necrosis due to cessation of blood supply (e.g. infarct Kiancy7" liquefactive necrosis due to degradation of tissue by hydrolytic enzymes (e.g. infarct brain), caseous necrasis due to lee with tubercle bacilli (e.g. tuberculosis lymph node) and a san necrosis due to enzymatic degradation of fatty tissue pancreas (e.g. acute pancreatitis). Morphology of these examples is discussed below. COAGULATIVE NECROSIS (INFARCT) KIDNEY _ Coagulativenecrosis isthe most common type ofnecrosis caused by irreversible cell injury, most often from sudden cessation of blood supply or ischaemia (infarction). The characteristic examples of coagulative necrosis are seen in infarcts of the kidney, heart and spleen, resulting from thromboemboli. Gross Renal infarcts are often multiple and may be bilateral. Characteristically, they are pale or anaemic and wedge-shaped with base resting under the capsule and apex pointing towards the medulla. Generally, a narrow rim of renal tissue under the capsule is spared because it draws its blood supply from the capsular vessels. The cut surface of renal infarct in the initial 2 to 3 days is red and congested but by 4th day the centre becomes pale yellow. At the end of one week, the infarct is typically anaemic and appears depressed below the surface of the kidney (Fig. 7.1). Microscopy i. The hallmark of coagulative necrosis of kidney is that architectural outlines of glomeruli and tubules may be preserved though all cellular details are lost. ii, The margin of infarct shows inflammatory reaction, initially by infiltrating polymorphonuclear cells but later macrophages and lymphocytes predominate. Simultaneously, there is proliferation of fibroblasts and capillaries (Fig. 7.2). é (26)FIGUAE 72 Conguatvenecross in nfrcrkiney The faced ee on ight side shows velaned cuties of tubules but the cal Inna ne tthiesappea homogeneous and nensalysosnophilewthpwt deat of mile anaejcplasm. The junelan of wb ancl non-wabiea8 hows non-specific liver ‘ersible Ifthe liver is PAN OLO CTO EMORES Grosiiy wwe wedi shange Is enlarged with a tense, glistening capauig rounded margins. The cut surface bulges slighty ant itpah selow to yellow and is greasy to touch (Fig. 49) Miroscopically, characteristic feature isthe presence of umerous ipidvacuolesin the cytoplasm ofhepatocyes thos iebecause fat in H & E stained section preparedby pavcthye embedding technique is dissolved in organic solvents used and appears as non-staining vacuoles (Fig, 3.39) 4) The vacuoles are initially small and are present arcund the nucleus (microvesicular). < “With progression of the process, larger pushing the nucleus to the (macrovesicular). iti) Attimes, the hepatocytes laden with large lipid vacuoles ‘may rupture and lipid vacuoles coalesce to form fatty cysts. §y) infrequently, ipogranulomas may appear as a reaction {oextravasated fat and consist of collections of lymphocytes, macrophages, and some multinucleated giant cells, ¥) Fat can be demonstrated in fresh unfixed tissue by frazen the vacuoles become Periphery of the cells section by fatstains eg. Sudan dyes (Sudan Il, 1V Sudan Black) and Oil Red O. Alternatively, osmic acid which isa fixative as wellasa stain can be used to demonstrate fat in the ee ] Cholesterol Deposits /htracellular deposits ofcholesterol and its esters in macrophages ‘nay occur when there is hypercholesterolaemia, This turns ‘macrophages into foam cells. The examples are as follows 1. Fibrojatty plaques of atherosclerosis (Chapter 15). 2 Clusters of foam cells in tumour-like masses called Zonthomas and xanthelasma. + Cholesterolosis is focal presence of cholesterol laden acrophages in the lamina propria of gallbladderin cholelithiasis (age 664) Stromal Fatty Infiltration oes uite different from ' form of lipid accumulation is q) pales romal fatty infiltration connective Parenchymal fatty change just described jphedeposition of mature adipose cellsin the stromal n of fat in the "sue in contrast to intracellular deposition of Figure 3.36 Fatty liver. Sectioned slice of the parenchyma with rounded borders, liver shows pale y Parenchymal cells in fatty change. The condition occurs often in patients with obesity. Two commonly affected or are the heart and the pancreas, Thus, heart can be the sit intramyocardial fatty changeas well as epicardial (stromal) infiltration, The presence of mature adipose cells in the st generally does not produce any dysfunction, INTRACELLULAR ACCUMULATION OF PROTEINS Pathologic accumulation of proteins in the ™ay occur in the following conditions: 1. _Inproteinuria, there is excessive renal tubular reabsor ‘of proteins by the proximal tubular epithelial cells which pink hyaline dropletsin theircytoplasm in H&E stained se The change isreversible; with control of proteinuria the p droplets disappear. 2. The cytoplasm of actively functioning plasma cells s pink hyaline inclusions called Russell's bodies represe synthesised immunoglobulins. 3. Inal-antitrypsin deficiency, the cytoplasm of hepat shows eosinophilic globular deposits of a mutant protein 4, Mallory’s body or alcoholic hyaline in the hepatc is intracellular accumulation of intermediate filame cytokeratin and appear as amorphous pink masses. It may be stated heree that amyloid is primar extracellular deposition of abnormal proteinaceous sub: but in advanced diseases it may be deposited in intrac location too (Chapter 5). cytoplasm of INTRACELLULAR ACCUMULATION OF GLYCOGEN Conditions associated with excessive accumulat intracellular glycogen are as under: 1. In diabetes mellitus, there is intracellular accumul: glycogen in different tissues because normal cellular of glucose is impaired. Glycogen deposits in diabetes are seen in epithelium of distal portion of proximal conFIGUI / ta Puig z especi ended with large fat vacuoles pushing the nuclei to the periphery (macrovesicles), while microvesicles). Inbox shows red colour in the cytoplasmic fat in the hepatocytes in Ol Gros patie heart small tan dot homogeneous and contains abundant granular brown-biack Micr y enlarges to melanin pigment (Fig. 9.3). i. The nay be flat or _ iii. The pigment is more marked in the naevus cells in the lowe! intra val outline. epidermis and upper dermis butthe cells in the mid-dermis and ii. Th lower dermis hardly contain any pigment. iii. Lij lipid: ng aggregates BROWN ATROPHY HEART tional naevus),_§ ——<$<_ "ew lying dermis Brown atrophy of the heart is the term used for intracellula" ra ntirely confined i ly sccurTulation of yellowish-brown lipid pigment calle Q1 9 oval cells and ‘iti scin (lipo = fat, fuscus = brown) in the m jal fibres: Be f is pigment is also known as [i yocardial fib Ans naevus cells is ageing pigment. Pochrome or wear and tea! 0! in 3eam 5B To learn pathology of primary mesenchymal benig farcoma) and metastatic deposits (eg. metastatic ArNCO 1M To describe salient gros and microscopic features f these na yr cinoma Pn Just like epithelial tumours, benign mesenchymal tumours origin (9) fibroma, lipoma liposarcor Ail malignant tumours have 2 common features—anaplasia and invasion or spread. Invasiveness of cancers may be by direct local spread, or may be distant spread to other sites by either lymphatics to lymph nodes (most carcinomas) or by hematogenous spread (most sarcomas) Representative examples of these tumours are discussed below. Examples of mesenchymal bone tumours are discussed Exercise 61 © suffixed as oma with prefix of cell o while malignant mesenchymal tumours 2f© of rosarcoma ith prefix of cell of origin (e.g a LIPOMA ‘Tipoma is 2 common benign tumour occurring in the subcutaneous tissues. Gross The tumour is small, encapsulated, round to oval. The cut surface is soft, lobulated, yellowish and greasy (Fig. 18.1). Microscopy i.A thin fibrous capsule surrounds the periphery ii The tumour is composed of lobules of mature adipose cells separated by thin fibrovascular septa (Fig, 1 =) UNDIFFERENTIATED SARCOMA. ee Undifferentiated sarcoma, previously called malignant fibrous histiocytoma (MFH) or pleomorphic sarcoma comprises ~20% of all soft tissue sarcomas. It occ commonly in males in the age group of Sth to 7th Most common locations are the lower and upper exc and retroperitoneum Urs more decades, tremities Gross Undifferentiated sarcoma or MFH is a multilobulated well-circumscribed, firm or fleshy mass, 5-10 em in diameter, Cut surface is grey-white, soft and myxoid (Fig. 18,3) oe FIGURE 18.1 Lipoma. T surface is soft, lobulated, Microscopy There is n ance: i.In general, there is ad cells and mononuclear |i. Spindle-shaped ce wheel or storiform pat The tumour cells 5 hyperchromatism, mite bizarre tumour giant ¢ METASTATIC CARee closed by thin fibrous capsule. s__ iv. Part of cortex and capsule of the lymph node are intact (Fig. n 18.6). METASTATIC SARCOMA LUNG monly metastasise throw mainly lungs, however, gh haematogenous iver, bones, brain Sarcomas com! too spread by e route to distant organs, and kidneys. Some carcinomas,‘To learn adaptive disorders of growth with com nodes, squamous metapalsia cervix, pa » To describe salient gross and microscopic features of these conditions. ples, e.g. testicular atrophy, cardiac hypertro Cellular adaptations are the adjustments which the cells make ir response to various stresses. These include decreasing or reasing the cell size (atrophy and hypertrophy), or increasing their number (hyperplasia), or changing the pathway of differentiation of cells (metaplasia and dysplasia). A few common examples of these are however dysplasia is discussed in Exercise 20. (Cresricutar ATROPHY ‘Atrophy means reduction in number and size of cells which were once normal (compared from hypoplasia which is developmentally small in size). Testicular atrophy may occur from various causes, senility being a common cause, size, firm and Gross In testicular atrophy, the testis is small fibrotic. Microscopy i Seminiferous tubules: There is progressive depletion of germs Call elements, The tubular basement membrane is thickene ' atneri i FIGURE 16-1 Testcularatrophy sad there is peritubular fibrosis. Some tubules M2¥ SNOW Sy els anyandne spam is thickened. The interstitium interstitial fbrovasculat O crrinence of Leyaia 3 i a RENDICITIS Acute inflammation of the appendix, acute appendicitis, is, the most common acute abdominal condition confronting the surgeon. The condition is seen more commonly in older children and young adults, and is uncommon at the extremes of age, The disease is seen more frequently in the West and in affluent societies which may be due to variation in diet—a diet ‘with low bulk or cellulose and high protein intake more often causes appendicitis, ETIOPATHOGENESIS ‘The most common mechanism is obstruction of the lumen from various etiologic factors that leads to increased intraluminal pressure, This presses upon the blood vesselsto produce ischaemic injurywhich in turn favours the bacterial proliferation and hence acute appendicitis. The ‘common causes of appengicitis are as under: Obstructive: Faecolith Caleuli Foreign body Tumour Worms (especially Enterobius vermicularis) Diffuse lymphoid hyperplasia, especially in children, . Non-obstructive: Haematogenous spread of generalised infection Vascular occlusion Inappropriate diet lacking roughage. eeopesgeenr pe MORPHOLOGIC FEATURES Grossly, the appeniance depends upon the stage at which the acutely lariamed appendix isexamined. In early acute cppondictis, the oxg20 is swollen and serosa shows hyperaer'a. in well-developed acuteinflammation called acute suppurative appendicitis, the serosa is coated with fibrinopurulent exudate and engorged ‘vessels on the surface. In further advanced cases calledacuie gangrenous appendicitis, here isnecrosis and ulcerations of ‘mucosa which extend through the wall so that the appen« becomes soft and friable and the surlace is coated with greenish- black gangrenous necrosis (Fig. 20.41). Neutrophil infitration Congested vessels _Neorotic mucosa inmuscularis laure20A2. Act Pe ee Reianau Denastment af Datla acdc ae rescopic appearance showing diagnostic neutrophilic inflation into th Congestion —_ Serosal exudate Impacted concretion Figure 20.41 Acute appendicitis. Goss appearance of long ‘opeved appendix showing impactedfeecolithin the len arden ‘on the seross, “Microscopically, the most important diagnostic histobgi) criterion is the neutrophilic infiltration of tne musculany Inearly stage, other changes besides acute inlammatoy changes, are congestionand oedema of the appendiceal yal, Inlater stages, the mucosa is sloughed off, the wall becomes necrotic, the blood vessels may get thrombosed and may be neutrophilic abscesses in the wall. neither case, impacted foreign body, faecolith, or concretion may be seen inthe lumen (Fig. 20.42). o; there is good correlation between macroscopic end nileroscopic findings in acute appendicitis. CLINICAL COURSE. Thepatient presents with featuresofacte abdomen as unde: 1. Colicky pain, initially around umbilicus but later lcalstd to right iliac fossa Nauseaand vomiting Pyrexia of mild grade Abdominal tenderness Increased pulse rate | roasts onl llfg, Neutrophilicleucocytosiswith igmost significant laboratory find An attack of acute appendicit torepeated attacks (recurrent acive it jater stage following acute attack (interval ane eon’ tt phological changes of healing by tibece! iyonic inflammation are observed, COMPLICATIONS Ifthe condition isnot the following complications may occur: ae cee 1, Peritonitis A perforated appendi ' tppendics may caus localised or genesaiaen ee ene 2, Appendix abscess This is due to rupture of an append giving rise to localised abscess in the right iliac fost. This abscess may spread to other sites such as between the liver and diaphragm (subphrenic abscess), into the pelvis ecwean th urinary bladder and rectum, and in the females may ae ‘uterus and fallopian tubes. toxic granules npc Branulesin neutrophils is predisposes the appendix ‘ppendicectomy), brosis of the wall and 3, Adhesions Late complications of acute appendicitis are fibrous adhesions to the greater omentum, small intestine and her abdominal structures. 4. Portal pylephlebitis Spread of infection into mesenteric eins may produce septic phlebitis and liver abscess. 5. Mucocele Distension of distal appendix by mucus following recovery from an attack of acute appendicitis is referred to as mucocele. It occurs generally due to proximal obstruction but sometimes may be due to a benign or malignant neoplasm in the appendix. An infected a may result in formation of, “empyema of the appendix. TUMOURS OF APPENDIX quite rare. These include: nnocarcinoma and Tumours of the appendix are carcinoid tumour (the most common), ade seudomyxoma peritonei CARCINOID TUMOUR Itisalready described on page 601, Both argentaffin and argyrophil types are encountered, the former being more common. ypendixis mostly situated 1s as a circumscribed eter, involving the wall Grossly, carcinoid tumour of the ap} hear the tip of the organ and appeal nodule, usually less than 1 cm in diam« ‘but metastases are rare. Histologically, carcinoid tum: other carcinoids of the midgut. our ofthe appendix resembles MUCINOUS ADENOCARCINOMA Awell-aifferentanss Mucinous adenocarcinoma called low-grade oP aaee heoplasm is specific to the appendiceal location. sm, the appendiceal wallis lined by atypical mucin wall of ‘nd the lumen contains mucin that may © *ppendix . Se aan ee cavity, it produces a clinical condition termec POT cinous Petitonel which is accumulation of gelatin ciated AScites. In assessing an ovarian mucinet® pena With pseuidomyxoma peritonei, the oe se associated oe somo Se origin cat uci sctend into the the peritoneal @ wenoy © Acute appendicitis is an acute abdomen associated with @ licky pain and neutrophilic leucocytosis. haracteristicaly, there is neutrophilic infiltration in the muscularis propria. Complications of acuteappendicitis are peritonitis, abscess formation, adhesions, portal pylephlebitis and mucocele. Tumours of the appendix include carcinoid and well- differentiated mucinous adenocarcinoma. The latter may produce pseudomyxoma peritone! NORMAL STRUCTURE The large bowel consists of 6 parts—the caecum, ascending colon, transverse colon, descending colon, sigmoid colon and rectum, and in all measures about 1.5 meters in length. The serosal surface of the large intestine except the rectum is studded with appendices epiploicaewhich are small, rounded collections of faty tissue covered by peritoneum. Histologically, the wall of large bowel consists of 4 layers as elsewhere in the alimentary tract—serosa, muscularis, submucosa and mucosa The mucosa lacks villi and there is preponderance of goblet cells over columnar epithelial cells. The lymphoid tissues less abundant than in the small bowel but ymphotd follicles are seen in the caecum and rectum. 4 ‘The muscularis propria of the large intestine is quite peculiar—the inner circular muscle layer ensheaths whole length of the intestine, while the outer longitudinal muscle layer is concentrated into 3 muscle bands called Taenia cali ‘The length of outer muscle layer is shorter than the length of the intestine and therefore, it forms the sacculations or ‘haustra of the large intestine. At the rectosigmoid junction, the three muscle bands fuse to form a complete covering, ‘The blood supply to the right colon is from the superio: ‘mesentericartery which also supplies blood to the small bowel ‘The remaining portion of large bowel except the lower part o rectum receives blood supply from inferior mesenteric artery ‘The lower rectum is supplied by haemozhoidal branches. “The innervation of the large bowel consists of 3 plexuses of ganglion cells—Auerhack’s or myenteric plexus lying between the two layers of muscularis, Henle’s plexus ying in the deep submucosa inner to circular muscle layer, and Meissner plexus thatlies in the superficial mucosa just beneath the muscularis mucosae. These are interconnected by non-myelinated nerve fibres. : ‘Anal canal, 3-4 cm long tubular structure, begins at the lower end ofthe rectum, though isnot ones wel Tneluded here to cover simultaneously lesions pertaining te thisregion. Its lined by keratinised or nonkeratinised stratifie Squamous epithelium. Anal verge i the junction between th | eanal and perineal skin, while pectinate ines the squamo gplumnar junction between the anal canal and the rectum, of large bowel discussed belov ‘Major groups of diseases of la b are congenital and non-neoplasi miscellaneous conditionEpithelioid cells Lymphocytes Lang a ons bates FIGURE 12.2 Fibrocaseous tuberculosis lung. The cavity shows caseation necro and some Langhans’ giant cells, and surrounded at the periphery by fibroscler Coated with caseous material. Advanced cases show transverse _ per fibrous strictures and intestinal obstruction (Fig. 12.5). the Microscopy lack i. Presence of caseating tubercles in all the layers of intestine Gre (Fig, 12.6), mel il. Ulceration of mucosa with slough on the surface. the lil, Variable fibrosis in the muscular layer. Mic iT LEPROMATOUS LEPROSY aaCHOLESTEROL PIGMENT atc (YELLOWAWHITE) (MULBERRYSHAPED) (HARD Figure 21.44 Pure gallstones of various types, © Mixed gellstones are the most common (80%) while pure and combined gallstones comprise 10% each, © Major complications of gallstones are cholecystiasis, choledocholithiasis, mucocele, empyema, biliary fistula, ileus, pancreatitis and gallbladder cancer, CHOLECYSTITIS ‘Cholecystitis or inflammation of the gallbladder may be acute, chronic, or acute superimposed on chronic. Though chronic cholecystitis is more common, acute cholecystitis is a surgical emergency. ACUTE CHOLECYSTITIS. Inmany ways acute cholecystitisis similarto acute anpenddicitis, The condition usually begins with obstruction, followed by infection later. ETIOPATHOGENESIS Based on the initiating mechanisms, acute cholecystitis occurs in two types of situations—acute calculous and acute acalculous cholecystitis. ‘Thickened perimuscular layer Rokitansky-Aschoff sinus Cholesterolosis 15 cholester copra of Figure 2145 cholesterooss of the gallbladder. Te amine Prop. the mucosa shows foamy macrophages. NIXED GALLSTONES: (MULTIFACETED) ‘COMBINED GALLSTONES (SMOOTH-SURFACED) Figure 21.46 Mixed and combined galstones. # Acute calculous cholecystitis In 90% of cases, acute cholecystitis is caused by obstruction in the neck of the gallbladder or in the cystic duct by a gallstone. The commonest location of impaction of a gallstone is in Hartman's pouch. Obstruction results in distension of the gallbladder followed by ‘acute inflammation which is initially due to chemical irritation, Later, however, secondary bacterial infection, chiefly by E.coli and Streptococcus faecalis, supervenes. % Acute acalculous cholecystitis The remaining 10% cases of acute cholecystitis do not contain gallstones, In such cases, a variety of causes have been assigned such as previous nonbiliary surgery, multiple injuries, burns, recent childbirth, severe sepsis, dehydration, torsion of the gallbladder and diabetes mellitus. Rare causes include primary bacterial infections like salmonellosis and cholera and parasitic infestations. MORPHOLOGIC FEATURES Except for the presence or absence of calculi, the two forms of acute cholecystitis are morphologically similar. Grossly, the gallbladder is distended and tense, The serosal surface is coated with fibrinous exudate with congestion and haemorthages. The mucosa is bright red, The lumen is filled ‘with pus mixed with green bile. In calculous cholecystitis, ‘Cholecysiis Mucocele Gallbadder cancer (Choledocholhiasis Biliary tistla ‘bstuctve jaundice Ascending cholangitis Abscess. Acute pancreatitis Figure21.47 Major clinical eects and complications of galstones.568 logy Path z Q a MORPHOLOGIC FEATURES Grossly, the gall ‘ily contracted but may be normal or en}, dey 2 stone may get impacted in the neck or in the cystic duct. When obstruction of the cystic duct is complete, the lumen. is gene! se 18), The wall ofthe gallbladder is thickened y sfilled with purulentexudate and the condition tsknownas iE. Li a grey-wnite due todense ubrossor est gallbladder ren aked. The mucosal folds may be intact ikon’ Microscopically, wall of the gallbladder shows marked 6, fattened and atrophied. The lumen commonly conging inflammatory oeclema, congestion and neutrophilicendate. _yyultiple mixed stones or a combined stone There miy-be frankahecesses ia thewall and gansreneis), | jysZofogically, the featires are as under (F821. 19) necrosis wh rupture int the peritoneal cavity (gangrenous fA sna congested mucosa but occasion ns mucosa may be totally destroyed ly 2. Penetration of the mucosa deep into the all ofthe INICAL FEATURES The patients of acute cholecystitis of gayjhladder up to muscularis layer to form Rokitansky ther type have similar clinical features, They present with Aschoff¥inuses. severe pain in the upper abdomen with features of pesitoneal Variable degree of chronic inflammatory reaction itation such as guarding and hyperaesthesia, The gallbladder ¢onsisting of lymphocytes, plasma cells and macrophage, s tender and may be palpable. Fever, leucocytosis with present in the lamina proprie and subserosal lave neutrophilia and slight jaundice are generally present. Early 4, Variable degree of fibrosis In the subserosal ang cholecystectomy within the fist three days has @ morality of —_ subepithelial layers than 0.5% and risk of complications such as perforation, 8 few morphologic variants of chronic cholecystitis ame ary fistula, recurrent attacks and adhesions is avoided, considered below joweve nent brings about resolution ina fairly Cholecystitis glandularis, when the mucosal folds fuse ge proper ses though chances of recurrence of _togetherdue to inflammation and resultin formation oer sk of epithelium buried in the gallbladder wall % Porcelain gallbladderis the pattern when the gallbladder CHRONIC CHOLECYSTITIS. wall is calcified and cracks like an eggshell Chronic sttis is the commonest type of clinical ® Acute on chronfe cholecystitis isthe tem use fo alld Lae GES AutGat nae mean at pho {acute cholecystitis superimposed 1 cholecystitis ETIOPATHOGENESIS ‘The association o 0 ronie cholecystitis in the right hypochondrium and epig erthe tight upper abdomen, Nausea. are common. Biliary colic may eccasionally oc inflam atients, repeated attacks of mild acute tendeme Figure 21.48 Chronic cholecysttis with cholelithiasis. A. diagrammatic view. The wall of the gallbladder is thickened ane’), stones, packed with welliting, multiple, multi-faceted, mixed galley cholecystitis with cholesterol cholaithasis. The wal of alti i lumen conta the lumen i *. 8 Chronie ders thicken ngle large, oval-and hard yellowhite gallstone, nee: Thea rant det 1a us M 7 Mononuclear inary Exercise 53 matory in filtrate Hypertrophied muscularis / ystitis, There is perimusculer thickening, chronic inflammatory celsi FIGURE 53.8 Chronic ch muco: ns G fe finns most common site for cancer of gallblad aillbladde: followed next in frequency by the neck of the itregul jer. The tumour may be infiltrating type seen as lar area of diffuse thickening and induration in the icroscopy i, Most common is ad features of anaplasia ii. The tumour may pattern (Fig. 53-10). der is gallbladder wall, or fu papillary or cauliflow may coexist with caremmon je to fibrosis pically transmural Due to contraction of muscularis Mucosal and submucosal Crypt abscess and non-specific acute and chronic eet as and infiltrate pecsetna aon inflammatory cells (ymphocytes, plasma cells, mononuclear cells (lymphocytes, 4sma cells and macrophages) tchy ulceration dened due to oedema and lymphoid gregates ltrated by inflammatory cells ssent 4+ THI yp TNF, I-12 neutrophils, eosinophils, mast cells) Haemorrhagic mucosa with ulceration Normal or reduced in width Usually spared except in cases of toxic megacolon Usually absent cD4+TH2 TGF-B, IL-4, 1L-5, 1-13 Positive in most ‘itive in a few smnal and external fistulae in 10% cases Extremely rare 3 May occur infrequently in disease of more than 10 years’ duration phoma more often than carcinoma Carcinoma more often than lymphoma »mon Never ROCOLITIS Intestinal Tuberculos e and chronic inflammatory ), large bowel (colitis), or eing more common. Hence, ll bowel and/or large bowel fer correlation of features. ms of inflammations of the ito infective enterocolitis and ronic inflammatory lesions aused by microorganisms _ and helminths). All these ndromes. Pathogenetically can cause enterocolitis by acteria producing ulcerative ng bacteria resulting innon- ms producing enterocolitis portant forms are described Intestinal tuberculosis ca and hyperplastic caecal 1, PRIMARY INTESTINAL TUBERCULOSIS Though an uncommon disease in the developed countries of the world, primary tuberculosis ofthe ileocaecal region is quite common in developing countries including India, In the pre-pasteurisation era, it used to occur by ingestion of unpasteurised cow's milk infected with Mycobacterium bovis, But now-a-days due t© control of tuberculosis in cattle and pasteurisation of milk, virtually all cases of intestinal tuberculosis are caused by M. tuberculosis. The predominant changes are in the mesenteric lymph nodes without any significant intestinal lesion. rin 3 forms—primary, secondary ruberculosis Grossly, the affected lymph nodes are enlarged, matted an¢ caseous (tabes mesenterica). Eventually, there is healing bY fibrosis and calcification (Fig, 20.31, A). Microscopically, in the initial stage, theres primary complex or Ghon’s focus in the intestinal mucosa as occurs elsewhere‘Ghon's focus Enlarged mesenteric, lymph nodes. ‘A, PRIMARY INTESTINAL. TUBERCULOSIS 8, SECONDARY INTESTINAL (TABES MESENTERICA) TUBERCULOSIS Figure 20.31 Intestinal tuberculosis, three pattems inprimary tuberculous infection (page $8). Subsequenth shemesentericlymph nodes are aflected which show typical tuberculous granulomatous inflammatory reaction with ‘caseation necrosis. Tuberculous peritonitis may occur due tospread of the infection 2, SECONDARY INTESTINAL TUBERCULOSIS Self swallowing of sputum in patients with active pulmonary tuberculosis may cause secondary intestinal tuberculosis, most commonly in the terminal ileum and rarely in the colon, Grossly, the intestinal lesions a prominent than the lesions in regional |y 1 secondary pulmonary tuberculosis (1 The lesions begin in the Peyer’s patches 01 the lymphoid follicles with formation of small ulcers that spread through the lymphatics to form large ulcers which are transverse fo the long axis of the bowel (compared from typhoid ulcers of Tan BACTERIAL ENTEROCOLITIS 1, Entero-invasive bacteria i, Matubereuiosis il, Samonelta ii, Campylobacter juni iv. Shigella ¥v. Escherichia coli i Yersinia enterocolitica 2. Enterotoxin-preducing bacteria i. Vibrio cholerae VIRAL ENTEROCOUITIS FUNGAL ENTEROCOLITIS i. Candida ji, Mucor D.PROTOZOAL AND METAZDAL INFESTATIONS i. Giardia lamblia. i, Entamoeba histolytica Bolantidium coll iv, Toenia sour +. Ascaris lumbricoldes vi. Ancylostoma duodenale vi Strongylodes stercoralis 2 ™ Thickened wall Stricture Transverse cer peritoneum ©. HYPERPLASTIC GAECAL. TUBERCULOSIS small intestine, Table 20.7), These ulcers may be coated with caseous material, Serosa may be studded with visible tubercles, In advanced cases, transverse fibrous strictures and intestinal obstruction are seen (Pig, 20.82, A, B), Histologically, the tuberculous lesions in the intestine are similar to those observed elsewhere i.e. presence of tubercles. Mucosa and submucosa show ulceration and the muscularis may be replaced by variable degree of fibrosis (Fig. 20.82, €). Tuberculous perito mayboobeeed9 . HYPERPLASTIC ILEOCAECAL TUBERCULOSIS ‘This is a variant of occurring secondary to pulmonary tuberculosis, Grossly, the terminal ileum, caecum and/or ascending colon are thick-walled with mucosal ulceration, Clinically, the lesion is palpable and may be mistaken for carcinoma, (Fig. 20.31, €). Microscopically, the presence of caseating tubercles distinguishes the condition from Grohr’s disease in which granulomas are non-caseating, Besides, bacteriological evidence by culture or animal inoculation and Mantoux test are helpful in differential diagnosis of the 1wo conditions. Enteric Fever “The term enteric fevers used to describe acute infection caused by Salmonella typhi (renamed as S. Enterlea causing typho! fever) or Salmonella paratyphi (paratyphold fever). Besides these 2 salmonellae, Salmonella typhimurium causes foo poisoning. i are ingested through HOGENESIS Typhoid bacilli are ingest PATHOGEN ES Tote Dung ein amptenatc fnoubation period of about 2 weeks, the bacll Invade the ati Mollicles and Peyer's patches ofthe small intestine Hae ae Following this, the bacilli invade the blood- and prolising bacteraemia, and the characteristic clinical stream cof he disease like continuous risein temperature and features orn the stin are observed. Immunological reactions iter about 10 days and peak titres are ihe third week Eventually, the bacilt are ‘rosespots’ (widal’s test) begin seen by the end ofSystemic Pathology f i Figure 20.32 intestinal tuberculosis. A, The external surfece of small intestine shows stricture and a lymph node in section having caseatin necrosis (arrow). 8, The lumen shows charecteristic transverse ulcers and two strictures (arrow. The wall of intestine in the area of narrowed lumen S thickened, C, Microscopy of intestine shows caseating epithelioid cell granulomas in the intestinal wall. localised in the intestinal lymphoid tissue (producing typhoid intestinal lesions), in the mesenteric lymph nodes (leading, o haemorrhagic lymphadenitis), in the liver (causing foci of parenchymal necrosis), in the gallbladder (producing typhoid cholecystitis), and in the spleen (resulting in splenic reactive hyperplasia) MORPHOLOGIC FEATURES ‘The lesions are observed in the intestines as well as in other organs. 1. INTESTINAL LESIONS Grossly, terminal ileur is affected most often, but lesions maybe seen in! 1 typhoid ulcers wi and colon. Peyer's patches show 0} their long axisalong the lengih of the bowel compared from tuberculous ulcers of small intestine, described already) Salient contrasting features of tuberulous and typhoid ulcers are given in Table 20.7. The base of the ulcers is black due to sloughed mucosa. The margins of the ulcers are slightly raised dueto inflammatory oedema and cellular proliferation, There is never significant fibrosis and hence fibrous stenosis seldom occurs in healed typhoid lesions. The regional lymph nodes are invariably enlarged (Fig. 20.33, A). Microscopically, there is hyperaemia, oedema and cellular proliferation consisting of phagocytic histiocytes (showing characteristic erythrophagocytosis), lymphocytes and plasma cells. Though enteric fever is an example of acute inflammation, neutrophils are invariably absent from the cellular infiltrate and this i relectediin the leucopenia with neutropenia and relative lymphocytosis in the peripheral blood (Fig. 20.33, B) ‘The main complications ofthe intestinal lesions of typhoid are perforation of the ulcers and haemorthage. OTHER LESIONS Besides the Intestinal involvement, various other organs and tissues showing pathological changes in enteric fever are as under: i) Mesenteric lymph nodes—haemorthagic lymphadenits fi) Liver—foci of parenchymal necrosis iii) Gallbladder—typhoid cholecystitis iv) Spleen—splenomegaly with reactive hyperplasia v) Kidneys—nephritis vi) Abdominal muscles—Zenker’s degeneration vil) Joints—arthritis s—osteomyelitis meningitis ‘orchitis rsistence of organism in the gallbladder or urinary tract cin passage oforganismsin the faeces or urine creating a Ene (iseraeeey FEATURE TUBERCULOUS TYPHOID ULCERS ULCERS Btiology M. tuberculosis ‘Salmonella typhi, '.Paratyphi 2 Commonsite tleunand caecum Terminal leu and jejunum 3. Orientation Perpendiculartolong Parallel oflona axis axis 4 Gross i) Transverse ulcers, ji. Longitudinal oval appeorance alongthe direction ulcers, ove Peyers ‘of phates patches i) Fibrous scaring i, Bowel wall thin common i, Intestinal il) Intestinal stricture perforation common and obstniction common 5. Microscopy Caseating epithelioid nitrate of cell ganuiomas Iymphocytes plasm cells and histiocytes erytrophagocytoss® some histioytes 6. Major Intestnal obstruction Intestinal perforation complications =las: : Bry cuenta therefor wall, and ili culosis can occur, ous organs where miliary He Oa Q.7. Name von spleen, liver, bonesan : kidneys spleen, Ans. Lungs, i icardium, epididymis bes, brain and meninges, pericar fallopian tubes, ehl-Neelsen star 9 iffe i erculosis and ci is Ziehl ini ifferent in tu’ d Q. 8. How Is ZiehI-N t different in t b leprosy? Intestinal mucosa Epithelioid cell granuloma Caseation necrosis. Langhans’ giant cells ws Lymphocytes sis res, val led FIGURE V2. Uberculosis SI 6 Ti Caseati ri ing pithelioid cell granulomas, ine. The wall Of intestine shows—_ Ke, nd by by st pe Mee {AGENT DISEASES, {INORGANIC (MINERAL) DusTs 1. coaldust i) Simple coat-workers Peumaconiosis i Progressive masive iii) Caplan’ syndrome oe 2 sila 1) Slicosis i) Caplanis syndrome 4, Asbestos I) Asbestosis i) Pleural diseases ‘i Tumours 4. Berylum i) Acute berylioss ii) Chronic beryliosis, 5, Ironoxide Pulmonary siderosis {8 ORGANIC (BIOLOGIC) DUSTS 1. Moudy hay Farmers lungs 2 Bagosse Bagassosis Cotton flax hemp dust Byssinosis Bird droppines Bird-breeders (bird fanciers) lung ‘Mushroom compost dust Mushroom-workes ung 3 4 5 & Mouldy barley, malt dist Malt-workers ung 7. Mouldy maple bark Maple-bark disease 8 Silage fermentation __Slovilles disease dust around which fibrous tissue is formed, Some macrophages tentertholymphatics and reach regionallymphnodes.The tissue response to infialed dust may be one of the following three ‘ypes © Fibrous nodules e.g, in coal-workers’ pneumoconiosis and stcosis 4 Interstitial fibrosis, in asbestos’ 4 Hypersensitivity reaction ex. in berylioss comprehensive list of various types of occupational lung diseases caused by inorganic (mineral) dusts and organic dusts ispresented in Table 17.9, The more common examples of pnoumoconioses are described here. ex WORKERS’ PNEUMOCONIOSIS isisthe commonestform ofpneumoconiosisandis defined as thelung disease resulting from inhalation ofcoal dust particles especialy in coal-miners engaged in handling soft bitumin”, Gil for ¢ number of years, often 20 to 30 years. exists forms. ainilder form of thedisease called simple coa! Worker pleumoconiosis and an advanced form termed YOST Ina fete (complicated coal-miners puewROCDn OS) Anthacosis onthe oer and snes Tung lsease neue sens Tea co enign and agympiomatie scimUlno Hee eee eerieea ek mest urban owelet, UE atmospheric pollution and clgare! on ree smoke (anthacile res {o-coal), Anthracotic pigmeat is deposite eles Fe eeecaer tana the respizatory onchises T ory the drintagtoph nodes bu: dooe nt produce APTS ‘ifficulty or radiologic changes. PATHOGENESIS Anthracosisy simple a diferent Oe eet progressive massive OD workers Stages inthe ss a Ton of fully developed cont ‘abrasis pram neuniosis: However, prowressits fe coal-workers! Older age of the miners, ok tors for various leucocytes (leukotrienes, 3 4 5. MORPHOLOGIC FEATURES 1m life, the pathologic Laue aMeel geet perme str oy ini appoamocaaco ane mee rae pct, The pathologie findings st axopsy of a opie aje forme of coalwrkers pauoconioes sane ered below under 3 headings: simple coal ao arercuamocontosh, progressive massive Abross and erie a pmeumoconis (plans s7zome) SIMPLE COAL-WORKERS’ PNEUMOCONIOSIS Gros Sore oo vena shows smal black focal esons Pee ty mmin daneterandevely dstrbuted ae re ung But Rave a tendency to be more eee ne pe les These are tome col mals er plese eae nodules. Te aiopactsaourd aa dated wih ite destruction afalvelr Ss ap A) Mug some woser ave called aa yaaa of coal miners (page 53), others cent ampayera tense ere 610 pte ot ven ofaealar wal ia BGK Sea re ound on the place aa in te lamer mpi nodes (P1721) : rei yellowing eres aeseen (FE 1732 Tre compen agers se 1 Goze sea ree nee nie ere alveolewalls Drones rar tents often a 2 ne th coal aCe tes Fe toes ad alec soins 2: Resp ged now spice desucon fe Scolar wall ‘ne sienna asstVE MENOSIS Cron se Ae I es fame poems nod eas easing more barack cere ete. Theyte aly ets an ore often in the upex parts of he cated oreo gene maser breakdown Tungs posteriorly. Some pecosis or due to wverculoss central due ate y pack sed ese foanlng ar a ar nego PD ne aes? tea oned a ibroue (171) are large em in diam bilateral and 9 3 3 3 3 ° 3 z eee EDOi ne SILICOSIS C, ASBESTOSIS pneumoconiosis. A, Coal-workers’ pneumoconiosis. The macrophages phagocytose large o the interstitial tissue of the lung and aggregate around respiratory bronchiole and cause , are toxic to macrophages. The dead macrophages release fibrogenic factor and eventually tiate lot of interstitial fibrosis and also form asbestos bodies. IVE SIS ple coal-workers! 3). Histologically, the fol! g features are present: 1. The fibrouslesions are composed almost entirely of dense collagen and carbon pigment. 2. The wall of respiratory bronchioles and pulmonary vessels included in the massive scars are thickened and their lumina obliterated. 3. There is scanty inflammatory infiltrate of lymphocytes and plasma cells around the areas of massive scars. 4. The alveoli surrounding the scars are markedly dilated. Progressive massive fibrosis probably has immunological pathogenetic basis as described above. RHEUMATOID PNEUMOCONIOSIS (CAPLAN’S SYNDROME) The development of rheumatoid arthritis a few cases of coal-workers’ pneumoconiosis, silicosis asbestosisis termed rheumatoid pneumoconiosis «ca syndrome.figure 17.32 Histologic appearance of the lung in coal-workers’ pneu- moconiosis. Coal macules composed of aggregates of dust-laden macrophages and collagens are seen replacing pulmonary parenchyma. Grossly, the lungs have rounded, firm nodules with central necrosis, cavitation + calcification. Histologically, (1. ‘\.g lesions are modified rheumatoid nodules with cent:«! zone of dust-laden fibrinoid necrosis enclosed by palisading fibroblasts and mononuclear cells. The lung lesions in Caplan’s syndrome have immuno- logical basis for their origin as evidenced by detection of theumatoid factor and antinuclear antibodies CLINICAL FEATURES Simple coal-workers’ pneumoconiosis is the mild form ofdisease characterised by chronic cough with black €xpectoration. The radiological findings ofnodularities in the lungs appear after working for several years in coal-mines. Progressive Massive fibrosis is, however, a serious disabling condition Manifested by progressive dyspnoea and chronic cough with jet- lack sputum, Recurrent bacterial infections may produce punilege Sputum, More advanced cases develop pulmonary hypertenst0® ‘i i ‘i ale),’The radiological nd ight ventricular hypertrophy (cor pulmonale) reulosis and ‘pPearance may suggest tuberculosis or cancer ° 0 Steins umatoid arthritis are more common In coal ee deaielae Beneral Population. Coal-workers have increased risk os omas of the stomach, probably dueto swallowing: 7 not Contain;, : ic carcinoma does ~ Maining carcinogens. But bronchogeme Livcee eee is filled with | Proteinosis (j to the comm formation of PATHOGEN! to silica dust number of ot the type of : mechanisms not clearly u been propos 1. Silica pa alveoli are tz New macroy of phagocyte 2. Somesil bronchioles, dust is trans and into th containing cells, mast c 3. Silica du is more fibre 4, Simulta This results (IgG and Ig circulatingi 5. Asnotec which engi macrophag growth fact proliferatior MORPHO. lung is stu nodules, throughou located int frequentlySECTION Ill + Systemic Pathology Coal dust ae macrophages é Os & eo Interstitial 2” macrophages ae =~ _ ss — Dust emphysema Na! J COAL-WORKERS' PNEUMOCONIOSIS [ B, SILIC Figure 17.30 Pathogenesis of three common forms of pneumoconic amount of coal dust particles which are then passed into the interstitia ftal lisck cowvevit ce elena enna— ota dup The pathogenetic mechanisms of both forms of Soitre can be dular Soitre is general as the end-stage of long-standing si reCie e 8 fundamental defect is deficie: : nt production of thyroid hormones due to various etiologic fa Aton nou ictors described below, but most common is dietary lack of iodine. Deficient thyroid hormone production causes excessive TSH stimulation which leads to ace hyperplasia of follicular epithelium as well as formation of Iterea Te. thyroid follicles. Cyclical hyperplastic stage followed by beter involution stage completes the picture of simple goitre. Repeated Pode and prolonged changes of hyperplasia result in continued growth aces of thyroid tissue while involuted areas undergo fibrosis, thus pile completing the picture of nodular goitre. rplasia. evelops DIFFUSE GO: COLLOID Go: MiP LE NON-TOXIC GOITRE, nt with ) Diffuse, nontos »ple or colloid goitre is the name given to nd with #ffuse enlargement of the thyroid gland, unaccompanied by nfoldings red 7 F imnar epithe! is z ‘ ry infoldings. by pi ich i: jing papillary infol i m, which is piled up at places forming Pa : a ne wact ee (Microimage reproduced with permission from Atlas ofSECTION Ill ¢ Systemic Pathe v Excessive TSH stimulation t Cyclic hyperplasia-involution involution Repeated hyperplasi Fibrosis of involuted areas Growth of hyperplastic areas \ f NODULAR GOITRE Figure 27.9 Pathogenesis of simple and nodular goitre. » a state of euthyroid though they may have passed ti stage of hypothyroidism due to inadequat SH levels are invariably elevated. In generel uimon in fernales, Simple goitre often appears at f n adolescence, following which it may either regress or may progress to nodular goitre. hyperthyroidism. Most ca ETIOLOGY Epidemiologically, goitre occurs in 2 forms endemic, and non-endemic or sporadic. Endemic goitre Prevalence of goitre in a geographic area in more than 10% of the population is termed endemic goitre. Such endemic areas are several high mountainous regions far from the sea where iodine content of drinking water and food is low Colloid-filled cysts L— ® cabbage sporadi simple g cases, th of causa followin i) Subs eg. inp ii) Gen iii) Diet iv) Her transpo v) Inb MORI the th 100-1: and tr Histo LH by tal infold 2. In varial follicl epith ljoDbu DENC Asalres long-st degree charact sufficieas such as in the regions of the Himalayas, the Alps and the Ande, Oflate, however, the prevalence in these areas has declineq due to prophylactic use of iodised salt. i Though most endemic goitres are caused by dietary lack of iodine, some cases occur due to goitrogens ae Senetic factors, Goitrogens are substances which interfere with the synthesis of thyroid hormones. These substances are drugs used in the treatment of hyperthyroidism and certain items of food such as. cabbage, cauliflower, turnips and cassava roots. Sporadic (non-endemic) goitre Non-endemic or sporadic simple goitre is less common than the endemic variety. In most cases, the etiology of sporadic goitre is unknown. A number of causal influences have been attributed. These include the following: i) Suboptimal iodine intake in conditions of increased demand e.g. in puberty, pregnancy ii) Genetic factors iii) Dietary goitrogenes iv) Hereditary defect in thyroid hormone synthesis and transport (dyshormonogenesis) v) Inborn errors of iodine metabolism MORPHOLOGIC FEATURES Grossly, the enlargement of the thyroid gland in simple goitre is moderate (weighing upto 100-150 gm), symmetric and diffuse. Cut surface is gelatinous and translucent brown (Fig. 27.10). Histologically, two stages are distinguished: 1. _Hyperplastic stage is the early stage and is characterised by tall columnar follicular epithelium showing papillary infoldings and formation of small new follicles. 2. Involution stage generally follows hyperplastic stage 4 variable period of time, This stage is characterised by follicles distended by af and lined by flattened epithelium (Fig. 27.11).ee Flattened epithelium Colloid-distended follicles a Ti. Y @ Peome, % 6 90097 0@, ue ho 8 gt AT) o@ ®, @ ae &@ 1% > to, a @ Fo yt “ Lg meer ass ae il a = on $2 a o 6 os oo oe £ ss Figure 27.1 ae goitre. Microscopy shows large follicles distended by co = cases may cause dsyphagia and choking due to compression of oesophagus and trachea. Most cases are in a euthyroid state but about 10% cases may develop thyrotoxicosis resulting in toxic ase. However, thyrotoxicosis nodular goitre or Plummer’s dise of Plummer’s disease (toxic nodular goitre) differs from that of Graves’ disease (diffuse toxic goitre) in lacking ia a ophthalmopathy and dermatopathy- Such ‘hot nod ae be picked up by CT scan or by RAIU studies. Since aaa re goitre is derived from simple goitre, it has ee sane Ca Preponderance but affects older individuals because it is a late Complication of simple goitre. skill 1 |! y ‘ iyugh dism ably nple wing tre. rms from s low roid ucent infoldings and formation of small new follicles, “SR 2. Involution stage generally follows hyperplastic stage aff variable period of time. This stage is characteriseq by large follicles distended by calloid and lined by flattened folicuis epithelium (Fig. 27.1 1); MODULAR GOITRE (MULTINODULAR GOITRE, DENOMATOUS GOITRE) As already stated, nodular goitre is regarded as the end-stage of 2. It is characterised by most extreme ment of the thyroid gland and characteristic nodulari zement of the gland may be sufficient to not onl rement, but inmany long-standing simple goit: degree of tumour-like enlargeFigure 27.61 pure yunre:ricroscopy shows large oliciee distended by a“ os a cases May aoa plone and choking due to compression of oesophagus and trachea. Most cases are in a euthyroi : roid state but about 10% cases may develop thyrotoxicosis resulting in toxi nodular as Parmer disease, However, yen of Plummer's disease (toxic nodular goitre) differs from that of Graves’ disease (diffuse toxic goitre) in lacking features of ophthalmopathy and dermatopathy. Such ‘hot nodules’ may be picked up by CT scan or by RAIU studies. Since nodular goitre is derived from simple goitre, it has the same female preponderance but affects older individuals because itis alate | complication of simple goitre. ETIOLOGY Et sic factors implicated in endemic and non-endemic 0 lic variety of simple goitre are involved in the etiology »dular goitre too. However, how nodular pattern is produced is not clearly understood. Possibly, epithelial hyperplasia, generation of newfollicles, and irregular accumulation of colloid in the follicles—all contribute to produce increased tension and stress in the thyroid gland causing Tupture of follicles and vessels. This is followed by haemorrhages, cystic change, scarring and sometimes calcification, resulting in development of nodular pattern. PSE NS ies TESS Gate al me lation Multinodularity Incomplete encapsu! Haemorrhages Scarring. Sa ae 1b Y Colloid and lined by flattened follicular epithelium, rf it c is at of Ly ad ed lar ly, lar ice ure tic ,in MORPHOLOGIC FEATURES Grossly, goitre shows asymmetric and extreme e 100-500 gm or even more. The five c: features are as under (Fig. 27.12): Nodularity with poor encapsulation Fibrous scarring the thyroid in nodular nlargement, weighing ‘ardinal macroscopic 2 3. Haemorrhages 4. Focal calcification 5. Cystic di Cut on. ally shows multinodularity but y be only one or two nodules which scribed (unlike complete encapsulation of thyroid adenoma, described below). Histologically, the same heterogenicity as seen on gross appearanc een. Corresponding microscopic features are as follows (Fig. 27.13): 1. Partial orincomplete encapsulation of nodules 2. The follicles varying from small to large ood lined by flat to high epithelium. A few may show macropapillary formation. wiayshs auli3s0ee ae ee ee ee Haemorrhage Scarring Partial capsule Calcification i Variable-sized Chronic Macropapilla follicles Pe out 27.13 Nodular goitre. The predominant histologic features are: nodul: and variable-sized follicles lined by flat to high epithelium and containing ab 3. Areas ofhaemorthages, haemosiderin-laden macrophages | and cholesterol crystals. ig 4. Fibrous scarring with foci of calcification. 5. Micro-macrocystic change: The contrasting features of diffuse and n summarised in Table 27.2, & s Non-neoplastic Diseases of Thyroid odular goitre aresep oe ep reeeeraLer © Unilateral or bilateral enlargement of male breast is known as gynaecomastia; it is mainly due to proliferation | of ducts and increased periductal stroma, | Two main examples of fibroepithelial (biphasic) tumours of the | breast are fibroadenoma and phyllodes tumour. Besides, abenign papillary tumour, intraductal papilloma, is also discussed here. (roe ibroadenoma © s0fibroma is a benign biphasic tumour of fibrous and epitliciial elements. It is the most common benign tumour of the fernale breast. Though it can occur at any age Compressed duct % Collagenic stroma RACANALICULAR PATTERN A, INT! icroscopic patterns. Figure 25.7 Fibroadenoma of the breast, ™m!Compressed ductules No lobules pastia. There is prominence of fibrous and ontaining compressed and dilated ductules yperplasia. There is absence of lobular tissue mission from Atlas of Histopathology by Ivan Brothers Medical Publishers Pvt Ltd, New Delhi) cystic disease with ar pular atypical hyper hanges has 4 to velopment later. { jlateral enlargement of male breast is scomastia; it is mainly due to proliferation -ased periductal stroma IBROEPITHELIAL TUMOURS iphasic) tumours of the mour. Besides, abenign js also discussed here. , of fibroepithelial (bit ma and phyllodestun traductal papilloma, denofibroma is ‘a benign biphasic tumour of ial elements. It iS the most common ee ale breast. Though it can occu at any r : ce fereaiatte , Most patients are between 15 to 30. “ars of age, Clinically, fibroaden year » fibroadenoma generally appears asa ey discrete, freely mobile nodule within the breast Rarely, adenoma may contain in situ or invasive lobular or ductal carcinoma carci i Guu tuonna or the carcinoma may invade the ibroadenoma from he adjacentprimary breast cancer, MORPHOLOGICFEATURES Grossly,typicalfibroadenoma is a small (2-4 cm diameter), solitary, well-encapsulated, spherical or discoid mass. The cut surface is firm, grey- white, slightly myxoid and may show slit-like spaces formed by compressed ducts. Occasionally, multiple fibroadenomas may form part of fibrocystic disease and is termed fibroadenomatosis. Less commonly, afibroadenoma ‘may be fairly large in size, up to 15 em in diameter, and is called giant fibroadenoma but lacks the histologic features of cystosarcoma phyllodes (discussed later). Microscopically, fibrous tissue comprises most of a fibroadenoma, The arrangements between fibrous overgrowth and ducts may produce two types of patterns which may coexist in the same tumour, These are intracanalicular and pericanalicular patterns (Fig, 25.7): Intracanalicular pattern is one in which the stroma compresses the ducts so that they are reduced to slit-like s lined by ductal epithelium or may appear as cords of ‘helial elements surtounding masses of fibrous stroma. Pericanalicular pattern is characterised by encircling masses of fibrous stroma around the patent or dilated ducts. Phe fibrous stroma may bequite cellular, or there may be areas of hyalinised collagen. Sometimes, the stroma is loose and myxomatous, VARIANTS A few morphologic variants of fibroadenomas have been described: 1. Complex fibroadenoma is composed of cyst 23 mm in size, sclerosing adenosis, calcifications and papillaryapocrine hyperplasia. 9, Juvenile fibroadenoma is an uncommon variant of fibroadenoma which is larger and rapidly growing mass seen in adolescent girls but fortunately does not recur after excision. 3, Occasionally, the fibrous tissue elementin the tumour is scanty, and the tumourisinstead predominantly composedof ‘losely-packed éuctular or acinar proliferation; thisis termed yseaig aul SZ YALdVHDyr SEU EININ TE Oe Figure 25.8 Phyllodes tumour. Gross appearance of phyllodes tumour showing firm, nodular mass having stlit-like compressed spaces. (Courtesy of Drlvan Damjanov, Department of Pathology and Laboratory Medicine, The University of Kansas School of Medicine, Kansas, USA). as tubular adenoma. Similarly, if an adenoma is composed ofacini with secretory activity, itis called lactating adenoma seen during pregnancy or lactation. Unlike fibroadenoma, both tubular adenoma ating adenomas are not true biphasic tumours b examples of benign epithelial hyperplasia but are ince they are named as SS PHYLLODES TUMOUR Cystosarcoma phyllodes w: in 1838 to an uncommon gross appearance ( clinical behaviour, age. Grossly, the t is distinguished h connective tissu as the nomenclature given by Miiller bulky breast tumour with leaf-like phyllodes=leaf-like) having an aggressive Most patients are between 30 to 70 years of ‘umour resembles a giant fibroadenoma but mace from the latter by more cellular e. Later, the WHO classification o aa bee Proposed the term ‘phyllodes tumour’ in ee aus ne term of Cystosarcoma phyllodes’ Phyllodes tumour € classified into benign, borderline and malignant on the basi is vi f oe ec pistologle features of stromal cells. Local recurrences ‘uch more frequent than metastases, Tage 10 ot FeATURES Grossly, the tumouris gen ; , 10- ameter, round t and. 2288 fully encapsulated than a tment so. Ob Bosselated, ands 7 Microscopy i, Anaplastic tumour cells cords, poorly-formed glan foci ii, There is infiltration by the: diffuse fibrous stroma and fat. Ficure 5 ductgia) i pericanalicular pattem (B) showing fibrous tissue encircling the ducts usjgi mies tenee surtace of the tu to yellowish with chalky streaks, into the surrounding fat (Fig. 59.3) Compressed duct Colegenic stroma foma breast. The tumour is MOUF I grey-white and often extends irregularly form various patterns —solid nests, \dular structures and some int s5€ Masses of tumour cells into ductal Ans, Fibrocystiechangets fife; ts incidence decines in post menopeel nag oe 2.2 Whatisthe prognosis of fbrocysc change? Soe. Nompolterative or simple voce change does not cry any tsk of development of breast cancer. Cases of ralfeccien, APrecystic disease without atypia have 15 to. timesineacea ne tic disease with atypia or atypical higher isk of beac cancer tater, 3, Whatis the common age for fbroadenoms? ‘Ans, Young females, 15-30 yeas of age 198 for occurence of bvcystc change? #eeninadultwomenin Seto sthdecades Colagenic stoma Patent du. PERICANALICULAR PATTERN a and compressed and composed of iniracanalicular growth pattern of strom: .EXERCISE | 93 Competencies (Outcomes) © Tolearn pathology of morphologically significant diseases of the chronic cholecystitis with cholelithiasis, gallbladder carcinoma). po —<—<— PEE liver and gall Diseases of Hepatobiliary System [INTEGRATION | ladder (e.g. cinhosis of iver hepatocelidar cacnong ‘8 To desctibe salient gross and microscopic features of these conditions The livers connected to thebiliary tract and the pancreas. Only. a few morphologically important conditions pertaining to these organs are discussed in thisexercise, Cirthosis of the liver is one of the leading causes of death which occurs following hepatocellular necrosis of varying etiology. Hepatocellular carcinomaisthe most common primary. malignant tumour of the liver, most often following cirthosis of varying etiology and exposure to chemical carcinogens. Most common forms of gallbladder diseases are chronic cholecystitis, gallstones, and gallbladder carcinoma. CIRRHOSIS LIVER Be Cirthosis of the liver is a diffuse disease having disorganised Tobular architecture and formation of nodules which are separated from one another by irregular bands of fibrosis, Gross Cirrho ‘orphologically categorised by the size of nodules into micronodular (when the nodules are less than 3 mm, Fig. 53.1), macronodular (when the nodules are bigger than 3 mm, Fig. 53.2), and mixed (when both small and large nodules are seen). Etiologically, common forms repostnecrotic, ‘normal ight brown) and shows diffuseand uniform sized e OM ‘of Pathology and Laboratory Medicine, the Universnyorka ocment ‘of Medicine, Kansas, USA). ‘@NSas Schoo} alcoholic, biliary, and others. On sectioned surface, the gay brown nodules are separated from one ancther by greyhte fibrous septa. Microscopy The etlolagic diagnosis of cirrhosis in routine microscopy may not be possible. In genera) salient featues cirrhosis are as under (Fig. 53.3) i. Lobular architecture of hepatic parenchyma islostandcental veins are hard to find. li Fibrous i na into nodules ii, parenchyma fem regenerati having disorganised masses of hepatocyte iv. Fibrous some monopyclear inflammator infiltrate anc J bile a) (Courtesy af odular pattern (nodules larger than 3" and Laborat esi story Medici cl of Me Aisne, The University of Kansas SchoO 1 of Kansas, Usa) (210)FIGURE 53.3 Alcoholic (micronodular) cirrhosis. It shows nearly uniforr septa dividing them. There is minimal inflammation and some reactiv highlighted by Masson's trichrome stain. (Microimages reproduced with f Brothers Medical Publishers Pvt Ltd, New Delhi). HEPATOCELLULAR CARCINOMA Hepatocellular carcinoma (HCC) or hepatoma is one of the aggressive primary cancers. Gross HCC may form one of the three patterns of growth (in decreasing order of frequency) (Fig. 53.4): i. Expanding type as 4 single large mass with central necrosis and haemorrhage.: : & : 3 8 1 sreptocoee- The prostate i MORPHOLOGIC FEATURES Gross, the gat Bato ‘hard ing the clinical impression of prostate carcinoma Inmen and tdnune Increasingly move Fequent above the age O50 and its eid However sproms approaches 75-80% I 30% yy y appre producing tn ae ine aaa ae me oma testseone “MonrHOLOGICFEATURES Gros tees pue noch rn and welghs2-tines ina “hay weigh up wo 40-00 gm The appestaneay Sed upon whether the hyperplasa ‘istologcaily in every cas, theres hyperplasia ofa tissue elements in varying proportions glandular Hb and muscular (Fig 23.17). Glandular hyperplasia predominates in mos css bovasculr cores The ng ei "woreyerd: tenner al clmpar maces ool defined borders and the outer euboidal eae “pihetum wit basal male x. 4 bromuciarhyperpata when present 2 dois ompnen appears a geese of sin al et An appcaance alin tbomjoma of he ver ‘hain wlan an crams ei ‘ihe hill erreur found inl ‘maphoestic aggregates, small areas of infarction. OPO amacea sno of squamous meeps Sometes, the patSection 6: Pathology of Systems Doyle layered epithelium Papillary infoldings cane (convolutions) Corpora amylace infoldings (convolution: -d by two layers of epithelium with basal polari of Histopathology by Ivan Damjanov 2012, Jaypee Brothers Medical Publ Q. 3. What is the prognostic relevance of lymphocytic i sel joma?, ‘Ans. Lymphocytic infiltrate, and sometimes gi the stroma is indicative of good host immi therapy? E Ans. Seminoma is highly eae tumour9 J = EXERCISE competencies (Outcomes) To ig Tolearn pathology of tubulointerstitialdisease system (2g. renal cell carcinoma, Wilms tumou (9. chronicpyelonephaits) and some © ig todesctbe salient gross and microscopic features one enor: Tubulointerstitial Disease and Tumours of Renal System ee CESSES EM CCAS samples of common primary tumours f renal eS ofthese conditions. feral tubules and interstitial tissues are together involved in infammatory disease of the kidneys, eg, pyelonephritis of vaious types. Tumours of renal system are classified based on th sforigi. A few common examples of such tumours are re cdleatcinoma (arising iaising from primitive renal tissue) and tran uothelial) carcinom: ng from urotheliur fm the pelvis of kid Morphology of th m renal tubular cells) A (ciRONIC PYELON hronic tubulointerstitial diseas Gonic pyelonephr inflammation and scarring Resulting from repeate te to infection. contracted, weighing reduction. The outer scars are of ial Gross The kidneys are usually small and bss than 100 gm each, showing unequal recht 2 surface of the kidneys is irregularly scarred. TNES” ON faible size and show irregular depression? °° RGURESS.1 small metry and inegular scaring inte. (6, i (Gross images courtesy cine, Kansas, USA). surface, The pelvis blunted and ma Microscopy the interstitium and ced interstitial ibrosis arying degree of colloid casts p tionof tubules ii-The wal ofdilatedpelvicalyeal system shows marked chron inflammation and scarring. iv. There is often periglomerular fibrosis and hyalinisation of some glomerul. ) mA RENAL CELL CARCINOMA ‘ ‘all renal cancers and occurs mo: comprises 70-80% of Commonly in 50-70years of age. versity of Kansas Schoo! ot face ef sal ertcoest se fcine TUN External trin 6: Pathology of Systems Hyalinised glomerulus Periglomerular fibrosis Hyalinised vessel Chronic Colloid cast Interstitial periglomerular fibrosis. Gross The tumour commonly arises from a pole, most often M upper pole, of the kidney as a solitary and unilateral tumour. 1. The tumour is generally large, golden yellow and circumscribed, pe Cut section of the tumour commonly shows large areas of re ischaemic necrosis, cystic change and foci of haemorrhages pr (Fig. 55.3). Another feature is the frequent presence of tumour pe thrombus in the renal vein. di icine sie RES saiacs zi“a These cysts are seen more commonly on the dorsum of frequently _ the balded portion of the skin. the hj ‘ands and on al cysts. Histologically, solar keratosis has following character; alisading features: ised layer i) Considerable hyperkeratosis aaa ii) Marked acanthosis alae iii) Dyskeratosis and dysplasia of the epidermal] cells yst walll is showing features such as hyperchromatism, loss of. , pleomorphism and increased number of mitotic figures, iv) Non-specific chronic inflammatory cell infiltrate in the | tenpresent Upper dermis encroaching upon the basement membrane face, along of the epidermis. 2. BOWEN’S DISEASE disease is also a carcinoma as well as in situ of the entire epid » but differs from solar keratosisin and sweat —_having solitary > t may occur on sun-exposed as wellas sun-unexpos te condition may occur anywhere on the skin but is founc non the trunk, buttocks and inherited extremities. Clinically, the lesions of Bowen’s disease aresharply ic nodules, circumscribed, rounded, reddish-brown patches which enlarge 1e, sternum slowly. Histologically, the characteristic features are as under (Fig- eral layers 26.25): mis glands i) Marked hyperkeratosis ii) Pronounced parakeratosis f ili) Marked epidermal hyperplasia with disappearance dermal papillae S, SENILE it iv) Scattered bizarre dyskeratotic cells distributed througho™ duced bya the epidermis ting in sun- ice for yple. Similar Bowen’s disease, may remain confined to the surf radiation, Many years than developing into invasive cancer. msidered to yr basal cell D- MALIGNANT TUMOURS = Ta thematous, | I. SQUAMOUS CELL CARCINOMA ‘Two important fa! sult ee x . . prolo surface and athogenesis of squamous cell carcinoma are: prol aAtypical squamous calls Dermo- ‘epidermal junction ivact See, y types, ~~ Figure 26.25 Bowen's disease. The sperms is thick with lois of rete ridges but the normal base to surface maturation of epidermal layers Is effaced, Instead, there are bizarre atypical squamous cells but the border between the epidermis and dermis is intact Le. the baer ‘membrane is not breached, exposure and lmmunosuppression, in a predisposed individual These etiologic agents induce DNA damage that is followed bby p53 mutation and other events leading to dysregulation of signalling pathw us predisposing conditions are as follows i) Xeroderma pigme: ii) HPV-5 and 8-induced infection in autosomal recessive disorder epidermadysplasia verruciformis fii) Solarkeratosis iv) Chronic inflammatory condition: and draining osteomyelitis s such as chronic ulcers N mmacroxopk ma, A Main sl earn sont 8 THe _— squamout h ngt ee eeate gure wing uCeates 2 esos Na endophyte pater Sn escle oFTMETS oth exootvtc d fin sur 7 ting rth. OF Ula aris chaky wife rating growth , Ucerating Tom gating (poypstd) aroHh °) Old burn sears axon Genius nae) vi) Pras HI infection 3) king ao xi) Inthe = Seelee tohaee os ails ete) € of cancer of oral cavity, chewing betel nats and Cancerof erotalstinin chimney sweepe tn which an cccupational ercinogen (soot w ‘Kangari cancer ofthe skin of inners ahdamen common innatives of Kasha skincancer due to chroniciriation (ka the frstcancer (soot) was implicated. ide of thigh and lower ris another example of ingariisan earthenware Dot containing glowing charcoal embers used byKashmiris close to their abdomen to keep them warm Squamous cell carcinoma ay arise on any part ofthe skin ‘and mucous membranes lined by squamous epithelium, Most ‘common locations are the face, pinna ofthe eas, back of hands and mucocutaneous junctions such as on the lips, anal canal and glans penis. Cutaneous squamous carcinoma arising in a pre-existinginflammatory and degenerative lesion hasa higher incidence of developing metastases. MORPHOLOGICFEATURES Grossly, squamous carcinoma of the skin and squamous-lined mucosa canhave one of the following two patterns (Fig. 26,26): i). More commonly, an ulcerated growth with elevated and indurated margin Is seen, ii) Less often, a raised fungating or polypoid verrucouslesion ‘without uleerationis found. “Microscopically, squamous cell carcinoma is an {avasive carcinoma of the surface epidermis characterised by the following features (Fig. 26.27): 4) There is irregular downward proliferation of epidermal cells into the dermis. ii) Depending upon the grade of malignancy, the masses ‘of epidermal cells show atypical features such as variation uns 2UL @ 97HALdVHDSECTION Il! @ Systemic Patholog Figure 26.27 Microscopic features of well-differentiated squamous cell carcinoma. The dermis is invaded by d masses of cells which show atypical features, A few horn pearls with central laminated keratin are present. The dermis between the masses of tumour cells. in cell size and shape, nuclear hyperchromatism, absence of intercellular bridges, individual cell keratinisation and occurrence of atypical mitotic figures. iii) Better-differentiated squamous carcinomas have whorled arrangement of malignant squamous cells forming horn pearls, The centres of these horn pearls may contain laminated, keratin material, iv) Higher grades of squamous carcinomas, however, have fewer or no horn pearls and may instead haye highly atypical cells. vy) Anuncommon variant of squamous carcinoma may have spindle-shaped tumour cells (spindle cell carcinoma). vi) Adenoid changes may be seen in a portion of squamous cell carcinoma (adenoid squamous cell carcinoma). vii) Verrucous carcinoma (Ackerman tumour) is a low- grade variant located most commonly in oral cavity in which the superficial portion of the tumour resembles verruca (hyperkeratosis, parakeratosis, acanthosis and papillomatosis) but differs from it in having downward proliferation as broad masses of well-differentiated squamous epithelium into deeper portion of the tumour. However, there is lack of significant cellular atypia. viii) Allvariants ofsquamous cell carcinoma showinflammatory reaction between the collections of tumour cells, while in pseudocarcinomatous hyperplasia there is permeation of the epithelial proliferations by inflammatory cells, Squamous cell carcinomas is often labelled by the pathologists with descriptive terms such as: well-differentiated, moderately-differentiated, undifferentiated, keratinising, non- keratinising, spindle cell type etc. Overall prognosis of squamous cell carcinoma induced by actinic keratosis is excellent, Superficial invasive tumour may metastasise locally. Prognosis of deeply invading tumour depends upon the TNM stagini Following conditions predisy basal cell carcinoma: i) Light-skinned people who ha ii) Prolonged exposure to strong Australia and New Zealand. iii) Inherited defect in DNA rep: pigmentosum. iv) Nevoid basal cell carcinoma dominant condition in which m appear at a young age (under { inherit one defective allele (PTCH, another allele undergoes mutatio (Knudson's two hit hypothesis). MORPHOLOGIC FEATURES | pattern isa nodulo-ulcerative be a slow-growing small nodule ur with pearly, rolled margins. TI by burrowing and by destroyin rodent and hence the name ‘r frequently non-ulcerated nodulé cell carcinoma and fibrosing var Rodent ulcer.General Principles of Pathology Whor's of malignant squamous cells Keratin pearis FIGURE 17.4 Squamous cell carcinoma, well-differentiated. The subepithel which show atypical features. A few horn pearls with central laminated kei tissue between the masses of tumour cells. The invading tumour cells are arranged in a variety of masses, sheets, islands, nests, etc, jual tumour cells are usually larger than the naevus is, contain large vesicular nuclei with peripherally condensed chromatin and having prominent eosinophilic nucleoli. The cytoplasm amphophilic (Fig. 17.6). ‘ iv. Mela! igment is present in the cytoplasm in the form of uniform fine granules (u ike coarse pigment granules at the G ulspindle-shaped tumour cells (spindle cell carcinoma) vi) Adenoid changes may be seen in a portion of squamous cell carcinoma (adenoid squamous cell carcinoma). vil) Verrucous carcinoma (Ackerman tumour) is a low- grade variant located most commonly in oral cavity in which the superficial portion of the tumour resembles verruca (hyperkeratosis, parakeratosis, acanthosis and papillomatosis) but differs from it in having downward proliferation as broad masses of well-differentiated squamous: epithelium into deeper portion of the tumour. However, there is lack of significant cellular atypia. viii) All variants ofsquamous cell carcinoma showinflammatory reaction between the collections of tumour cells, while in pseudocarcinomatous hyperplasia there is permeation of the epithelial proliferations by inflammatory cells. Squamous cell carcinomas is often labelled by the pathologists with descriptive terms such as: well-differentiated, moderately-differentiated, undifferentiated, keratinising, non- keratinising, spin 1 type etc. Overall prognosis of squamous cell carcinoma induced by actinic ke Superficial invasive tumour may metas! isis of deeply invading tumour d stag ng) ELL CARCINOMA (RODENT ULCER) Typically, 1 is a locally invasive, slow-growing that rarely metastasises. It occurs lusively on hairy skin, the most common location (90%) being the face, usually above a line from the lobe of the ear to the corner of the mouth (Fig. 26.28). tumour of middle (Knuc MO. patt ask witl by! rod free cell Fig cel