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At autopsy, the spleen of a patient is noted to have a thickened capsule and many small, scarred areas.

Microscopic examination of the scarred areas reveals fibrosis with hemosiderin and calcium
deposition. This type of spleen is usually seen in conjunction with which of the following

A. Hepatic cirrhosis

B. Hodgkin's disease

C. Rheumatoid arthritis

D. Sickle cell anemia

E. Trauma


The correct answer is A. The spleen shows the changes of chronic congestive splenomegaly, typically
associated with hepatic cirrhosis. The described small scars are called Gandy-Gamma nodules, and are
thought to be the result of organization of old hemorrhages.

Hodgkin's disease (choice B) produces large splenic nodules in which Reed-Sternberg cells can be found
surrounded by mature lymphocytes, eosinophils, and neutrophils.

Rheumatoid arthritis (choice C) and many other chronic inflammatory disorders induce reactive
hyperplasia of the spleen with formation of many large germinal centers in the splenic follicles.

Sickle cell anemia (choice D) produces many small (often triangularly shaped) infarctions in
the spleen.

Trauma (choice E) can cause splenic rupture.

A 30-year-old man with an undiagnosed cardiac anomaly has been unable to do strenuous exercise
throughout his life. Auscultation demonstrates an immediate diastolic murmur, which has been be
present since childhood. The patient has never been cyanotic. Which of the following disorders
would most likely cause the patient's findings?

A. Bicuspid aortic valve

B. Common pattern transposition of the great arteries

C. Patent ductus arteriosus

D. Tricuspid atresia

E. Truncus arteriosus


The correct answer is A. Isolated bicuspid aortic value is a very common congenital anomaly,
which may be completely asymptomatic or may cause modest noncyanotic obstruction related to
stenosis. It is associated with an immediate diastolic murmur, related to some degree of
aortic insufficiency that is often recognized in early childhood. Surgical correction of even
mild to moderate stenosis or insufficiency is now recommended to prevent long-term damage to
the heart muscle.
The common pattern of transposition (choice B) of the great vessels produces early cyanosis.

Uncorrected patent ductus arteriosus (choice C) produces a continuous ("machinery") murmur and late

Tricuspid atresia (choice D), which is usually accompanied by an atrial septal defect,
produces early cyanosis.

Truncus arteriosus (choice E) produces early cyanosis.

A 60-year-old male presents to the dermatologist with a complaint of tender blisters on his arm and
flank. Physical examination reveals blisters and flaccid bullae; a few have ruptured, leaving
red, sore, denuded areas. Which of the following findings would suggest the diagnosis of
pemphigus vulgaris as opposed to bullous pemphigoid?

A. Eosinophils within bullae

B. IgA deposits on basement membrane

C. IgG autoantibody activity

D. Negative Nikolsky sign

E. Oral mucosal lesions


The correct answer is E. Pemphigus vulgaris is associated with chronic, severe bullae formation
on the skin and oral mucosa. Mucosal lesions are extremely rare in bullous pemphigoid. This can
be used clinically to guide therapy, although a skin biopsy should be taken to confirm the
diagnosis. Both diseases are characterized by formation of tender bullae that can rupture,
leaving red, raw areas. Pemphigus vulgaris patients eventually become febrile and lose weight,
and if untreated, most will die within one year. Bullous pemphigoid lesions tend to heal and
the patients do very well. This prognostic difference is an important distinction in
dermatologic medicine.

Eosinophils within blisters (choice A) provide an important clue supporting bullous pemphigoid
as the diagnosis which must be ascertained with histologic examination. The vesicles in
pemphigus vulgaris mostly contain rounded acantholytic keratinocytes "floating" within.

IgA deposits seen with immunofluorescence on the basement membrane (choice B) is characteristic
of a third bullae-forming disease known as dermatitis herpetiformis. Vesicles form between the
dermal-epidermal junction. The disease is associated with gluten sensitivity and celiac

IgG autoantibody activity (choice C) is common to both pemphigus vulgaris and bullous pemphigoid.

Nikolsky's sign consists of separation of the epidermis upon manual stroking of the skin.
Bullous pemphigoid is characterized by a negative Nikolsky's sign (choice D), but Nikolsky's
sign is positive in pemphigus vulgaris due to the IgG-mediated destruction of intercellular
bridges between keratinocytes.

A five-year-old girl is brought to a pediatrician because she is developing breasts. Physical

examination shows large hyperpigmented macules with irregular margins on one side of her back.
Which of the following bony abnormalities would most be likely associated with these symptoms?
A. A combination of osteitis fibrosa cystica and osteomalacia

B. A generalized thinning of bony spicules

C. Excessive bony deposition with obliteration of marrow

D. Formation of new bone beneath the periosteum of phalanges

E. Multiple localized whorls of connective tissue


The correct answer is E. McCune-Albright syndrome is the combination of precocious sexual development,
irregularly shaped ("coast of Maine") pigmented skin macules, and polyostotic fibrous
dysplasia. The latter condition is characterized by local bony defects containing unmineralized
whorls of connective tissue.

Renal osteodystrophy refers to a constellation of bony changes occurring in the context of

chronic renal failure. Features may include those of osteitis fibrosa cystica (marrow fibrosis,
bony resorption and cyst formation within the marrow cavity) and osteomalacia (choice A).

Osteomalacia results from vitamin D deficiency in adults, and is characterized by a generalized

thinning of bony spicules (choice B).

Osteopetrosis is characterized by excessive bony deposition that can obliterate marrow (choice
C), causing anemia.

Formation of new bone beneath the periosteum of the phalanges (choice D) is characteristic of
hypertrophic osteoarthropathy, which may be associated with thoracic cancer, chronic lung
disease, and chronic liver disease.

During a pelvic examination, a gynecologist discovers an adnexal mass in a 32-year-old woman. Resection
of the mass demonstrates a malignant ovarian tumor. The tumor suppressor gene strongly
associated with this tumor is also associated with cancer of which other organ or tissue?

A. Breast

B. Colon

C. Pancreas

D. Peripheral nerve

E. Stomach


The correct answer is A. The tumor suppressor gene most strongly associated with ovarian carcinoma is
BRCA-1, which is also associated with breast cancer. This tumor suppressor gene is located on 17q.

Associate APC (5q), DCC (18q), and p53 (17p) with colon cancer (choice B).

Associate DPC (18q) with pancreatic cancer (choice C).

Associate NF-1 (17q) with neurofibromatosis type I, which is associated with peripheral nerve
tumors (choice D).
Associate DCC (18q) with stomach cancer (choice E).

A 30-year-old woman presents to a physician with rather non-specific complaints of fatigue, malaise,
low-grade fever, and arthralgias. Screening serum chemistries demonstrate an elevated BUN. The
urine shows proteinuria. Testing for which of the following will be most helpful for making the

A. Anticentromeric antibody

B. Antimitochondrial antibody

C. Antinuclear antibody

D. Anti-TSH receptor antibody

E. Rheumatoid factor


The correct answer is C. Systemic lupus erythematosus is a favorite on board examinations, and
should be considered in any 15- to 45-year-old woman with chronic, poorly defined symptoms.
Clues that help are malar rash, anti-double-stranded DNA antibodies, and renal involvement.
Antinuclear antibody is a good screening test (it is also positive in some other autoimmune
diseases) and should be used first in working this patient up. Renal involvement is unusual in
most other autoimmune diseases.

Anticentromeric antibody (choice A) is a marker for the CREST form of scleroderma.

Antimitochondrial antibody (choice B) is a marker for primary biliary cirrhosis.

Anti-TSH receptor antibody (choice D) is a marker for Graves' disease.

Rheumatoid factor (choice E) is a marker for rheumatoid arthritis.

An adult with newly diagnosed tuberculosis is most likely to have which of the following types of

A. A single lesion in a lung apex

B. A single lesion in the gastrointestinal tract

C. A single lesion subjacent to the pleura

D. Both a lesion subjacent to the pleura in the lower part of an upper lobe and active disease in the
mediastinal lymph nodes

E. Multiple tiny masses throughout the body


The correct answer is A. This is something of a trick question, but it stresses an important
fact many medical students do not realize. Primary tuberculosis infection characteristically
involves the lung subjacent to the pleura in either the lower part of the upper lobe or the
upper part of a lower lobe of one lung. The mediastinal nodes are also usually involved (choice
D), rather than having a single lesion subjacent to the pleura (choice C) without lymph node
involvement. However, the "trick" part of this question rests on the fact that roughly 80% of
newly diagnosed pulmonary tuberculosis cases in adults are actually due to reactivation of an
often clinically unsuspected infection acquired years-to-decades previously. The reinfection
site usually is in the apex of the lung.

You should also be aware that the lungs are not the only site where tuberculosis can occur (it
can occur throughout the body), and isolated gastrointestinal involvement (choice B) is (uncommonly)
also seen.

Miliary tuberculosis (rare) is a widely disseminated and dangerous form of tuberculosis

characterized by small lesions throughout the body (choice E).

A 40-year-old woman has the following family and personal history: her mother died of breast cancer at
age 64, she smokes one pack/day, she drinks five or more cups of coffee/day, she has no
children, and she takes birth control pills. Which of the following is the most significant
risk factor for breast cancer in this patient?

A. Birth control pills

B. Caffeine consumption

C. Cigarette smoking

D. Family history

E. Nulliparity


The correct answer is D. Positive family history is definitively the most significant risk
factor of developing breast cancer among the ones mentioned in the list. About 5% to 10% of
cases are attributable to inheritance of autosomal dominant genes. Most hereditary cases of
breast cancer are due to two genes, BRCA1 and BRCA2, which are tumor suppressor genes probably
involved in DNA repair. There are additional rare "susceptibility" genes, namely those causing
Li-Fraumeni syndrome (mutations of p53), Cowden syndrome (mutations of a gene on chromosome
10), and ataxia-telangiectasia (mutations of ATM gene). Note, however, that 80% to 90% of women
with breast cancer do not have a positive family history.

The role of exogenous estrogens, including those administered with birth control pills (choice A) or
postmenopausal replacement therapy, is still debated. If there is any associated risk for
breast cancer, this is minimal.

There is no convincing evidence linking caffeine consumption or cigarette smoking (choices B

and C) to breast cancer.

Breast cancer is more frequent in nulliparous women than in multiparous women. Nulliparity
(choice E) is therefore a risk factor, but its role is considered less important than family
history. Similar to a long duration of reproductive life and late age at first intercourse,
nulliparity seems to increase breast cancer risk by increasing exposure to endogenous estrogen
during the menstrual cycle.

Biopsy of a small, rounded rectal polyp demonstrates glands and sawtooth crypts composed of a
proliferation of goblet and columnar epithelial cells. No atypia is seen. This polyp is best
classified as which of the following?

A. Hyperplastic polyp
B. Peutz-Jeghers polyp

C. Tubular adenoma

D. Tubulovillous adenoma

E. Villous adenoma


The correct answer is A. This is a hyperplastic polyp; these polyps comprise 90% of all colonic
polyps and have no malignant potential.

Peutz-Jeghers polyps (choice B) also have no malignant potential, but tend to be larger and
have a complex branching pattern.

Tubular adenomas, tubulovillous adenomas, and villous adenomas (choices C, D, and E) are all
true neoplastic polyps containing dysplastic epithelium; the malignant potential of these
polyps increases with size and the percentage of the polyp which has a villous configuration.

A 52-year-old Caucasian male presents with sinus pain and drainage, bloody nasal discharge, and nasal
mucosal ulceration. On laboratory examination, the man is found to have proteinuria, hematuria,
and red blood cell casts. A biopsy of the upper airway tissue reveals granulomatous inflammation
with necrosis. Renal biopsy confirms the existence of glomerulonephritis. Blood tests show the
presence of antineutrophil cytoplasmic antibodies (c-ANCA). What is the most likely diagnosis?

A. Allergic angiitis

B. Goodpasture's syndrome

C. Non-infectious granulomatous disease

D. Tumors of the upper airway

E. Wegener's granulomatosis


The correct answer is E. Antineutrophil cytoplasmic antibodies yielding a cytoplasmic

immunofluorescence pattern (c-ANCA) are found in over 90% of patients with Wegener's granulomatosis.
classic clinicopathologic complex of Wegener's granulomatosis usually provides ready differentiation
from other disorders in which c-ANCA is positive. c-ANCA is not considered pathognomonic, but has a
strong association with Wegener's and is not found in any of the other diseases listed.

c-ANCA is generally negative in patients with allergic angiitis (choice A), non-infectious
granulomatous disease (choice C), and tumors of the upper airway (choice D).

c-ANCA is typically negative in Goodpasture's syndrome (choice B), but p-ANCA have been
detected in some patients with Goodpasture's syndrome.

A tall man with gynecomastia and testicular atrophy has a testicular biopsy that shows sparse,
completely hyalinized seminiferous tubules with a complete absence of germ cells and only rare
Sertoli cells. Leydig cells are present in large clumps between the hyalinized tubules. Which
of the following genetic disorders should be suspected?

A. Testicular feminization syndrome

B. Trisomy 18

C. Trisomy 21

D. 45, XO

E. 47, XXY


The correct answer is E. The testicular changes described are those observed in Klinefelter's
syndrome, most often due to 47, XXY genetics.

Testicular feminization syndrome (choice A) is due to a genetically determined unresponsiveness to

testosterone that produces a phenotypic female in an individual with 46, XY chromosomes.

Trisomy 18 (choice B) is Edwards' syndrome, characterized by facial features that are small and

Trisomy 21 (choice C) is Down syndrome, the most common trisomy. Characteristics include
oblique palpebral fissures, epicanthal folds, endocardial cushion defects, simian creases, and
high-arched palate, among other anomalies.

Turner's syndrome, 45, XO (choice D), produces a sterile but phenotypic female individual of
short stature with webbing of the neck.

A 54-year-old woman presents with complaints of abdominal fullness and early satiety. She denies a
change in bowel habits and says that constipation is her normal state. A radiographic bowel
series shows an "apple core" lesion in her sigmoid colon. Which of the following markers is
expected to be elevated in this patient?

A. Alpha-fetoprotein (AFP)

B. Carcinoembryonic antigen (CEA)

C. Human chorionic gonadotropin (hCG)

D. Lactate dehydrogenase (LDH)

E. Prostatic acid phosphatase (PAP)


The correct answer is B. CEA is a glycoprotein (200,000 daltons) that is found in the
gastrointestinal mucosal cells and pancreatobiliary system secretions. It becomes elevated when breaks
in the mucosal basement membrane occur due to tumor growth. Some other conditions can also cause
elevations of CEA (e.g., cirrhosis, pancreatitis). The patient described above has colonic carcinoma,
and the "apple core" lesion is the classic radiographic finding of this tumor. Although CEA is not used
for screening because of the large number of false positives, it can be used to guide treatment in known
cases. It returns to normal levels 30-45 days after tumor resection. If it begins to rise again, tumor
recurrence is likely.
AFP (choice A), or alpha-fetoprotein, is an alpha globulin (70,000 daltons) made by the liver
and yolk sac of the human fetus. It is elevated with hepatocellular carcinoma and germ cell
neoplasms. It is not particularly specific.

hCG (choice C), or human chorionic gonadotropin, is a glycoprotein secreted by trophoblastic

epithelium of the placenta. It is useful (sensitive and specific) for germ cell tumors of the testis and

LDH (choice D), or lactate dehydrogenase, is a very non-specific test that can be elevated in
many conditions, including malignancy.

PAP (choice E), or prostatic acid phosphatase, is a sensitive marker used for detecting prostatic

A 54-year-old man is admitted to the hospital with cough and dyspnea, which over a period of years has
led to marked respiratory embarrassment and cyanosis. Chest x-ray film of the lungs shows
bilateral lower lobe ground-glass infiltrates. Wedge biopsy of the lung demonstrates airspaces
filled with macrophages containing lipid, periodic acid-Schiff (PAS)-positive granules, and
lamellar bodies. There is an accompanying interstitial pneumonitis, hyperplasia of the septal
lining epithelial cells, and desquamation of epithelial cells into alveoli. The lamellar bodies
within the macrophages are composed of which of the following?

A. Amyloid

B. Calcitonin

C. Fibrin

D. Hemosiderin

E. Surfactant


The correct answer is E. The disease is desquamative interstitial pneumonitis (DIP), which is
an idiopathic process related to idiopathic interstitial fibrosis. DIP may respond to steroid
therapy but may also progress to end-stage lung disease. The lamellar (layered) bodies within
macrophages contain surfactant derived from type II pneumocytes.

Amyloid (choice A) is deposited extracellularly and is not part of the DIP process.

Calcitonin (choice B) is found in medullary carcinoma of the thyroid.

Fibrin deposition (choice C) can be part of the DIP process, but occurs as eosinophilic
extracellular deposits, rather than as intracellular lamellar bodies.

Hemosiderin (choice D) can accumulate in pulmonary macrophages, usually in the setting of

congestive heart failure with microhemorrhages, and produces golden brown granules.

Over a one month period, a 35-year-old man develops symptoms of hyperthyroidism with tachycardia and
heat intolerance. Thyroid biopsy demonstrates a heavy mononuclear cell infiltrate with
multinucleated giant cells, follicular disruption, and loss of colloid. About one month later,
the patient develops symptoms of hypothyroidism. To which of the following is this patient's
condition thought to be most closely related?

A. Blocking TSH receptor autoantibodies

B. Carcinoma

C. Lymphoma

D. Stimulating TSH receptor autoantibodies

E. Viral infection


The correct answer is E. The patient has subacute thyroiditis, also known as granulomatous
giant cell or de Quervain's thyroiditis. This condition is thought to be due to viral infection
of the thyroid gland, and may follow an upper respiratory infection. Early in the process, the
follicular destruction causes inappropriate release of thyroid hormone with resulting
hyperthyroidism. Later, the destruction can proceed to the point that hypothyroidism occurs.

Antibodies that block the TSH receptor (choice A) are a feature of Hashimoto's disease.

Thyroid carcinoma (choice B) usually does not produce hyperthyroidism.

Lymphoma (choice C) of the thyroid is more likely to occur in the setting of Hashimoto's disease.

Stimulating TSH receptor antibodies (choice D) are a feature of Graves disease.

A 3-year-old boy with an enlarging, left-sided, abdominal mass undergoes diagnostic biopsy. The tumor
reveals a variety of cellular patterns: dense immature islands of epithelial cells, ribbons of
spindled fibroblast-like stromal cells, and poorly formed tubular structures. This triphasic
histology is most suggestive of which of the following childhood neoplasms?

A. Embryonal rhabdomyosarcoma

B. Ewing's sarcoma

C. Hodgkin's disease

D. Neuroblastoma

E. Wilms' tumor


The correct answer is E. Wilms' tumor, a neoplasm of the embryonic renal blastema, contains
both a neoplastic epithelial and stromal component. In addition to organizing as islands of
stromal or epithelial cells, these cells characteristically organize into recognizable
glomerular and/or tubular structures that may represent a minority or sizeable component of the

Rhabdomyosarcoma (choice A) is a malignancy of skeletal muscle origin, and the cells are
recognized by their cytoplasmic content of eosinophilic muscle proteins (thin and thick
filaments). Rhabdomyosarcoma has an embryonal, alveolar, and pleomorphic variant, but none
demonstrates a triphasic histology.

Ewing's sarcoma (choice B) appears as a monotonous mass of primitive, small, round cells with a
thin rim of clear cytoplasm. Ewing's sarcoma is a tumor of bone; presentation as an abdominal
mass is distinctly unusual.
Hodgkin's disease (choice C) is a lymphoid malignancy that presents with lymphadenopathy,
typically in the cervical or mediastinal nodes. The cellular component contains varying amounts
of inflammatory cells and Reed-Sternberg cells.

Neuroblastoma (choice D) frequently presents as an abdominal mass in children; however, it does

not have an epithelial component. The cell population of neuroblastoma ranges from primitive,
small, blue, round cells to well-differentiated neuritic cells resembling ganglion cells.

A 60-year-old man presents to a physician because of difficulty in reading and coming down stairs, which
he attributes to an inability to "look down." Physical examination reveals that the patient
looks around by moving his head rather than his eyes and also shows a distinctive axial
rigidity of neck, trunk, and proximal limb muscles. He shows poverty of movement and dysarthric
speech. Mentally, the patient responds very slowly but has better memory and intellect than are
initially apparent. Which of the following pathologic findings of the brain would most likely
be present?

A. Depigmentation of the substantia nigra and locus ceruleus

B. Diffuse cortical atrophy with relative sparing of primary motor and sensory areas

C. Selective frontal and temporal lobe atrophy

D. Striking degeneration of the caudate nucleus

E. Widespread neuronal loss and gliosis in subcortical sites


The correct answer is E. The disease is progressive supranuclear palsy, a degenerative disorder
characterized by ophthalmoplegia, pseudobulbar palsy, axial dystonia, and bradykinesia. The
presentation described in the question is typical. The pathologic changes consist of widespread
neuronal loss and gliosis in subcortical sites with sparing of the cerebral and cerebellar

Pigmented neurons in the substantia nigra (pars compacta) and locus ceruleus (choice A) selectively
degenerate in Parkinson's disease.

In Alzheimer's disease, there is diffuse cortical atrophy (choice B), especially over the
association cortex of frontal, temporal, and parietal lobes, with relative sparing of primary sensory
and motor areas.

Selective frontal and temporal lobe atrophy (choice C) is characteristic of Pick's disease.

The caudate nucleus and putamen undergo severe atrophy (choice D) in Huntington's disease. Cortical
atrophy occurs to a lesser extent.

A 2-year-old girl is evaluated because of deteriorating vision. On physical examination, a whitish hue
is noted in the right pupil, along with strabismus. Palpation of the eye elicits apparent pain
and tenderness. The patient is referred to an ophthalmologist, who schedules surgery, and
removes a multifocal tumor from the right eye. The pathology report notes the presence of
rosettes composed of cuboidal-to-columnar cells surrounding a central lumen in the tumor. In all
likelihood, this child's condition stems from a mutation in a gene on chromosome

A. 5
B. 7

C. 9

D. 13

E. 21


The correct answer is D. The description of this case is classic for retinoblastoma, the most
common malignant eye tumor of childhood. Retinoblastoma presents as in the question, and
is composed of neuroepithelial cells that form characteristic rosettes (Flexner-Wintersteiner rosettes).
Familial retinoblastoma is often bilateral or multifocal, as in this case. A preexisting mutation of a
tumor suppressor gene, Rb, located on chromosome 13 (13q14) is present, but causes no symptoms. A
second, somatic mutation in a retinal cell leads to loss of a nuclear protein that prevents the retinal
cell from exiting G1, allowing development of the tumor. In cases of sporadic retinoblastoma, mutations
must occur in both chromosomes 13 of a somatic cell, a rare event, hence sporadic retinoblastoma is
always unifocal and unilateral.

A 25-year-old man presents to the emergency room with severe abdominal pain. Guaiac test on stool
demonstrates occult blood. The patient is taken to exploratory laparotomy, at which a small
area of infarcted small bowel is found and surgically removed. Histologic studies on the
removed section of bowel demonstrate a recent thrombus occluding a small muscular artery. The
adjacent vessel wall shows fibrinoid necrosis with a mixed inflammatory infiltrate containing
neutrophils, eosinophils, and mononuclear cells. Which of the following is the most likely
cause of the small bowel infarction?

A. Atherosclerosis

B. Cystic medial necrosis

C. Mnckeberg's arteriosclerosis

D. Polyarteritis nodosa

E. Wegener's granulomatosus


The correct answer is D. The lesion described is that of polyarteritis nodosa. This condition
is often considered to be the prototype for the vasculitides, and characteristically affects
small or medium-sized muscular arteries, with a predilection for the gastrointestinal tract and
kidney (causing hematuria, albuminuria, or renal failure). Patients are typically young adult
males, although both sexes and all ages may have the condition. Characteristically, vascular
lesions of different stages may be present. Corticosteroid and cyclophosphamide therapy has
improved a formerly poor prognosis.

Atherosclerosis (choice A) can cause bowel infarction, but the histologic description would be
that of a plaque.

Cystic medial necrosis (choice B) predisposes for dissecting aortic aneurysm.

Mnckeberg's arteriosclerosis (choice C) is a benign condition characterized by ring-like

calcifications of vessel walls.
Wegener's granulomatosus (choice E) affects the lungs, upper airways, and kidneys.

Which of the following is most likely to cause a hypochromic microcytic anemia?

A. Folate deficiency

B. Hereditary spherocytosis

C. Iron deficiency anemia

D. Sickle cell anemia

E. Vitamin B12 deficiency


The correct answer is C. Conditions that produce microcytic anemia include iron deficiency,
thalassemia minor, anemia of chronic disease, and the anemia produced by erythrocyte fragmentation.

Folate deficiency (choice A) usually produces a macrocytic anemia.

Hereditary spherocytosis (choice B) usually produces an anemia with cells of normal volume.

Sickle cell anemia (choice D) usually produces an anemia with cells of normal volume.

Vitamin B12 deficiency (choice E) usually produces a macrocytic anemia.

A 28-year-old female presents to the doctor complaining of syncopal episodes that last a few minutes.
She is not taking any medications and has no previous medical history. EEG and EKG studies are
and are unremarkable. An echocardiogram shows a single ball-shaped mass dangling in the left atrium near
the mitral valve. The most likely diagnosis is

A. angiosarcoma

B. mesothelioma

C. myxoma

D. rhabdomyoma

E. rhabdomyosarcoma


The correct answer is C. The vignette illustrates a typical presentation for a tumor of the
heart. Primary cardiac tumors are rare and usually require an intensive work-up to pinpoint the
diagnosis. 75% of primary cardiac tumors are benign and among these, myxoma is the most common.
The tumors are usually single; the most common location is the left atrium. They may cause
syncopal episodes or even shock and death due to obstruction by a "ball valve" mechanism.

Angiosarcoma (choice A) is a malignant tumor of vascular origin that can occur as a primary
cardiac tumor. It is the most common malignant primary cardiac tumor, but it is still very
rare. Angiosarcoma usually affects the right side of the heart.
Mesothelioma (choice B) is a benign tumor of mesothelial origin that can rarely present as a
primary cardiac tumor. It is usually a small intramyocardial tumor that presents with
disturbances of the conduction system of the heart.

Rhabdomyoma (choice D) is a benign tumor of muscle origin. It can occur as a primary cardiac
tumor, typically in infants and children, in whom it may be associated with tuberous sclerosis.
It usually occurs in the ventricles.

Rhabdomyosarcoma (choice E) is a malignant neoplasm that can also occur as a rare primary
cardiac tumor. It is of muscle origin and usually affects the right heart.

The day after playing in the high grasses of a neighbor's fields, an 8-year-old boy develops a weeping,
vesicular, erythematous, and itchy rash on his arms, legs, and neck. Which of the following best
describes this inflammatory response?

A. Erythema nodosum

B. Pemphigus

C. Psoriasis

D. Spongiotic dermatitis

E. Urticaria


The correct answer is D. Spongiotic dermatitis is seen in cases of contact dermatitis, such as
poison ivy exposure. The accumulation of inflammatory cells in the superficial dermis causes
marked edema, which splays epidermal keratinocytes apart and giving a spongy appearance to
intercellular bridges. Grossly, the skin has a weepy appearance with frequent blistering.

Erythema nodosum (choice A) is a form of panniculitis, which is chronic inflammation in the

subcutaneous fat lobules. Erythema nodosum presents as painful erythematous nodules, often with
fever and malaise. It is associated with infections and drug reactions, and is not a contact

Pemphigus (choice B) is a genetic blistering disorder due to the production of antibodies to

the intercellular cement substances in skin and mucous membranes.

Psoriasis (choice C) is a common chronic inflammatory disease causing plaques and scales, typically on
elbows, knees, and scalp. The pathogenesis of psoriasis is still unclear; it may be a
complement-mediated autoimmune process.

Urticaria (choice E) is an IgE-driven hypersensitivity process, usually occurring in adults

between 20 and 40 years old. Urticaria is characterized by wheals (edematous pruritic plaques),
and typically affects the trunk and distal extremities.

A 30-year-old woman presents complaining of nosebleeds. She also notes easy bruising and excessively
heavy bleeding during her periods. The patient denies taking any medications. Physical
examination is remarkable for scattered petechiae. The spleen is normal-sized. Laboratory
examination is remarkable for a platelet count of 45,000/microliter and a bleeding time of 17
minutes. The bone marrow shows an increased number of megakaryocytes. Antinuclear antibody is
negative. Autoantibodies directed against which of the following antigens would likely be found
in this patient's serum?
A. Acetylcholine receptor

B. Erythrocyte membrane protein

C. Glycoprotein IIb/IIIa

D. Intrinsic factor

E. Type IV collagen


The correct answer is C. The history of nosebleeds and menorrhagia, the petechiae,
thrombocytopenia and increased bleeding time all suggest a platelet disorder. The decreased platelet
count suggests a thrombocytopenic disorder rather than a platelet function disorder. The absence of
antinuclear antibody argues against systemic lupus erythematosus (a significant cause of
thrombocytopenia). The negative drug history rules out drug-associated thrombocytopenia. After other
causes have been ruled out, a tentative diagnosis of idiopathic thrombocytopenic purpura can be made.
This disorder, also called immune thrombocytopenic purpura, is an acquired thrombocytopenia caused by
formation of autoantibodies directed against the platelet membrane proteins glycoprotein IIb/IIIa,
followed by splenic destruction of opsonized platelets. The disease typically occurs in women from 20-40
years of age. Splenectomy and immunosuppressive therapy can generally control the thrombocytopenia.

Antibodies to the acetylcholine receptor (choice A) are seen in myasthenia gravis.

Antibodies to erythrocyte membrane proteins (choice B) are seen in autoimmune hemolytic anemia.

Antibodies to intrinsic factor (choice D) are seen in pernicious anemia.

Antibodies to Type IV collagen (choice E) are seen in Goodpasture's syndrome.

A 37-year-old woman has cyclical premenstrual pain. Her breasts have a "lumpy-bumpy" texture on
palpation. A biopsy is performed. The histopathologic features include small cysts lined by
epithelial cells with apocrine metaplasia, calcium deposits, areas of fibrosis, increased
number of acini (adenosis), and foci of florid hyperplasia of ductal epithelium. Which of these
changes increase the risk of breast cancer?

A. Adenosis

B. Apocrine metaplasia

C. Calcium deposits

D. Cysts

E. Epithelial hyperplasia


The correct answer is E. Fibrocystic changes usually come to clinical attention by causing pain
(often cyclical, in premenstrual phase), palpable lumps, or mammographic densities and calcifications. A
"lumpy-bumpy" texture is caused by cysts and fibrosis. Fibrocystic changes, per se, do not increase the
risk of developing breast cancer, unless there are associated proliferative changes. Epithelial
hyperplasia is defined as an increase in the number of epithelial cell layers in the ductal epithelium.
Florid epithelial hyperplasia leads to an increased risk of developing carcinoma, especially if there is
associated cellular atypia (atypical ductal hyperplasia).
Adenosis (choice A) refers to an increase in the number of acini and can be observed in
fibrocystic changes as well as in other breast conditions, such as sclerosing adenosis.
Physiologic adenosis is part of the changes that occur during pregnancy. Adenosis is not
associated with increased risk of breast cancer, except as a component of sclerosing adenosis.

Apocrine metaplasia (choice B) describes a benign change of breast epithelial cells that come
to resemble the apocrine epithelium of sweat glands. Apocrine cells have abundant granular
eosinophilic cytoplasm. Apocrine metaplasia is seen frequently in fibrocystic changes, as well
as in normal breast.

Calcium deposition (choice C) is a nonspecific finding that may occur in a number of both
benign and malignant breast changes, including fibrocystic changes, ductal carcinoma in situ,
and invasive carcinoma. Calcification is not clinically significant except for its diagnostic
value. Mammographic detection of calcium may serve to guide biopsy procedures.

Cysts (choice D) are frequent in fibrocystic changes and result from dilatation of ducts. The
nodularity of breasts with fibrocystic changes is due in part to the presence of cysts of
various sizes. A classic gross description is that of blue-dome cysts, which appear brown to
blue because of their turbid fluid content. The epithelial lining may undergo apocrine
metaplasia or produce papillary projections. There is no direct link between cyst formation and
breast cancer.

A patient has had years of intermittent diarrhea and abdominal pain, but has never consulted a
physician. Eventually, he begins to pass fecal material in his urine and he seeks medical
attention. Which of the following diseases is most likely to cause this complication?

A. Celiac disease

B. Crohn's disease

C. Diverticulitis

D. Ulcerative colitis

E. Whipple's disease


The correct answer is B. Passing fecal material in urine strongly suggests the possibility of
a fistula between the bowel and bladder. Of the diseases listed, only Crohn's disease (a type
of inflammatory bowel disease) commonly produces fistulas. Fistulas are produced in Crohn's
because the disease affects the entire thickness of the bowel wall, rather than being
restricted to the mucosa (e.g., ulcerative colitis).

Celiac disease (choice A) is a mucosal disorder of the small intestine caused by intolerance
to certain components of gluten from wheat and other grains.

Diverticulitis (choice C) can cause bowel perforation with peritonitis but does not usually
cause fistula formation.

Ulcerative colitis (choice D) is much less commonly associated with fistula formation than is
Crohn's disease.

Whipple's disease (choice E) is a small intestinal disorder caused by infection with

Tropheryma whippelii.
A 29-year-old man presents with hemoptysis and hematuria. Renal biopsy shows inflammation of the
glomeruli. X-ray shows focal pulmonary infiltrates. Which of the following is likely to be found
with an immunofluorescence study of the glomeruli and alveoli?

A. Electron-dense humps on epithelial side of basement membrane

B. Linear IgG deposits on alveolar and glomerular basement membranes

C. Mesangial deposition of IgA

D. Spike and dome IgG deposits on the glomerular basement membrane


The correct answer is B. This is a classic case of Goodpasture's syndrome. It is autoimmune in

origin and is characterized by hemorrhagic pneumonitis leading to hemoptysis and
glomerulonephritis progressing to renal failure. Most cases involve the presence of anti-
basement membrane antibodies. It occurs mostly in young men. Under immunofluorescence, there
are linear deposits of IgG on alveolar and glomerular basement membranes.

Electron-dense humps (choice A) are found under electron microscopy, not with
immunofluorescence. These humps are found in poststreptococcal glomerulonephritis;
immunofluorescence in this case would show C3, IgM, and IgG granular deposits.

Mesangial deposition of IgA (choice C) occurs in Berger's disease or IgA nephropathy.

Spike and dome IgG deposits (choice D) are found in membranous nephropathy, a cause of the nephrotic

A patient presents to a physician because of a markedly inflamed and painful great toe. Physical
examination additionally demonstrates small nodules on the patient's external ear. Aspiration of
the metatarsal-phalangeal joint of the affected toe demonstrates needle-shaped, negatively
birefringent crystals. Of which of the following are the crystals most likely composed?

A. Bile pigments

B. Calcium pyrophosphate

C. Cystine

D. Monosodium urate

E. Struvite


The correct answer is D. The patient has gout, which is due to precipitation of monosodium
urate crystals in joint spaces (notably the great toe) and soft tissues (causing tophi, which
are often found on the external ears).

Bile pigments (choice A) are found in some gallstones.

Calcium pyrophosphate (choice B) crystals are deposited in pseudogout, which classically

affects the knee or other large joints.
Cystine (choice C) and struvite (choice E) can form kidney stones.

Which of the following features characterizes apoptosis but not necrosis?

A. Disaggregation of polyribosomes

B. Eosinophilia

C. Inflammation

D. Karyolysis

E. Peripheral aggregation of chromatin


The correct answer is E. Apoptosis is a form of cell death that serves to eliminate unwanted
cells during development, maintain cell numbers in intact organs or tissues, and eliminate
immune cells after an immune response has faded. Apoptosis also occurs in response to noxious
agents and in the aging process. The process is the result of execution of an internal program
mediated by the expression of a number of different genes. In the process of apoptosis, cells
shrink and cytoplasmic organelles become more densely packed. Cytoplasmic blebs may form, and
apoptotic bodies (membrane-bound cellular fragments) can be produced. The most characteristic
feature of apoptosis is a distinctive peripheral aggregation of chromatin, sometimes
accompanied by breaking up of the nucleus into several fragments. In necrosis, the chromatin
may become more pale (karyolysis; choice D), or form irregular clumps, and the nucleus itself
may shrink into a dense pyknotic body.

Disaggregation of polyribosomes (choice A) is characteristic of the initial stages of cellular

injury and necrosis.

Eosinophilia (choice B) characterizes both apoptosis and necrosis.

Inflammation (choice C) is typically absent in apoptosis, in contrast to necrosis.

A man living in southern Japan contracts HTLV-1 infection through sexual contact. Twenty-five years
later he develops generalized lymphadenopathy with hepatosplenomegaly, a skin rash,
hypercalcemia, and an elevated white blood count. This man has most likely developed which of
the following?


B. Autoimmunity

C. Delayed hypersensitivity reaction

D. Leukemia

E. Recurrent infection


The correct answer is D. HTLV-1, or human T-cell lymphotrophic virus 1, is an enveloped,

single-stranded, RNA retrovirus endemic to southern Japan and the Caribbean basin, but
sporadically seen in the United States. Infection by HTLV-1 can lead to T-cell leukemia 20-30
years after the infection. The HTLV-associated T-cell leukemia generally presents as described
above, and is very aggressive, progressing to death in under 1 year.

AIDS (choice A), acquired immunodeficiency syndrome, is transmitted through the HIV virus.
Although both viruses are RNA retroviruses and both infect CD4+ T cells, the diseases they produce are

Autoimmune diseases (choice B) produced after infection are typified by rheumatic fever after
infection with Streptococcus. There is speculation that EBV virus (Epstein-Barr virus) may
produce the autoimmune reactions in rheumatoid arthritis, but autoimmunity plays no role in
leukemia after HTLV-1 infection.

Delayed hypersensitivity reactions (choice C) are T-cell-mediated immune responses typified by the
subcutaneous reaction to tuberculin in sensitized individuals. It characteristically occurs 2-3
days after an exposure, and is a local lymphocytic response.

Recurrent infections (choice E) occur when latent viruses are reactivated in the host at the
site of primary infection. Recurrent infections are most common with the herpesviruses,
especially HSV-1, HSV-2, and VZV (varicella-zoster virus).

A 25-year-old female presents with a 12-month history of palpitations, intermittent diarrhea, anxiety,
and a 1-month history of "bulging of both eyes." What is the most likely cause of her symptoms?

A. Graves' disease

B. Hashimoto's thyroiditis

C. Multinodular toxic goiter

D. Papillary carcinoma

E. Subacute thyroiditis


The correct answer is A. Graves' disease is the most common cause of hyperthyroidism in a young
female and is the only one that causes exophthalmos ("bulging of both eyes"). Grave's disease
is an autoimmune disorder in which a thyroid-stimulating IgG immunoglobulin (TSI) binds to the
TSH receptors causing increased release of thyroid hormone. The exophthalmos is caused by
lymphocytic infiltration of the extraocular muscles.

Hashimoto's thyroiditis (choice B) results in hypothyroidism and is associated with a diffusely

enlarged thyroid gland and antimicrosomal antibodies against the thyroid parenchyma.

Multinodular toxic goiter (choice C) causes hyperthyroidism, but does not result in exophthalmos.

Papillary carcinoma (choice D) will only very rarely present as a hypersecreting nodule. Most
cases will be nonsecreting, cold nodules. There is no exophthalmos. This is the most common
thyroid cancer and has the best prognosis of all thyroid cancers.

Subacute thyroiditis (choice E) is an uncommon form of thyroiditis that lasts approximately 8

months and is self-limited. Early on, with destruction of thyroid tissue, there may be release
of thyroid hormone and symptoms of hyperthyroidism, but exophthalmos is generally absent.

The 10-year-old daughter of a United Nations ambassador in Turkey develops a severe sore throat, which
resolves after a few days. 10 days later, the mother notices dark stains on the child's
underwear, and takes her to the pediatrician. A urine sample is smoky in color, and red cell
casts are noted in the urinary sediment. If a renal biopsy were obtained from this child it
would probably show

A. dense deposits

B. fusion of podocyte foot processes

C. linear deposition of IgG

D. mesangial IgA deposits

E. subepithelial humps


The correct answer is E. The history suggests streptococcal pharyngitis, followed by poststreptococcal
glomerulonephritis. Subepithelial humps composed of proteinaceous material can be seen
projecting outward from the outer capillary wall to the urinary space by light, or especially,
electron microscopy. Granular deposits of IgG and C3 can be seen by immunofluorescence

Dense deposits (choice A) are characteristic of Type II membranoproliferative glomerulonephritis.

Fusion of podocyte processes (choice B) is seen in minimal change disease.

Linear deposition of IgG (choice C) is seen in Goodpasture's syndrome.

Mesangial IgA deposits (choice D) are characteristic of Berger's disease.

A 40-year-old woman has severe, disabling rheumatoid arthritis. Rheumatoid factor is positive. What
would a biopsy of the synovium of her knee most likely reveal?

A. A nearly normal synovium with scattered inflammatory cells

B. A non-proliferative synovitis with abscess formation

C. A non-proliferative synovitis with many neutrophils

D. A proliferative synovitis with many eosinophils, neutrophils, and plasma cells

E. A proliferative synovitis with many lymphocytes, macrophages, and plasma cells


The correct answer is E. Severe rheumatoid arthritis causes a proliferative synovitis with
extensive damage to the synovium of the joint. The synovial membrane becomes markedly thickened
formation), with edematous villous projections that extend into the joint space. The intense
inflammatory infiltrate that is present is typically composed of plasma cells, lymphocytes, and

A 3-year-old child is seen by a pediatrician because he has developed multiple isolated lesions on his
face and neck. Physical examination reveals many lesions up to 4 cm in diameter with golden
crusts, while in other sites small blisters and weeping areas are seen. Which of the following
is the most likely diagnosis?
A. Aphthous ulcers

B. Erysipelas

C. Herpes simplex I

D. Impetigo

E. Measles


The correct answer is D. This is impetigo, which is typically seen in preschool children with
poor hygiene, particularly in the summer in warm climates. The characteristic lesion has a
large golden crust. Most cases are caused by Staphylococcus aureus; Streptococcus pyogenes is
occasionally implicated. Impetigo is highly infectious, and mini-epidemics can occur in daycare
settings. The initial treatment is typically with penicillins and topical preparations.
Methicillin-resistant strains are presently rare in this setting, but can occur.

Aphthous ulcers (choice A), commonly known as "canker sores," are painful, shallow ulcers of
the oral cavity.

Erysipelas (choice B) is a different type of skin infection, often caused by Streptococcus

pyogenes (also sometimes others including Staphylococcus), and is characterized by large erythematous

Herpes simplex I (choice C) causes tiny oral and perioral vesicles, but not large golden crusts.

Measles (choice E) causes a blotchy erythematous rash.

A 6-year-old girl manifests acute vomiting and nuchal rigidity. MRI reveals a tumor in the posterior
fossa consisting of a large cyst with a nodular mass attached to its wall (cyst with "mural
nodule"). Histologic examination shows elongated astrocytes with long bipolar processes and
numerous Rosenthal fibers. Which of the following is the most likely diagnosis?

A. Astrocytoma, WHO grade II

B. Ependymoma

C. Glioblastoma multiforme

D. Medulloblastoma

E. Pilocytic astrocytoma


The correct answer is E. Location, gross appearance, and histologic features are typical of pilocytic
astrocytoma, an astrocytic tumor with an indolent growth pattern that usually affects children.
Cerebellar and hypothalamic regions are the most frequent locations. The presence of Rosenthal
fibers is an important histopathologic clue. Rosenthal fibers are corkscrew-shaped, intensely
eosinophilic structures deriving from accumulation of αβ-crystallin within
astrocytic processes. Rosenthal fibers are found in pilocytic astrocytoma, reactive gliosis
(especially around tumors and vascular malformations), and a rare leukodystrophy known as
Alexander disease. Pilocytic astrocytomas have excellent prognosis in the posterior fossa, but
complete surgical excision is difficult with tumors in the hypothalamic region. The tumor is
classified as a grade I astrocytoma in the WHO system. Remember: a tumor in the cerebellum
appearing as a cyst with a mural nodule and containing abundant Rosenthal fibers = Pilocytic

Astrocytoma, grade II (choice A) and glioblastoma (choice C) are both astrocytomas, ie, tumors
of astrocytic origin. Glioblastoma is grade IV according to the WHO system. As their grades
suggest, grade II astrocytoma is less anaplastic (ie, less malignant) than grade IV
astrocytoma. These tumors grow in a diffuse manner, do not possess a cystic component, and
usually arise in the white matter of the centrum semiovale.

Ependymoma (choice B) originates from the ependyma and develops near the ventricular walls (4th
ventricle in children). Ependymomas of the 4th ventricle fill the ventricular cavity but can be
easily differentiated from pilocytic astrocytomas in their histologic appearance: ependymal
cells organized around small vessels (perivascular pseudorosettes) or around small lumina (true
ependymal rosettes), mimicking the primordial ependymal canal.

Medulloblastoma (choice D) refers to a malignant neoplasm of childhood that presumably originates from
immature glioneuronal precursors. It is located in the midline posterior fossa and infiltrates
the cerebellar vermis. This tumor is solid (not cystic) and consists of undifferentiated small
cells arranged in patternless sheets.

A 36-year-old male presents with a complaint of passing dark-reddish urine. He states that yesterday he
played racquetball for 4 hours, which was the first time he had exercised in 4 months. He awoke
this morning with sore muscles and discolored urine. Physical examination is unremarkable. The
urine is reddish-brown in color; dipstick test for blood is positive, the pH is 5.1, the
specific gravity 1.03. Microscopic examination of the urine reveals no red blood cells. What is
the most likely etiology for this presentation?

A. Hemolyzed blood in the urine

B. Ingestion of foods that contained red dye

C. Myoglobinuria

D. Nephrolithiasis

E. Prostatitis


The correct answer is C. The appearance of a dark-reddish urine is suggestive of a number of

conditions, including hematuria; however, there are no red blood cells present on microscopic
examination. Furthermore, the dipstick test for blood is positive, which is suggestive of
myoglobinuria. Myoglobin is a pigment that, if present in the urine, will produce a positive
dipstick test, even in the absence of red blood cells. Myoglobinuria can be caused when an
unconditioned individual partakes in intense physical exertion. This extreme physical activity
leads to muscle cell breakdown and the release of myoglobin into the blood, which is then
filtered by the kidneys and excreted into the urine.

If there was hemolyzed blood in the urine (choice A), a few red blood cells should have been
detected on urinalysis.

Ingestion of foods that contained red dye (choice B) can discolor the urine; however, it would
not produce a positive dipstick test.

Nephrolithiasis (choice D) generally results in the appearance of blood cells in the urine.
Prostatitis (choice E), an inflammation of the prostate gland, is generally caused by an
infection. Prostatitis produces symptoms of dysuria, urinary frequency, and cloudy urine; hematuria is

A woman who is heterozygous for glucose-6-phosphate dehydrogenase (G6PD), a polymorphic enzyme

transcribed from the X chromosome, develops chronic myeloid leukemia. Restriction fragment length
polymorphism (RFLP) studies on the tumor cells for G6PD reveal that only a single form of the enzyme is
transcribed. This finding supports which of the following features of neoplasia?

A. Genetic mutation

B. Monoclonality

C. Mosaicism

D. Oncogene activation

E. Point mutation


The correct answer is B. G6PD is an enzyme involved in carbohydrate metabolism-it is neither an

oncogene nor a tumor suppressor, and its altered expression in tumor cells is solely due to its
location on the X chromosome. Each somatic cell expresses only one X chromosome, and thus only
one of the two isotypes of G6PD. The presence of only one form of G6PD in the tumor cells
reflects the monoclonal origin of the cells. Cells contained in the neoplasm express only a
single isotype of G6PD because they are all derived from a single progenitor cell.

Genetic mutation (choice A) does not underlie the monotypic expression of G6PD in the tumor
cells. The allele for G6PD not expressed in the monoclonal cell line was inactivated in
embryogenesis (in the Barr body). Although genetic mutation is a requirement of neoplasia, it
is not demonstrated by this phenomenon.

Mosaicism (choice C) is the expression of two or more different phenotypes heterogeneously

throughout an organ or organism. Mosaicism usually reflects an asymmetry of mitotic division in

G6PD is not an oncogene (choice D), it is a metabolic enzyme expressed constitutively in all
cells. Altered expression of G6PD does not produce any growth advantage in a cell.

Although point mutations (choice E) underlie much of the genetics involved in neoplasia, no
point mutation is required for monoclonal expression of G6PD.