerotic rim of bone. C, Tumor cells are arranged into lobules that have less cellular central areas and cellular periphery.
C

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Fig. 17-45. Chondroblastoma. A, Epiphysis of femur contains a lucent but demarcated lesion. B, Tumor is composed of small roue chondroblasts. C, Chondroblasts are surrounded by amorphous material ("chondroid").

medium-sized cells, many of which resemble chondroblasts. Some osteoclast-like giant cells are seen, but mitoses are rare. Immunohistochemically the cells are positive for S-100 proteins, which indicates their cartilaginous nature. Tumors are treated by block resection because curettage alone is accompanied by an 80 percent recurrence rate. Chondroblastoma is a rare, benign, cartilaginous tumor that accounts for 1 percent of benign bone tumors. It may occur at any age but most often it is diagnosed in the second decade of life. It typically occurs in the epiphyses of long bones but extends into the metaphyses as it grows. Radiologically the lesion is eccentric in 75 percent of cases. It has a geographic pattern of bone destruction with a sclerotic rim of dense bone at the periphery, consistent with the slow growth of the tumor over prolonged periods (Fig. 17-45). Grossly the lesion consists of reddish-brown hemorrhagic tissue, with occasional small calcifications. Microscopically the tumor consists of chondroblasts, islands of cartilage, giant cells, and calcifications. The chondroblasts are polygonal or round cells with indented or grooved nuclei, without nucleolus and abundant light tan–pink cytoplasm. These cells stain positive for S-100 protein. Mitotic figures are found in most tumors and range from 1 to 3 per 10 high-power fields. Nuclear atypia and focal necrosis may be found, but these changes alone do not imply malignancy. Cartilage is found in the form of small islands but appears as ill-defined amorphous pink material that may resemble osteoid. It contains collagen but is depleted of proteoglycans and is referred to as " chondroid." Giant cells, which may be sparse or abundant, represent osteoclasts. Calcifications are of two types: small, irregular, and ill-defined; or lacy, " chicken wire " type, i mparting to the lesions a honeycomb appearance. Ossification that simulates osteoblastoma is found in 5 percent of lesions. Aneurysmal bone cyst formation is a common secondary phenomenon that might be associated with a higher degree of recurrences. Most tumors are benign and respond

C

well to conservative management with curettage. Recurrences are expected in 15 percent of cases. Metastasizing malignant chondroblastomas are extremely rare.

Malignant Cartilage-forming Tumors
Chondrosarcoma is the second most malignant bone tumor. It is classified as central (medullary) if it is located in the medullary cavity or peripheral (juxtacortical) if it is found on the surface of the bone. Microscopically it is categorized as classic chondrosarcoma or as chondrosarcoma variants . Chondrosarcomas may arise de novo or as a secondary malignancy in a preexisting cartilage lesion, such as enchondromas of Oilier disease. Chondrosarcomas occur mostly in adults, generally those between 20 and 70 years of age. The most common sites of involvement are the pelvis, femur, scapula, humerus, and ribs (Fig. 17-46). Radiographic findings are typical. Scattered calcifications, described as punctate, annular, popcorn-like, stippled, and so on, are indicative of cartilaginous tumors but do not help in distinguishing benign from malignant tumors. Classic chondrosarcoma is the most common type of this malignancy. On gross examination the tumors have a glistening, lobulated cartilaginous appearance irrespective of their intramedullary or surface location. As the tumors grow, they tend to compress tissues or invade and trap adjacent structures. Microscopically chondrosarcomas may be composed of morphologically benign cells or apparently malig-

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Fig. 17-46. Chondrosarcoma. A, Humerus shows extensive diaphyseal and metaphyseal involvement with scalloping of endosteum. B, Cartilaginous mass originates from the surface of ilium.

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nant and undifferentiated cells (Fig. 17-47). Histologic grading of lesions, which usually is done on a scale from 1 to 3, is an important part of the evaluation of all cartilaginous tumors. Low-grade lesions are made up of hyaline cartilage showing sparse cellularity and rare lacunae with binucleated cells. The nuclei of tumor cells are dark, round, and not larger than the nuclei of lymphocytes. Higher grade lesions are more cellular and are composed of tumor cells that have larger nuclei with finely dispersed chromatin and occasional nucleoli. There is increased variation in the size and shape of nuclei, some of which are spindle-shaped, vesicular, or bizarre. The number of lacunae with binucleated cells is increased. High-grade lesions show nuclear atypia, pleomorphism, and mitotic activity. Two or more mitoses per 10 highpower fields are found in grade 3 lesions. Grade 1 lesions have an excellent prognosis and may be cured by local treatment, in contrast to grade 3 lesions, which tend to metastasize and have a 10-year survival rate of 55 percent. Chondrosarcoma variants include (1) dedifferentiated chondrosarcoma, (2) mesenchymal chondrosarcoma, and (3) clear cell chondrosarcoma. Dedifferentiated chondrosarcoma is a rare tumor that accounts for 1 percent to 2 percent of malignant bone tumors. It has the worst prognosis of all chondrosarcomas and invariably is considered to be fatal. Most tumors occur in the elderly and most often are located in the pelvis and femur. Radiologically the tumors are speckled like other cartilaginous tumors, but they also have a large lytic component and extend outside the bones. On gross examination they are large infiltrative tumors, with variable foci of obvious cartilage. Histologically the diagnosis is made upon finding areas of cartilage adjacent to high-grade sarcoma, which usually appears like malignant fibrous histiocytoma or unclassified spindle cell sarcoma or osteosarcoma. Despite radical surgery survival rates are dismal. Mesenchymal chondrosarcoma is a rare tumor that accounts for 0.3 percent to 0.5 percent of primary malignant

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Fig. 17-47. Chondrosarcoma. A, Grade I tumor is composed of innocuous bland cells that have nuclei the size of those of lymphocytes. B, Grade 2 tumors have enlarged nuclei, fine chromatin, and occasional nucleoli. C, Grade 3 lesions show hypercellularity and nuclear anaplasia.

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Both lesions tend to involute spontaneously. 17-48). which may be lipid-laden and vacuolated. (5) desmoid tumor of bone (desmoplastic fibroma). 17-49. En bloc resection cures most lesions and the five-year survival rate is 85 percent. loculated lesion rimmed by a zone of sclerosis. Clear cell chondrosarcoma is an extremely rare tumor that has a relatively good prognosis. and frank malignancies. 66417308 : ¸Ÿ±U 24 ¥°Q . Osteoclastic giant cells appear in clusters or are scattered throughout the tumor. bone tumors. Both lesions are found in children. Radiologic findings are nonspecific. depending on the amount of lipid and blood-derived pigment (Fig. locally aggressive lesions. but others have the same morphology and biologic properties as their equivalents in soft tissues. and hemorrhagic. Any bone may be involved. Some of these lesions are unique to bones. it is rare in children. They usually are asymptomatic and are discovered incidentally during radiographic examination. although in some cases chemotherapy has been beneficial. 17-49). together with foci of calcification. (3) xanthoma. On gross examination they appear yellowish to rusty brown.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Management is surgical. Fibrous Lesions of Bone Fibrous neoplasms of bone include benign lesions. The prognosis is poor. 17-48. The blood vessels have thin walls. They are classified as (1) fibrous cortical defect and nonossifying fibroma of bone. Nonossifying fibroma is larger and presents as an eccentric metaphyseal. The small cell component may simulate Ewing sarcoma or hemangiopericytoma. radiolucent. and (6) malignant fibrous histiocytoma. The tumor consists of small undifferentiated cells and foci of cartilage. Osteoid and bone spicules may be found. Histologically it consists of two components: a primitive small cell neoplasm and hyaline cartilage that either appears benign or shows features of low-grade malignancy (Fig. especially the head of the femur. The stroma is scant and usually includes only fine capillaries juxtaposed to tumor cells. which is the most common location. It has a peak incidence in the second decade. Clear cell chondrosarcoma. Histologically these lesions are composed of bland fibroblasts and histiocytes.377 A Fig. Tumor cells have clear cytoplasm. B. Grossly it appears as calcified or ossified foci alternating with cartilaginous-like material enclosed within the bone but also extending into the surrounding tissues (Fig. A. 17-50). B Fig. (4) osteofibrous dysplasia and fibrous dysplasia. and 80 percent of all patients are younger than 40 years old. fibrous cortical defect presents as a small radiolucent defect in the cortical part of the metaphysis of long bones. (2) fibrous histiocytoma. It occurs in the epiphysis of long bone.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Radiologically. red-brown. Microscopically it consists of clear polygonal cells with round nuclei. On gross examination the tumor is meaty. Mesenchymal chondrosarcoma. Fibrous cortical defect and nonossifying fibroma are closely related entities that differ in size but histologically are iden - tical and have a tendency to self-heal. The tumor in the head of femur shows central calcification surrounded by darker tissue.

Metaphyseal brown tumor is rimmed by a zone of sclerosis. Osteofibrous dysplasia. giant cell tumors of bone develop after the bones stop growing. Fibrous dysplasia. and spicules of bones lined by osteoblasts. come in various shapes and have been likened to Chinese letters or alphabet soup. Fibroblasts are in direct contact with bone spicules of variable shape. The trabeculae. 17-51. Proximal tibia contains a well-demarcated lesion that has a typical "ground glass" appearance. and 80 percent of patients are in the range 20 to 40 years old. it arises in the cortex. Microscopically the lesions are composed of fibroblasts intermixed with bone spicules. Fibrous dysplasia is a relatively common benign disorder that affects children and young adults. Fibrous dysplasia. 17-51).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .378 A B Fig. Microscopically it is composed of fibroblasts. 66417308 : ¸Ÿ±U 24 ¥°Q . A. Approximately two thirds of cases of fibrous dysplasia are diagnosed in persons younger than 30 years of age. is a rare lesion of children that typically is found in the tibia and fibula. occasionally showing a storiform pattern. It may present in the more common monostotic form or a less common polyostotic form. Considered a developmental anomaly rather than a neoplasm. and endocrine dysfunction is a component of the syndrome. also known as ossifying fibroma. A. Unlike fibrous dysplasia. Radiologically fibrous dysplasia presents with typical " ground glass" lesions in the medullary cavity (Fig. B. No treatment is required except in cases of pathologic fracture caused by the lesion. it consists of fibroosseous tissue replacing the normal marrow spaces. Fibroblastic cells are arranged in a storiform pattern. Polyostotic fibrous dysplasia may be combined with cafe au lait skin spots. 17-50. With a few exceptions. On radiograph it may be purelylytic or may have a " ground glass" appearance and a sclerotic rim. Nonossifying fibroma.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Radiologically giant cell tumors present as radiolucent lesions of the epiphysis reaching the ar- B Fig. Fibrous dysplasia requires no treatment because most lesions stop growing after puberty. Giant Cell Tumor of Bone Giant cell tumor of bone is a common benign bone lesion that accounts for 21 percent of all bone tumors and is the only one that affects the epiphysis and metaphysis of long bones. B. which are composed of woven bone.

Giant cell tumor of bone. Tumor is composed of multinucleated giant cells and mononuclear cells. Microscopically two components are recognized: multinucleated giant cells and mononuclear stromal cells. B. and xanthomatous macrophages are seen in varying proportions. Magnetic resonance imaging (MRI) is most useful for evaluating the extent of bone involvement. Ewing sarcoma most often occurs in the medulla of long bones of the extremities and in the pelvis.379 ticular cartilage and often extending into the metaphysis. Radiologically it presents as an intramedullary and extramedullary growth that imparts to the bone a mottled or moth-eaten pattern (Fig. lacks glycogen. but it also may occur in any other bone. has an increased number of mitoses. and (4) Hodgkin lymphoma. Mitotic activity is variable. Atypical Ewing sarcoma is a variant that shows nuclear variation. Marrow Tumors Tumors that originate from the bone marrow include (1) Ewing sarcoma. but with modern therapy the five-year survival rate is 65 percent except for patients with widespread disease and distant metastases. foci of hemorrhage. 66417308 : ¸Ÿ±U 24 ¥°Q . The tumor may destroy the cortex. Aneurysmal bone cyst components may replace most of the tumor in some cases. Some malignant tumors arise after radiotherapy of benign giant cell tumors. and forms neoplastic vascular structures. distending the periosteum and usually infiltrating the soft tissues. The cytoplasm is clear because of its high glycogen content. It is composed of undifferentiated small cells. Blood vessels. 17-53). In the past it invariably was fatal. but usually there is no or only focal sclerosis around it. Giant cell tumors have a tendency to recur after curettage and are considered by some authorities to be a low-grade malignancy. soft. Stromal cells are spindle-shaped and contain a moderate amount of cytoplasm. who have a poor prognosis. Histologically Ewing sarcoma is composed of a monotonous population of primitive small blue cells that have round to oval nuclei and scanty cytoplasm. All forms of Ewing sarcoma have the same chromosomal changes. Males are affected twice as often as females. and it is distinctly uncommon in African-Americans. Reactive osteosclerosis may be seen in the medullary cavity with a "sunburst" form on the periosteum as it is lifted from the bone. the nature and origin of which has not been determined unequivocally.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . which are typical of this entity. It is a tumor of children and young adults. Multiple myeloma and lymphoid neoplasms are illustrated in Chapter 5. hemosiderin. A. with a peak incidence in the second decade. glistening tissue permeating the bone and typically breaking through the cortex. B A Fig. Malignant giant cell tumors are rare. (2) multiple myeloma and solitary plasmacytoma. Tumors of the same morphology occur in soft tissues. Ewing sarcoma is a malignant tumor accounting for 6 percent to 14 percent of all bone tumors.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . (3) non-Hodgkin lymphoma. The nuclei have finely dispersed chromatin and small nucleoli. On gross examination they consist of reddish-brown soft tissue filling a cystlike space inside the bone (Fig. 17-52. The epimetaphysis contains a hemorrhagic meaty tumor that destroys the cortex and expands the periosteum. Immunohistochemically tumor cells display macrophagerelated markers. Nonepiphyseal giant cell tumors are rare. Generally there also is a large soft-tissue component with illdefined margins. 17-52). which may produce an onionskin pattern. Another important feature of Ewing sarcoma is the presence of reactive bone within the medullary cavity and the periosteum. On gross examination Ewing sarcoma appears as grayish-white.

Approximately 15 percent to 30 percent of tumors recur or metastasize. hemangiopericytoma. and the prognosis is relatively favorable. Aneurysmal bone cyst (ABC) is a relatively common bone lesion of uncertain origin.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Management is surgical. A large soft-tissue component is barely visible. The epithelial cells may resemble basal or squamous cells of the skin and often are palisaded along the periphery of these nests. as well as malignant tumors such as hemangioendothelioma. Radiologically it presents as a destructive lesion of bone extending into soft tissue. with reactive thickenings of the cortex and laminated periosteal reaction. Electron microscopy shows aggregates of glycogen in the cytoplasm of tumor cells. 17-55). spindle-shaped. Most adamantinomas of long bones (90 percent) have been reported in the shaft of the tibia. The medullary cavity of the distal end of the tibia is permeated with tumor that extends into the soft tissue even though it is still covered by periosteum. A. 17-53. arranged into lobules separated by strands of connective tissue (Fig. Histologically the tumor is composed of round. and polygonal cells in a loose myxomatous matrix. Tumor is composed of uniform small blue cells. Microscopically these tumors correspond to their soft-tissue counterparts. which has been described as a " soap bubble " pattern because of numerous cysts rimmed by sclerotic bone. typical of chordoma. On gross examination the tumor appears lobulated and is grayish-tan because of a high content of fibrous tissue. Radiologically the tumors have a typical appearance. B. Most cells show numerous cytoplasmic vacuoles. Chordoma is a tumor of notochord that typically occurs in the midline of the spinal column. 17-54). A fibrous dysplasia component often is seen. The prognosis depends on the size and location of the tumor. glomus tumor. Approximately one half of the tumors are found in the sacrococcygeal region and 37 percent are at the base of the skull in the sphenooccipital region. Multiple cystlike spaces are surrounded by thick sclerotic bone. Miscellaneous Tumors and Tumor-like Conditions Adamantinoma of long bones is a rare low-grade malignant tumor that shows both epithelial and mesenchymal differentiation and microscopically resembles adamantinoma of the jaw. In major cancer treatment reference centers it accounts for 4 percent of all bone tumors. C. Most tumors recur but few metastasize. It occurs in two forms: as a primary ABC arising de novo or as a secondary ABC that de - 66417308 : ¸Ÿ±U 24 ¥°Q . Ewing sarcoma. Its peak incidence is in the sixth decade. epithelial membrane antigen (EMA). D. has been likened to jellyfish. skeletal angiomatosis and lymphangiomatosis. Microscopically the tumor consists of epithelial nests and stroma.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . but they also may occur in other bones (Fig. Chordoma cells are positive for keratin. and S-100 protein. On gross examination the tumor is grayish-white with myxoid areas and foci of necrosis and hemorrhage. B A C D Vascular Tumors Vascular tumors include benign lesions such as hemangioma. The vacuolated cytoplasm of physaliphorous cells. and angiosarcoma. and the cortex may be scooped out or totally destroyed.380 Fig. Radiograph shows a large lytic tumor in the shaft of long bone. Management is surgical. but larger lesions also require radiotherapy.

Fibroblastic wall of the cyst contains osteoclasts grouped around a space filled with blood. 17-55. Over a myxoid background there are cords of large cells with vacuolated cytoplasm. A. 66417308 : ¸Ÿ±U 24 ¥°Q . B. The shaft of tibia shows extensive lytic lesions. B. C Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Radiograph shows an eccentric lytic lesion in the metaphysis of the distal femur. giving it a "soap bubble" appearance. Adamantinoma of long bones. C. C. Chordoma.381 A B A C B Fig. Aneurysmal bone cyst. Fig. A. Hemorrhagic cyst has a thin bone capsule. Bivalved segment of the tibia shows a medullary tumor that is destroying the cortex and elevating the periosteum. 17-54. 17-56. Nests of basaloid cell infiltrates are surrounded by fibrous stroma.

382 A B Fig. Numerous cartilaginous bodies were removed from the joint cavity. A. villi are composed of spindle cells and scattered hemosiderin-laden macrophages. B. Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Villonodular synovitis. Histiocytes with vesicular nuclei are surrounded by eosinophiles. Histologically. 17-58. Birbeck granules appear as rod-shaped structures in the ectoplasm of Langerhans cells. B. 17-59. Synovial chondromatosis. A. A B Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Eosinophilic granuloma. 17-57. Brown tissue removed from the joint.

17-58). Cancer 75:203-210. Its peak incidence is in the second decade of life. The femur. Malignant transformation is rare. Clin Orthop 97:52-63. Beabout JW: The spectrum of osteoblastoma. differential considerations (review). Pathol Res Pract 189:33-41. Skel Radio/ 22:485-500. Greenspan A: Benign bone-forming lesions osteoma. Am J Surg Pathol 3:47-60.383 velops on a preexisting bone lesion. Loizaga JM. 1993. Sim FH: High grade surface osteosarcoma: a clinicopathologic study of 46 cases. Ackerman LV: Malignant chondroblastoma. Okada K. Askin FB. These histiocytes are positive for S-100 protein and contain Birbeck granules visible by electron microscope. Czerniak B: Bone cancers. A histopathological and immunohistochemical study of 23 cases. Unni KK. McLeod RA. Cancer 83:2105-2119. On gross examination the lesions appear as intraarticular villous brownish-yellow tissue (Fig. 1963. spindle-shaped cells. Maygarden SJ. and radius most commonly are involved. Jaffe N: The pathologist's role in the diagnosis and treatment of osteosarcoma in children. Lipid-laden macrophages and hemosiderin account for the brownish-yellow color of the tissue. Unni KK. and (3) nodular giant cell tumor of the tendon sheath. Dahlin DC. Wood RM. Ivins JC. Raymond AK. in variable proportions. editor: Arthritis and applied conditions. multinucleated giant cells. Grossly ABC consists of multiple hemorrhagic cysts and a solid component. imaging. Price CHG: Aneurysmal bone cyst. Unni KK et al: Primary chondrosarcoma of long bones and limb girdle. ed 9. 1985. but other joints also may be involved. and osteoblastoma. Siegal GP et al: Ewing sarcomas of bone in infants and toddlers. which usually is not too prominent. Dosoretz DE. 1993. Clinical and morphological features of 162 cases. Swee RG. Unni KK. Murphy GF et al: Primary lymphoma of bone. 1969. Arch Pathol 88:371376. Bone invasion and recurrences are encountered in the diffuse form of villonodular synovitis. Clinical. Matsuno T: Malignant (fibrous) histiocytoma of bone — fact or fancy? Cancer 39:1508-1516. Roessner A et al: Adamantinoma of long bones. Jundt G. Pathol Res Pract 191:112-120. Murray JA. Cancer 50:1009-1014. hemangiopericytoma. 1995. 1998. 66417308 : ¸Ÿ±U 24 ¥°Q . 1979. but up to 40 percent of lesions recur. Report of two cases and review of the literature. McLeod RA. Bjornsson J. 17-59). deSantos LA. but in some lesions solid fibrous areas predominate. macrophages. 1995. Dorfman HD. A clinicopathologic report from the Intergroup Ewing's Study.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . but primary tumors of the joints are quite rare. Ayala AG: The value of percutaneous needle biopsy in the management of primary bone tumors. Cancer43:735744. Slitlike spaces lined by flattened or ovoid cells that resemble normal synovial surfaces also are seen. Eosinophilic granuloma is a form of Langerhans cell histiocytosis involving bones. Pigmented villonodular synovitis (xanthofibroma) is a tumor-like joint lesion that occurs in several forms: (1) diffuse pigmented villonodular synovitis. Primary ABC accounts for 1 percent to 6 percent of all bone lesions. Cancer 85:1044-1054. Semin Diagn Pathol 2:42-62. 1999. Pathogenesis and long term results of treatment. Dahlin DC: Hemangioma. Proliferation of Langerhans histiocytes is accompanied by infiltrates of eosinophiles (Fig. Cancer 27:1403-1414. Lopez Barea K et al: Osteoblastoma and osteoid osteoma. The relationship of morphologic diversity to clinical behavior. Radiologically the lesion is located in the metadiaphysis and appears as a blown-out eccentric lytic lesion with a sclerotic rim on the inner side and destructive cortical edge (Fig. 1979. The diffuse variant most often occurs in the knee joints of young persons. A review of 25 cases. Clough JR. Schiller AL: Diagnosis of borderline cartilage lesions of bone. 1982. 1973. Am J Roentgenol 126:321-335. Raymond AK. Synovial chondromatosis is a rare condition that is characterized by multiple metaplastic nodules of cartilage developing in the synovium. Beabout JW. Dahlin DC. Dahlin DC: Premalignant tumors and conditions of bone. 1971. 1984. Kahn LB. and scattered osteoclastic giant cells. Reed RJ: Fibrous dysplasia of bone. tibia. Microscopically the synovial fronds are composed of ovoid cells. osteoid osteoma. Arch Pathol 75:480-495. Yaw KM: Pediatric bone tumors. 1993. They are classified as benign or malignant. Calvo M. 1977. which may fill the joint (Fig. 1979. Sem Surg Oncol 16:173-183. Remberger K. Lea & Febiger. 1976. The altered synovial fronds detach to become loose intraarticular bodies. 1999.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . (2) localized nondestructive villonodular variant. Further Reading Ayala AG. Unni KK. In McCarty DJ. Sokoloff L: Pathology and pathogenesis of osteoarthritis. and various chronic inflammatory cells. Hum Pathol 15:258266. Histologically the nodules are composed of mature cartilage surrounded by fibrous tissue. Histologically the wall of cysts is composed of fibroblastic stroma. and hemangioendothelioma (angiosarcoma) of bone. Management includes curettage with bone packing. Tumors and Tumor-like Lesions of Joints Theoretically any component of the joint may give rise to a neoplasm. macrophages. 17-57). Philadelphia. Cancer 71:2109-2118. It most often is found in the knee joints of young persons. 17-56).

·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .66417308 : ¸Ÿ±U 24 ¥°Q .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

extraocular. Enzyme histochemistry shows that the central portion of each muscle fiber lacks oxidative enzyme activity (Fig. a mild proximal muscle weakness of infants and children. By EM the central core consists of disorganized sarcomeres. Nemaline myopathy. which are thought to be derived from Z-band material of the myofibrils. Central core disease. which shows typical hollow tubular structures in the cytoplasm of scattered muscle fibers (Fig. A. A A B B Fig. which may be best demonstrated by enzyme histochemistry or electron microscopy (EM). B. cell membrane. MUSCULAR DYSTROPHIES The unsophisticated historical term dystrophy is used clinically to refer to a variety of genetic diseases that are characterized by progressive muscular weakness. Nemaline (rod) myopathy presents in childhood as muscle weakness that predominantly involves the proximal parts of the extremities and the facial muscles. Many small. occasionally with type I muscle fiber hypotrophy (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . B. some of which are listed in Table 18-1. By EM the nemaline rods appear as condensed filaments resembling Z-band material. Some congenital myopathies are mild and become symptomatic only in later childhood. or perimysial basement membrane (Diagram 18-1). and many congenital myopathies have been linked to specific gene defects. By EM the central core appears as a disorganized aggregate of myofilaments. Enzyme histochemical technique for demonstrating oxidative enzymes was used to show reduced enzyme activity in the center of each muscle fiber. 18-2). Recent genetic studies have shown that such diseases may be linked to mutations of genes encoding unique structural proteins of the muscle fiber cytoplasm. Pathologic findings are constantly being amplified with molecular biology findings. Sarcotubular myopathy describes a heterogeneous group of diseases that may present early in life or even in adulthood. The diagnosis is established by EM. which may appear in childhood or adulthood. They usually present early in life in the form of the so-called floppy infant syndrome. hypotonia. which includes a triad of adaxial weakness. 18-4). 18-2. 18-1). dark blue–stained rods are seen in some muscle cells in this Gomori trichromestained slide. Axial.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and decreased spontaneous muscular motor activity. Muscle fibers contain centrally located nuclei. Morphologically it is possible to identify several distinct entities. and facial muscles are involved. A.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 18-3). is characterized by specific changes in the muscle. Central core disease. whereas others are not diagnosed until adult life.386 CONGENITAL MYOPATHIES Congenital myopathies are a diverse group of diseases. 18-I. Rods. may be seen in muscle fibers stained with trichrome or by EM (Fig. Fig. Centronuclear myopathy refers to a heterogeneous group of diseases whose presenting symptom is muscle weakness.

all rights reserved. This EM photograph shows cytoplasmic tubules derived from the sarcomeres.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Sarcotubular myopathy. 18-3. Fig. Dystrophin-sarcoglycan complex of striated muscle cells consists of several proteins that are essential for muscle contraction.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . the best known of these proteins. Dystrophin. with permission). (© Copyright 1997 Massachusetts Medical Society. Type I fibers are abnormally small. From Duggan DJ et al: N Engl J Med 1997. 336: 618-24. Deficiency of dystrophin and related proteins has been identified as the cause of muscle diseases. 18-4. contain a central unstained region corresponding to nuclei. Centronuclear myopathy. and the darker type II fibers are enlarged.387 Congenital Myopathies Fig. which stain lighter in this slide and react for ATPase at pH 9. Diagram 18-1. is linked to several other plasma membrane proteins such as dystroglycans and sarcoglycans. Type I muscle fibers. 66417308 : ¸Ÿ±U 24 ¥°Q .4.

D. are unique features of this disease that distinguish it from other dystrophies. Myotonic muscular dystrophy is a multisystemic disease with a prevalence of 1 in 8000. 18-6). Duchenne muscular dystrophy is a lethal disease. A C D B Fig. upper back. which are found during ingravescent stages of the disease. and proxi mal limbs. Enzyme histochemistry techniques for demonstrating oxidative enzymes are most useful for demonstrating the abnormal muscle fibers. shoulders. In early stages of disease dead and dying fibers are phagocytized by macrophages. Lost muscle fibers are replaced by fibrous and fat tissue. muscle fiber atrophy. Several distinct genetic diseases have been known to present in this form. Duchenne muscular dystrophy. B. In terminal stages of the disease muscle fibers have been replaced by fibrous and fat tissue. which is caused by milder alterations of the dystrophin gene. and florid compensatory hypertrophy.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . a multitude of internal nuclei. and although it has a slower downward course. a structural protein that links the muscle cell membrane to the contractile elements. associated with muscle fiber splitting (Fig. C. Regeneration ensues but is unable to compensate for the muscle fiber loss. Becker muscular dystrophy. and arms. Facioscapulohumeral dystrophy is a relatively mild disease that affects the muscles of the head and neck. Myotonia is an early symptom. The muscle from Becker dystrophy patients shows patchy staining. It is a less severe form of dystrophy. 18-5). Abnormal muscle fibers become rounded up and are recognizable in routine sections stained with hematoxylin and eosin because of their eosinophilic cytoplasm as " hyaline fibers. Immunohistochemical studies with antibodies to dystrophin show a lack of immunoreactive dystrophin in the muscle of patients with Duchenne dystrophy. it also is invariably fatal. The affected muscles show numerous atrophic and hypertrophic muscle fibers but little necrosis or regeneration. Positive control was stained with antibodies to basement membrane laminin. is a progressive muscle disease that affects teenagers and young adults. 18-5. It is linked to a mutation of a gene on chromosome 19 that shows amplification of cytosine-thymidine-guanine triplet repeats. Muscle biopsy shows typical atrophy of type I fibers. The muscle biopsy shows internalization of sarcolemmal nuclei. Limb girdle dystrophy is characterized by a declining strength of muscles of the shoulder. 18-8). pelvic girdles. It has been linked to abnormalities of the gene for dystrophin. Symptoms begin in early adult life and slowly progress over many years. which appear mottled or moth-eaten because of uneven staining of their cytoplasm (Fig. Muscle does not react with antibodies to dystrophin. 18-7). which phagocytize dead muscle fibers (Fig. Scattered lymphocytes.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . which may even enlarge the muscles (pseudohypertrophy).388 Duchenne muscular dystrophy is a severe X-linked muscle disease that affects 1 in 3500 boys. 66417308 : ¸Ÿ±U 24 ¥°Q . A." Muscle fiber necrosis attracts macrophages. and ring fiber formation (Fig.

but occasionally it may result in rhabdomyolysis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig. 18-7. Similar changes may be seen in some patients with acquired immunodeficiency syndrome (AIDS). Facioscapulohumeral dystrophy. 66417308 : ¸Ÿ±U 24 ¥°Q .389 Fig. Hypertrophic fiber in the center has split into six smaller segments. Systemic lupus erythematosus. 18-6. I NFLAMMATORY MYOPATHIES Inflammatory myopathies are a diverse group of diseases that are related to infections or immune reactions and are encountered in systemic autoimmune diseases. In systemic viral diseases it causes muscle pain. B. the muscle fibers appear moth-eaten and contain numerous small. Muscle fiber injury may be accompanied by infiltrates of lymphocytes and macrophages. or hypersensitivity and allergy to drugs and other exogenous antigens (Table 18-2). Many fibers show centrally located nuclei.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . In the former case the changes are indistinguishable from those of polymyositis. 18-8. unreactive sarcoplasmic areas. Myotonic dystrophy. Limb girdle dystrophy. poorly demarcated. Ring fibers consist of a central core in which the cross-striations run in a different direction than the crossstriations of the peripheral ring. immunemediated myositis (polymyositis or dermatomyositis). In this slide stained for demonstrating oxidative enzymes. The muscle contains numerous hypertrophic fibers. A. Inflammatory Myopathies SLE. A B Fig. Viral myositis probably is the most common muscle infection.

18-12). Immune complexes have been localized to blood vessels. but in 60 percent of patients the muscle does not show inflammation. 18-9). 66417308 : ¸Ÿ±U 24 ¥°Q . A B Fig. These infiltrates consist predominantly of CD4 + helper T lymphocytes. 18-11). Drug-induced myositis usually represents a hypersensitivity reaction. Immunohistochemistry shows that most lymphocytes are CD8+ cytotoxic or suppressor cells. which is caused by Trichinella spiralis. B. and plasma cells (Fig. Polymyositis is an autoimmune disease in which the muscle inflammation is mediated primarily by CD8 + T lymphocytes (Fig. may be seen in the muscle (Fig. The muscle contains encysted parasites. By EM the vacuoles contain remnants of cytoplasmic membranes and bundles of viruslike tubulofilamentous structures. Trichinosis. Microscopically. Histologic findings are suggestive of polymyositis. It may have an indolent course or a slowly progressive course that is resistant to steroid treatment. In all cases the muscle fibers show vacuolar inclusions consisting of rimmed vacuoles and granules (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Muscle fibers undergo necrosis individually or in small groups and are surrounded or infiltrated with lymphocytes and macrophages. Vascular changes typically are associated with perifascicular atrophy of muscle fibers (Fig. 18-9. It affects males more often than females and has a peak incidence in the 50 to 70 year age group. 18-14). it is an antibody-mediated disease.390 The most common cause of parasitic myositis is trichinosis. 18-10. usually with a prominent contribution of eosinophils (Fig. it is characterized by inflammatory changes and muscle cell necrosis and inflammatory changes. Dermatomyositis also is an autoimmune disease but in contrast to polymyositis. A. Similar virus-like particles are found in the muscle cell nuclei. Polyarteritis nodosa and Churg-Strauss syndrome may affect small arteries in the muscle and also cause interstitial inflammation. which usually are surrounded by inflammatory cells. 18-13). Muscle is invaded by lymphocytes. B lymphocytes. 18-10).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Polymyositis. Fig. The encysted parasites. which often are surrounded by inflammatory cells and fibrous tissue. Inclusion body myositis is an inflammatory myopathy of unknown origin.

Undulating tubular profiles are seen in endothelial cells. The edge of the fascicle shows perifasicular atrophy. Dermatomyositis. 18-14. 18-12. which is referred to as perifascicular. 66417308 : ¸Ÿ±U 24 ¥°Q . 18-13. Fig. B Fig. Dermatomyositis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . This cryostat section stained with Gomori trichrome shows the characteristic vacuole containing numerous small red granules.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Inclusion body myositis. B. A Fig. By EM the rimmed vacuole contains numerous membranous profiles and bundles of virus-like tubulofilamentous structures.391 A B Fig. The edge of the fascicle at the top of this picture shows atrophy. A. The infiltrate contains prominent eosinophils. Drug-induced myositis. A. 18-I I. B.

which is seen only in some muscle fibers.392 GENETIC-METABOLIC MYOPATHIES Genetic-metabolic myopathies may be grouped into three broad categories: (1) carbohydrate storage diseases.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Debranching enzyme deficiency in an adult. embedded in paraffin. Carbohydrate Storage Diseases Carbohydrate storage diseases include disorders of glycogen storage and degradation. Fig. Susa fixative–fixed tissue. 18-16. These diseases traditionally have been designated eponymically or numerically. or Andersen disease) is characterized by abnormal deposits Fig. 18-15). Infantile form of acid maltase deficiency. depending on the extent of glycogen storage. and trichrome stained. as may be seen by EM (Fig. Adult form of acid maltase deficiency. the muscle fibers show extensive vacuolation caused by massive accumulation of glycogen beneath the sarcolemma and between the myofibrils. the muscle shows deposits of basophilic material that is periodic acid–Schiff (PAS) positive but resistant to diastase digestion. The tissue was fixed in Susa fixative. but because the enzymatic defect is known for all of them it is more appropriate to label them according to the underlying deficiency. In addition. Vacuolation and glycogen accumulation are seen in debranching enzyme deficiency (type III glycogenosis. All fibers contain subsarcolemmal vacuoles or show extensive clearing of the central and peripheral cytoplasm. (2) lipid storage myopathies. Fig. Scattered muscle fibers are vacuolated. and the extent of glycogen storage in the muscle. the nature of the metabolic defect. 18-17).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 18-16). Branching enzyme deficiency (type IV glycogenosis. I8-15. In the infantile form of acid maltase deficiency (type II glycogenosis. Pathologic changes vary. Fig. and (3) mitochondrial myopathies. Branching enzyme deficiency in a young child. 18-18. or Pompe disease). the adult form is characterized by less prominent vacuolation. There is severe vacuolation of muscle fibers combined with basophilic deposits of mucopolysaccharides in this paraffin embedded. 18-17. In contrast. or Forbes disease) but generally the vacuolation is more prominent (Fig. The muscle fibers contain numerous bluish polyglycosan bodies. The basophilic mucopolysaccharide deposits are not seen (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Symptoms usually appear only during exercise or periods of intense energy demand. There are numerous large vacuoles in the muscle fibers.

Smaller deposits may form vacuoles in the central parts of the fibers. whereas the patient's tissue is unstained and light yellow (From Schochet SS Jr: Diagnostic pathology of skeletal muscle and peripheral nerve. stain dark. or by EM (Fig. 18-22). 18-21) or Sudan red 0. Muscle of patients with lipid storage myopathies contains increased amounts of lipids. however. 18-18). 66417308 : ¸Ÿ±U 24 ¥°Q . 18-21. 18-19. 18-19). deficiency of carnitine palmitoyltransferase.393 of polysaccharides in the peripheral cytoplasm of the affected fibers (Fig. Myophosphorylase deficiency. Lipid accumulation is. In this frozen section stained with Sudan red 0. Carbohydrate deposits form so-called polyglycosan bodies. The muscle fibers Fig. The control sections have peripheral vacuoles. not diagnostic of lipid storage diseases and may occur in a variety of other conditions. where they undergo beta-oxidation. Conn. Polyglycosan bodies are PAS positive and diastase resistant. which ultrastructurally appear as unbounded aggregates of branched fibrils and granular material. lipid droplets are more prominent in type I fibers. and defects of beta-oxidation. 1986. 18-20). and it typically gives negative results (Fig. Fig.) Fig. Norwalk. In this frozen osmium tetroxide—stained section. Myopathies may result from lack of carnitine.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig. Lipid storage myopathy. 18-22. which contain more lipid even under normal circumstances. or McArdle disease) is characterized by small subsarcolemmal vacuoles or blebs in most muscle fibers (Fig. Myophosphorylase deficiency (type V glycogenosis. which may be demonstrated as cytoplasmic droplets in frozen sections stained with osmium tetroxide (Fig. Lipid storage myopathy.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . The long-chain fatty acids must be combined with carnitine to pass through the mitochondrial membranes to the matrix compartment. Appleton-CenturyCrofts. Lipid Storage Myopathies Skeletal muscle cells use long-chain fatty acids as a major source of energy during fasting and sustained exercise. An enzyme histochemical assay for demonstrating myophosphorylase is used to confirm the diagnosis. This material is PAS positive and at least partially digestible. Myophosphorylase deficiency. 18-20. the lipid droplets are larger in type I fibers than in type II fibers. These fat droplets are more prominent in type I fibers.

Fig.394 Mitochondrial Myopathies Mitochondria are organelles that are involved in generating energy.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . mitochondrial abnormalities may manifest as ragged red fibers in histologic trichrome-stained sections or enzyme histochemically by a technique for demonstrating oxidative enzymes (Fig. In some of these muscle diseases the muscle shows no distinct histologic findings. whereas in others the muscle fibers show mitochondrial abnormalities. Mitochondrial myopathy. 18-25 and 18-26). 66417308 : ¸Ÿ±U 24 ¥°Q . Mitochondrial myopathy (Kearns-Sayre syndrome). Fig. Clustering of mitochondria in the peripheral cytoplasm leads to darker staining of the peripheral cytoplasm in this enzyme histochemical preparation for demonstrating oxidative enzymes. Numerous mitochondrial myopathies have been described. By EM the muscle fibers were found to contain increased numbers of normal mitochondria. Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Mitochondrial myopathy. Ragged red fiber has clusters of red-staining mitochondria beneath the sarcolemma in this trichrome-stained slide. 18-25. By EM the mitochondria appear abnormal. but they also contain deoxyribonucleic acid (DNA) and are important for the transmission of maternal cytoplasmic genetic material through the cytoplasm of the oocyte. 18-23. Mitochondrial abnormalities are better seen by EM when they appear in the form of an increased number of normal mitochondria or as structurally abnormal mitochondria (Figs. When evident. 18-23 and 18-24). Mitochondrial myopathy. Fig. 18-26. 18-24.

Notice that the previous type II. reinnervation. Reinnervation. Early denervation. In chronic denervation. Denervation results in muscle cell atrophy (Diagram 18-2). and subsequent denervation of the reinnervated fibers. Atrophic fibers in the diseased motor unit II (dark) are angular and randomly distributed. Notice that the fibers from each motor unit are geographically dispersed and are not grouped together. By neurotrophic influences.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . A. Two oversimplified motor units are shown (I and II). Normal motor unit. dark fibers have been converted to type I. because the motor neuron governs the fiber type within the motor unit. This process of reinnervation leads to type grouping. Each motor neuron (MN) innervates only muscle fibers of the same type. B. Denervating Diseases Normal motor unit Early denervation A B Reinnervation Late denervation C D Diagram 18-2.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Schema of the normal motor unit and three stages of denervation. Grouped atrophy. C. groups of atrophic fibers result from the process of denervation. the motor neuron determines the fiber type within the motor unit. The remaining motor neuron I (light) has reinnervated the type II. 66417308 : ¸Ÿ±U 24 ¥°Q . D.395 DENERVATION-RELATED MUSCLE DISEASES The welfare of muscle fibers depends on their proper innervation. dark fibers by means of sprouting collateral axons. light fibers. It may occur in a number of diseases involving the central nervous system or peripheral nerves (Table 18-3).

18-30. Denervated atrophic fibers show increased esterase activity as indicated by their brown color in this enzyme histochemical preparation for demonstrating esterase activity. Denervation with reinnervation results in a loss of normal checkerboard distribution of type I and type II fibers and type-specific grouping of muscle fibers (Fig. Atrophic fibers are angular and compressed between the normal fibers. 18-28).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. Fig. Denervation atrophy caused by amyotrophic lateral sclerosis. the entire fascicle. Fig. Denervation atrophy. Fig. Chronic neurogenic atrophy.39 6 Atrophy may involve single muscle fibers.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Chronic neurogenic atrophy shows group atrophy (Fig. They stain dark in this enzyme histochemical preparation for demonstrating oxidative enzymes. 18-31). 18-29). They typically show increased activity of nonspecific esterase (Fig. 18-32). 66417308 : ¸Ÿ±U 24 ¥°Q . 18-28. Chronic denervation. Single atrophic denervated fibers are smaller than normal and angular (Fig. Enzyme histochemistry for oxidative enzymes shows that the atrophic fibers stain darkly and are surrounded by normal-sized fibers that have a targetoid appearance (Fig. depending on the type and the location of nerve injury. 18-27). Spinal muscular atrophy tends to be more prominent and is termed fascicular because it involves entire large groups of muscles (fascicles) (Fig. Target fibers have pale centers in this enzyme histochemical preparation for demonstrating oxidative enzymes. or the entire muscle. 18-29. groups of fibers. 18-30). Atrophic fibers are found in groups. 18-27.

J Neuropathol Exp Neurol 52:339-348. Denervation with reinnervation. 66417308 : ¸Ÿ±U 24 ¥°Q . Wewer UM. Confalonieri P. 1997. In Mastaglia FL. Banker BQ: The polymyositis and dermatomyositis syndromes. Dubowitz V: The muscular dystrophies—clarity or chaos? NEngl JMed 36:650-651. Conen PE: Histopathological changes in Duchenne muscular dystrophy. Type-specific grouping has replaced the normal checkerboard pattern in this slide stained for demonstrating ATPase at pH 9. Dubowitz V: Procedure of muscle biopsy: a practical approach. Am J Clin Pathol 112:63-68. Virchows Arch 431:227-233. Engvall E: Merosin/laminin-2 and muscular dystrophy. 1996. 1994. Further Reading Amato AA. 1993. Cornelio F: Inflammatory myopathies and systemic disorders: a review of immunopathogenetic mechanisms and clinical features. Cell 80:675-679. Curr Opin Neurol 6:695-704. Clinicopathologic study of 12 cases. eds: Skeletal muscle pathology. London. In Engel AG. Ishihara T. Campbell KP: Three muscular dystrophies: loss of cytoskeleton-extracellular matrix linkage. 1997. editors: Myology. 1992. Franzini-Armstrong C. 18-3I. Prayson RA: Granulomatous myositis. 1999. 1992. Anderson JR: Recommendation for the biopsy procedure and assessment of skeletal muscle biopsies. Severe atrophy involves entire fascicles. Bell CD. J Neurol 244:277287. ed 2. Bailliere Tindall.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Dalakas M: Inflammatory and toxic myopathies. New York. Bernascone P.4. J Neurol Sci 7:529-544. Curr Opin Neurol Neurosurg 5:645-654. Infantile spinal muscular atrophy. Heffner RR: Inflammatory myopathies: a review. Engel AG. NeuromuscDisord 6:409-418. 1997. 1989. George EB: Toxic neuropathies and myopathies. McGraw-Hill. ed 2. N Engl J Med 320:138-142. 1995. 1999. Ann Neu ro140:581-586.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig. Kamakura K et al: Mosaic expression of dystrophin in symptomatic carriers of Duchenne's muscular dystrophy. Kuncl RW. 18-32. Schmalbruch H: The muscular dystrophies. 1968.397 Fig. Churchill Livingstone. Hohlfeld R. 1996. Gronseth GS. Jackson CE et al: Inclusion body myositis: clinical and pathological boundaries. Arahata K. Walton JN. 1985. London. Mantegazza R.

·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .66417308 : ¸Ÿ±U 24 ¥°Q .

it is not surprising that cerebral malformations are quite common. Severe elongation of the medulla and vermis. "Beaking" of the tectum (white arrow) and dilatation of the aqueduct (open arrow) caused by compression of the fourth ventricle. craniorrhachischisis. The calvaria are missing. and spina bifida. I9-2. Major developmental disorders are associated with distinct clinical syndromes. is characterized by incomplete formation of the bony cranial vault. A.400 DEVELOPMENTAL AND GENETIC DISORDERS The morphogenesis of the brain depends on the interaction of numerous genes. Posterior view shows the reflected cyst wall communicating with a unicameral ventricle. 19-2). Many of these abnormalities are not compatible with life and are associated with intrauterine fetal demise and abortion. 19-1). Neural tube defects are attributed to failure of fusion of lateral folds of the neural plate (dysraphism) or rupture of a previously closed tube (neuroschisis).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. which must be activated and inactivated sequentially and in an orderly spatial manner to ensure normal development. Holoprosencephaly is a severe disturbance of forebrain induction that results in incomplete separation of cerebral hemispheres (Fig. all of which might cause developmental disturbances. and the base of the skull is covered with a dark red tissue layer called the area cerebrovasculosa. This group of disorders includes anencephaly. 19-I. 66417308 : ¸Ÿ±U 24 ¥°Q . Arnold-Chiari malformation. and a reddish spongy mass (area cerebrovasculosa) covered by a thin membrane occupies the gap in the skull (Fig. Because this sequence of events may be disturbed by numerous endogenous and exogenous influences. Calvaria is missing or is only rudimentary.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Holoprosencephaly. the most severe neural tube defect. meningocele. At the other end of the spectrum are minor defects that cause no significant clinical symptoms. encephalocele. Arnold-Chiari malformation and Dandy-Walker malformation result from abnormal development of the hindbrain Fig. Anencephaly. A B Fig. B. Anencephaly. 19-3.

Dandy-Walker malformation. 19-5. The section was made through the ganglionic eminence at foramen of Monro (arrow). Hypoplastic vermis and cyst are reflected to expose a dilated fourth ventricle. Such hemorrhages are especially common in infants born before week 34 of pregnancy or those who weigh less than 1500 g. The germinal matrix is bilaterally infiltrated with extravasated blood. "morocco leather" surface. Subependymal hemorrhage. The brain has a puckered. Agyria-pachygyria complex in Miller-Dieker syndrome. In polymicrogyria the brain surface exhibits numerous small irregular gyri (Fig. Hemorrhages usually develop within hours of delivery and are associated with high mortality. Ischemia is considered to be one of the most important causes of brain injury in this period of life.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . PERINATAL BRAIN LESIONS The brain is susceptible to a variety of injuries during intrauterine life and the perinatal period.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 19-8). The brain has a smooth surface agyria or shows a few broad convolutions with shallow sulci ( macrogyria and pachygyria) (Fig. Fig. Subependymal and intraventricular hemorrhages are the most common major intracranial complications of prematurity. 19-3 and 19-4). Fig. although their pathogenesis is conjectural. 19-5). whereas the remaining brain has broad gyri and shallow sulci. Complicated or prolonged delivery and maternal ill health predispose to brain injuries. 19-6. It is well known that premature infants are more prone to such injuries than term infants. Blood from the largest hematomas may diffusely infiltrate the brain parenchyma. 19-7). 19-7.401 and several related posterior fossa structures (Figs. Fig. 19-4. Agyria-pachygyria complex represents a severe defect in neuronal migration. These hemorrhages may begin anywhere in the periventricular germinal matrix but most often are located near the sulcus terminalis just posterior to the foramen of Monro (Fig. Frontal lobe is devoid of gyri (arrow). The nature of these injuries is not always obvious. Polymicrogyria. 19-6). Malformed and misplaced parts of the central nervous system (CNS) cause hydrocephalus. 66417308 : ¸Ÿ±U 24 ¥°Q . Trauma is an important contributory factor but its role often has been overstated. The hemorrhages often are bilateral and vary in size from focal patchy extravasations of blood to large hematomas that rupture into the ventricles (Fig. Fig.

Fig. is debatable. and irregularly swollen axons that undergo mineralization. irregular. whereas the crest remains relatively intact.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 66417308 : ¸Ÿ±U 24 ¥°Q . Fig.402 Fig. Porencephaly. Periventricular leukomalacia. is bordered by polymicrogyria. The entire brain has been transformed into numerous irregularly shaped cystic cavities. sepsis. 19-8. The affected gyri appear mushroom-shaped. Ventricles contain coagulated blood. If the infant survives the insult. Subependymal hemorrhage extending into the ventricles. the funnel-shaped defect. 19-9. particularly in the rostral frontal lobes and parietooccipital regions (Fig. 19-1 I. such as subependymal hemorrhages. Ulegyria. The cortex in the depth of the sulci is reduced to a glial scar. 19-10. The pathogenesis of these lesions. Multicystic encephalopathy. yellowish or chalky white lesions in the white matter adjacent to the lateral ventricles. Porus. Chalky white lesions are indicated by arrows. or hypoxia. periventricular leukomalacia may transform itself into unilocular or multilocular cysts. Histologically the lesions are composed of foamy macrophages. Infarcts of the brain occur in anatomic areas that correspond to the distribution zones of major cerebral arteries. 19-12.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . It is thought that they represent shock lesions associated with other CNS lesions. 19-9). which most often occur in premature infants. 19-10). reactive astrocytes. Ule- Fig. Ulegyria is a consequence of such ischemic lesions and is characterized by the appearance of mushroom-shaped gyri (Fig. Fig. Periventricular leukomalacia presents in the form of multiple.

19-13. the cerebral hemispheres are transformed into multilocular cavities separated by gliovascular trabeculae (Fig. 19-12).403 gyria often is seen in arterial border zones. Contusions are bruises in which there is extravasation of blood into tissues whose integrity is retained. Contusion. If the head is in motion (acceleration) as in a fall and comes to an abrupt standstill (deceleration). Lacerations at the pontomedullary junction and tears in medullary peduncles have been described in severe hyperextension of the neck accompanied by basal fractures of the TRAUMA OF THE BRAIN AND THE SPINAL CORD Trauma of the brain and the spinal cord. 404). In the Unites States the incidence of hospitalization for craniocerebral injuries is 2 per 1000 persons and the mortality rate for accident-related deaths is 0. 19-11). A direct blow to a resting but mobile head causes deformation and bending of the skull bone and produces maximal contusions at the site of cranial impact. ging brain is flung back and forth against the temporarily deformed skull. these contusions are known as contrecoup lesions (Fig. usually made of arachnoid cells. 19-13). The porus may be surrounded by polymicrogyria. before the immature brain is able to mount sufficient glial reaction to injury. Fig. Hemorrhage into brain tissue is accompanied by a loss of parenchyma. which are known as coup contusions (Fig. and usually is bilateral. fluid-filled vesicles. Porencephaly refers to linear or funnel-shaped defects of the cerebral hemispheres (Fig. p. Diagram 19-1. Lacerations occur in the same locations as contusions. In hydranencephaly the cerebral hemispheres are converted to thinwalled. resulting in major contusions on the surface of the brain diametrically opposite the site of cranial impact. is a major cause of morbidity and mortality in industrialized countries. 19-15). The defect or porus communicates with the ventricular cavity. but sometimes a thin membranous diaphragm. but many brain contusions and even lacerations occur in closed head injury without apparent fracture. or radially arranged gyri that histologically exhibit abnormal cortical lamination. Coup lesion with hemorrhage perpendicular to the surface was caused by a direct blow to the head with a blunt object. 19-15. Laceration is a lesion that is characterized by bleeding into tissue whose integrity has been disrupted. Contrecoup lesion in the frontal and temporal poles are (arrows) are located opposite to a small coup lesion over the cerebellum (small arrow). Contusion of the brain. at sites of depressed fractures. Brain injuries often are associated with skull fractures. and with penetrating or perforating head injuries (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . often related to vehicular accidents.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . seals it from the ventricle. Fig. Porencephaly and hydranencephaly represent sequelae of major destructive brain lesions and usually occur during the first six months of fetal life.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . the lag- Fig.3 per 1000 persons. 19-14. 19-14. In multicystic encephalopathy. especially between the anterior and the middle cerebral arteries. Laceration. nodular heterotopias.

Fig. A. Old contusion of orbital surface of left frontal lobe is accompanied in this case by destruction of olfactory bulb and nerve. Comparison of impact and nonimpact injuries. 19-16. 19.17. 66417308 : ¸Ÿ±U 24 ¥°Q . The gyri appear flattened and the sulci are narrow. Fig. B. Edema of the brain. Herniation of the parahippocampal gyrus.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 19-18. Nonimpact contreceoup contusions caused by sudden angular acceleration of the head. C.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .40 4 Diagram 19-1. Fig. Plaque jaune. Contrecoup contusions diametrically opposite impact site. Unilateral herniation of the parahippocampal gyrus on the left side is accompanied by brainstem hemorrhages. Coup contusions at impact site.

406). such as alcoholics (Fig. Chronic subdural hematomas is encountered in the elderly in whom cerebral atrophy causes widening of the subdural space. (3) spontaneous rupture of congenital aneurysms or arteriovenous malformations. 19-17). 19-18).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .g. (2) hypertension. which most often is found on the orbital surfaces of the frontal lobes and olfactory bulbs in persons who have suffered repeated brain injuries.. thus exposing the bridging veins to a greater risk of rupture when subjected to angular shearing forces. or both. increased intracranial pressure leads to displacement of parts of the brain. arterial or venous). 66417308 : ¸Ÿ±U 24 ¥°Q . under the falx cerebri. hemorrhage. Granulation tissue growth into the hematoma from the inner dura forming a "neomembrane" (Fig. and (6) tumors that are either hypervascular (e. Brain trauma often is accompanied by cerebral edema. Dura was removed to show the hematoma and intact Ieptomeninges.. which are known as herniations..g. Acute subdural hematoma. Fig. Subdural hematoma is caused by hemorrhage between the dura and the outer surface of the arachnoid membrane (Diagram 19-2. Acute subdural hematomas often are associated with severe head injuries and are bilateral in 20 percent of cases. Intracranial Hemorrhages Intracranial hemorrhages may be caused by (1) trauma. The bleeding is from arteries or bridging veins that drain cortical veins into the superior sagittal sinus and often are associated with underlying cerebral contusion. (5) ischemic necrosis (infarcts) caused by thrombosed atherosclerotic cerebral arteries or emboli. Because of the space constriction provided by the rigid dura and skull. 19-19. Reflected dura reveals the outer membrane and the resected anterior segment of the hematoma exposing its cavity and inner membrane." Acute subdural hematomas are space-occupying lesions that require emergency intervention (Fig. hemangioma) or necrotic and destructive (e. a condition referred to as "burst lobe. 19-19). Unilateral herniation of the parahippocampal gyri leads to secondary brainstem hemorrhages (Fig. 19-20). (4) systemic diseases such as hemorrhagic diathesis or fat emboli. into the sella turcica. or pathogenesis (e.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . or the ventricles. or through the defect in the fractured calvaria. Herniations preferentially occur down into the floor of the anterior fossa. brain parenchyma.405 posterior fossa. subdural. into the tentorial notch into bony orifices. Oozing of blood usually is gradual and spreads over a large surface overlying the brain. p. Chronic subdural hematoma. down into the foramen magnum. traumatic. CIRCULATORY DISTURBANCES Circulatory disturbances of the brain present as hemorrhage or ischemia and may be classified according to location.g. Epidural hematoma usually is located in the ternporoparietal region and is related to rupture of the middle meningeal artery caused by fracture of the temporal bone. 19-20.. Fig. hypertensive.g. over the sphenoid wing. Brain edema also accompanies most space-occupying brain lesions and infections recognizable by the flattening of gyri and narrowing of sulci (Fig. and subarachnoid spaces). Traumatic hemorrhages may take place in one or more of the potential spaces surrounding the brain (epidural. 19-16). and so forth). glioblastoma multiforme). Old contusions and lacerations appear as yellow discoloration (plaque jaune). the type of blood vessel affected (e.

A. Torn middle meningeal artery at skull fracture (arrow) with accumulation of blood in epidural space causing midline shift with uncal and incipient cingulate herniations. Chronic subdural hematoma. Epidural hemorrhage. 66417308 : ¸Ÿ±U 24 ¥°Q . B.406 A B Diagram 19-2. Ruptured bridging vein secondary to angular acceleration with accumulation of blood in the subdural space.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . midline shift with uncal and incipient cingulate herniations.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

Acute subarachnoid hemorrhage. There are a few accentuated areas over superficial cortical contusions. Massive bleeding into the central part of the left hemisphere is associated with intraventricular extension. Such hemorrhages are located at the base of the brain and may penetrate the brain or spread throughout the brain. Hemorrhage is associated with contusion. 19-21). Fig. tearing of spinal ligaments. Fig. 19-24). but often they are so massive that the exact source cannot be determined (Fig. Acute hypertensive hemorrhage. 19-23). A berry aneurysm at trifurcation of the middle cerebral artery is indicated by black arrow. Many hypertensive hemorrhages begin in the external capsules. 19-2I. The localized hemorrhage and contusion were caused by fracture dislocation of the spine. 19-24. Intracerebral hemorrhage usually occurs in older adults as a typical complication of long-standing hypertension. causing death within minutes or hours after rupture of the aneurysm. Fig. The subarachnoid space is infiltrated by blood.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 40 percent of which is attributable to motor vehicle accidents. Subarachnoid hemorrhage also may result from spontaneous rupture of aneurysms of the circle of Willis (Fig.g. Spinal cord hemorrhages usually are associated with trauma. The basal subarachnoid space is filled with blood. and subluxation or fracturing of vertebrae. gunshot wound). but more often it is a closed injury in which the spinal cord is damaged by either hyperflexion or hyperextension. White arrow points to the rupture into the temporal horn.. laceration.. Such traumatic hemorrhages are secondary to superficial contusions or lacerations of the brain that release blood into the subarachnoid space (Fig. or complete transection of the spinal cord (Fig. Fig. 19-23.407 Subarachnoid hemorrhage occurs in any craniocerebral injury of substantial magnitude. 19-22). Trauma may cause open injury (e. 19-22. 66417308 : ¸Ÿ±U 24 ¥°Q . Spinal hemorrhage.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Subarachnoid bleeding caused by rupture of berry aneurysm.

19-25). which is referred to as encephalomalacia. multiinfarct state. These changes may be diffuse. One of the earliest changes is loss of affinity of myelin and neuropil for stains. 19-28).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Hemorrhagic infarct consists of blood-infiltrated and necrotic tissue (arrows) Fig. In embolic infarcts.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 19-25. Reactive astrocytes. including formation of lacunae. An infarct undergoes sequential microscopic changes reflecting its age. in which case the condition is known as etat lacunaire (Fig. Vascular changes of diabetes and hypertension lead to formation of small cystic spaces. and the neuropil becomes vacuolated. 19-26). Pale infarct (approximately two weeks in duration) with "cracks" (arrows) demarcating it from intact tissue. in this case involving the gray and white matter. 19-27). Fig. Old infarct. which may be seen within six to eight hours (Fig. macrophages. On cross section the brain shows multiple small cystic cavities (etat lacunaire). Occlusion of an artery for a sufficient time results in infarction. and subcortical arteriosclerotic atrophy of cortex. A B Fig. and capillaries begin to appear by the fourth day. precise timing of these changes could not be reproduced from one study to another. is an early sign of ischemia. B. In the meantime. especially around the blood vessels. Macrophages with foamy cytoplasm ( "gitter cells " ) or filled with hemosiderin are seen in later stages. 19-28. Missing tissue and cysts are found at the site of an old infarct in the middle cerebral artery distribution. A. which are most prominent in the basal ganglia (arrows). Acute cerebellar infarct. 19-26. granular atrophy of cortex. systemic hypotension. Infarcts may be pale or hemorrhagic (Fig. or shock. 66417308 : ¸Ÿ±U 24 ¥°Q . Many of these cysts represent small old infarcts. however. Chronic cerebral ischemia produces a variety of changes. Atherosclerosis is the most common cause of cerebrovascular disease. Fig. neutrophils and erythrocytes permeate the blood vessels during the first 24 to 48 hours and soon are replaced by macrophages. gray matter neurons undergo eosinophilic degeneration. Cerebral infarcts in the middle cerebral artery distribution. 19-27. Hypertension and diabetes are major predisposing factors that accelerate or aggravate the course of the disease. and their numbers increase with time.408 Cerebral Ischemia Cerebral ischemic lesions may be acute or chronic and localized or widespread. Ischemia usually is related to occlusion of blood vessels or hypoperfusion of the brain as a result of heart failure. Pallor. Tissue lysis accompanied by phagocytosis of the debris leads to formation of pseudocysts filled with serous fluid (Fig. Multiple lacunae.

The granularity of cortex is a result of microscopic scarring of numerous wedge-shaped or stellate intracortical infarcts. Granular atrophy of cortex superficially resembles granularity of renal cortex in nephrosclerosis (Fig. the spinal cord. multiple infarcts. Such infections may result in widespread inflamma - Fig. Binswanger subcortical arteriosclerotic leukoencephalopathy. 19-30). Fig. The gyri in the affected regions are thinned. 19-29). These pathogens may gain entry through (1) hematogenous spread. which typically accounts for CNS infections with herpesvirus and rabies virus (Diagram 19-3).409 but others are related to resolved old hemorrhages. including viruses. and hemispheric white matter. The arcuate fibers typically are spared. Microscopically myelin destruction and loss are associated with gliosis and scattered foamy macrophages. granular. Granular atrophy of cortex sometimes is associated with lacunae. such as the paranasal sinuses or middle ear. and their envelopes may be caused by a variety of pathogens. INFECTIONS Infections of the brain. Subcortical arteriosclerotic leukoencephalopathy (Binswanger disease) is a rare cause of vascular dementia that is characterized by multicentric or diffuse degeneration of white matter (Fig. Major tumors of CNS by location and age. The intraparenchymal blood vessels have thick walls and appear hyalinized.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and the overlying blood vessels often are stenotic and thick. and fungi. (2) extension from local structures. 19-29. basis pontis. The matter of centrum semiovale (arrows) appears gray. (3) direct implantation through wounds. as is the case in most viral infections and many bacterial and fungal infections related to sepsis. Granular atrophy of cortex. 19-30. Diagram 19-3. Arrows point to the border zone distribution of the surface granularity of the cortex. and distribution and usually are accompanied by dementia. and shrunken. or both. and some may even represent dilated perivascular spaces caused by increased tortuosity and spiraling of the perforating arteries because of hypertension. (4) axonal transport. In multiinfarct state the brain contains numerous infarcts that vary in size. shape. 66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . internal capsule. bacteria. Lacunae are most prominent in the basal ganglia.

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tion of the entire CNS or may be localized to certain structures. They are recognized as meningitis, cerebritis, encephalitis, myelitis, or abscesses, which are designated by their location as epidural, subdural (empyema), or intracerebral. Bacterial infections may be localized and present as foci of suppuration leading to abscess formation or diffuse cerebritis, meningitis, or meningoencephalitis and myelitis. Bacterial meningitis is characterized by exudation of inflammatory cells into the subarachnoid space. In acute purulent meningitis neutrophils predominate, and on gross examination the subarachnoid space appears filled with pus (Fig.

19-31). In chronic bacterial infections lymphocytes and macrophages predominate. In tuberculosis the subarachnoid space at the base of the brain is obliterated by granulomas (Fig. 19-32). Bacterial invasion of brain tissue results in cerebral abscess formation (Fig. 19-33). Over time the abscess becomes walled off by granulation tissue (Fig. 19-34). Incomplete encapsulation leads to the formation of daughter abscesses. Some abscesses may rupture into ventricles or subarachnoid space. Fungal infections of the brain most often are encountered in immunosuppressed persons. Such infections may be caused by Candida albicans, Aspergillus fumigatus, Histo-

Fig. 19-3 I. Bacterial meningitis. Streaks of purulent material (small arrows) are obscuring the sulci (large arrow).

Fig. 19-32. Tuberculous meningitis. Dense organizing exudate is obliterating the basilar subarachnoid space encasing the cranial nerves (arrows).

Fig. 19-33. Brain abscess. The abscess is accompanied by daughter abscesses (arrows). (Courtesy of Dr. L. Forno.)

Fig. 19-34. Chronic brain abscess. Central area filled with pus (white arrow) is surrounded by granulation tissue (open arrow) and edematous brain tissue (dark arrow).

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plasma capsulatum, and other fungi, which reach the brain hematogenously and produce multiple foci of ischemic necrosis and hemorrhage (Fig. 19-35). Histologically the fungi are found in the wall of the blood vessels and usually are associated with thrombosis, which causes ischemic infarction of the brain tissue. Fungi also invade the tissue around the blood vessels, causing direct destruction of the brain parenchyma. Mucormycosis of the brain, which typically is found in persons with diabetes, may be caused by infections that spread directly from the nasal mucosa, or it may be related to hematogenous dissemination of fungi. Rhinocerebral mucormycosis is characterized by large areas of necrosis, predominantly basilar, representing foci of hemorrhagic infarction and acute cerebritis caused by intravascular growth of fungi (Fig. 19-36).

Protozoal infections usually are found in immunosuppressed persons. Toxoplasma gondii infection is the most prevalent protozoal infection of the CNS in patients with acquired immunodeficiency syndrome (AIDS). It is characterized by foci of necrotizing cerebritis that evolve into chronic abscesses, usually in the deep gray matter. Microscopically the irregular patches of necrosis are surrounded by zones of vascular congestion, intense mixed inflammatory exudate, reactive astrocytosis, and variable numbers of dormant cysts, pseudocysts, and extracellular tachyzoites (Fig. 19-37). Metazoal infections are rare in the United States but are more common in Asia, Africa, and South America. Cerebral cysticercosis is produced by larvae of the pork tapeworm, Taenia solium, and presents with space-occupying lesions corresponding to encysted parasites (Fig. 19-38).

Fig. 19-35. Cerebral aspergillosis. Multiple foci of hemorrhage, hemorrhagic and pale necrosis, and early abscess formation are seen distributed at random.

Fig. 19-36. Rhinocerebral mucormycosis. Necrosis of the medial temporal lobe simulating a contusion or herpesvirus I infection is accompanied by necrosis of the ipsilateral optic nerve (large arrow) and occlusion of the internal carotid artery by fungus

(small arrow).

Fig. 19-37. Toxoplasmic encephalitis. The tissue is infiltrated with various inflammatory cells and contains free tachyzoites and a cyst releasing tachyzoites.

Fig. 19-38. Cysticercosis of the brain. Multiple cysts are seen, most often at the junction between the gray matter and the white matter.

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Viral infections of the CNS occur in a mild and transient form during systemic viral diseases, whereas encephalitis and meningitis caused by encephalitogenic viruses are associated with considerable morbidity and mortality. Viruses evoke a rather stereotypic response, such as diffuse or multifocal distribution, predominant involvement of neurons (gray matter), glial hyperplasia in response to neuronal injury, and perivascular cuffs of lymphocytes (Fig. 19-39). Some viruses have a predilection for certain parts of the brain. Herpesvirus type I commonly involves the limbic areas of the brain (orbitofrontal cortex, insula, cingulate gyrus, amygdala, and hippocampus). Infected areas show massive hemorrhage and

necrosis, and virions maybe demonstrated in neurons by immunohistochemistry or electron microscopy (EM) (Fig. 19-40). Slow viral infections characterized by chronic encephalitis include subacute sclerosing panencephalitis, progressive multifocal leukoencephalopathy, and progressive rubella encephalitis. Subacute sclerosing panencephalitis is attributable to the measles virus. CNS infections related to prions cause Creutzfeldt-Jakob disease, kuru, and Gerstmann-Straussler-Scheinker syndrome. All of these diseases are characterized by spongiform changes of the brain (Figs. 19-41 and 19-42).

Fig. 19-39. Acute viral encephalitis. The blood vessels are surrounded by cuffs of lymphocytes, whereas the brain tissue shows reactive changes evoked by neuronal damage.

Fig. 19-40. Herpesvirus encephalitis. Infection is accompanied by hemorrhage and necrosis. Inset shows immunoreactive infected virus cells.

Fig. 19-41. Creutzfeldt-Jakob disease. The gray matter shows extensive spongiform (vacuolar) degeneration of the neuropil between nerve cell bodies.

Fig. 19-42. Creutzfeldt-Jakob disease. EM shows swelling of neuritic processes with loss of internal organelles and formation of lacy, abnormal membranes within the vacuolated cytoplasm.

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METABOLIC AND TOXIC DISEASES
The nervous system is directly or indirectly affected by numerous congenital and acquired metabolic diseases. Central to understanding the pathophysiology and distribution of various lesions is the concept of selective vulnerability, which states that specific cell types or cell populations are more susceptible to a particular insult. An abridged classification of metabolic and toxic diseases of the CNS is given in Table 19-1. Wernicke disease, which most often is encounteretl in alcoholics, is caused by a deficiency of thiamine. It may occur in an acute form, which often produces no gross findings or only minor hemorrhages. Histologic findings include endothelial swelling and proliferation, spongiosis of the neuropil, and astrocytosis in the presence of intact neurons. These changes are most prominent in the mamillary bodies, medial dorsal nuclei of the thalamus, and other nuclei around the third and fourth ventricles. In chronic Wernicke disease mamillary bodies typically show brownish discoloration and atrophy, often associated with calcifications (Fig. 19-43). Microscopically these areas show neuronal loss and astrogliosis and often contain foci of hemosiderin deposition and calcification (Fig. 19-44). Central pontine myelinolysis is a disease that may present with coma, quadriplegia, or no symptoms at all. It is an iatrogenic demyelinating disease caused by overzealous correction of chronic hyponatremia and excessive swings in serum osmolality. It typically affects middorsal-crossing fibers of the pons (Fig. 19-45). Microscopically the affected areas show axonal loss, spheroids, lipophages, and astrocytes with atypical nuclei (Fig. 19-46). Marchiafava-Bignami disease, another rare disease that is associated with alcoholism, shares some of the demyelinating features of central pontine myelinolysis but primarily affects the corpus callosum. Subacute combined degeneration of the spinal cord is caused by deficiency of vitamin B12 (cyanocobalamin). Typically associated with atrophic gastritis and pernicious anemia, it presents with spongy changes in myelin, followed by axonal and oligodendrocytic loss, astrocytosis, and mac -

Metabolic and Toxic Diseases of the CNS

Fig. 19-43. Wernicke encephalopathy. Periventricular hemorrhages and discoloration of mamillary bodies.

Fig. 19-44. Wernicke encephalopathy. In chronic stages there is neuronal loss and fibrillary gliosis.

Fig. 19-45. Central pontine myelinolysis. The pons shows a sharply demarcated area of demyelination.

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rophagic response. The localization of these changes to the posterior and posterolateral columns, particularly in the upper thoracic cord, their asymmetry, and their transgression of tract boundaries are characteristic (Fig. 19-47). White matter changes also are detected elsewhere. Wilson disease (hepatolenticular degeneration) is a congenital metabolic disorder of the metabolism of copper. Copper accumulates in the liver and brain with cytotoxic effects. CNS lesions resulting from excess copper are most prominent in the putamen, which may show rare active spongy change progressing to cavitary necrosis (Fig. 19-48). Rarely, neocortical layers V and VI are involved.

Inborn Errors of Metabolism
Many genetic diseases affect the brain and produce changes in the gray matter, the white matter, or both. Each disease is characterized by a typical set of pathologic changes, which often occur preferentially in certain parts of the CNS. Lysosomal disorders refer to a diverse group of diseases that are also known as lipidoses and neuronal storage diseases. The deficiency of a catabolic enzyme in these autosomal

recessive diseases results in the accumulation or storage of substrates and intermediate metabolites that cannot be processed further. This group of diseases includes (1) sphingolipidoses (Tay-Sachs or Niemann-Pick disease); (2) glucosaminoglycanoses (mucopolysaccharidoses; Hurler, Hunter, and Sanfilippo syndromes); (3) sialidoses, mucolipidoses, and glycoproteinoses (mannosidoses and fucosidosis); and (4) glycogenoses (Pompe or Andersen disease). Tay-Sachs disease, which is caused by a deficiency of hexosaminidase A, is a prototype of sphingolipidoses. The brain contains ballooned neurons that have vacuolated cytoplasm (Fig. 19-49). By EM these vacuoles correspond to lipid-rich membranous cytoplasmic bodies (Fig. 19-50). Leigh disease (subacute necrotizing encephalomyelopathy) produces changes similar to those seen in Wernicke disease, which may lead to massive necrosis of the putamen, thalamus, brainstem, and cerebral and cerebellar white matter (Fig. 19-51). Leukodystrophies are diseases of infancy and childhood that typically demonstrate diffuse, confluent dysmyelination and atrophy of cerebral and cerebellar white matter. These

Fig. 19-46. Central pontine myelinolysis. Demyelination is accompanied by the formation of spheroids (arrows), lipophages, reactive astrocytes, and relative neuronal sparing.

Fig. 19-47. Subacute combined degeneration. Spinal cord shows loss of myelinated axons, most prominently in the posterior columns.

Fig. 19-48. Wilson disease. Cross section of the brain shows cavitary necrosis of the putamen.

Fig. 19-49. Tay-Sachs disease. Neurons have finely vacuolated cytoplasm and appear ballooned.

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changes are accompanied by significant axonal loss and relative sparing of arcuate (subcortical U) fibers (Fig. 19-52). In addition to common features that include loss of myelin and oligodendroglia, accumulation of myelin breakdown products, and reactive astrogliosis, each specific disease shows additional characteristic light and electron microscopic features. Globoid cell leukodystrophy (Krabbe disease) is characterized by accumulation of large uninuclear or multinuclear globoid cells that are periodic acid—Schiff-positive (Fig. 19-53). Myelinolytic diseases are characterized by widespread demyelination of axons. Spongy degeneration of the CNS in infancy (Canavan-Van Bogaert-Bertrand disease) is a prototype of congenital myelinolytic disorders that primarily affect the white matter . of the CNS, which undergoes grossly visible gelatinous to aqueous transformation (Fig. 19-54). Histologically there is spongy vacuolar myelinopathy, with a paucity of myelin breakdown products and macrophages.

Fig. 19-50. Tay-Sachs disease. Whorls of membranes forming round cytoplasmic bodies are typical of sphingolipidoses, especially gangliosidoses.

Fig. 19-51. Leigh disease (subacute necrotizing encephalomyelopathy). Cross section of the brain shows necrotic lesions in the caudae and putamen.

Fig. 19-52. Leukodystrophy (globoid cell). Cross section of the brain shows confluent demyelination with relative sparing of arcuate fibers (arrows).

Fig. 19-53. Globoid cell leukodystrophy (Krabbe disease). Brain contains numerous multinucleated globoid cells.

Fig. 19-54. Spongy degeneration of the CNS in infancy (CanavanVan Bogaert-Bertrand disease). The white matter shows gelatinous transformation, which is most noticeable at arcuate fibers.

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DEMYELINATING DISEASES
Demyelinating disease are sporadic inflammatory diseases that are characterized by immune or infectious destruction of biochemically normal myelin or its supporting cells, with relative sparing of axons. This group of diseases includes multiple sclerosis, acute disseminated encephalomyelitis, and infectious diseases such as progressive multifocal leukoencephalopathy and subacute sclerosing panencephalitis. Multiple sclerosis is a relatively common neurologic disease of young adults (20 to 40 years). It has both a genetic and an environmental component, as evidenced by the predominance of disease among persons of certain human leukocyte antigen (HLA) types and its geographic distribution. Clinical and laboratory data suggest that the disease has an autoimmune pathogenesis. The pathologic hallmark of the disease, the demyelinative plaque, is a sharply demarcated lesion, which usually is focal, asymmetric if bilateral, and disrespectful of anatomic boundaries such as tracts or gray matter—white matter junctions (Figs. 19-55 and 19-56). Sites of predilection for the plaques are the pial surface of the optic

nerves and optic chiasms, basis pontis, spinal cord, and periventricular white matter, that is, white matter close to cerebrospinal fluid spaces and deep cerebral veins. Acute lesions contain CD4 + and CD8 + lymphocytes, macrophages, and scattered plasma cells (Fig. 19-57). Demyelination of oligodendroglial cells and relative sparing of axons are typical of chronic lesions (Fig. 19-58). Subacute sclerosing panencephalitis (SSPE) is a demyelinating disease attributable to infection caused by measles virus that lacks a membrane (M) protein. It typically occurs several to many years after infection and has a fatal course. The brain shows destruction and loss of white matter and also loss of neurons from the gray matter. The white matter typically is infiltrated with lymphocytes and plasma cells and shows gliosis. Demyelination and axonal loss are associated with typical intranuclear inclusions in oligodendroglial cells (Fig. 19-59).

Fig. 19-55. Multiple sclerosis. Most prominent preventricular demyelinative plaques are accompanied by others at the corticomedullary junction (arrow).

Fig. 19-56. Multiple sclerosis. In unfixed state the medulla oblongata appears grayish-pink. The lesions do not respect anatomic boundaries.

Fig. 19-57. Multiple sclerosis, acute stage. Lesions are infiltrated with lymphocytes and macrophages.

Fig. 19-58. Multiple sclerosis. Chronic lesions show extensive demyelination.

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Fig. 19-59. Subacute sclerosing panencephalitis. Demyelination of white matter is accompanied by chronic inflammation, reactive astrocytosis, and intranuclear inclusions in the oligodendroglial cells. Intranuclear inclusions have a halo separating them from the nuclear membrane.

Fig. 19-60. Progressive multifocal leukoencephalopathy. Oligodendroglial cells, which show typical intranuclear inclusions, are surrounded by atypical astrocytes and lipophages.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease that is seen in immunocompromised persons and is believed to be caused by JC polyomavirus. Multifocal destructive lesions of the white matter consist microscopically of lipophages, bizarre hypertrophic astrocytes, demyelinating axons, and enlarged oligodendroglial nuclei that contain amphophilic inclusions (Fig. 19-60).

Neurodegenerative Diseases

DEGENERATIVE DISEASES OF THE CENTRAL NERVOUS SYSTEM

Degenerative diseases constitute a heterogeneous group of idiopathic diseases that are primarily germane to the CNS. They share a gradual symmetric loss of specific neurons, groups of neurons, and nerve fiber tracts that often are functionally related (multisystem degeneration). These diseases may be classified according to whether they primarily affect the cortical or subcortical parts of the cerebrum, cerebellum, brainstem and spinal cord, or motor neurons (Table 19-2). Alzheimer disease (senile dementia of Alzheimer type) is characterized by atrophy of gyri and widening of sulci, most prominently in the frontal and temporal lobe and notably the hippocampi (Fig. 19-61). The disease is characterized by a loss of neurons and the typical appearance of senile plaques and neurofibrillary tangles (Fig. 19-62). Senile plaques, also known as neuritic, dendritic, and amyloid plaques, are argyrophilic and are best seen in silver-impregnated slides. They appear as spherical bodies often are located near capillaries. Mature plaques have an amyloid core surrounded by a ring of radiating bulbous irregular neurites and processes of microglial and astrocytes. Neurofibrillary tangles are cytoplasmic bodies composed of coarse linear fibrils. Their appearance varies, depending on their stage and the shape of the cell in which they are located. They are faintly basophilic in routine hematoxylin-eosin (H&E) sections and are best demonstrated by silver impregnation techniques.

Diseases shown in boldface type are the best characterized.

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Fig. 19-61. Alzheimer disease. Compared with an age-matched control (lower specimen), the affected brain is smaller and shows narrow gyri and widened sulci.

Fig. 19-62. Alzheimer disease. Senile plaques appear as spherical bodies in silver-impregnated slides. Neurofibrillary tangles are formed of coarse fibrils that react with silver (inset).

Fig. 19-63. Pick disease. Atrophy of gyri is most prominent in the frontal lobe ("knife edge gyri") (arrow).

Pick disease is an uncommon cause of sporadic dementia. It typically presents with severe brain atrophy (lobar sclerosis), classically involving the orbitofrontal and anterior temporal regions (Fig. 19-63). The corresponding white matter is greatly attenuated and firm, resulting in hydrocephalus ex vacuo. Atrophy of the caudate nucleus may simulate Huntington disease. Microscopically the affected gyri show considerable neuronal loss, prominent astrogliosis, ballooned neurons (Pick cells), and intracytoplasmic globular agyrophilic masses (Pick bodies) (Fig. 19-64). Huntington disease is an autosomal dominant neurodegenerative disease that becomes symptomatic in the fourth decade. It is characterized by dementia, emotional disturbances, and chorea. The most prominent change in the brain is atrophy of the caudate nucleus, which results in enlarge-

ment of the anterior horns of the lateral ventricles (Fig. 19-65). The putamen also is affected, but involvement of other nuclei and cortex is not constant. Microscopically the disease is characterized by astrocytosis and a loss of small and medium-sized neurons. Multisystem atrophy is a term that refers to three clinicopathologic entities: striatonigral degeneration, olivopontocerebellar atrophy, and Shy-Drager syndrome. The disease becomes symptomatic between the fourth and sixth decades and is characterized by parkinsonism, cerebellar atrophy, and autonomic dysfunction. Loss of neurons and myelinated fibers results in atrophy of the cerebellum and pons (Fig. 19-66). Argyrophilic cytoplasmic inclusions in oligodendroglial cells and Pick-like inclusions in neurons are a typical microscopic findings.

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Fig. 19-65. The ventricles are dilated because of atrophy of the caudate nuclei on their lateral sides. in which such cytoplasmic inclusions are seen in cortical neurons. 19-67). exposure to toxins. Major pathologic changes are found in the substantia nigra and the locus coeruleus. Parkinson disease. Parkinson disease (idiopathic parkinsonism) is a common neurodegenerative disease that has its highest prevalence in the eighth decade. Fig. Parkinson disease. may be associated with dementia. Fig. 19-67. Some of the surviving neurons are slightly enlarged and pale. Fig. 19-68).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Substantia nigra is depigmented. 19-64. as evidenced in the atrophic specimen (left) compared with an age-matched control (right). but it also may be secondary to infectious disease. Pick cell has a ballooned cytoplasm and an eccentric nucleus (left). 19-68. Pick body appears as a basophilic globule in the perikaryon (right). Huntington disease. 66417308 : ¸Ÿ±U 24 ¥°Q . Pick disease. whereas others display the diagnostic cytoplasmic inclusions. Olivopontocerebellar atrophy. Diffuse Lewy body disease. which are known as Lewy bodies. Cerebellar hemispheres appear disproportionately small and the pontine bulge is flattened. 19-66.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . These inclusions. It usually is sporadic and idiopathic. Lewy bodies appear as round cytoplasmic masses in the pigmented neurons.419 Fig. which appear pale because of the destruction of neuromelanin-containing neurons (Fig. or drugs. appear as spherical eosinophilic cytoplasmic bodies (Fig.

Neoplasms of the CNS may be grouped into several major categories: (1) astrocytic. It is an autosomal recessive disease that becomes clinically apparent in the second decade. 19-69). Attenuation and fattening of dorsal spinal cord caused by nerve fiber loss in ascending tracts (c. and (8) pineal tumors. They occur in all age groups and are an especially significant cause of morbidity and mortality in children and young adults. ependymal. medulloblastoma. Amyotrophic lateral sclerosis. oligodendroglial. Both upper and lower motor neurons are involved. (7) germ cell tumors. Cross section of the spinal cord shows pale crossed (long arrow) and uncrossed (short arrow) pyramidal tracts. gracile. 19-70. (4) nerve sheath tumors. causing progressive loss of muscle strength. 19-71). neuroblastoma. and primitive neuroectodermal tumor (PNET). Spinal cord changes are secondary to loss of motor neurons. These neoplasms occur at a rate of 10 to 20 per 100. most prominently in the lateral corticospinal tracts (Fig. Friedreich ataxia. Amyotrophic lateral sclerosis and motor neuron disease are two terms that are used interchangeably to describe the same disease of unknown etiology and pathogenesis. The spinal cord shows loss of myelinated fibers. It affects persons over the age of 55 years and occurs at a rate of 1. The spinal cord is thin because of loss of ascending and descending myelinated fiber tracts and their replacement with astrocytes (Fig. posterior spinocerebellar) and descending pyramidal (py) tracts.000. In the first decade of life brain tumors account for 15 to 18 percent of all malignant tumors (Diagram 19-4). cuneate. (2) neuronal. psc. Mixed cerebellar and sensory ataxia caused by peripheral neuropathy dominate the clinical picture. mixed neuronal-glial and neuroendocrine tumors including medulloepithelioma.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Most cases are sporadic. The anterior spinal roots are atrophic and gray (Fig. and choroid plexus tumors. g. Fig. but 10 percent have a family history and are inherited in an autosomal dominant manner.420 Fig. 19-69.000. Amyotrophic lateral sclerosis. glial neoplasms. 66417308 : ¸Ÿ±U 24 ¥°Q . and most patients die within five years after onset of symptoms.000.5 per 1. 19-70).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . best appreciated in the hypoglossal nuclei and anterior horns of the cervical and lumbosacral enlargements of the spinal cord. (5) vascular neoplasms. 19-71. (3) meningeal tumors. Atrophic and gray posterior roots of cauda equina (black arrow) in contrast to normal posterior roots (white arrow). It has a rapid downhill course. Fig. (6) hematopoietic and lymphoid cell tumors. Friedreich ataxia is the best characterized of the hereditary degenerative spinocerebellar syndromes. NEOPLASMS Primary neoplasms of the CNS account for 9 percent of primary cancers.

nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 66417308 : ¸Ÿ±U 24 ¥°Q . Major tumor of CNS by location and age.421 Diagram 19-4.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

Ependymoma Ependymomas are composed of neoplastic ependymal cells. On gross examination they appear relatively well demarcated from the surrounding brain tissue. 19-75). These tumors account for 5 percent of all primary CNS neoplasms and 10 percent of CNS tumors in children and adolescents. 19-72. 19-73. which gives them a " fried egg" appearance. Glioblastoma multiforme is a highly malignant invasive neoplasm.19-80). The blood vessels usually are prominent and typically show endothelial cell hyperplasia. with occasional cystic areas and calcifications. Oligodendroglioma Oligodendrogliomas are tumors composed of oligodendrocytes. So-called cellular type is the most common variant. or bizarre cells (Figs. 19-78). and glioblastoma multiforme.422 Astrocytic Tumors Astrocytic tumors include astrocytomas. where it usually arises from the floor as a globular to lobulated exophytic mass. Astrocytomas infiltrate the normal structures of the brain. Cystic astrocytoma of cerebellum in a child. 19-73). Anaplastic oligodendroglioma is a rare variant that exhibits more pronounced nuclear atypia. Microscopically it may exhibit uniform or diverse cytologic fea- tures and is composed of small. but 60 percent to 70 percent are infratentorial. Cerebellar astrocytomas of childhood typically are cystic (Fig. Endothelial cells are prominent. The tumor appears cystic. which usually are more cellular. 19-74). A favorite site is the fourth ventricle. In anaplastic astrocytomas. Nuclei of typical ependymomas display little pleomorphism. It involves the cerebellar hemisphere and partly fills the fourth ventricle. Tumor cells show moderate anaplasia. They represent 10 percent of all primary brain tumors and usually occur in middle-aged adults. 19-74.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Less common variants include astroblastoma and pleomorphic xanthoastrocytoma. 19-79). The cytoplasm of these cells is clear. however. Astrocytoma of pons. tend to expand within the adjacent brain rather than grow into the ventricles (Fig. Diffusely infiltrating glioma has caused irregular enlargement of the pons and middle cerebellar peduncles. causing them to enlarge or expand (Fig. the nuclei are more anaplastic (Fig. Fig. However. 19-76 and 19-77). Ependymomas may occur anywhere in the CNS. and aqueduct. 66417308 : ¸Ÿ±U 24 ¥°Q . and if the tissue is not promptly fixed. It may protrude from the roof foramina and partially encircle the brainstem. in anaplastic ependy- Fig. welldefined cell borders and round nuclei (Fig. On cross section the tumor has a variegated appearance because of large areas of necrosis and hemorrhage. Less common sites are the cerebellopontine angle. Microscopically astrocytomas are composed of fibrillar or protoplasmic astrocytes that have slightly atypical nuclei. large. anaplastic astrocytomas. Ependymomas are the most common intraspinal tumor. which may assume glomeruloid features. 19-72). in which cells form sheets or align themselves around blood vessels. which may extend from one hemisphere to the other (Fig. Microscopically oligodendrogliomas are composed of sheets of uniform cells that resemble oligodendroglial cells. a perinuclear halo forms. These cells have closely apposed. Fig. forming " perivascular pseudorosettes" (Fig. posterior third ventricle. Supratentorial ependymomas. Microscopically there are several variants.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Astrocytic tumors represent 70 percent of all primary CNS tumors. Anaplastic astrocytoma.

This cellular type of ependymoma is composed of uniform cells that form perivascular pseudorosettes.423 Fig. The tumor involves the splenium of corpus callosum spreading into adjacent hemisphere. Endothelial cells are prominent and there are areas of necrosis. Ependymoma. Capillaries are delicate. 19-75. Oligodendroglioma. The tumor distorts the pons and compresses the cerebellum. 66417308 : ¸Ÿ±U 24 ¥°Q . Ependymoma. Glioblastoma multiforme. 19-80. Tumor cells show marked pleomorphism. Fig. Fig. Glioblastoma multiforme. 19-79.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Tumor cells have round nuclei surrounded by clear cytoplasm in the form of a halo. 19-77. Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig. The tumor is composed of small cells showing primitive palisading. 19-78. Fig. Glioblastoma multiforme. I9-76.

Choroid plexus papillomas are rare tumors that account for 1 percent of all primary brain neoplasms. undifferentiated neoplasms composed of small cells (Fig. which are arranged into sheets or lobules and intervening paucicellular fibrillated zones forming rosettes Fig. mostly appearing as infiltrative. and neuroblastoma are designated in the World Health Organization classification as embryonal and cytologically pluripotential neoplasms. Microscopically they recapitulate the features of the choroid plexus. filling in part the fourth ventricle. 19-83. They protrude into the fourth ventricle. and Neuroendocrine Neoplasms Medulloepithelioma. Fig. Choroid plexus carcinomas have all the features of malignant epithelial tumors. with modern surgical ablation and radiotherapy. Fig. Tumor cells may form Homer Wright or Flexner-Wintersteiner rosettes and even "fleurettes" indicative of photoreceptor differentiation. except that the cells lining fronds are more crowded and mildly pleomorphic (Fig. infiltrate its floor.424 moma the cells show marked pleomorphism and nuclear atypia. and extend into the cerebellar peduncles. 19-82). Microscopically medulloblastomas exhibit highly variable histologic features. accounting for 7 percent to 8 percent of all primary brain neoplasms. and some cells form Homer Wright rosettes. It has two peaks of incidence. Pineocytomas tend to be more localized and slower growing than pineoblastomas. Pineal Tumors Most pineal tumors originate from misplaced germ cells and are similar to the more common germ cell tumors of the testis or ovary.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . up to 75 percent of patients may survive 5 to 10 years. Tumors composed of neoplastic pineal cells are called pineoblastomas or pineocytomas. Medulloblastomas are highly malignant neoplasms. they have a poor prognosis because they tend to recur after resection and disseminate into the subarachnoid space. Choroid plexus papilloma. Mixed Neuronal-Glial. They have a predilection for the lateral ventricles in children and the fourth ventricle in adults. medulloblastoma. 19-82. The tumors have a cauliflower-like granular surface expanding the cavity in which they arise. Medulloblastoma. one at 10 and the other at 22 years of age. This cerebellar tumor appears partially necrotic. The cells have carrot-shaped ovoid nuclei with coarse dark chromatin and scant or no visible cytoplasm. After cerebellar astrocytoma it is the most common CNS neoplasm of children. 19-81. 66417308 : ¸Ÿ±U 24 ¥°Q . 19-84). 19-83). Neuronal. Pineocytomas are formed of relatively mature uniform cells. Medulloblastoma. Although they are radiosensitive.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 19-81). and it may be difficult to distinguish them from metastatic adenocarcinomas. Medulloblastomas typically arise in the vermis of cerebellum and usually appear as a well-demarcated grayish mass with variable zones of necrosis and hemorrhage (Fig. Nevertheless. The tumor is composed of papillae lined by cuboidal cells. Such tumors are composed of poorly differentiated cells that have the cytologic and histologic features of a medulloblastoma. Pineoblastomas are tumors of children and young adults (Fig. The tumor is composed of primitive cells that have elongated nuclei and scant cytoplasm. highly cellular. Medulloblastoma is the most common. Mitoses and necrosis may be found.

Tumor cells typically have ovoid pale nuclei. 19-87. Pineocytoma. Although such invasion does not herald malignancy. which show some whorling. which may contain centrally located psammoma bodies (Fig. bone. Sagittal section reveals a large necrotic mass extending from the pineal region into the diencephalon. osteoblastic. reactive. or dural sinuses. including syncytial. 19-87). Several degenerative. Tumors typically are attached to the dura. (Fig. 19-85). chondroid. Pineoblastoma. Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . psammomatous. They occur less Fig. 19-84. lipoblastic. angioblastic. xanthomatous. 19-86. Cell form nests. Meningioma.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 19-85. Meningioma. the rate of which is estimated to be in the range of 15 percent over the five-year period after removal. Pineocytes surrounded by fibrillar material form vague rosettes. Several histologic types are recognized. which are most concentrated in the parasagittal arachnoid granulations and dural sleeves of the spinal canal. and inflammatory changes. 19-86). The prognosis is variable but is considered more favorable than that of pineoblastoma. it is responsible for most recurrences. Fig. They arise from leptomeningeal arachnoid cells. Hemangioblastomas present as intraaxial lesions of the cerebellum or brainstem. or metaplastic changes may complicate the recognition of its meningeal origin: myxomatous. The cells often form whorls. representing 10 percent of posterior fossa tumors. Hemangiopericytomas represent an invasive malignant tumor that has a 50 percent recurrence rate. They are indolent in their growth but commonly invade dura.425 Fig. It occupies a cavity that has formed by the tumor pushing itself into the cerebral hemisphere. but the criteria for their histologic recognition are imprecise. are firm. and so forth. Meningioma Meningiomas are tumors that are composed of meningothelial cells. with vacuoles of cytoplasmic invaginations (often exaggerated in frozen sections) and well-developed cytoplasm that shows no distinct borders. Tumor cells have oval nuclei and inconspicuous cytoplasmic borders. fibroblastic. This midline well-circumscribed tumor originated from the falx (not shown). secretory. 66417308 : ¸Ÿ±U 24 ¥°Q . Vascular Neoplasms Hemangiopericytoma and hemangioblastoma are the most common vascular tumors in the cranial cavity. microcystic. and compress the adjacent brain or spinal cord (Fig. which are larger than those of astrocytes. chordoid. Malignant meningiomas rarely occur. Meninges also may give rise to sarcomas and malignant melanomas.

The initial lesion usually is followed by secondary changes in other compartments. Hemangioblastomas are well demarcated. linear chains of myelin ovoids are readily visualized as round or fusiform bodies in the confines of individual nerve fibers.426 Fig. Peripheral nerves are composed of axons. The tumor is composed of thinwalled vessels surrounded by vacuolated clear stromal cells. such as amyloidosis. which appear as vacuolated spaces and eosinophilic material arranged in the form of a linear chain. and blood vessels. Demyelination refers to pathologic processes that selectively interfere with the ability of Schwann cells to maintain 66417308 : ¸Ÿ±U 24 ¥°Q . myelin sheaths. peripheral neuropathies are thus classified as (1) axonal injury (axonopathy or primary axonal degeneration). the internodal length of regenerated axons appears uniformly shorter than normal. Hemangioblastoma. They may be multiple in patients with Lindau or von Hippel–Lindau disease. and etiologically as inflammatory. or solid. mononeuropathy. These changes are better appreciated in plastic-embedded thick sections (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . regenerating axons may be recognized as thinly myelinated axons clustered closely together (Fig. Chronic axonopathy is characterized by a loss of axons. Pathogenetically. arachnoid cysts. Colloid cysts usually are located in the anterior roof of the third ventricle (Fig. many consist of a solid yellow to red mural nodule in a cyst filled with yellow or brown fluid. Microscopically the tumors consist of small to dilated vascular channels lined by hypercellular endothelium and surrounded by pericytes and vacuolated stromal cells (Fig. 19-89). which is known to be related to a tumor suppressor gene defect. chronic relapsing-remitting neuropathy. nutritional. 19-90). Disease may begin in any of these anatomic structures. 19-88). (2) myelin sheath injury (primary demyelination or demyelinating diseases). or mononeuropathy multiplex. These components of the nerve are best evaluated in nerve biopsy specimen prepared not only for paraffin embedded routine sectioning but also by embedding it in plastic for thin sectioning and EM and by submitting it for tease preparation. and (4) diseases caused by deposition of extraneous substances in the connective tissue. The necrotic debris is derived from the axon and the corresponding myelin sheath enclosed within the parameter of the original nerve fiber. DISEASES OF PERIPHERAL NERVES Peripheral Neuropathies Peripheral neuropathies may be classified as acute or chronic. acute axonopathy is characterized by abundant degenerating fibers. Malformative and Nonneoplastic Mass Lesions This heterogeneous group includes tumors such as craniopharyngioma. Axonal degeneration is accompanied by axonal regeneration. or cryptogenic. Clinically they present in the form of several syndromes such as acute ascending paralysis. In teased-fiber preparations. which appears as sprouting of axons. connective tissue forming the endoneurium and perineurium. Because the interval from injury to total axonal fragmentation is generally less than two weeks. cystic. 19-92). The number of axons per cross-sectional diameter is diminished. By EM they are surrounded by a band of Biangner. 19-88.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . chronic progressive sensorimotor neuropathy. Hemangioblastomas infiltrate parenchyma to some degree and tend to recur if they are incompletely excised. resting on a collagenous capsule. Cyst is located in the third ventricle. and colloid cysts. subacute sensorimotor neuropathy. limited to one nerve (mononeuropathy) or involving several nerves at the same time (polyneuropathy or mononeuropathy multiplex). dermoid cysts. often in the spinal cord. 19-89. Colloid cyst. ischemic. The lumen of the cyst is filled with colloid. (3) vascular diseases involving nerves such as ischemic neuropathy or neuropathy caused by vasculitis. but later it is taken up by macrophages. Fig. They are congenital lesions that are derived from misplaced endoderm. In teased-fiber preparations. 19-91). Acute axonopathy may be recognized in routine H&E–stained slides as myelin ovoids. In plastic-embedded thin sections. metabolic/toxic. The cysts are lined by columnar pseudostratified epithelium containing ciliated or mucus-producing cells. and the endorieural space is filled with collagen replacing the lost axons (Fig.

Fig. Because each Schwann cell myelinates the segment of the axon between two nodes of Ranvier. injury to individual Schwann cells leads to internodal loss of myelin surrounding segments of the axon. A. In plasticembedded sections. the nerve contains normal axons and axons whose myelin sheath is too thin for their caliber (Fig. In teased-fiber preparation the demyelinated segment (between arrows) had a thin myelin sheath and is shorter than adjacent internodes. 66417308 : ¸Ÿ±U 24 ¥°Q . 19-93).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . This variability in myelin thickness in plasticembedded cross-sectioned nerves is a hallmark of a demyelinating neuropathy.427 A B C Fig. 19-90. 19-91. Disintegration of myelin is accompanied by preservation of the axon. Repetitive episodes of demyelination and remyelina - Fig. The nerve contains only a few myelinated axons. Most axons are in acute stages of axonal degeneration. Therefore. 19-92. Fig. C. Chronic axonopathy. B. after emyelination. 19-94). Segmental demyelination cannot be assessed in routinely processed paraffin-embedded tissue. which appears segmentally denuded in teased-fiber preparations (Fig. Degenerating axons with myelin debris completely replacing the axonal profile in cross section of the nerve embedded in plastic and sectioned at I micron thickness (arrow). the internodes are of variable length and myel' kness varies along the length of a single fiber (Fig. myelin sheaths. Myelin ovoids (teased fiber preparation). whereas most others have been lost and have been replaced by collagen. Remyelinated axons appear in teased-fiber preparations thin er and have shorter internode segments. Axonal sprouts appear as clusters of small myelinated axons (arrows). Segmental demyelination. 19-93). 19-93.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Acute axonopathy. Axonal regeneration.

Charcot-Marie-Tooth disease ( MCT) is the most common hereditary neuropathy. This variation typically is seen in nerves that have undergone segmental demyelination. 19-94.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .428 tion are accompanied by formation of additio 1 periaxonal layers by Schwann cell processes ( " onion formation" ). with an estimated prevalence of 1 in 2500. which are reminiscent of changes seen in hypertrophic axonal neuropathies. Hereditary Neuropathies Hereditary neuropathies occur in several clinically distinct forms.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Axons of the same caliber have myelin sheaths that vary in thickness. Type I is more common Fig. Segmental demyelination. Two major groups are recognized: hereditary motor and sensory neuropathies (HMSN) and hereditary sensory and autonomic neuropathies (HSAN) (Table 19-3). Hereditary Peripheral Neuropathies 66417308 : ¸Ÿ±U 24 ¥°Q . It is inherited as an autosomal dominant trait and occurs in two forms.

Immunohistochemistry shows that axonal spheroids contain neurofilaments. They appear as ill-defined layers of Schwann cell processes and are accentuated by the appearance of two Schwann cell nuclei adjacent to a single fiber. Type I MCT is characterized by a moderate loss of large caliber axons and prominent onion bulb formation (Fig. 19-97.429 and presents as a demyelinating neuropathy. Microscopically the nerves show prominent onion bulb formation. I9-96. B. onion bulbs are composed of concentric layers of Schwann cell cytoplasm with only occasional Schwann cell nuclei identifiable. A A B B 66417308 : ¸Ÿ±U 24 ¥°Q . Charcot-Marie-Tooth disease. type I. In plastic sections a few fibers Fig. Dejerine-Sottas disease. In plastic-embedded tissue sectioned at I micron thickness. Cross section of peripheral nerve shows numerous onion bulbs. Onion bulbs may be difficult to identify in routine histologic sections. Immunohistochemistry shows that these spheroids are filled with neurofilaments. B.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº Fig. Tomaculous neuropathy is an autosomal dominant hereditary neuropathy that is characterized by a tendency to develop compression neuropathy. whereas type II presents as axonal neuropathy. A. Prominent eosinophilic enlarged axons are distributed at random and are occasionally surrounded by rings of Schwann cells (Schwann cell hyperplasia). Microscopically it is recognized by the presence of greatly enlarged axons that appear in routine sections as homogeneous eosinophilic spheroids (Fig. Dejerine-Sottas disease is a hereditary neuropathy of childhood that is inherited as an autosomal recessive trait.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 19-96). 19-95. 19-95). which is readily apparent in routine H&E—stained sections (Fig. Fig. Giant axonal neuropathy is an uncommon peripheral neuropathy of childhood that is inherited as an autosomal recessive trait. Giant axonal neuropathy. A. Type II MCT is characterized by axonal loss and onion bulbs are not prominent. . 19-97).

66417308 : ¸Ÿ±U 24 ¥°Q . In teased-fiber preparation the nerve fibers show fusiform thickening. B. Fig. Ischemic neuropathy. include acute demyelination and foci of inflammation composed of lymphocytes and macrophages (Fig. It is considered to be an immune-mediated disorder. 19-100). 19-99). which are most prominent in the spinal roots. 19-100. most often derived from transthyretin. The diagnosis is made by identifying foci of polyarteritis in the nerve biopsy (Fig. Ischemic Neuropathies Microangiopathy caused by diabetes.430 A have excessively thick myelin sheaths. Although they have been described in several parts of the world. which typically is segmental. in patients with AIDS. and atherosclerosis accounts for most ischemic neuropathies.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . which in teased-fiber preparations have been likened to sausages (Latin: tomaculum) (Fig. many appear to be based on mutations of the same segment of the transthyretin gene. Nerve biopsies show chronic axonal loss that involves both large caliber and small caliber myelinated axons. Fig. Amyloid deposits in the form of homogeneously eosinophilic material are present in the wall of blood vessels and the endoneurium. 19-98).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . hypertension. Microscopically amyloid is found in the endoneurium and in the wall of blood vessels (Fig. Hereditary amyloid neuropathy is characterized by endoneurial deposition of amyloid. Nerve changes. and with infection by Campylobacter jejuni. 19-98. 19-102). Inflammatory Neuropathies B Guillain-Barre syndrome is an acute or subacute demyelinating peripheral neuropathy with an incidence of 1 to 2 per 100. Fig. Polyarteritis nodosa and Churg-Strauss syndrome may cause acute and chronic neuronal ischemia. Tomaculous neuropathy. A. 19-99. after immunization. Familial amyloid neuropathy. It usually occurs after a self-limited viral disease. which are replaced by collagenous tissue (Fig.000. Cross section of the nerve shows loss of axons from broad areas. Cross section of the nerve shows scattered "hypermyelinated" axons with thickened myelin sheaths. 19-101). following surgery.

19-105. 19-104.431 Chronic inflammatory demyelinating polyneuropathy is similar to Guillain-Barre syndrome in its immune-mediated pathogenesis and targeted demyelination. Guillain-Barre syndrome. Fig. Microscopically the affected nerves show chronic demyelination.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . In cross section the nerve shows marked variation in the thickness of myelin sheaths and focal axonal loss. Scattered axons show acute demyelination (arrow). Infections of nerves with viruses such as herpes simplex or bacteria such as Mycobacterium leprae produce distinct morphologic changes and variable destruction of nerve tissue. 19-101. it is distinguished by an insidious onset. Perineuritis. and variable response to therapy. 19-103). 19-105). Polyarteritis nodosa. 19-103. It is characterized by chronic granulomatous inflammation that is restricted to the perineural layers (Fig. The blood vessel is infiltrated by inflammatory cells. Variation in the thickness of myelin sheaths of axons of the same caliber also is evident. The perineurial layers contain chronic inflammatory cells forming granulomas. However. 19-102. Systemic inflammatory diseases such as sarcoid6sis may involve nerves. 66417308 : ¸Ÿ±U 24 ¥°Q . which typically contain granulomas (Fig. Fig. Chronic inflammatory demyelinating polyradiculoneuropathy. Fig. which often is perivascular or not present at all (Fig. Fig. Sarcoidosis. 19-104). with variable amounts of inflammation. progressive course. Sensory perineuritis is a disease of unknown etiology. The epineurium contains noncaseating granulomas. Fig.

and those that are myxomatous are called Antoni B areas (Fig. Fig. Microscopically the tumors are composed of uniform Schwann cells that have elongated nuclei with tapering ends. Neurofibromas tend to infiltrate nerves and ganglions and may contain entrapped neural elements. On gross examination they appear soft and malleable with a mucoid translucent cut surface (Fig. perineuroma. Neurofibroma. perineurial cells. 19-108. encapsulated tumors that may ostensibly be attached to a peripheral nerve (Fig. Densely cellular areas are termed Antoni A areas. Schwannoma. Schwannoma. The tumor is grayish-yellow. Blood vessels are seen on its surface. 19-107. The tumor is composed of spindleshaped cells that show typical palisading. Some tumor cells stain with antibody to S-100 protein. 19-108). Malignant tumors are uncommon. fusiform expansion of the involved nerve segment (plexiform neurofibroma). 19-109). 19-109. some of which resemble Schwann cells. encapsulated. Most schwannomas present in the form of firm. they form interwoven fascicles. and lobulated. 19-106. In neurofibromatosis type I (von Recklinghausen disease). Perineurioma is a localized mass that occupies a single nerve and expands each of its fascicles. Each individual fas- Fig. Fig. as evidenced by the presence of scattered ganglion cells between elongated tumor cells. neurofibromas may be multiple.432 Neoplasms of Peripheral Nerves Peripheral nerve tumors are common but usually are small and benign and thus of limited clinical significance. It may present as a solitary intradermal lesion or perineurial masses. Neurofibroma is a benign tumor composed of nerve sheath—derived cells. like perineurial cells. 66417308 : ¸Ÿ±U 24 ¥°Q . ganglioneuroma. like Schwann cells. and Morton neuroma. Microscopically they consist of elongated cells and moderately abundant matrix (Fig. Neurofibroma.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . and still others do not express any markers and are considered to be fibroblasts.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Palisading tumor cells forming rows that alternate with acellular areas are called Verocay bodies. Tumor lobules follow the course of the nerve. Other benign tumors and tumor-like conditions of peripheral nerves that have distinct features are granular cell tumor. Fig. 19-106). In parallel alignment. or it may cause ropelike. others stain with antibodies to epithelial membrane antigen (EMA). Neurofibroma has infiltrated a ganglion. Schwannoma (neurilemoma) is the most common peripheral nerve tumor. or endoneurial fibroblasts. 19-107).

1993. Am J Surg Pathol 22:231238. Fujimura H et al: The peripheral neuropathy of necrotizing arteritis. The tumor cells lie concentric to the perineurial sheath or concentrically around individual nerve fibers (Fig. Asbury AK. fascicle 10. Minazzi M: Alcoholic neuropathy. Dyck PJ. Clinicopathologic and immunohistochemical studies. Smith M. Histologic assessment of the age of recent brain infarcts in man. Wick MR. 1998. Morton neuroma. I9-1 10. Coffin CM. 66417308 : ¸Ÿ±U 24 ¥°Q . Amason BG. 1996. Godfrey A. Tredici G. An autopsy study of 133 patients. 1993. J Neuropathol Exp Neurol 44:32-46. Pathol Annu 19(pt 2):89-119. 1998. Hart MN. Kepes JJ. The diagnosis of metastases to the central nervous system.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . A morphological overview. 1996. Chuaqui R. A clinicopathologic study. Vonsattel JPG. usually between the third and fourth metatarsal bones. 1998. 1992. 1975. J Neuropathol Exp Neurol 52:481-489. Prusiner SB: Etiology and pathogenesis of prion disease. Goulon-Goeau C. 19-110). Scheithauer BW. Washington. 1986. The focal segment of the affected nerve is thickened because of fibrosis of the perineurium compressing the nerve trunk showing a loss of axons (Fig. Medicine 48:173-215.433 Fig. Terry RD: Making the diagnosis of Alzheimer's disease. Ludwig C. cicle is enlarged and is hypercellular with a single cell species. 1986. J Neuropathol Exp Neurol 55:1181-1193. 1988. Ann Neurol 19:15-21. J Neuropathol Exp Neurol 57:531543. Bjornsson J. Said G. DeArmond SJ. Armbrustmacher V: A clinicopathologic study of 323 patients with oligodendrogliomas. Ann Neurol 35:559-569. J Neuropathol Exp Neurol 57:991-999. Golden JA: Holoprosencephaly: a defect in brain pattering. Said G. A clinicopathologic analysis of 15 new cases and review of the literature. Burger PC. Its role in pathogenesis. Like neurofibromas. Kepes JJ. Lie JT: Primary (granulomatous) angiitis of the central nervous system. Koppen AH: The hereditary ataxias. Bigner SH. J Neuropathol Exp Neurol 57:369-384. Mod Pathol 9:579-597. 1994. Moulonguet A: Nerve biopsy findings in different patterns of proximal diabetic neuropathy. Dehner LP: Choroid plexus neoplasms. Inagawa T. Moral LA. Ann Neurol 23:461-465. Leech RW: Intracranial germ cell tumors. Lacroix C. Schold SC. Neurosurg Rev 9:177-216. Armed Forces Institute of Pathology. 19-I 1 I . Okazaki H. 1996. An electron-microscopic study. DC. 1986. Hum Pathol 23:164-171. Fibrosis of the perineurial layer is accompanied by a central loss of axons. 1984. 1996. Hirano A: Ruptured intracranial aneurysms. Atlas of tumor pathology. 1969. Report of four cases. Forno LS: Neuropathology of Parkinson's disease. Adams RD: The inflammatory lesion in idiopathic polyneuritis. Arch Pathol Lab Med 120:26-34. Females are affected more often than males. Difiglia M: Huntington disease. 1995. Braun JT. Lacroix-Ciaudo C. series 3.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Perineurioma. Arch Pathol Lab Med 117:132-144. Further Reading Anthony DC. Mirra SS. Am J Pathol 146:785-811. Crain BJ: Peripheral nerve biopsies. 1998. 1985. The latter pattern is reminiscent of onion bulbs in the hereditary hypertrophic neuropathies and has led to the synonymous term localized hypertrophic neuropathy. Morton neuroma (perineurial fibrosis) is a painful enlargement of an interdigital plantar nerve. 1990. Wilkenson SB et al: Rhabdoid transformation of tumor cells in meningiomas: a histologic indication of increased proliferative activity. Pathobiological and immunohistochemical aspects of 70 cases. perineuriomas may occur as intraneural plexiform tumors or as solitary extraneural tumors (intramuscular perineuriomas). 1994. Am J Surg Pathol 10:394-404. Giannini C: Pathologic alterations in the diabetic neuropathies of humans. 19-111). Tapia J. Scheithauer BW: Tumors of the central nervous system. J Neuropathol Exp Neurol 55:259-272. Concentrically oriented cells create a hypercellular endoneurium. Scheithauer B: Pathology of selected neoplasms of central nervous system. JNeurol Sci 25:333-346. Fig. Jellinger K: Vascular malformations of the central nervous system. Surg Neurol 33:117-123.

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Fig. Fungal endophthalmitis. retina (retinitis). ciliary body (cyclitis). 20-3. Multiple vitreous microabscesses developed due to Fusarium infection acquired during cataract surgery. giant papillary conjunctivitis. chronic conjunctivitis. lacrimal gland (dacryoadenitis). allergic conjunctivitis. iris and ciliary body (iridocyclitis). trachoma) (Fig. drugs and chemicals. Chalazion. eyelid (blepharitis). Chronic follicular conjunctivitis. or it is classified according to the etiologic agent (bacterial conjunctivitis. Fig. 20-2. chronic follicular conjunctivitis. choroid. granulomatous conjunctivitis. Multiple vitreous microabscesses are a characteristic finding in fungal endophthalmitis. It may be related to infections. viral conjunctivitis. mechanical devices. optic nerve (optic neuritis).436 I NFLAMMATION OF THE EYE AND OCULAR ADNEXA Inflammation of the eye is common. systemic diseases. Sympathetic uveitis. pseudomembranous conjunctivitis. cornea (keratitis). Empty lipid vacuoles are necessary for the diagnosis of li pogranulomatous inflammation. Inflammation may be limited to the conjunctiva (conjunctivitis). membranous conjunctivitis. cornea and conjunctiva (keratoconjunctivitis). vernal conjunctivitis). A Dalen-Fuchs nodule of epithelioid histiocytes elevates the retinal pigment epithelium (RPE) from Bruch membrane at right. 20-1). uvea (uveitis). iris (iritis). irritants.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . episclera (episcleritis). choroid and retina (chorioretinitis). 20-2). Chalazion is an inflammation associated with obstruction of sebaceous glands (meibomian or Zeis glands). pars plana of ciliary body (pars planitis). orbital connective tissue (orbital cellulitis). The choriocapillaris is visible ("spared"). 20-I. Fig. Fig. or the ocular contents and cornea or sclera (panophthalmitis). 66417308 : ¸Ÿ±U 24 ¥°Q . Conjunctivitis is classified according to the nature of the inflammatory reaction (acute conjunctivitis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . the intraocular contents with sparing of the sclera and orbit (endophthalmitis). choroid (choroiditis). sclera (scleritis). The retina is detached. and tumors. A mass of chronic inflammatory cells is seen anterior to the tarsal plate of the eyelid. vitreous (vitritis). inclusion conjunctivitis. 20-4. The conjunctiva's normal resident population of lymphocytes has been stimulated to proliferate. Histologically it presents as a chronic lipogranulomatous reaction (Fig. allergies. The choroid is massively thickened by a diffuse chronic inflammatory infiltrate composed of epithelioid histiocytes and lymphocytes. This follicle contains a germinal center. ligneous conjunctivitis. corneal stroma (interstitial keratitis).

These thickened muscles are fibrotic and histologically show lymphocytic myositis (Fig. or fungi is characterized by destruction of the corneal epithelium and the Bowman layer. Hard exudates are seen as pools of proteinaceous fluid centered on outer plexiform layer at right. cytomegalovirus Fig. Acute keratitis and scleritis caused by Pseudomonas aeruginosa. some of which are listed in Table 20-1. Fig. 20-5. and by prominent inflammatory infiltrates (Fig. microaneurysms. thought to represent an autoimmune response to sensitization to ocular isoantigens and is characterized by chronic lymphocytic inflammation (Fig. or parasites occasionally may be identified (Fig. usually complicated by incarceration of uveal tissue in the wound. or neovascularization of the eye background (Figs. 20-4). Sympathetic uveitis is a rare but very important bilateral granulomatous reaction that follows unilateral ocular injury or surgery. 20-3). atherosclerosis. Keratitis caused by bacteria.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Pathogens such as cytomegalovirus (CMV). These diseases produce a variety of changes in the retina. 20-6). Cotton wool spot and hard exudates of retina. The most important among these systemic diseases are hypertension. Histologic examination of the eye rarely provides an insight into the cause of the disease. EYE CHANGES IN SYSTEMIC DISEASES The eye is involved in numerous systemic diseases. 66417308 : ¸Ÿ±U 24 ¥°Q . and vitroretinal part of the eye. 20-7 to 20-10). 20-7. and diabetes mellitus. all of which are related either to ischemia or to microvascular injury.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . herpesvirus. viruses. 20-5).437 Endophthalmitis and panophthalmitis may be classified as an endogenous or exogenous intraocular infection that results in abscesses and chronic destructive inflammatory lesions (Fig. The condition is. Several cytoid bodies in cotton wool spot contain darkly-staining nucleoids of dammed organelles. Eosinophilic abscess contains fragment of nematode larva. Pathologic changes correspond to those seen on ophthalmoscopy as cotton wool spots. Extraocular muscles are involved in Graves disease. iris. Pseudomonas infections of the cornea often extend posteriorly as an acute infectious scleritis. Examples of Systemic Diseases That Affect the Eyes CMV. Ocular toxocariasis. 20-6. 20-11). Blockage of axoplasmic flow thickens nerve fiber layer at left. Fig.

acterized by optic neuropathy associated with a characteristic excavation of the optic disk and a progressive loss of visual field sensitivity. The condition may develop without an apparent antecedent underlying ocular disease (primary glaucoma). Graves disease. 20-12. depending on whether the iridocorneal angle appears open 66417308 : ¸Ÿ±U 24 ¥°Q . Hemorrhage is present in the vitreous and the subhyaloid space. In most cases the intraocular pressure is elevated. Fig. which is thought to represent an arterial macroaneurysm. Primary and secondary glaucomas are subdivided into open-angle and closed-angle types. Whole mount of retina shows saccular dilatations (Courtesy of Dr. SPECIFIC OCULAR DISORDERS Glaucoma Glaucoma is a term that denotes a group of disorders char- Fig. Neovascularization occurs on anterior surface of retina and extends onto the posterior face of the detached vitreous. Madison. 20-8. Bloodworth. Eye involvement is a typical feature of neurofibromatosis type I and von HippelLindau disease (Fig. 1984). Fibrin surrounds dilated vessel in inner retina. Lipidized stromal cells are found between the capillary vessels. Diabetic microaneurysms of the retina. The vitreoretinal membrane is beginning to cause a tractional retinal detachment.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Although they often are called retinal capillary hemangiomas. or it may follow or occur concomitantly with a known ocular disorder (secondary glaucoma). 20-10. von Hippel-Lindau disease. Wisconsin. histopathologically the retinal tumors are identical to cerebellar hemangioblastomas. Proliferative diabetic retinopathy. Postmortem exenteration specimen showing massive enlargement of extraocular muscles. 20-9. 20-12).) Fig. (Case reported by Hufnagel TJ et al. Retinal arterial macroaneurysm with hard exudates. J.M.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Hereditary tumor syndromes that involve more than one organ system also may involve the eye. Retinal capillary hemangioma.B. 20-11.438 Fig. Fig. Ophthalmology 91:141 I. Hard exudates and hemorrhage are seen in outer plexiform layer.

20-14. 20-17. Pathologic alterations relevant to the cause of the glaucoma may also be apparent. The lamina cribrosa is bowed posteriorly. These abnormalities include the presence of epithelium on the surface of the iris and even Fig. 20-13. The iris root and first ciliary process are displaced posteriorly. and optic atrophy (Figs. excavation of the optic nerve head ( "glaucomatous cupping"). With long-standing glaucoma the corneal endothelium may be deficient and the cornea may have features of a bullous keratopathy. Primary open-angle glaucoma. such as a loss of ganglion cells and axons in the retinal nerve fiber layer.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. the most common form. 20-16. Narrow angle.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . posterior bowing of the lamina cribrosa. Fig. 20-13 to 20-18). Pathologic studies on eyes with glaucoma disclose abnormalities relevant to the effects of elevated intraocular pressure. End-stage glaucomatous cupping of optic nerve head. Patients with the narrow angle configuration are at risk for developing an acute attack of angle closure glaucoma. Postcontusion angle recession (recessed angle). depending on the time of onset. 66417308 : ¸Ÿ±U 24 ¥°Q . The anterior surface of the peripheral iris is adherent to the trabecular meshwork. or closed.439 Fig. The ciliary muscle has a fusiform shape caused by ischemic atrophy of its inner part after tear into face of ciliary body during contusion injury. Glaucoma also may be subdivided into congenital (developmental) or acquired types. The peripheral stroma of the iris is in close proximity to the trabecular meshwork. Uveal melanoma was the indication for enucleation. Glaucomatous retinal atrophy. Atrophy is limited to the ganglion cell and nerve fiber layers of the retina. Most enucleated blind glaucomatous eyes have secondary closed-angle glaucoma. This massively excavated nerve head has a bean pot configuration. anterior chamber. eye with pseudoexfoliation syndrome. A few glial cells are seen in the nerve fiber layer. Peripheral anterior synechiae. 20-15. Fig. Congenital glaucoma is the least common form. affects 1 percent to 3 percent of all persons over 40 years of age.

Fuchs corneal dystrophy. Stroma contains aggregates of intensely eosinophilic crystalloids with "rock candy" appearance. Corneal enlargement occurs when the intraocular pressure is elevated in childhood. 66417308 : ¸Ÿ±U 24 ¥°Q . Stretching may produce spontaneous tears in Descemet membrane called Haab striae. Fig. and Fuchs corneal dystrophy (Figs. The healed ruptures are seen as radiating lucent ridges on the posterior corneal surface in the photo. Granular corneal dystrophy. The endothelial cells are absent. the most common and clinically significant form of secondary closed-angle glaucoma. Stroma has edematous "cotton candy" appearance. Corneal graft rejection may cause similar changes. Bullous keratopathy is a common disease in which the corneal stroma and epithelium become edematous and bullae form between the epithelium and the Bowman layer. Pseudophakic bullous keratopathy. 20-19. The changes are classified according to the cause of epithelial loss: cataract extraction (aphakic bullous keratopathy). although their nature is not fully understood. Fig. Diseases of the Cornea Diseases of the cornea often show unique features. 20-21.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . cataract extraction combined with implantation of a prosthetic intraocular lens (pseudophakic bullous keratopathy).440 in the vitreous ( "epithelial downgrowth"). Lattice corneal dystrophy.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Guttate excrescences of abnormal basement membrane material stud posterior surface of thickened Descemet membrane. Fuchs corneal dystrophy. Congenital glaucoma. Some residual endothelial cells contain granules of melanin pigment from iris. and the stroma is edematous. Smudgy oval deposit of stromal amyloid stained positively with Congo red and showed apple-green birefringence and dichroism on polarization microscopy. gross photo showing enlarged cornea with healed ruptures of Descemet membrane. Fig. Descemet membrane is normal. Material stains intensely with Luxol fast blue and shows acid fuchsinophilia (red staining) with Masson trichrome. 20-20. 20-22. 20-18. Endothelial damage caused by cataract surgery and prosthetic intraocular lens implantation is the most common indication for corneal transplantation. which accounts for many corneal specimens submitted for pathologic examination in the Fig. Fig. Neovascularization of the iris is found in cases of neovascular glaucoma. 20-19 to 20-23).

Macular dystrophies are characterized by accumulation of keratan sulfate—related glycosaminoglycan within the fibroblasts.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . is characterized by multiple. A single row of residual cone nuclei comprises the outer nuclear layer in the posterior retina. Fleischer iron ring in corneal epithelium. Fig. Most important among these disorders are macular degeneration and retinal detachment (Fig. Hale colloidal iron technique and the Alcian blue stain are particularly useful in coloring the abnormal accumulations. This poorly understood disorder may be familial and occasionally is associated with other hereditary disorders such as Marfan syndrome. The remaining inner segments are atrophic. finely granular storage material (abnormal nonsulfated keratan sulfate) are seen in anterior interlamellar spaces. 20-24). Detached hemorrhagic-retinal pigmentary epithelium is undergoing organization into a collagenous disciform scar. 20-23. The inherited lattice corneal dystrophies are characterized by irregular linear opacities caused by stromal amyloid deposits in corneas with an unremarkable Descemet membrane and endothelium (Fig. which is better known by the generic misnomer retinitis pigmentosa. centrally located. wartlike excrescences ("corneal guttae " ) on a thickened Descemet membrane in addition to features of bullous keratopathy (Fig. 20-26). Retinitis pigmentosa. The central corneal stroma is markedly ectatic. a term that encompasses a large group of progressive degenerative diseases of the retina. A Retinal Degenerative Diseases Retinal degenerative changes may occur at any age but are more common in older people. is characterized by a loss of retinal photoreceptors and by perivascular accumulation of pigment within the retina (Fig. and in the Descemet membrane (Fig. Keratoconus. 20-21). Fig. 20-24. Keratoconus is a common progressive disease that is characterized by thinning of the central corneal stroma. Age-related macular degeneration.441 United States. Retinal atrophy is confined to the photoreceptors. Histologically the epithelium of the cornea is ectatic and the Bowman layer contains typical dehiscences. B Fig. Pigmentary retinopathy. A. among the collagen lamellae. Deposits of lucent. 20-25). B. The retinal pigmentary epithelium and the inner retinal layers are intact. without evidence of inflammation or vascularization. In this area the corneal epithelium has undergone compensatory hyperplasia. Dehiscences are seen in the Bowman membrane. 20-25. in the endothelium of the cornea. which causes conical distortion of the cornea. 20-26.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig. Excessive eye rubbing is common in patients with keratoconus and may precede the formation of a conical cornea. 20-23). 66417308 : ¸Ÿ±U 24 ¥°Q . The retina is shallowly detached by serous fluid. Macular corneal dystrophy. The epithelium often contains a ring of stainable iron surrounding the cone (Fleischer ring) (Fig. 20-22).

20-29). or migrate posteriorly. A fibrous papillary membrane rests on the anterior surface of this cataract. Most cataracts are associated with aging. An increase in the index of refraction of the lens causes lenticular myopia. Posterior subcapsular cataract with Wed! cells. Morgagnian globules of degenerated lens protein fill cleft in lens cortex. 20-27). Within the plaque the cells are surrounded by basement membrane material that is periodic acid—Schiff positive. Nuclear cataracts occasionally contain oval birefringent crystals of calcium oxalate.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Fig. (2) nuclear. Proliferation and fibrous transformation of residual lens epithelial cells is a major cause of posterior capsular fibrosis after extracapsular cataract extraction. Nuclear sclerotic cataract. Anterior subcapsular cataract is characterized by inflammation and adhesions between the iris and the lens (posterior synechiae). Cataracts may have numerous causes and are classified as genetic. The colored lens absorbs blue light. Nucleus shows intense homogeneous staining and lacks artifactitiously intercellular clefts seen in cortex. Wed! cells represent abortive attempts by lens epithelial cells to form new lens fibers. 66417308 : ¸Ÿ±U 24 ¥°Q . Fig. Fig. The osmotic effect of the degenerated cortex causes the lens to imbibe aqueous and swell. which distorts color vision. Cortical (soft) cataracts result from degeneration of the lens cells or fibers and are characterized by fractures.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . There initially is formation of vacuoles or clefts in the lens cortex. 20-27 to 20-30). Other factors besides inflammation occasionally stimulate the anterior subcapsular monolayer of cuboidal lens epithelium to proliferate.442 Cataracts A cataract is an opacity in the lens that usually is severe enough to impair visual acuity. undergo metaplasia. The sclerotic nucleus usually resists liquefaction. reflecting the accumulation of the photooxidation pigment urochrome. druginduced. and so forth. 20-29. Total cortical liquefaction eventually may ensue. Cortical cataract. bearing testimony to the lens epithelial lineage of the cells. The proliferating lens epithelial cells synthesize a thick plaque of collagen beneath a sinuously folded anterior lens capsule (Fig. Nuclear sclerosis is characterized microscopically by increased eosinophilia and homogeneity of the lens nucleus. Artifactitious cleft separates dense sclerotic nucleus from degenerated cortex. leading to the formation of a so-called morgagnian cataract. An aggregate of Wedl or bladder cells formed by posterior migration of the lens epithelium is seen next to thin posterior lens capsule. Four basic types of cataract are recognized histopathologically: (1) cortical. which lacks the artifactitious clefts that are observed in a normal lens cortex (Fig. and liquefaction of the fiber cells of the lens cortex (Fig. 20-30. (3) anterior subcapsular. 20-28). 20-27. degen- eration. Basement membrane capsules surround residual lens epithelial cells within plaque. 20-28. Collagenous plaque made by distressed lens epithelial cells is seen beneath folded anterior lens capsule. Fig. metabolic. Anterior subcapsular cataract. and (4) posterior subcapsular (Figs. but subsequently interrupted and folded lens fibers and cortical clefts are filled with morgagnian globules. In the nuclear sclerotic cataract the hardened central lens nucleus appears yellowish or brown.

some pigmented lesions. 66417308 : ¸Ÿ±U 24 ¥°Q . In traocular tumors are more unique. Basal cell carcinoma.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . including epithelioid cells. Invasive malignant melanoma was found nearby. Choroidal malignant melanoma. Only approximately 1500 new intraocular melanomas are diagnosed in the United States yearly. The mushroom configuration is typical of uveal melanoma. Primary acquired melanosis with atypia in conjunctiva. 20-33 and 20-34). which results when the tumor perforates Bruch membrane and grows in the subretinal space. Conjunctival epithelium is massively thickened by atypical melanocytes. 20-3I. cornea. and parts of individual tumors often vary greatly in pigment content. Globular transparent aggregates of lens cortical material called Elschnig pearls. or multinodular growth pattern occasionally occurs but is more typical of of lens epithelial cells posterior to the normal termination of the epithelium at the lens equator. Occasionally. Tumor is composed of basaloid cells showing peripheral palisading. which occasionally develop after extracapsular cataract surgery. diffuse. 20-32). and choroid. but even these neoplasms rarely exhibit features that are not seen in other locations. 20-33. A flat. Fig. Intraocular malignant melanomas arise from melanocytes in the iris. Bruch membrane is intact overlying an almond-shaped tumor. 20-32. This melanoma has a characteristic mushroom or collar button configuration. They usually are solitary and unilateral. ciliary body. and various mesenchymal cells of the orbit. so a characteristic mushroom or "collar button" configuration is assumed (Figs. Substantia propria contains lymphocytes and plasma cells. Choroidal malignant melanoma. 20-34. Extraocular tumors originate from the conjunctiva. Melanomas of the choroid or ciliary body initially are ovoid. These tumors range from totally amelanotic white lesions to jet-black masses. reflect an identical proliferation of residual lens epithelial cells. Situated abnormally. the cells retain their nuclei and form large aberrant globular lens fibers called bladder or Wedl cells (Fig. adnexal glands. Fig. but choroidal tumors often rupture through Bruch membrane and proliferate in the subretinal space. may pose problems. which remains confined to the choroid. The overlying retina is detached by the mushrooming head of the tumor and adjacent serous fluid. The tumor is variably pigmented. 20-30).·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . palpebral skin. Fig. These tumors are histologically similar to equivalent tumors in other sites (Fig. Persons of fair skin are at greater risk of developing melanoma than are those who have a dark complexion. such as primary acquired melanosis. Fig. although it is regarded as rare. TUMORS Benign and malignant tumors of the eye and ocular adnexa may be classified as extraocular or intraocular.443 Posterior subcapsular cataract results from the migration Melanoma Melanoma is the most common primary intraocular tumor of adults.

20-36. spindle A cell type. Nuclei are large and round and have prominent nucleoli. mixed spindle and epithelioid cell type. Complications include hemorrhage. Poorly differentiated melanomas sometimes contain abundant cytoplasmic lipid ( " balloon cell degeneration" ) or bizarre giant cells. These cells are poorly cohesive. Some spindle cells have slender nuclei (occasionally with a prominent longitudinal fold in the nuclear membrane) without nucleoli (spindle A cells) (Fig. forming a syncytium. indistinct nucleoli. and their chromatin clumps along the nuclear membrane. have one or more prominent nucleoli. Fig. Fig. uveal melanomas are composed of spindle-shaped or epithelioid cells. The chromatin is often clumped along the inside of the nuclear membrane (peripheral margination of chromatin). retinal detachment. finely dispersed chromatin. Less differentiated epithelioid cells are larger. Histologically. and pigmentation of the tumor. Malignant melanoma. Most primary uveal melanomas contain variable numbers of spindle A and B cells and epithelioid cells (mixed cell melanomas) (Figs. 20-35).nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . epithelioid cell type. Epithelioid cell nuclei are round or oval. 66417308 : ¸Ÿ±U 24 ¥°Q . with distinct cytoplasmic margins. The five-year survival rate is in the range of 55 percent to 85 percent. Choroidal malignant melanoma. polygonal. cataract. and inflammation. This field contains a prominent clone of amelanotic epithelioid cells. glaucoma. 20-36). 20-35. 20-37. Other prognostic factors include the location. Spindle-shaped melanoma cells grow in a cohesive manner. Fig. 20-37 and 20-38).444 metastatic than primary tumors. Fig. Spindle A cells have slender cigar-shaped nuclei. Malignant melanoma. histologic type. Other spindle-shaped cells have plumper nuclei with small distinct nucleoli (spindle B cells) (Fig. Spindle B cells have plumper oval-shaped nuclei with a distinct nucleolus. Malignant choroidal melanoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and poorly cohesive. spindle B cell type. 20-38. Necrosis is common in all melanomas. and a chromatin stripe caused by a longitudinal fold in the nuclear membrane. In some mixed tumors epithelioid cells are admixed diffusely among the spindle cells. depending primarily on the size of the tumor.

The degree of differentiation varies from one tumor to another. A lumen is not present. Retinoblastoma. This exophytic growth arising from outer layers of the retina has caused total retinal detachment. scant cytoplasm. Most tumors are diagnosed before the age of two years. This eye had secondary closed-angle glaucoma. The retina adheres to the posterior surface of lens. which is displaced anteriorly. 20-42. Fig. 20-39. Retinoblastoma. Clinically they produce leukokoria. endophytic.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Tumors may show an exophytic. Retinoblastoma originates from the retinal cells or their precursors. or mixed endophytic and exophytic growth pattern. 20-40). The cells forming the rosettes are joined by a series of zonulae adherens analogous to the outer li miting membrane of the normal retina. is a classic sign of retinoblastoma. hyperchromatic nuclei. and prominent mitoses. Tumors are composed of primitive cells that correspond to fetal retinoblasts and their neuroblastic precursors. The nuclei are Fig. 20-39). The apices of the cells comprising the rosette are joined by zonulae adherens like the external limiting membrane of the retina. which is analogous to the subretinal space. Some tumors are composed of densely packed. Flexner-Wintersteiner rosettes have a true lumen. Retinoblastoma. 20-41). whereas larger tumors fill the eye (Fig. a white papillary reflex. Approximately 90 percent of tumors are sporadic and 10 percent are familial. 20-41. Retinoblastoma. poorly differentiated neuroblastic cells with round. others contain typical Flexner-Wintersteiner rosettes consisting of a central round lumen surrounded by more differentiated cells that have a well-developed apical cytoplasm corresponding to the subretinal space (Fig. Fig. Fig. Tumors are related to deletion or inactivation of the retinoblastoma (Rb) gene. Bilateral tumors are found in approximately 10 percent of cases.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . The center of a Homer VYright rosette contains a tangle of neural processes. Leukokoria.445 Retinoblastoma Retinoblastoma is the most common primary malignant eye tumor of children. 20-40. which often is associated with strabismus (Fig. Relatively nonspecific Homer Wright rosettes are found in other tumors such as neuroblastoma. 66417308 : ¸Ÿ±U 24 ¥°Q . Small tumors cause retinal detachment.

Medulloepithelioma Medulloepithelioma is a rare pediatric tumor composed of cords or sheets of polarized neuroepithelial cells that form elongated tubules and line cystic spaces in a loose mesenchymal stroma that is rich in hyaluronic acid. they have a favorable prognosis. and other intraocular basement membranes. Favorable histologic findings include the presence of numerous fleurettes or Flexner-Wintersteiner rosettes. and viable tumor cells cuffing blood vessels may impart the appearance of pseudorosettes. indicating that these cells are showing photoreceptor-like differentiation. The tumor is located on the inner surface of ciliary process. Parts of medulloepithelioma may resemble retinoblastoma.446 Fig. . The tumor shows photoreceptor differentiation and forms fleurettes and bouquets composed of neoplastic photoreceptor inner segments. 20-44. 20-44). the lens capsule. choroidal. 20-42). Neovascularization of the iris is common and may cause peripheral anterior synechiae and neovascular glaucoma. the trabecular meshwork. and in most developed countries the rate is in the range of 90 percent. Long-term survival may be achieved with appropriate therapy. Deoxyribonucleic acid released from the necrotic tumor cells may precipitate and impregnate intraocular blood vessels. 20-43). These tumors are almost completely composed of fleurette-forming cells. Fig. Patients with germline deletions of the Rb gene occasionally develop a benign counterpart of retinoblastoma called retinocytoma or retinoma. which are composed of bulbous eosinophilic cell processes that correspond to photoreceptor inner segments (Fig. 20-43.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . the iris. The most differentiated tumors contain bouquet-like aggregates of relatively bland neoplastic photoreceptors called fleurettes. similar to primitive vitreous (Fig. 66417308 : ¸Ÿ±U 24 ¥°Q . Retinoblastoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Extensive areas of necrosis often leave only a few perivascular cells intact. and although they may evolve into retinoblastoma. The tumor consists of bands of thicker cells corresponding to primitive medullary epithelium and flat cells lining cystic spaces filled with vitreous-like fluid placed abluminally. Ominous prognostic signs are optic nerve. Less frequently the neuroblastic cells form Homer Wright rosettes that lack a central lumen and resemble those in neuroblastomas (Fig. Medulloepithelioma of the ciliary body. and orbital invasion. and such tumors may invade the cranium through the optic nerve.

Ophthalmology 93:1643-1647. 1998. Castellarin AA. Arch Ophthalmol 117:736-741. Baerveldt G et al: Glaucoma associated with uveitis. Zarbin MA: Endophthalmitis. 1986. Akhtar S.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Am J Ophthalmol 123:729-741. 1998. Margo CE. Seregard S: Conjunctival melanoma. Sun' Ophthalmol 38:169-192. 1999. Montague P: Gross examination of eyes removed for ciliary body or choroidal melanoma. A populationbased study of non-basal cell and non-squamous cell malignant neoplasms. 1998. Meek K. 1996. Kresloff MS. 1997. Verdick R. 1998. Mermoud A. Berger TG et al: Intraocular coccidiooidomycosis diagnosed by skin biopsy. De Jong PTVM: Prognostic parameters in uveal melanoma: a review.447 Further Reading Albert D: The ocular melanoma story.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Arch Ophthalmol 116:613-616. Sur) Ophthalmol 43:193-224. Sur. Ridgeway AEA et al: Deposits and proteoglycan changes in primary and recurrent granular dystrophy of the cornea. Ophthalmol 41:361-394. Folberg R. Arch Ophthalmol 116:801-803. Sun/ Ophthalmol 41:215-228. 1997. Shields JA. Cree IA. Ophthalmol 41:321-228. Clinicopathologic correlation. Bryan RG: Malignant epithelial tumors of the lacrimal gland. Dunlop AAS. 1996. Tezel G. Margo CE. Edward PD: Clinial and ocular histopathologic findings in a patient with normal pressure glaucoma. 1998. Mooy CD. Arch Ophthalmol 117:310-321. A clinicopathologic study of 21 cases. Arch Ophthalmol 116:674677. Arch Ophthalmol 116:993-1001. Font RL. Mercado G et al: Adenoma of the iris pigment epithelium: a report of 20 cases. Hague S et al: Muitifocal chorioiditis. Sun. 1998. Weingeist T. 1993. Shields CL. Smith SL. Arch Ophthalmol 116:195-198. Seiff SR. Waltz K: Basal cell carcinoma of the eyelid and periocular skin. 1999. 66417308 : ¸Ÿ±U 24 ¥°Q . The 1998 Pan-American lecture. Mulla ZD: Malignant tumors of the eyelid. Moorthy RS. Wax MB. Cunnigham ET.

66417308 : ¸Ÿ±U 24 ¥°Q .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

66417308 : ¸Ÿ±U 24 ¥°Q .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .

some clinicians consider it neoplastic. and other pathogens. 21-I. Such infections may be caused by bacteria. The earlobe is of normal shape but is hot and erythematous. It presents in the form of recurring bouts of inflammation that involve the cartilage of the ear. A. and occasionally keratin squames may even implant in deeper tissues and cause a keratin implantation granuloma (Fig. 21-2). 66417308 : ¸Ÿ±U 24 ¥°Q . angiolymphoid hyperplasia.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Later the anterior surface may assume a cobblestone appearance. Clefts of cholesterol and lipid-laden macrophages are seen on microscopic examination (Fig. and the auricle may undergo atrophy. which shows signs of degeneration. or atypical pyogenic granuloma. the heart. Histologically the ulceration of the acanthotic epidermis extends into the underlying cartilage. Microscopically the lesion consists of granu- lation tissue invading the cartilage (Fig. 21-3). may occur in the ears of patients with hereditary hyperlipidemia. It is also known as benign angiomatous nodule. appears degenerated. and they usually evoke a histiocytic reaction. A scaly ulcerated nodule is seen on the upper part of the helix. In some cases the inflammation is caused by foreign material. albeit rarely. Microscopically the lesion is composed of proliferating capillaries lined by plump. Epithelioid hemangioma is a skin lesion that has a particular predilection for the pinna and the external auditory canal. The collagen in its center shows increased eosinophilia. Keratin deposits may form on the tympanic membrane. Chondrodermatitis nodularis chronica helicis. Deposits may occur in the subcutaneous tissue and in bone. The cause of some inflammatory lesions. is not known. such as chondrodermatitis nodularis chronica helicis or relapsing polychondritis. Surgical resection is recommended because spontaneous regression may occur. Infections may be acute or chronic. usually in the superior portion of the helix (Fig. 21-5). the larynx. viruses. whereas others think that it is a form of chronic inflammation. Solid plugs may fill the external canal (keratosis obturans). Chondrodermatitis nodularis chronica helicis presents as a small painful nodule on the auricle. Antibodies to type II collagen may be demonstrated in the blood but their significance remains unknown. occasionally multilayered endothelium. eosinophils. and the cartilage itself shows signs of degeneration. and surrounded by loose connective tissue infiltrated with lymphoid cells. such as people with acquired immunodeficiency syndrome (AIDS) and those with debilitating diseases and malnutrition. Grossly it appears as small red or reddish-blue nodules or plaques that tend to coalesce and obstruct the external auditory canal. and the eye. Xanthomas. The ground substance of the cartilage becomes more acidophilic and stains more deeply with periodic acid-Schiff.450 INFLAMMATORY LESIONS OF THE EXTERNAL AND MIDDLE EAR Infections of the external and middle ear are common. Relapsing polychondritis is a multisystemic disease that often involves the ear. Keratin plugs form from cells that exfoliate from the skin of the external canal. and mast cells (Fig. The pathologic changes they cause do not differ from those that are induced by similar infections in other anatomic sites. and is surrounded by granulation tissue and chronic inflammatory cells. The perichondrium of the underlying cartilage is inflamed. such as keratin or cholesterol crystals deposited in tissues. macrophages. Microscopically the nodule usually shows ulceration with pronounced irregular acanthosis at its margins. Its nature is a subject of controversy. 21-1). The cause of this lesion is not known. They are more common in children and in some populations that are at greater risk. which are deposits of cholesterol.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 21-4). A B Fig. B.

Epithelioid hemangioma of the pinna. Chronic otitis media. Fig. Cholesterol granulomas often are formed from lipids released Fig. Fig. Fig. which normally are not found in the middle ear (Fig. 21-7). Granulation tissue may be so extensive as to form polyps or protrude through the perforation of the tympanic membrane. 66417308 : ¸Ÿ±U 24 ¥°Q . 21-8). The patient had type V hyperlipoproteinemia. and it may show surface irregularities and bulges (Fig. 21-6. The lesion consists of blood vessels lined by plump endothelial cells and loose stroma infiltrated with lymphocytes. 21-6). Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . and such fibrosis may replace normal middle ear elements and extend into the bone (Fig. Relapsing polychondritis. 21-4. 21-5. 21-3. The mucosa of the tympanic membrane may be thickened and congested. and macrophages. eosinophils. Keratin implantation granuloma of ear canal. Repeated bouts of acute otitis media may progress to chronic otitis media. The tubotympanic region and mastoid air cells most often are involved. The cartilage is invaded by granulation tissue. Granulation tissue ultimately matures into dense connective tissue. Keratin has evoked a granulomatous reaction with foreign body giant cells. Cholesterol clefts are seen between bone trabeculae.451 Otitis media is a common disease in children but it also may occur in adults. The tympanic membrane appears thickened and bulges irregularly. which is characterized by a variety of pathologic changes. which usually is devoid of tubuloalveolar glands. 21-2. proliferates and gives rise to tubuloalveolar glands. The epithelium of the middle ear. Xanthoma of mastoid bone.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº .

Fig.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig. Tympanosclerosis develops as a result of the deposition of aggregates of hyalinized collagen on the tympanic membrane. Squamous epithelium extends downward into the stroma.452 from the blood and other cells. Squamous epithelium forms keratin-filled cysts (Fig. The adjacent middle ear stroma shows chronic inflammation and glandular metaplasia. 66417308 : ¸Ÿ±U 24 ¥°Q . The lesion is lined by keratinizing squamous epithelium. Tympanosclerosis. The tympanic membrane consists of laminated hyalinized material and metaplastic bone. it is assumed that it results from proliferation of irritated squamous epithelium within the confines of the middle ear. 21-9). Chronic otitis media of the middle ear. They may be congenital or acquired. Fig. Cholesteatoma. Low-grade otitis media in an AIDS patient. AlFig. Although the precise pathogenesis of cholesteatoma is not known. The mastoid air cells contain connective tissue and tubuloalveolar glands. 21-7. It may have a laminated appearance and may contain metaplastic bone (Fig.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Cholesteatomas are space-occupying lesions of the middle ear that are composed of keratin-forming squamous epithelium. Acquired cholesteatomas often are found in ears affected by chronic inflammation. Ruptured cysts may evoke a foreign body giant cell reaction and intensify the chronic inflammation. The connective stroma contains newly formed tubuloalveolar glands (glandular metaplasia of the middle ear). 21-8. 21-9. 21-10). Fig. 21-10. 21-I I. Cholesteatoma.

but this usually occurs in later stages of disease. which reach the inner ear hemotogenously. 21-12). Fungal diseases are rare and most often are found in immunosuppressed persons. osteopetrosis. Fig. bacteria. 21-11). The damaged inner ear shows marked cochlear hydrops (Fig. Cryptococcal infection in AIDS. Viral infections. it may extend into adjacent structures and it often infiltrates the mastoid air cells (Fig. and phloxine.453 though the squamous epithelium that lines cholesteatomas is composed of benign cells. Fig. and in the preimmunization ear intrauterine rubella virus was a common cause of congenital deafness. These changes may be classified as (1)-developmental malformations. The preparation was stained with osmic acid. presbycusis.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Surface preparation of perfused cochleas stained for light microscopy shows considerable losses in the outer hair cells. 21-14. Paget disease. 21-14). 66417308 : ¸Ÿ±U 24 ¥°Q . spiral ganglion cells. (3) infections. but they also may be hematogenous. 21-12. Ossification is accompanied by prominently bluish globuli ossei (calcified cartilage cells). 21-13. Presbycusis. Degenerative changes in at least four different sites in the cochlea have been implicated as the pathologic basis for the hearing loss. and basilar membrane. Presbycusis is the hearing loss that occurs in aged persons and which cannot be ascribed to any cause other than old age. Fig. The numbers of spiral ganglion cells are reduced. with lengthening and thickening of stereocilia emanating from some surviving outer hair cells (Fig. Surface preparation of the middle coil of the cochlea show a diminished number of outer hair cells and giant stereociliary degeneration. or fungi. and (4) idiopathic conditions of unknown etiology and pathogenesis. and otosclerosis. such as Meniere disease. 21-13). The developing ear is especially susceptible. Fungi fill spaces in the basilar membrane that normally are occupied by nerve fibers. These sites are the hair cells. are an important cause of hearing loss. PATHOLOGIC CHANGES OF THE INNER EAR Pathologic changes of the inner ear cause deafness and loss of balance. Suppurative labyrinthitis or petrositis usually is a complication of local bacterial infections that spread by contiguity to the inner ear. 21-15. Rubella infection. Cochlear hydrops is the main consequence of this fetal viral infection associated with deafness. Alcian blue. Infections of the inner ear may be caused by viruses. (2) ototo)ic conditions. stria vascularis.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . such as those who have AIDS (Fig. possibly secondary to the primary atrophy of hair cells. Fig.

21-16). Otosclerotic deposits not associated with hearing loss have been noted at autopsy in 10 percent to 13 percent of adults and are found in the otic capsule bone anterior to the oval window.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . Otosclerosis is a common but poorly understood focal lesion of the otic capsule that is found principally in relation to the cochlea and footplate of the stapes. 21-15). Otosclerosis. Basal cell carcinoma. 21-20. Fig. At autopsy the focus of otosclerosis appears well demarcated and pink because of prominent evenly distributed blood vessels (Fig. 21-17. Fig. Microscopically. Conductive deafness occurs in a smaller number of such persons as the extension of this otosclerotic lesion to the footplate of the stapes. Ceruminous adenoma. 66417308 : ¸Ÿ±U 24 ¥°Q .·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . Fig. 21-16. 21-17). The tumor is composed of glands lined by a bilayered epithelium. Some nests contain round hyaline globules. 21-19. Fig. It is an important cause of hearing loss. Cylindroma of the external canal. Otosclerosis. Tumor nests in hyalinized stroma are arranged in a jigsaw puzzle—like pattern. Lobules of basal cells are found in the upper dermis. which may be traced to changes in the periosteal and endochondral part of the labyrinth (Fig. otosclerotic foci are made up of trabeculae of woven bone with abundant osteoblasts (Fig. Paget disease is a disease of unknown origin that primarily affects bones. Microslice of temporal bone shows a hypervascular focus of otosclerosis adjacent to the cochlea. The cells have uniformly round nuclei and show aprocrine secretion. 21-18.454 Fig. Cystic change in the deeper dermis imparts an adenoid cystic appearance to the tumor. Otosclerotic foci composed of woven bone involve the footplate of the stapes.

Ceruminous adenoma is a benign tumor of the ceruminous glands. The cytoplasm of tumor cells contains acid-fast fluorescent pigment similar to that found in normal ceruminous glands.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 21-21. is the most common tumor of the inner ear. Groups of epithelioid cells are surrounded by sustentacular cells in a typical "Zellballen" appearance. although benign. Microscopically it is composed of a small tubular gland with a back to back appearance (Fig. Malignant ceruminous gland tumors are rare. 21-21).A solid or trabecular arrangement may result in apparent loss of the glandular pattern. Tran LP. Histologically it is composed of a rounded mass of small. Squamous cell carcinoma of the external ear accounts for 7 percent of all squamous cell carcinomas of the head and neck. meningiomas. Squamous cell carcinoma is the most common malignant neoplasm of the middle ear. Neumann HPH. Selesnik SH: Benign lesions of the external auditory canal. Kuhel WI. Fechner RE: Middle ear adenoma. 1984. which is bilateral in 10 percent of cases. 21-22). Paraganglioma. Tumors of the Middle Ear Adenoma of the middle ear is a rare benign tumor arising from the metaplastic glands that form from the inner ear epithelium as a result of chronic inflammation. Adenoma of the middle ear. It typically occurs on the sun-exposed pinna and is rare in the auditory canal. and rhabdomyosarcomas are rare. It is a papillary low-grade adenocarcinoma (Fig. Mills SE. hemangiomas.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 21-23. Low-grade adenocarcinoma of the endolymphatic sac. Fig. Fig. Cylindroma is a benign tumor that occurs in the external canal. Selesnik SH: Cancer of the external auditory canal and temporal bone. Further Reading Kempermann G. 1996. 66417308 : ¸Ÿ±U 24 ¥°Q . 1998. Other middle ear tumors are neuroendocrine adenomas or low-grade malignancies (carcinoids) and paragangliomas. Otolaryngol Clin N Amer 29:827-852. No myoepithelial layer is seen. 21-22. 21-18). darkly stained cells that fit together in a jigsaw puzzle—like pattern (Fig. Low grade adenocarcinoma of probable endolymphatic sac origin may be associated with von Hippel-Landau disease. The cells are cuboidal or columnar. A cytologically uniform neoplasm displaying a variety of architectural patterns.455 NEOPLASMS Tumors of the Outer Ear Basal cell carcinoma is the most common neoplasm of the ex- ternal ear. Histopathology 33:2-10. Am J Surg Pathol 8:677-685. Grundfast KM. 1996. 21-20). 21-19). Volk B: Endolymphatic sac tumours. Other tumors are rare. Fig. The tumor forms papillae projecting into spaces filled with proteinaceous material. It is identical to basal cell carcinoma in other sites (Fig. Tumors of the Inner Ear Acoustic neuroma. it lacks a definite capsule and is composed of regular glands lined by a bilayered epithelium (Fig. Paragangliomas have a typical lobular " Zellballen" appearance in which the main cells are surrounded by sustentacular cells (Fig. The luminal surface of tumor cells shows cytoplasmic projections. Glandlike spaces are filled with the same material. The tumor is composed of small glands arranged in a back to back pattern. Otolaryngol Clin N Amer 29:807-826. 21-23) reminiscent of choroid plexus papilloma. Hume CR. Microscopically. Papillary adenocarcinomas. and the lumina may contain secretions.

269f of stomach. 267-268 clear cell of ovary. 113f Ameloblastoma. 51f Acetaminophen. 152. 243f Acral lentiginous melanoma. 268f 269f staging of. 199. 1831 pleomorphic. 210. 50. 441f Agenesis gonadal. 418f 419f Amebiasis. 410. 248f odontogenic. 154f Alcoholic liver diseases. 357f Ameloblastic fibroma. 213-214. 268. 258t renal. 453f low-grade otitis media in. 138f 139 of pancreatic ducts. 173f lactating. 197f pituitary. 200f Adrenal masses. 321 myocardial. 781 Acute stress erosions. 201d Adrenoleukodystrophy. 198. macronodular hyperplasia of. 352f 353 Alzheimer disease. 328. 202f 203 Adrenocortical disease. 455. 430f 66417308 : ¸Ÿ±U 24 ¥°Q . 242. 346 Alveolar soft-part sarcoma. 112f Adenomatous hyperplasia. 329f Acute Iymphoblastic leukemia. 202. 116f 117 Acoustic neuroma. 201f Adrenal cortex diseases of. 331-333 ADPKD. 199-201 syndromes. 265. 184f tubular. 265. 430. 418. 250. see Atypical intraductal hyperplasia Adnexa. 266f Adenosquamous carcinoma. 276f 277 of ductal origin. 269f Adenocarcinoma acinic cell. 104t psoriasiform dermatitis of. 210. mucinous. 188-190. 135f in tubular adenoma. 201-203. 1 immune-mediated. 16f pyogenic. 392f Acinar cell carcinoma. 16. 117f mucinous. 268. 250 blunt duct. 130. 268f Adenofibroma. 117. diffuse. 455 Acquired immunodeficiency syndrome cryptococcal infection in. 435-446 Adnexal tumors. 199-201. 122. 268. 268f villoglandular papillary. 114f prolactin cell. 151.456 INDEX A Abnormalities. 68f in pleomorphic adenoma. 112. 298. 229t Adamantinoma. 287 positional. 153. 430. 200f diffuse. 78f classification of. 277f Adenoid basal cell tumors. idiopathic. 277 mullerian. 198 Adenoacanthoma. 271f Adenosis. 251f atypical. 229f toxic. 356f Acid maltase deficiency adult form. see Acute myeloid leukemia Amnion rupture. 78. 105. 173f Adenomatoid malformation. clear cell adenocarcinoma in. 139. 150f brain. 410. 58. 201f aldosterone-producing. 261-263. 249 Adenoid cystic carcinoma. 51f Adenomatoid tumors. 201-203. 298f of middle ear. 132f hepatic. 203-206 hyperplasia of. 67f Alveolar rhabdomyosarcoma. 298. 200f in Cushing disease. congenital cystic. 150. 114. 296 sclerosing. 401f AIDS. 210f Agyria-pachygria complex.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ .nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 172. 28Sf cystadenocarcinoma. 116f 117 of cervix. 161. 174. 114f prostatic Gleason grading system of. 150f 156. 253. 130 Amelia. 248. 271. 255f 255t Adenocarcinoma-cont ' d prostatic-cont'd variants of. 268. 161 f hyalinized trabecular. 174. 198-203 hyperfunction of. 175f ADH. 172. 118f 119f low-grade of endolymphatic sac. 298f 299 ceruminous. 189f hepatocellular. encephaloid. 276f 277 well-differentiated. 78. 314-316. 152f Achondroplasia. 52. 104. 277f. 392. 202f ALH. 172. 228-229. 114. see Acquired immunodeficiency syndrome Albers-Schonberg disease. 123f Age-related macular degeneration. 59f Allergy. 392. 249 Adenoma adrenal. 392f infantile form. 278 of vagina. 201f basal cell. 454f 455 corticotroph. 231f 232 Amyloid neuropathy familial. see Atypical intralobular hyperplasia Allergic drug reactions. of pancreas. 268. 356. 205 Adrenal medulla diseases of. 214f Alveolar damage. 153-154 Aldosterone-producing adrenocortical adenomas. 195-196. 258t mixed gonadal.76f Accessory lobe. 116f 117 Adenoid cystic-like tumor. 327 invasive. 114. 296 microglandular. 455f oncocytic (Hurthle cell). 410f cerebral. 139. 441. 183f 184. 199. 199. 248. 118. 401. 105f AML. 430f hereditary. 289 Amniotic fluid. 115f 249 with bizarre nuclei. 409d Acanthocytosis. renal. 410f cholangitic. 277. 185f follicular. 327. 157f lung. 139f of uterus. 74. I90f of breast. 199. 288f. 139f villous. 316f testicular. 451. 200f nodular. 268. 250. 184f frequency of. 68. 201d Adrenal gland. 380. 53f Amyloid. 154. 175f Acinic cell adenocarcinoma. 134. early. primary pigmented nodular. 54. 188. 173f peripheral. 268. 139f metastasis from. 184. 202. 198f Aganglionosis. 184. 55f Munro microabscesses. 199. 2691 endometrioid. 190. 174f endometrial. 268 villoglandular. 277. 228-229. 409. 138f 139 adenocarcinoma in. 42 Alport syndrome. 198-199 Adrenocortical tumors. 269f with squamous differentiation. 285. 250. pulmonary. 203. 151f Amebic colitis. 124 Acute tubular necrosis. 199f infectious. 154f Alcoholic hepatitis. 199-201. see Autosomal dominant polycystic kidney disease Adrenal adenoma. ocular. 455f polymorphous. 79f Acute myeloid leukemia. 455. 174. 201-203. 56 Alveolar proteinosis. 277f of esophagus. 328f Actinic keratosis. 265. 199. 202f Adrenocortical carcinoma. 66. 251f endometrial. endometrioid. 112. 200f 201 Adrenocortical hyperplasia. 173f parathyroid. aspiration of. 265f from DES exposure in utero. 3811 Addison disease. 254t of rete testis. 50. 201f adrenocortical. 190f intraductal papillary mucinous. 296 vaginal. 203f Adrenalitis f autoimmune. 201-203. 265f 266f of colon. 190f papillary. 201-203 Adrenogenital syndrome. 210d Abscesses biliary hepatic. 112f unicystic. 453. 262f Adenosarcomas. 356 Alcoholic cirrhosis. 172. 248f serous papillary. 112. 198f 199 Adrenocortical adenomas. 190. 452f oral manifestations of. 139. 357. 150. 200f Adrenocortical insufficiency. see also Anomalies placental.

32f hyperplastic. 8f degenerative calcific. 133 Bacterial arthritis. 27f Balloon cell degeneration. 419f prostatic. 76f 77 peripheral blood smears in. 77f. 36f ventricular. 248 spinal muscular fascicular. 363 Arthropathies. 422f of pons. 396f glaucomatous retinal. 410f Ball valves. 426. 259f Anemias. 420. 212-213. 411f fungal vasculitis of. 363 crystal-induced. 324f lentiginous junctional melanocytic nevus with moderate architectural disorder and. 140. 53f Asthma. 140 Analgesic abuse nephropathy. of aorta. 103f Aplasia. 35 berry. 129-130. 222 Anaplastic astrocytoma. 420f 421f denervation atrophy caused by. 422f cystic. 35f retinal arterial macroaneurysms with hard exudates. 363 Bacterial cholangitis. 80t sickle cell. 410-411. 124. 34f. 324f minimal. 140 Anal intraepithelial neoplasia. 14f Aortic valve bicuspid. 4. 324. 140 malignant. 36. syphilitic. 198. 396f Anal carcinomas. 103. 396. 212f Autosomal recessive polycystic kidney disease. 9f Aspergillosis cerebral. 32 Arteriosclerotic leukoencephalopathy. 50 of upper digestive tract. 83f Amyotrophic lateral sclerosis. 102f Anovulatory cycle. 38. 52. 76f 77. 34f 35 Atherosclerosis. 363. 130. 74f 75f classification of. 140. 422. 364f 365f 366f seronegative. 396. 364 tuberculous. Paget disease of. 102-103 of esophagus. 122 renal. intersex syndromes affecting. 74. 140f vulvar intraepithelial neoplasia with. 12f on chronic rheumatic endocarditis. 210. 64. 325-326. 409. 396. 1lf on chronic healing endocarditis. 396. 397f Atypia. 198f 231f 232 of heart. 136. 58f Arteriosclerosis. 6. 7d. 94f Angiodysplasia. 104. 397f infantile. cytologic lentiginous junctional melanocytic nevus with minimal architectural disorder and. 392 Androgen insensitivity. 79f Autoimmune adrenalitis. neonatal. 324f severe. 301f Atypical intraductal hyperplasia. 400f Aneurysmal bone cysts. 93f Backwash ileitis. 7f chronic rheumatic endocarditis of. 118f 66417308 : ¸Ÿ±U 24 ¥°Q . 313-314 Bacterial meningitis. 19f renal. 34f 35. 20. 301. intestinal. 11. 7d congenital. 75f-76f pernicious. 324. 35. 261-263. 324f moderate.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 64d Asbestosis. 141f types of. 194. 150f Bacterial endocarditis.' ATN. 78f tissue changes in. 438f dissecting. 281f Anomalies bronchial. l if dissecting aneurysms of. 74-77. 410 of skin. 344. 125f Angiofibroma. 265f Angiosarcoma. Takayasu. 426. 3f Atrophic thyroiditis. 419f neurogenic. 34f. 342f 343 Annular tubules. 6. 12f Bacterial infections acute. 59f Astrocytic tumors. 264. 75f refractory. 325f Atypical ductal hyperplasia. 396. 258t Appendicitis. 239 Anaphylactoid or rheumatoid purpura. 324f lentiginous junctional melanocytic nevus with severe architectural disorder and.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 34f Atherosclerotic aneurysms. 78f Anencephaly. 103 placental. 74t hemolytic. 35 atherosclerotic. 439f granular. 81f B-cell lymphoma large cell immunoblastic. 21d severe. 380-383. 408 Atherosclerosis—cont ' d coronary. 136. 35. 144. 103 of tongue. 437. 37f Aphthous ulcers. 409. 301. 240f 241 Apparent females. 224-225 a 1 -Antitrypsin deficiency. due to dilatation of aortic root. 145f Anus. 410. 130-132 mutinous cystadenoma of. 155f Autoimmune liver diseases. 439. 35f Aortic insufficiency. 4d developmental of lungs. 118. 325f 326f junctional melanocytic nevus with. germ cell. I95f Andersen disease. 438f syphilitic. 213f Axonal regeneration. 324. see Acute tubular necrosis Atrial septal defects. 149-150 of nervous system. 324. 82. 74. 74. 13. 419. 44. 78. 35f diabetic microaneurysms of retina. Ludwig. 344f Angiomyxoma. 422f Anaplastic carcinoma. noninfectious. 51f of teeth. 150. 137f Architectural disorder compound melanocytic nevus with. 137f tumors of. 74. 58. 155-156 Autosomal dominant polycystic kidney disease. 65f Aschoff bodies. 11f Aortitis. 407. 155. 6. 155 Autoimmune hepatitis. 35. 32 hyaline. 50. of cerebellum. 141f Anal gland carcinoma. 80. 9. 301f Atypical intralobular hyperplasia. 111 f with dysplasia. 58. 396f olivopontocerebellar. in child. chronic. 38f Arthritis bacterial. 437. 301f 302 Auer rods. S2f Atheroma. 426. 324. sex cord stromal tumors with.457 Amyloidosis. aggressive. 110. 419. 364-367 Asbestos. 20f 21f outcomes of. 427f Axonopathy acute. 261f Anti-glomerular basement membrane disease. 18. 10. 427f chronic. 20. 12. chronic. 188 Atrophy denervation. 45f Angioleiomyomas. 281. 141f Aorta coarctation of. 92. 36 Aspiration of infected amniotic fluid. 74f bone marrow changes in. plexogenic pulmonary. 140 benign. 64. 422. 163. 32. 409f Arteritis. 422. basaloid type. 12. 50 conotruncal. 6. 212. 422. 52. 13. 409f multisystem. 102. 199f Autoimmune chronic hepatitis. 32. juvenile nasopharyngeal. 400. 324. 301-302. acute. 92 T-cell rich. 104f Angiocentric lymphoma. 301f 302 Atypical lobular hyperplasia. 287 positional of gastrointestinal tract. 24f Angina. 400-401. 14f Aortic stenosis. 2. 131f Appendix inflammation of. 35. 199. 324. 444 Barrett esophagus. 400f ARPKD. 77. acute. subcortical. 32-35 forms of. of thyroid. 422 Astrocytoma anaplastic. 422f Atelectasis. 74-77 aplastic. 360-361 rheumatoid. 364-366. 381f Aneurysms. 301-302. 140. 363f viral. 35f subarachnoid hemorrhage caused by rupture of. 407f cirsoid. 210d pulmonary. 325f Arnold-Chiari malformation. 24. 263f 264 Anal tumors. 9. 427f B B-cell lymphocytic leukemia. 32f 33f hypertensive. 2 fossa or secundum. 140. see Autosomal recessive polycystic kidney disease Arteriopathy. 94. 35.

306 bronchioloalveolar. 278. of thyroid. 32. 163. 161-162. 69f of cervix. 331 breast immunohistochemistry of. 450. 380-383. 175f adenoid cystic. 51f Bronchus. 290. 50f Bronchopneumonia. 68. 296d fibrocystic changes. impact vs nonimpact. 74. 296. 454f 455 types of. 374f degenerative diseases of. 69f of small intestine. 367-383 Paget disease of. 354 fibrous lesions of. 357-359 developmental disorders of. 278f Bronchial anomalies. 373-375. 52. 381f mastoid. 330f 331 features of. 140. 249f Berger disease. 263. 378-379. 363-364 inflammatory diseases of. see Urinary bladder Blastoma. 306 cribriform. 248-250. 268. 346 Botryoid sarcoma. Monckeberg medial. 306-308 noninvasive. 222 Berry aneurysms. 118. 60. 74f 75f Bone marrow-coned normal adult. 193f features of. 68. 285. 246f 282. 195f basal cell. 304f infiltrating lobular. 305f 305t histologic types. 267f cholangiocellular. 118f embryonal of ovary. 157f Bile lakes. 13. 331 Becker muscular dystrophy. 349-350. 136. 202f 203 anal. 388 Becker nevus. 332f 333 Blunt duct adenosis. 116f 117 early. 13f Carcinoid heart syndrome. 303-305 variants of. 379f infections of. 54. 61f Bullous keratopathy. "chicken wire. 196d Call-Exner bodies. see also Adenocarcinoma acinar cell. 308f of endometrium. 16lf 162f Hiirthle cell. 35. 401f perinatal lesions. 332f 333 cellular. 118f follicular. 156. chronic. 69f goblet cell. 292f features of. 317f Burkitt lymphoma. 303t immunohistochemistry of. of pancreas. 277f epithelial-myoepithelial. 33f Calcifications. adenoid. 331 of outer ear. 380-383 locations of. pseudophakic. 113f Calcium balance. 174. 245. 377-378 genetic disorders of. 305. 306f intraductal papillary mucinous. xanthoma of. 118. 136f strum!. 328. basaloid type. 405f Butterfly rash. see Benign prostatic hyperplasia Brain circulatory disturbances of." 405. 50 Bronchial carcinoid. 74f tumors. 163f choriocarcinoma. extralobar. 118f Basal cell adenoma. 369-370 Bone marrow changes in anemia. 305. 298-308 Breast carcinoma grading of. 306 Brenner tumors. 403-405 Brain abscesses. Bizarre leiomyoblastoma. 305. 146-147 diseases of. 173f invasive 66417308 : ¸Ÿ±U 24 ¥°Q . 141f anaplastic. 392-393 Carcinoid heart disease. 451f metabolic diseases of. 141f anal gland. 70. 410-411 " Cannonball " lesions. 30 endothelial tumors of. 438. 31-39 diseases of. 296. 440f Bullous pemphigoid. 248-250. 279f Campylobacter jejuni infection. 407. 191-193. 278 colloid. 195. 156. 309f infiltrating ductal not otherwise specified. 156. 135d hepatocellular. 306-308 noninvasive. 54f Bronchopulmonary dysplasia. 283. 70. 407f Berylliosis. 438f Caplan lesions. 71f Capillary hemangioma. 14f Calcific sclerosis. 303-305. 367 in coal workers ' pneumoconiosis. 53f Bronchopulmonary sequestration. degenerative. see Carcinoma Candida albicans infection. 307f cystic. 318f C Calcific aortic stenosis. 409. 117f of esophagus. squamous cell carcinoma of. 331 Basal cell hyperplasia. 118. 303-305 invasive variants. 195. 404f. 307. 356-357 diseases involving. 356-357 giant cell tumor of. 64. in young child. 35f subarachnoid hemorrhage caused by rupture of. 157f Biliary tract circulatory disorders of. 156.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . pulmonary. 440. 150 Biliary obstruction. 295-309 development of. 318. 13. 345. 379 Bone tumors. 409-410 injuries to.458 Barrett esophagus-coned with early carcinoma. 392f Breast. 330f 331 of outer ear. 248 atypical. 156f primary. 405 infarcts of. 248. 146. 345f Bladder. 249f variants. 302 variants of. 359. 410. 269f of ovary. 245f endometrial. peripheral. 68. 404d " morocco leather" surface. 357-359 neoplasms of. 303-305. 64f Bile infarcts. 134. 192f of gallbladder. " 375 Calcifying epithelial odontogenic tumor. 430 Canavan-Van Bogaert-Bertrand disease. 296 Bone(s). 60 Bronchiolitis obliterans. 66. 304f nuclear atypia in. 380-383 Bone cysts. 359f Budd-Chiari syndrome. adamantinoma of. 380. 415. 112. 61f Bronchogenic cysts. 60. 52. 137f pulmonary. 140. 349t benign. 74-77 Blood vessels. 282 of testis. 278. 369. 95f ovarian. 172. 155f Biliary hepatic abscesses. 268. 196d Calcium metabolism. 266. 308. 69f Bronchitis. 68. 363-367 long. 190t infiltrating ductal. 13. 174. 150. 276f 277. 403. 62. 303. 355-383 chondromyxoid fibroma of. 116f 117 adenosquamous. 156. subpleural. 13f Carcinoid tumors bronchial. 341t Blue nevus. 165f gastric. 402 infections of. 329f BPH. 405-409 edema of. 194. 359f 360f tumor-like conditions of. 115f 249 Basal cell carcinoma. 68. 68f Brown tumors of hyperparathyroidism. 401. 50. 316. 68. 284f Carcinoma. 410f Branching enzyme deficiency. 70f Blood smears. 157f causes of. 244. Barrett esophagus with.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . aneurysmal. retinal. 117. 268. 146f Bullae. 164. 415f Cancer. 266f Bowen disease. 150f Biliary infections. adenoid. 291t clear cell of breast. 323 Benign prostatic hyperplasia. 359-360. 249 Basosquamous carcinoma. not otherwise specified. 297f lesions of. 305f invasive. 69f Bronchiectasis. 94-95. 114. 248f 249f atropic variant. 249 Basal cell tumors. 302-303 categories of. 66f Bronchioloalveolar carcinoma. 157f Biliary cirrhosis. 193. 363 Botryoid rhabdomyosarcoma. 294 tumors of. 381f Bone-forming tumors. 142 Binswanger disease. 302-303 variants of. 50. 63f Carbohydrate storage diseases. 268t endometrioid. 401-402 trauma of. 156. 285f " Burst lobe. 156t extrahepatic. 175f adrenocortical. 308. 76f . 409f Bite cells. 309f invasive. 392-393. 150-151 ascending. 308. 369d Borrelia burgdorferi infection. 136. 155-156. 266. 341. 367-369 malignant. 454f 455 basosquamous.

of ovary. 349-350. 155f primary sclerosing. 18. 408-409 chronic. 267f CIN Il.459 66417308 : ¸Ÿ±U 24 ¥°Q . 442 Cavernous hemangioma. 36. 117f 332f 333 secretory. 128. 18d congenital. 193-194. 244. 112f of vocal cord. 387f Cerebellar infarcts. 163f Cholangitic abscesses. 266. 194f 306. 374f Chondromatosis. 377f dedifferentiated. 245. 428-429. 84. 267f Cervix. 275. 454f 455 Cervical intraepithelial neoplasia. 46f of skin. 195f of thyroid glandoncocytic (Hiirthle cell). 190r. 2d Carditis. 408. 242. 174. 350. 96 "Chocolate" cysts. 236f 237 verrucots anal. 375-376. 450f Chondroid. synovial. 308. 289f . 268f of vulva. 264. 195f of urinary bladder. 174f 175f papillary invasive. 47f vulvar. 18d secondary. 350. 17f causes of. 85f Cataracts. 163. 118f hilar. 117. 289-290. 436f Charcot-Leyden crystals. 428-429 type I. 267. granulomatous giant cell vasculitis of. 263f 264. 45-47. 302f lobular. 47. 411f Cerebral cortex. 266. 410f Cerebral arteries. 308f small cell of esophagus. 267. 308f metastatic. 192f parathyroid. 307f undifferentiated of pancreas. 164. 47f of nasal vestibule. 267. 156. 442f 443 types of. acute. 442f posterior subcapsular. 68. 307f of large intestine. 112. 19f causes of. 47. 450. 413. 386f Central nervous system degenerative diseases of. 102. 263 of stomach. 408f Cerebral ischemia. 18d Cardiovascular diseases. 302. 376 extraskeletal myxoid. 409f Cerebral infarcts in middle cerebral artery distribution. 9. 267. 153f Cholesteatomas. 85f hyaline vascular type. giant congenital. 237f vulvar. 266-268 Chagas disease. 59f Charcot-Marie-Tooth disease. 442f anterior subcapsular. 308f serous. 375. 386. 17. in infancy. 386. 134f 135f teratocarcinomas. 118. 308. 307. 193. 194. 245f thymic. 413f 414f Centronuclear myopathy. 308f sebaceous. 236f 237 tubular. 150f chronic nonsuppurative destructive. 17 types of. 112 verrucous. 350. 452f Chondroblastoma. in child. 165f follicular. 68f invasive of cervix. 375 "Chicken wire " fibrosis. 263. 375 Chondroma. 154f Children. 194. 193f features of. 442. 18. 17-18 dilated. 184 polymorphous low-grade. 18d hypertrophic. 243f of urinary bladder. 376-377. 437. 126. 6-9. 381f Chorioamnionitis. 2. 306. 408. 250-253. 263-264. 16. tumors of. 174. 246 Chlantydia infection. 264f yolk sac. 409. 398 metabolic diseases of. 306-308 invasive papillary. 308. 265 variants of. 46f oncocytic (Hiirthle cell). 308. 376f classic. 36f Cerebral aspergillosis. 267. 308. 117. 306-307. 164f chronic. 248. 442-443. 302-303. 303-305 of cervix. 375-377 Castleman disease. acute. 380. 54 Celiac disease. 197f pituitary. 164f acute. 150. 16f Chalazion. 275f signet-ring. 127f " Chicken wire " calcifications. 421-426 classification of. 422. 164f mucinous (noncystic) of breast. 376 Chordoma. 307f variants of. that affect eyes. 84. 17. 47. 68f of urinary bladder. 47f of vulva. cystic astrocytoma of. 308f of large intestine. see also Infancy cystic astrocytoma of cerebellum in. 284. 164f chronic active. 68. 190t. 190t of prostate. 422. 422f Cerebral abscesses. 372-375 malignant. 154. 191f variants of. 68. 302. 85f plasma cell variant. 282f Carcinoma in situ ductal comedo type. 263 Carcinosarcomas. 442-443. 99f thyroid. 418-420 denervating diseases of. 234f of rete testis. 117 nasopharyngeal. 415. 155. 374f Chondrosarcoma. 139-140 of pancreas. 442f cortical (soft). 251f 252f renal cell.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 164. 237. 2 Cardiac tumors. 307f variants of. 68f esophageal. 308. 373-375. 410. 18f 19f primary. rheumatic. 47. 164. 413. periosteal. 263f Cholangiocellular carcinoma. 452-453. 45. 118 with hypercalcemia. 18. 413. 332f 333 Cellular leiomyomas. 84. 422f teratomas of. 277 Cardiac malformations. 413t Central pontine myelinolysis. 267f CIN III. 442. 117f salivary gland—like.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº Carcinoma—cont'd invasive—cont ' d of breast. 436. 382f 383 Chondromyxoid fibroma. 195f Merkel cell. 421d Central nervous system—cont 'd spongy degeneration of. 134. 70. 140. 373. 47f medullary. 328. 408-409 Ceruminous adenoma. 413t neoplasms of. 282. 377. 237. 260 Chloroma. 377f of soft tissue. 7d Cardiovascular shunts. 17 restrictive. 408f old. 174. 164. 112. 9f Cartilage-forming tumors. 375. 408f Cerebellum. 235f of urinary bladder. 128f Cellular blue nevus. 284f of lung. 416t location and age. 3491 benign. 112f of vocal cord. 152. 266. 71f metastatic to liver. 395t diseases of. 303f noncomedo type. granular atrophy of. 375f Chondrodermatitis nodularis chronica helicis. 163. 248f salivary duct. 329f of vagina. 150f 156. 27 Cardiomyopathy. 117. 271 Central core disease. 194. 266. 175f of thyroid. 303f testicular. 235. 117f poorly differentiated of thyroid. 190-191. 376f clear cell. 234. 156f Cholecystitis. 442f nuclear sclerotic. 175f mucoepidermoid. 191. 150. 268f cribriform. 139-140 of larynx. 157f Cholangitis bacterial. 237f squamous cell of bronchus. 308f of thyroid gland. 190t of pancreas. 437t Cardiovascular obstructions. 267f CIN I. 350f variants. 408. 103f Cavitary tuberculosis. 98. 264f of larynx. 429f Chemical gastritis. 196. 190t Carcinoma—cont ' d transitional cell—cont'd of renal pelvis. 332f 333 metaplastic. 410-411. 415f toxic diseases of. 141f oral. 164 Cholestasis. 18f 19f causes of. 350f mesenchymal.

106f polycystic kidney disease. 232. 265. 20-24 recanalization. 233 acute. 124f lymphocytic. 232f Cryptococcal infection. 140. 185f " Cotton candy lung. 201d macronodular hyperplasia of adrenal in. 102. 440-441. 319 Conotruncal anomalies. 426f Colon. 440f Congenital heart disease. 35f CIS. 324-325.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 380-383. 446. 172. 60 Churg-Strauss syndrome. 123f Congenital myopathies. 377 Corticomedullary differentiation. 446f CIN. 439-440. 440. 278 Clear cell chondrosarcoma. 213f odontogenic. 151f fissural (nonodontogenic). 261f CML. 6. 443f epithelioid cell type. 132 pseudomembranous. 212-213 polycystic ovarian disease. 156. 233f caused by prostatic hyperplasia. 146f chronic. 106d orthokeratotic. 285f neuroendocrine tumors of. 440-441. 132f eosinophilic. 308f of endometrium. adenocarcinoma of. 377f Clear cell sarcoma. 426f dental. 50. 102f Clostridium difficile infection. 133f 133t. giant. 275-277. 130 Clue cells. 158f Cirsoid aneurysms. 442f Cortical defects. 9. 60. I73f Cysticercosis. 146. 412f Cribriform carcinoma. 240. 275. 291t Choroid plexus papillomas. 183. adenoid. 11f Colitis amebic. 124f Curshman spiral. 140f Congenital aortic stenosis. mucinous. 183f Crotalaria alkaloids. 306 Colloid cysts. 61f 168. 169f Cystic hyperplasia. 199. 390. 105f Cytologic atypia lentiginous junctional melanocytic nevus with minimal architectural disorder and. 132 noninfectious. 158 macronodular. 307. 454f 455 Cystadenocarcinoma. 140. 403. 441f Corneal guttae. 146 Cryoglobulinemia. 124. 324f 66417308 : ¸Ÿ±U 24 ¥°Q . 387t Congestion. 283f Cystic tumors. 233. 436f Conn syndrome. 107f unicystic ameloblastomas. 114 Cystic adenomatoid malformation. see Cytomegalovirus Coal workers' pneumoconiosis. 411f Cystitis. 18. fibrous. 268. 262f 263 radicular. see Chronic obstructive pulmonary disease Cornea diseases of. 324-325. 116f 117 Cystic developmental kidney diseases. 158. 262f Cystic-like tumors. strlmal. mixed. 7d. 4d Constrictive pericarditis. 139. 424f Choroid sympathetic uveitis. 50. 422. benign.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 199. 2-9 Congenital hypertrophic cardiomyopathy. 292f features of. 403. 213. 131f 132f ulcerative. 200f 201d Cushing syndrome. 105. 172. 21f Corrosive esophagitis. 6f Compound melanocytic nevus. 146f Conjunctivitis. 57-58 Cirrhosis. 325f 326f congenital. 51f Cystic astrocytoma. 172 of appendix. 130 ischemic. 18f 19f Congenital hypoplasia. 132. 139f sigmoid. 444f Chronic myeloid leukemia. 6. 133. 158. 35. 276f 277 Cystadenoma of borderline malignancy mucinous endocervical (miillerian). 285. solid. 325f Congenital cystic adenomatoid malformation. 133f Collagenous colitis. 444." 263. 124. 22. 50f "chocolate. 403f Craniopharyngioma. 110. 440f-441f enlarged. 443. 441. 263f colloid. 233. 249 Cystic teratoma. 26f Contraction band necrosis. endometrial. 260. 453f Cryptorchidism. 277f 278 of vagina. 325-326. 21f Coronary atherosclerosis. 139. 132. 403. 107f of pancreas. 154f biliary. 182f 183 Crescentic glomerulonephritis. 402f 403 multicystic renal dysplasia. 377. 233f Cysts aneurysmal bone. 325f Condyloma acuminatum. 102 Cleft palate. 386. 282. 424. 172-174. 439." 60. 218. 249. 132 infectious. 302 Complete transposition of great arteries. 201d Connective tissue disease. 105. 199-201. 109f multicystic encephalopathy. passive acute. 61f " Cotton wool spots. 403f postcontusion angle recession. 6. 233f massive hemorrhagic. 283f Edrinococccusgranulosus. 212. see Carcinoma in situ Clear cell adenocarcinoma of ovary. 436. 158f 159f alcoholic. 444f mixed spindle and epithelioid cell type. 276f mucinous. 403. 21d Coronary thrombus. 403f Contusions. 261-263. 20f 21f outcomes of. 172f I73f 273-275. 290. 308. 159 mucous retention. 8f Congenital cavernous hemangioma. 107. 158f micronodular. 412. 225 Creutzfeldt-Jakob disease. 158. 232f 233 chronic. 233. 184. 249f Crohn disease. 20. 130 collagenous. 25. 324. 132f Collapsing glomerulopathy. 20. see also Large intestine adenocarcinoma of. 200f Cylindroma. 151. 168. 156f primary. 245. 360-361 Curling ulcers. 103f Congenital compound melanocytic nevus. 324-325. 106t of liver. 233. 426. 422f Cystic carcinoma. 325f with architectural disorder. 155-156. 443 Colloid carcinoma. 439-440. 146-147 pulmonary. 426. 146. 20. 442. 403f coup. 50. 20. 105-107 dentigerous. 106d of jaws. 275f 276f of pancreas. medulloepithelioma of. 158t classification of. I39f metastasis from. 260. 440f 441 macular. 440f lattice. 348 Cleft lip. 246f 282. 269f of ovary. 436f 437 Choroidal malignant melanoma. 439f COPD. 140f right. 63f Coarctation of the aorta. congenital. 136. 405-409 gastrointestinal. 155f causes of. 80. 6. 108. 219f " Collar button" configuration. adenocarcinoma of. 130. 232f 233 interstitial. 111f Cortical (soft) cataracts. 62. 381f bronchogenic. 441 Coronary artery diseases of. 307f Cribriform hyperplasia. see Chronic myeloid leukemia CMV. 265f 266f Clear cell carcinoma of breast. 105f dermoid. 224-225 diseases that present as. 437f Coup contusions. 444. 440f granular. 199. 453. 124 hepatobiliary. 102. 154. I37f intestinal. 122. 98f Corticotroph adenoma. 172f serous. 4. 436 chronic follicular. 134f Crooke hyaline. 132-133. 168f parakeratotic. 282. adenoid. 240f Crystal-induced arthritis. 139." 437. 440f Corneal dystrophy Fuchs. 212d Cystic fibrosis. papillary. 51f Congenital glaucoma. 233f pseudomembranous.460 Choriocarcinoma. 23f Contrecoup lesions. 59f Cushing disease. 275-277. 260f anal. 98. see Cervical intraepithelial neoplasia Circulatory disturbances of brain. 224t. 8f Congenital lymphangiectasia. 139f Comedo-like necrotic material. 274f Cystadenoma lymphomatosum. 107. 391f 430 Ciliary body. 80f Chronic obstructive pulmonary disease. 411. 276f mucinous intestinal.

440f lattice. 96f Denervation chronic. 212. 210. in infancy. 441f muscular. 337f Desmoplastic melanoma. I52f-153f 152t Drug-induced myositis. 397f related muscle diseases. 296. 110d Diastolic and systolic disorder. 387d Dystrophy Becker. senile. 448 external (outer) inflammatory lesions of. 361. chronic inflammatory. 60. 395-396. 417-420 of joints. 396f with reinnervation. of brain. 437. 452f inflammatory lesions of.461 Cytologic atypia-cont'd lentiginous junctional melanocytic nevus with moderate architectural disorder and. 61f panacinar (panlobular). 439-440. 414f Degenerative diseases of bones. 39. 316-319 inflammatory. 102-103 Developmental disorders of bones and joints. 453-454 tumors of. chronic inflammatory. 105f Dermatitis psoriasiform. 50 of upper digestive tract. 429. 144. 266f Dieulafoy ulcer. 303f Ductal hyperplasia. 427. 152f Drug-induced liver diseases. 441 Duchenne. 316 Dyscrasias. see Diethylstilbestrol Descemet membrane. 318. 112 Dentigerous cysts. 437. 391f Dermatoses immune-mediated. 283f DES. 177-179. 438f Diaphragmatic hernia. 100 Dilated cardiomyopathy. 265. 324 Dysraphism. 395. 440-441. 47. 229f 230f diffuse. 440. 392. 210 of kidney. 98. 282 of testis. 282. 357-359 calcific aortic stenosis. 14f of central nervous system. 302f lobular. 57 saddle. 316f seborrheic. 450-453 tumors of. 240-241 of nervous system. 300. 297f Ductal papilloma. 312. 259f mixed gonadal. 82t Dysgenesis gonadal. 441 Dejerine-Sottas disease. 110d Meckel diverticulum. 388. 444 hepatolenticular. 450. 356-357 cystic. 212d of female reproductive system. 66. 126f esophageal. 388. 337f Elliptocytosis. 305. 327f Desmoplastic small round cell tumors. 389f limb girdle. 389f E Ear. 427f 428f Dendritic cell sarcomas. cylindroma of. 440f Desmoid tumor. 124. 301-302. 449-455 diseases of. allergic. 301f florid. 1784 179. 126f Drug-induced hepatitis. 431. 110. 16. 388. 303f noncomedo type. 314-316. 400 Dystrophin-sarcoglycan complex. of kidney. 296 atypical. 229. 400-401 of pancreas. 319. 405 Elastofibroma.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº Developmental anomalies of lungs. 316. 98f Dysplastic junctional melanocytic nevus. 386. 324f lentiginous junctional melanocytic nevus with severe architectural disorder and. 74. infiltrating not otherwise specified. 60 centriacinar (centrilobular). 125f Digestive tract. 152. 322f Dermatitis herpetiformis. 178t. 16f Discoid lupus erythematosus. 388 corneal Fuchs. 414 multisystem. 105. 229 secondary. 244f Embryonal carcinoma of ovary. 378 renal. 440f granular. 426-427 segmental. 57. 302. 454f. 392f Degeneration balloon cell. plasma cell. of spinal cord. 312f 313f de Quervain thyroiditis. 198f 199 viral pneumonia caused by. 56. 179. 258t. 351f Desquamative interstitial pneumonia. 300. 18d Diphtherial myocarditis. 300f subareolar type. 388f Ductal breast carcinoma. 321. see Dermatofibrosarcoma protuberans Diabetes mellitus. exposure in utero to. 451. 388. 105-107 Dental tumors. 404f. 220. 17. 259f Dysgerminoma. 396. 288f 289 Echinococcus granulosus cyst. 35. 431. 122. 391f Drug-induced vasculitis. 152. 53f fibrous. 110. 396f Dense deposit disease. 395d Denervation atrophy. 362f retinal. 52. 415. 413-414. 67f 67t 66417308 : ¸Ÿ±U 24 ¥°Q . 338f Dermatomyositis. see also Gastrointestinal tract upper. 288f 289 Edema. 302. 213f thymic simple. 337. 455 Ear canal external. intraabdominal.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 179f classification of. 389f macular. 230f Diabetic microaneurysms. 39f Drug reactions. 400-401. 96. 220f Dental cysts. 386-388 myotonic. 126. 151. 378. 101-119 diseases of. 47f osteofibrous. 186. 213. 319f 390. 210-214 of male' reproductive system. 210-214 DFSP. 346f of vagina. 429f Dementia. 317f Dermatofibrosarcoma protuberans. 59f Dubin-Johnson syndrome. 61f paraseptal or irregular. 300f Duhring disease. proliferative. 242-244. 440f. 325f Cytomegalovirus infection. 17f causes of. 305f Ductal carcinoma in situ comedo type. 60 . 179f Diabetic glomerulosclerosis. 302-303. 266f Emphysema. 401f Darier disease. 455 neoplasms of. 303-305. 396. 266. 318f Dissecting aneurysms of aorta. 362d. see Restrictive cardiomyopathy Diastolic disorder. see Hypertrophic cardiomyopathy Diethylstilbestrol. 179f type 1 (insulin-dependent). 60. 187f Debranching enzyme deficiency. 57f Embryoid bodies. 177-179 of chronic pancreatitis. 418 spongy. 151f Ectopia crossed. 282. 438f Diabetic retinopathy. 418 Demyelinating diseases. 75f Emboli pulmonary. 436f 437 Dandy-Walker malformation. 296. 82-83. 178f 178t type 2 (non-insulin-dependent). 338. 388. 282f Dysplasia Barrett esophagus with. 144f Duchenne muscular dystrophy. 455 inner pathologic changes of. 327. 324. 396. 122f Diverticulosis. 350. 304f nuclear atypia in. 126. 122 of kidney. 179. 346. 258 of gastrointestinal tract. 416-417 Demyelinating polyneuropathy. 168 of urinary tract. 56f D Dalen-Fuchs nodules. 35f Diverticula. 388f facioscapulohumeral. 177 renal lesions of. of retina. 118. 39St stages of. 415f subacute combined. 390. 324. 98f with stromal corticomedullary differentiation. 455 middle chronic otitis media of. 431f Demyelinating polyradiculoneuropathy. 13. 378f keratinizing intraepithelial. 455 keratin implantation granuloma of. 450-453 tumors of. 210f Ectopic pregnancy. 244. 441. 58. 98. 45lf The early amnion rupture sequence. 210d. 149 adrenal. of CNS. 118f bronchopulmonary. 431f Demyelination. 336. 229. 245f Embryonal rhabdomyosarcoma. 316-323 Dermoids.

12. 422-424. 277. 1 l 1 f Esophagus anomalies of. 378. 268t classification of. 181-207. 126f 263 ovarian. 11Of Esophagitis. head of. 297f Fibrohistiocytic tumors. 320f Erythroderma desquamativum. 268. 112f Epulis. 211. 261-263. 270. 67t idiopathic. 12f acute rheumatic. 352f 353 Epithelium. 277f Endometrioid adenofibroma. " 154. 336-337 Fibroblastic tumors. 235. 34f 35 Female pseudohermaphrodite. 277. 10. 74. 110. 270f benign. 437f438f diseases of. 58. 257-293 developmental disorders of. 153. 320. 437t tumors of." 156. 263. 443. 455 Extralobar bronchopulmonary sequestration. of urinary bladder. 172t Exocytosis. 437 fungal. 25. 437f 438f Eye(s). 110. 262f with atypia. 75f Erythroplakia. 259f Femur. 12. 248f classification of. tumors of. 450-453 tumors of. 336f Fatty liver. 336-337. 184f Exstrophy. 241f Epidural hematoma. 110-111 Esophageal tumors. 25t perineurial. 433 periportal hepatic "pipe stem" type. 439-440 Epithelial-myoepithelial carcinoma. 451f Epithelioid leiomyomas. 279 Fibrosis " chicken wire. 454f 455 External ear inflammatory lesions of. 388. 182d. 262f complex (adenomatous). 261-263. 110. 118f with early carcinoma. 345. 320f Erythema multiforme. cylindroma of. complex. 264. 113t of urinary bladder. 139f Familial amyloid neuropathy. 118f carcinoma of. 338. 262f simple (cystic). 176-177 Endolymphatic sac. 162f Fibromas. 372-373. 243t Epididymoorchitis. 258t Feminization. 337f Fibrous histiocytoma. 269t Endometrial carcinoma. multicystic. 28f Epidermal necrolysis. 256 Familial adenomatous polyposis coli. 389f Falciparum malaria. 270-271 low-grade. 269f staging. 279f ameloblastic. 153f Fatty streaks. 276f Endocrine glands. 10f Endocervical (miillerian) cystadenoma. 152f pulmonary forms of. 435-446 changes in systemic diseases. 59f Ependymoma. 277f Endometriosis. 130. 336t 66417308 : ¸Ÿ±U 24 ¥°Q . 271 Epithelioid leiomyosarcomas. 103-104.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 261-263. 361. 113f of salivary gland. 11f on chronic healing endocarditis. 118 Esophageal varices. 317 Epidermal tumors. 289 Fibrinohemorrhagic pericarditis. 316-317. 323 Epicardium. see also specific glands diseases of. 270 Endometrial stromal sarcoma. 112. 411. 261-263. 12f infective. 270f Endometrial stromal tumors. 163f 342f 343 Epithelioid hemangioma. 16. 264f Extramedullary hematopoiesis. 434 inflammation of. 172-174 benign. 154f "onionskin. subacute necrotizing. 298f Fibroblastic lesions. 320. 50. 437-438. 412. 276f 277 well-differentiated. 111f with dysplasia. 238 tumors of. 377. 402f 403 Enchondroma. 130. 317 Erythema nodosum. 11f of mitral valve. 377-378 classification of. 152f Fallopian tubes. 258t Female reproductive system. 336. 341. 41 If viral. 345f Epithelioid sarcoma. 112. 241. 11-12. 139. 235t Epithelioid hemangioendothelioma. 13. 25. testicular. 104. 298. 321 Erythroid hyperplasia. 296. 110. 377 Fibrous dysplasia. 132f Enteritis. 337 Fibrosarcomas. 263-264. 336-337 Fibrocystic changes. 163. 268. 214. benign. 74f Erythroid hypoplasia. 110. 423f Ephelis. 341t Entamoeba histolytica. 26f Fibrinoid necrosis. 67f replacement. 74. 275-277. 51f Extramammary Paget disease. 436-437 systemic diseases that affect. 151. 270. 412. 270 Endometrial adenocarcinoma. 338t Fibrolamellar hepatocellular carcinoma. 405 Epidural hemorrhage. 105f erosive or corrosive. 405. 256 hormonally induced changes. 211f External canal. 243f Endocarditis acute bacterial. 112. 11f fungal. low-grade adenocarcinoma of. 129f Enterobius vermicularis. 408f Ewing sarcoma. 183 Encephalitis herpesvirus. misplaced. acute. see Endometrial stromal sarcoma Etat lacunaire. 455. 430. 383 Eosinophilic myocarditis. 129. 12. 361f Fetoplacental infections. 350. tumors of. 443-446 F Fabry disease. 241 Esophageal diverticula. l l if ulcerative. 110d Esophageal lesions. 377 Fibrous tissue tumors. 382f. 277f Endometrioid carcinoma. 118f diseases of. 378f Fibrous hamartoma of infancy. 10. 450. 373-375. 12t nonbacterial thrombotic. toxic. 102f Facioscapulohumeral dystrophy. 379. 450 of pinna. 118. 111 f Erythema induratum. 117. 328 Escherichia coli infection. 296 Epithelial tumors. metastatic melanoma of. 13f verrucous. 408 Encephalomyelopathy. 104f Erosive or corrosive esophagitis. 10. 374f nonossifying. 59f Eosinophilic granuloma. 17f Fibrous cortical defect. 279. 12. mucinous. " 110 ESS. 414. 443f Extraskeletal myxoid chondrosarcoma. malignant. 339f Fibrous lesions of bone. 268t Endometrial hyperplasia. 12f chronic rheumatic acute bacterial endocarditis on. 1 1 1f reflux. 437. 211 Epithelial downgrowth. 328-331 Epididymis diseases of. 336. 110. 415f Encephalopathy. 113f chondromyxoid. 10. 183 primary. 261-263 intersex syndromes affecting. 336f proliferative. 102. 12f of aortic valve. 248. 156f pericardial. 242. 180 Endocrine pancreas. 172-174 of borderline malignancy. in myocardium. 32. 336. 12f complications of. suppurative. 268. fungal. 215f Facial malformations. 25f Fibroadenoma. 110.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 77f Extraocular tumors. 412f Encephalomalacia. 131f Eosinophilia. 100 " nutcracker. 25. 161-163 calcifying odontogenic. 112. 151. 33f Fibrinous pericarditis. 373f End-stage testis disease. 406d Epispadia. 11. 378f Fibromatoses. 277 high-grade. 103 Barrett. 338. 162. 12. 277. 276f. 17. 12f on chronic rheumatic endocarditis. 437. 430f Fasciitis nodular. 408. 436f 437 Endothelial tumors. 317f Erythema multiforme minor. 17f Eosinophilic pneumonia. tumors of. 77. 117f Epithelial proliferative lesions. 268. osteonecrosis of. intersex syndromes affecting. 258t Females. 268. 262f Endometrial stromal nodules. 58. 455f Endolymphatic stromal myosis. 118. 263f Endophthalmitis. 350f Exudates. 380f Exocrine pancreas. 27. hard retinal. 118. 66. 270-271 Endometrioid adenocarcinoma. squamous. 10f chronic healing. 112. 258 diseases of. 412f toxoplasmic.462 Empty sella syndrome. 112f Erythroplasia of Queyrat. 172-174 classification of.

101-119 Gastropathy. 296. 342f Granuloma annulare. 92f predominantly large cell. 378f . 440f Granulated lymphocytic leukemia. 137f Goiter. 400-401 of pancreas. 217t Glomerulosclerosis diabetic. 253 Glial neoplasms. 148f 149 " Ground glass " lesions of fibrous dysplasia. 214. 290. 291t Giant axonal neuropathy. 164. 416t Germ cell tumors classification of. 290f-292f definition of. infections of. 84. 378. 122 diseases of. " 408 Glandular malignant schwannoma. 81f Granuloma eosinophilic. 134-140 upper. see International Federation of Gynecology and Obstetrics Fissural cysts. 314 Fungal vasculitis. 439. 190t minimally invasive type. 416t Glioblastoma multiforme. 219f "primary. 134. 290 features of. chronic. 50. 165f Gallstones. 165f porcelain. 242-244. 220-222. 128.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº Gastritis-cont ' d infectious. 144. 241-242 Granulomatous thyroiditis. 84f lymph node. 392 Foreign bodies. 218.463 FIGO. 214f Glomerular diseases hereditary. 315f pyogenic. 378-379. 186. 423f Friedreich ataxia. 190. 85f Genetic disorders of bones and joints. 420. 228f Granulomatous orchitis. 229. 289-290. 356-357 of kidney. 217-226 Glomerulonephritis chronic. 243d of testis. 90. 313 Geographic pattern. 314f. 429. 450. 188 with bizarre nuclei. 127f 128t type B. 226f focal and segmental. 343f Glycogen storage diseases. 60. 392-394 Genitalia female. 227f postinfectious. 436f 437 Fungal enteritis. 279f Graves disease. 91f 92f mixed small cleaved and large cell. 224. 210-214 Genetic hemochromatosis. 36. 247f Goodpasture disease. 258t Gonadoblastomas. 189f atypical. 227. 156. 128f 66417308 : ¸Ÿ±U 24 ¥°Q . gastrointestinal. granulomatous. 186. 36. 215f type II. 438f pathophysiologic mechanism of. 188-190. 135d Gastric tumors. 289f G Gallbladder carcinoma of. 90. 436. 13f Florid hyperplasia. 440f Fucosidosis. 36f Giant congenital cavernous hemangioma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 247f of ovary. 319f 320f Granulomatosis lymphomatoid. 261f Gastric carcinoma. 126. 323 "Fried egg " cells. 224-225 thin basement membrane nephropathy. 129. 440-441. 127f 1281 Gastrointestinal tract. I l 1 f fungal. 261f Follicular thymitis. 230. 126-128. 157f 164. 439. 134 Gastritis. 252f. 94 Wegener. 191-193. 379f Giant cell vasculitis. 438 congenital. 100. 242-246 Gerstmann-Straussler-Scheinker syndrome. 189f variants of. 168 of urinary tract. 439f Gleason grading system of prostatic adenocarcinoma. 122 tumors of. 187f Granulosa cell tumors. 343. 80. 84f lymphoid. 186f 187f 437. 90. 415. 153f keratin implantation. 102. 98 Follicular lymphoma. 164 hydrops of. 319 Granulomatous giant cell vasculitis. 392 type III. 290. 231f 360. 103-104. 103-104. 319-320 noninfectious. chronic. 438 primary. 226f systemic lupus erythematosus. 121-141 circulatory disturbances of. 259f with normal karyotype. 164. 219-220 membranous. 152. 186d Gray hepatization. 440f open-angle. 213-214 immune-mediated. 224-225 Gout. 218f 218t Glomus tumors. 188. I85f Gonadal agenesis. 229f 230f diffuse. 81f Follicular adenoma. 188. 410-411 of skin. 54f "Ground glass " hepatocytes. 126. 165f diseases of. 258t Gonadal dysgenesis. 144f Glycogenosis type I. 259f with abnormal karyotype. 164 Follicular conjunctivitis. 36. 126-133 positiorral anomalies of. 392 Goblet cell carcinoid. 230f focal and segmental. 438 Glaucomatous cupping. 190f hyalinizing trabecular pattern. 247. 392 type IV. 106d Fistula. 60f Granulomatous diseases. 429f Giant cell tumor of bone. 424 Flexner-Wintersteiner rosettes. 127f hypertrophic. 92f predominantly small cleaved cell. 240f 241 Germ cell teratomas. 279f juvenile. 98. 104f "Gitter cells. 126. 278. pyogenic granuloma of. 164. 190f microfollicular pattern. 221f 222f 226. 439f-440f closed-angle. 409f Granular corneal dystrophy. 225 Henoch-Schonlein purpura. 224t. 424 Floppy mitral valves. 126 corrosive. 224-225 diseases that present as. 439-440. 217-218. 222-223 membranoproliferative. 206. 314. 282-283 pathogenesis of. persistent. 319. 80. 84. 126 type A. 13. 186. tracheoesophageal. 210-214 of male reproductive system. 229. 278-279. 225 Glomerulopathy collapsing. 124 developmental disorders of. 192f 193 Follicular cholecystitis. 2581 male. 96. 120 organ-specific diseases of. 185 nodular. 125 Freckles. intersex syndromes affecting. 439f Glaucomatous retinal atrophy. 348 Glaucoma. 127f chronic. 144. 422. 241-242 Genodermatoses. 103f Gingiva. 128f Generalized lymphadenopathy. 255f 255t of prostatic carcinoma. 438-440. 214. 50d Fleurettes. 206f Ganglioneuroma. 188 Follicular carcinoma. 136. 423f Globoid cell leukodystrophy. 420f Fuchs corneal dystrophy. 126. 409. 382f 383 hepatic. 104f 341. 225-226. 260. 451f Majocchi. 438 secondary. 96f Follicular hyperplasia. 412 Gestational trophoblastic disease. 36f Granulomatous interstitial nephritis. end-stage. 224f proliferative diffuse. 414 Fungal endocarditis. 223f 224. 90. 126-128 acute. 192f 193 widely invasive type. 260. 54. 416t mixed stromal. 224f crescentic. 258t mixed. 206. 185. 84. 129f Fungal gastritis. 84f Germ cell aplasia. 297f "Flower-shaped " nuclei. 192f features of. 84. 188. 12f Fungal endophthalmitis. 12. 440. " 217. 145f Genetic metabolic myopathies. 422. 36f Fusobacterium infection. 99f Forbes disease. 36lf Granular atrophy. 164f Ganglioneuroblastoma. 91f Follicular salpingitis. 206f Gardnerella vaginalis. of optic nerve head. 436f Follicular dendritic cell sarcomas. subacute. 127f Fungal infections of brain. 225-226. 240-241 of nervous system. 126 chemical. 110. 258t with male karyotype. 128. 415f Glomerular basement membrane anti-glomerular basement membrane disease. 247. 189f with papillary hyperplasia.

201d Hyperbilirubinemias. 54f red. Ilif Hydropericardium. 233 Histiocytic necrotizing lymphadenitis. 27. 32f " Hyaline fibers. 450 of pinna. 29l t invasive. sclerosing. 431f Gynandroblastoma. 124. 84. 260 Herpes simplex virus infection " ground glass" nuclei of. extramedullary. massive. 97f Hamartoma fibrous. 80. 201d Hyperparathyroidism. 144. 148f 149 chronic. 190f Hurthle cell carcinoma. 154f autoimmune. 70. 182f 183 Histoplasma capsulatum. 105f of papillary carcinoma. 125f retinal capillary. 405 Herpes simplex virus. 2914 292f Hydrochloric acid ingestion. 146-147 hereditary metabolic diseases that affect. 162-163. 312. 73-99 diseases of. 405. 193. 153f drug-induced. 315f Herpesvirus encephalitis. 147f histopathology of. 42 Healing endocarditis. 218. 233. 233f Huntington disease. 430f Hereditary glomerular diseases. 222-223 Hepatic abscesses. 85f Histiocytoma. 149-150 chronic. 22. 104. 161f Hepatocellular carcinoma. 104. 162f Hepatocytes. 162f Hepatocellular adenoma. 165f Hyperaldosteronism. 189f Hashitoxicosis. 233. 430. 339f Histiocytosis. 149f infectious.152f herpesvirus. 450. 223f Henoch-Schonlein purpura glomerulonephritis. 52. 250. chronic. 39f 222-223. 149. 88f lymphocyte predominance type. 290f ' features of. 233f Hemorrhagic pancreatitis. 155 drug-induced.464 Ground glass " lesions-cont ' d of osteofibrous dysplasia. 9-10 Heinz bodies. 102. 88f Holoprosencephaly. 152f HBV-induced massive. 378 " Ground glass " nuclei of herpes simplex-infected cells. 85f Human papillomavirus infection. 343 Hemangiopericytoma. 251f 66417308 : ¸Ÿ±U 24 ¥°Q . 150f Hepatic amebiasis. acute. 161-162. 405 subdural acute. 149f Herpesvirus infection. 163. 359f Hyperplasia adenomatous. 1481 Hepatization gray. 28f Hematoma epidural. 52f Hyaline necrosis. 148t Hepatitis E. 199. 315f Herpes zoster. 13f congenital. 103f intestinal. 338. 407. 87 reticular type. 428-430. 416t Hematopoietic proliferations. 144f Hermaphrodites pseudohermaphrodites female. 163f 342f 343 forms. 313f Hairy cell leukemia. 147-149. 2581 true. 154 Hyalinized trabecular adenoma. 77. 405f chronic. 77f Hematopoietic neoplasms. periportal. 211f HPV. 405. 84. 343-344. 424 Horseshoe kidney. 54 Histoplasma capsulatum infection. 213-214 Hereditary hyperbilirubinemias. see Human immunodeficiency virus Hodgkin disease. 62. 291 t. see Human papillomavirus HSV. 88. 344f 425-426 Hemangiosarcoma. 1451 Hypercortisolism. 337f pulmonary. 210. 110. 12f Heart. 76f 77 Helicobacter pylori infection. 410-411 Histoplasmosis. 407f intracranial.nlA 16 ·IMIÃi : ºIzº yºHjn¼º «¹ÀoÎ » ÂUHnIzTºH ¾vw¼¶ §ú»oT§²H ozº . 312 Hereditary spherocytosis. 404f. 125 diaphragmatic. 198f 199 HIV. 67t Hard metal disease. 315f Hunner ulcer. 148f 149 autoimmune. Langerhans cell. 343 epithelioid. 260f Hibernoma.·Ho¿U ½I«zºHj ÂMoš Jnj ®MI£¶ . 145f Hemolytic anemia. 314. 144 Hereditary peripheral neuropathies." 148f 149 Hepatolenticular degeneration. 407. 81f of spleen. 340f Hilar squamous cell carcinoma. of tongue. 159-161 tumors of. 76f 77 Hemorrhage epidural. 87-88 lymphocyte depletion type. 407 " Hemorrhage-cont'd subependymal. 88. 95-96 Hematopoietic system. 88f nodular sclerosis type. 400f Homer Wright rosettes. 155f caused by pathogens other than hepatitis viruses. 169f 170f Henoch-Schonlein purpura. 188-190. xx carcinoid. 123f Histiocytes. 190t. 87f mixed cellularity type. 195. 259f Hernias. 290. see Herpes simplex virus Human immunodeficiency virus -associated nephropathy. 152. 126-128. 169-170. 70. 87f classification of. 290. 87-88. 193f Hyaline arteriosclerosis. 159-163 Hepatoblastoma. 405. 164. 314. 152f Hepatic granulomas. acute. 412f Herpesvirus hepatitis. 149. malignant fibrous. 425-426. 340. 39. 258t Hernia uteri inguinalis. von Hansemann. 72 Hemochromatosis. 190. 187 Hay fever. 87-88. 18. 96. 343 Kaposiform. 217 Hydatidiform mole complete. 77. 144 tumor-like conditions of. hereditary. 260. 23f 25 Hematopoiesis. 426f Hemangioendothelioma. 186-187. 86f. 153. 199. 290. 419f Hurthle cell adenoma. 148f 149 Hepatitis C. 144. 406d hypertensive. 1481 Hepatitis B virus infection chronic. 152. 150. 401. 144. 54. 68f Hirschsprung disease. 419. 412. 152. 25 Hydropic abortus. 149f viral. 147-151 Q fever. 110. 95f Histiocytosis X. 148t Hepatitis B. 438f sclerosing. 407. 293f Hydrops. 163. 144. 405f 406d Hematopericardium." 388 Hyaline membrane disease. "ground glass. 169d. 401f 402f Hemorrhagic cystitis. 148f 149 Hepatitis. 105f of skin. 292f partial. 290. 316f -related lymphadenopathy. 71f variants. 2581 male. 13. 122. 12. 151. 2-9 rheumatic. 359. 87t histopathologic subtypes. 151f Hepatic fibrosis. 1-29 amyloidosis of. 187-188. of infancy. 191f Guillain-Barre syndrome. 127f 128f Hemangioblastomas. 148f 149 massive hepatic necrosis caused by. 407f intracerebral. 88. 405-407 spinal. 343 Hemangioma. I88f fibrous variant. 343 epithelioid. 414 Hereditary amyloid neuropathy. 451f giant congenital cavernous. 145t Hereditary metabolic diseases. 153f Hepatic necrosis acetaminophen-induced. 32. biliary. 54 Hepatobiliary tract. 149. 213-214 Hereditary tyrosinemia. 281 H Hailey-Hailey disease. 336-337. 145f Hepatitis A. 407f subarachnoid. 314. 147 alcoholic. 155. 143-165 circulatory disorde