1

A 35-year-old man with a history of rhinitis and asthma presents to his physician with complaints of
intermittent severe abdominal pain and a chronic maculopapular rash. Peripheral blood smear
demonstrates a marked eosinophilia. Biopsy of a skin lesion demonstrates necrotizing vasculitis
with large numbers of eosinophils. Which of the following diagnoses is most likely?

A. Churg-Strauss syndrome

B. Leukocytoclastic angiitis

C. Mnckeberg's arteriosclerosis

D. Temporal arteritis

E. Wegener's granulomatosis

Explanation:

The correct answer is A. The most likely condition is Churg-Strauss syndrome, also known as
allergic granulomatosis and angiitis. This variant of polyarteritis nodosa is clinically
associated with asthma and eosinophilia. The vascular lesions are those described in the
question stem. Granulomas are present in many, but not all, cases. Pulmonary involvement may be
prominent, but this is not always the case. In this case, the patient's abdominal pain is
related to GI vasculitis, and his skin rash is related to dermal vasculitis. Churg-Strauss
syndrome should be suspected in any patient with vasculitic symptoms, eosinophilia, and asthma.

In leukocytoclastic angiitis (choice B), the dominant inflammatory cells are neutrophils.

In Mnckeberg's arteriosclerosis (choice C), there is vessel calcification.

In temporal arteritis (choice D), which especially affects the cranial vessels, giant cells are
found.

Wegener's granulomatosis (choice E) affects the respiratory and renal systems.

An 11-year-old boy complains of pain in his left leg with no history of prior trauma. The pain is not
relieved by acetaminophen and slowly progresses. Radiographic examination shows a femoral tumor
 2

with an "onion-skin" pattern of circumferential reactive periosteal bone. Examination of biopsy

material stained with hematoxylin and eosin reveals small uniform blue round cells. On the basis
of this information, which of the following is the most likely genetic mutation?

A. del 1p

B. t(2,13)

C. t(11,22)

D. t(12,22)

E. t(X,18)

Explanation:

The correct answer is C. This is the chromosomal mutation for Ewing sarcoma. This case
demonstrates the typical presentation of Ewing sarcoma, occurring mainly in the long bones of
children and adolescents. It presents with pain and has a unique onion-skin effect on x-ray.
Histologically, it is known as a small, round, blue-cell tumor. A number of different tumors
look similar, and molecular methods are increasingly used for diagnosis.

del 1p (choice A) is associated with leiomyosarcoma, which is mainly found in the extremities,
subcutis, and retroperitoneum. It is located outside of bone in the soft tissues and
histologically is composed of bundles of spindle cells.

t(2,13) (choice B) is associated with alveolar rhabdomyosarcoma, a tumor of young persons that
can affect the extremities. It is composed of small round blue cells that form small nests or
alveoli. The radiographic appearance shows a soft tissue mass rather than a bony lesion. This
is an aggressive malignancy.

t(12,22) (choice D) is associated with clear cell sarcoma, also known as malignant melanoma of
soft parts. It appears like a malignant melanoma, which arises in the soft tissue rather than
the skin. It usually is found on the tendons of extremities of young patients. Histologically,
the cells can have pigment or clear cytoplasm.

t(X,18) (choice E) is associated with synovial sarcoma, which is a tumor arising around a joint
 3

space, usually in a young person. The knee and shoulder are the most common location.
Histologically, the cells can be spindled or plump, pink, and epithelioid.

A terminally ill HIV infected patient develops focal neurologic signs, dementia, and coma. Amoebic
parasites are demonstrated in CSF. Which of the following organisms is most likely to be the
causative agent?

A. Acanthamoeba sp.

B. Entamoeba histolytica

C. Giardia lamblia

D. Naegleria fowleri

E. Trichomonas vaginalis

Explanation:

The correct answer is A. Two types of free-living amoeba can infect the brain and meninges:
Naegleria fowleri and Acanthamoeba species. The former affects healthy adolescent or adult
divers, while the latter causes infection in patients with immunosuppression because of
diabetes, alcoholism, cancer, or HIV infection. The brain infection characteristically has a
prominent perivascular character, which causes a multifocal hemorrhagic necrotizing
meningoencephalitis. Skin ulcers, nasal infection, or pneumonia may also be present. It is
thought that the organisms may release a toxin causing host tissue necrosis. Systemic
antifungal agents (e.g., amphotericin) have some activity against this organism, but most cases
are fatal.

Entamoeba histolytica(choice B) causes amoebic dysentery and liver abscess.

Giardia lamblia(choice C) is a flagellate, rather than an amoeba, and causes diarrhea.

Naegleria fowleri(choice D) is an amoebic cause of meningoencephalitis in previously healthy

swimmers and divers.

Trichomonas vaginalis(choice E) is a flagellate, rather than an amoeba, and causes vaginitis.

 4

A 46-year-old woman presents with insidious onset of shortness of breath, chest pain, and fatigue. Chest
x-ray films reveal bilateral pulmonary infiltrates and enlarged hilar lymph nodes. A biopsy of
one of these lesions shows non-necrotizing granulomas. Special stains for fungi and
mycobacteria are negative. The patient works as a secretary and has no history of occupational
exposure to airborne minerals or organic dusts. Which of the following is the most likely
diagnosis?

A. Asbestosis

B. Berylliosis

C. Byssinosis

D. Sarcoidosis

E. Tuberculosis

Explanation:

The correct answer is D. The diagnosis of sarcoidosis is usually made by exclusion. This
disease is characterized by non-necrotizing granulomas developing most frequently in the lungs,
lymph nodes, retina, heart, spleen, skin, and liver. Non-necrotizing granulomas may be seen in
a number of other conditions, however, such as infections and certain forms of pneumoconiosis,
which must be ruled out before making a diagnosis of sarcoidosis. The etiopathogenesis of
sarcoidosis is obscure. Cell-mediated mechanisms are thought to be involved in an immune
response to as yet unidentified antigens. About two-thirds of patients with sarcoidosis recover
without residual functional deficits, 20% have permanent pulmonary or visual damage, and 10%
die of pulmonary or cardiac involvement.

Asbestosis, berylliosis, and byssinosis are all lung diseases caused by inhalation of airborne
dusts.

Asbestosis (choice A) is due to chronic inhalation of asbestos fibers, which may affect workers
involved in installation and removal of insulation. Asbestosis leads to diffuse fibrosis of the
lungs. In this case, granulomas are absent or scanty; the most characteristic sign of asbestos
exposure is the asbestos body, which is an elongated beaded rod composed of asbestos fibers
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coated by proteins.

Chronic exposure to beryllium in mining and fabrication leads to berylliosis (choice B), a
granulomatous condition of the lungs indistinguishable morphologically from sarcoidosis.
Clinical history is therefore essential in excluding this condition.

Byssinosis (choice C) results from occupational exposure to cotton fibers. This condition
belongs to a diversified category of diseases mediated by a hypersensitivity reaction against
inhaled organic dusts. Farmer's lung, pigeon breeder's lung, air-conditioner lung, and
byssinosis are typical examples of these conditions, which lead to a granulomatous reaction
that may progress to diffuse pulmonary fibrosis. Again, clinical history is crucial in the
identification of this etiology.

Tuberculosis (choice E) is usually associated with necrotizing granulomas. The type of necrosis
is also described as caseating because the necrotic material resembles cheese on gross
examination. The absence of acid-fast organisms in the biopsy material helps rule out this
diagnosis.

Radiographic studies of a 2-year-old child brought to an emergency room reveal a new fracture of the
humerus and evidence of multiple old fractures in ribs and long bones of the extremities. A
social worker wants to initiate prosecution of the parents for child abuse, but an alert
emergency room physician notices that, despite the broken arm, the toddler shows minimal
bruising. A very careful, directed, physical examination reveals that the toddler has "peculiar
teeth," a blue tinge to the sclera, and unusually mobile joints. The disease that the physician
suspects the child has is characterized by an abnormality of which of the following biochemical
functions?

A. Collagen type I synthesis

B. Collagen type II synthesis

C. Collagen type III synthesis

D. Collagen type IV synthesis

E. Collagen type V synthesis

 6

Explanation:

The correct answer is A. The child has the most common variant (type I) of osteogenesis
imperfecta, which is an autosomal dominant genetic defect in the synthesis of type I collagen,
due to decreased synthesis of the procollagen alpha1(1) amino acid chain. This defect (unlike
that of the perinatal, lethal, type II form of osteogenesis imperfecta) is compatible with
survival, but does cause skeletal fragility, dentinogenesis imperfecta (abnormal teeth), blue
sclera, joint laxity, and hearing impairment. Unfortunately, a number of families with this
defect have had their children removed because of "abuse," only to find that the broken bones
continue in the new environment. Type I collagen is found in skin, bone, tendons, and most
other organs.

Type II collagen (choice B) is found in cartilage and vitreous humor.

Type III collagen (choice C) is found in blood vessels, uterus, and skin.

Type IV collagen (choice D) makes basement membranes.

Type V collagen (choice E) is a minor component of interstitial tissues and blood vessels.
There are also type VI-XI collagens, which are minor constituents of various tissues.

A 57-year-old man is seen in clinic for a chronic cough. Chest x-ray demonstrates a lung mass;
bronchoscopy with bronchial lavage and biopsy reveals a tumor composed of small neoplastic
cells with prominent crush artifact that do not stain with immunohistochemical stains for
lymphocyte common antigen (LCA). Which of the following oncogenes has been associated with this
tumor?

A. bcl-2

B. erb-2

C. L-myc

D. N-myc

E. ret
 7

Explanation:

The correct answer is C. The presence of a lung mass suggests carcinoma. The small size of the
neoplastic cells suggests that the tumor may be small cell carcinoma (oat cell carcinoma). The
other possibility on morphologic grounds is lymphoma, but lymphoma can be excluded by the
negative LCA study. The oncogene associated with small cell carcinoma of the lung is L-myc.

bcl-2 (choice A) is associated with follicular and undifferentiated lymphomas.

erb-2 (choice B) is associated with carcinomas of the breast, ovary, and stomach.

N-myc(choice D) is associated with neuroblastoma.

ret(choice E) is associated with multiple endocrine neoplasia, types II and III.

A patient with severe arthritis suddenly becomes unable to move his arms or legs. He is admitted to the
neurology floor of the hospital, but his quadriplegia does not improve with time. If the
quadriplegia is due to his arthritis, which of the following types of arthritis does this
patient most likely have?

A. Ankylosing spondylitis

B. Gouty arthritis

C. Osteoarthritis

D. Rheumatoid arthritis

E. Septic arthritis

Explanation:

The correct answer is D. Involvement of the cervical spine occurs in almost 80% of patients
with rheumatoid arthritis, and involves the atlanto-axial joint in up to 25% of patients
hospitalized for rheumatoid arthritis. Fortunately, large degrees of subluxation of the joint
are rare, but if present, can be associated with quadriplegia, and even sudden death if the
odontoid peg separates from the arch of the atlas and compresses the spinal cord.
 8

Serious complications of ankylosing spondylitis (choice A) include atrioventricular block,

bladder and bowel dysfunction, uveitis, pulmonary fibrosis, psoriasis, and inflammatory bowel
disease.

Serious complications of gout (choice B) include renal impairment.

Serious complications of osteoarthritis (choice C) are uncommon, but the local manifestations
can be crippling.

Serious complications of septic arthritis (choice E) include joint destruction, osteomyelitis,

and systemic infection.

A 72-year-old black woman has the abrupt onset of right-sided weakness affecting the face and arms. MRI
is consistent with an infarct in the territory of the middle cerebral artery. Pathologic
examination of the patient's brain would likely show

A. caseous necrosis

B. coagulative necrosis

C. enzymatic fat necrosis

D. gangrenous necrosis

E. liquefactive necrosis

Explanation:

The correct answer is E. Liquefactive necrosis occurs in brain or other neural tissues and in
pancreatic tissue. In this type of necrosis, the tissue appears liquefied under the microscope,
without preservation of cell outlines. Liquefactive necrosis can also be seen in some bacterial
infections, especially those caused by pyogenic Staphylococci, Streptococci, or certain
coliform bacteria.

Caseous necrosis (choice A) is generally an indication of infection by Mycobacterium

tuberculosis. The term caseous refers to the appearance of the tissue, i.e., soft, white
 9

necrotic areas that have a cheese-like appearance. Microscopically, the necrotic areas are
lightly eosinophilic (stain light pink), with little or no discernible cellular detail. The
eosinophilia reflects staining of residual cellular proteins.

Coagulative necrosis (choice B) is a more common type of necrosis, characteristic of anoxic

injury and most infarcts. Cellular outlines are preserved, but proteins are denatured, and the
cells stain in an eosinophilic manner.

Enzymatic fat necrosis (choice C) is seen primarily with pancreatic injury when pancreatic
lipases are released and digest fat to form free fatty acids. These fatty acids complex with
calcium, resulting in the production of calcium soaps (saponification) in the pancreatic tissue
or in extrapancreatic fatty tissues (eg, omentum).

In gangrene (choice D), bacterial infection is superimposed on a background of massive necrosis

and putrefaction.

A 58-year-old male alcoholic with chronic pancreatitis develops a palpable abdominal mass. Ultrasound
reveals a 9-cm cystic lesion adjacent to the pancreas. An important complication that might
occur if this cyst ruptured would be

A. anaphylactic shock

B. carcinomatosis

C. disseminated infection

D. hypoglycemia

E. intestinal hemorrhage

Explanation:

The correct answer is E. The patient most likely has a pancreatic pseudocyst, which is a
complication of pancreatitis. Pancreatic pseudocyst is not a true cyst; it is lined by
granulation tissue and collagen. It contains pancreatic juices and lysed blood, so rupture
would spill the active digestive enzymes onto the adjacent viscera, particularly the stomach,
small intestine, and transverse colon. Digestive action produces potentially severe
 10

gastrointestinal hemorrhage.

Anaphylactic shock (choice A) results from massive activation of the IgE-mediated branch of the
immune system. Pancreatic secretions do not elicit an IgE response. The classic abdominal cyst
that ruptures, producing anaphylactic shock, is a hydatid cyst.

Carcinomatosis (choice B) is widespread serosal spread of a carcinoma, typically due to tumor

spillage into a body cavity. Although this may occur with pancreatic mucinous
cystadenocarcinoma, this disease is far less likely to occur than is pancreatic pseudocyst in a
patient with chronic pancreatitis.

Pancreatic pseudocyst is not an infective disease. Although septic abscesses do occur in the
abdomen, and may even complicate a pancreatic pseudocyst, the danger of rupture is more
associated with tissue destruction by pancreatic enzymes than with infection (choice C).

Hypoglycemia (choice D) would occur if the pancreatic pseudocyst contained an insulin-like

compound; however, pancreatic pseudocysts contain exocrine pancreatic enzymes, not hormones
from the endocrine pancreas.

A 35-year-old patient presents to his clinician because of a painful great toe. Physical examination
demonstrates that the toe is exquisitely painful, inflamed, and warm. On questioning, the
patient reveals that this has happened before, generally occurring the morning after a previous
evening's "partying." Which of the following would most likely be demonstrated by aspiration of
joint fluid?

A. Giant cells and acid-fast positive rods

B. Needle-like crystals that are strongly negatively birefringent

C. Numerous neutrophils and gram-negative rods

D. Numerous neutrophils and intracellular gram-negative cocci

E. Roughly cuboidal crystals that are weakly positively birefringent

Explanation:
 11

The correct answer is B. The disease is acute gout, which is characterized by strongly
negatively birefringent needle-like crystals of uric acid in the joint fluid. Colchicine is
able to interrupt these attacks of acute gout.

Tubercular arthritis causes granuloma formation with giant cells and acid-fast mycobacteria
(choice A).

Infectious arthritis due to Salmonella (sickle cell patients) or Haemophilus (children) would
be associated with neutrophils and gram-negative rods (choice C) in joint fluid.

Infectious arthritis due to N. gonorrhoeae would be associated with neutrophils and

intracellular gram-negative cocci (choice D).

Calcium pyrophosphate (pseudogout) produces roughly cuboidal crystals that are weakly
positively birefringent (choice E).

In which of the following respects do a seminoma involving the testis and a germinoma involving the
ovary differ most significantly?

A. Most common age of presentation

B. Number of mitoses

C. Potential to contain foci of more aggressive tumors

D. Radiosensitivity

E. Ultrastructural appearance

Explanation:

The correct answer is A. Seminomas and dysgerminomas are very similar tumors but differ in two
significant respects: the most common age of presentation in men is in the fourth decade, while
in women, it is in the third decade. Also, seminomas are relatively common in men (30% of
testicular germ cell tumors), while dysgerminomas are rare in women (1% of ovarian tumors).

Both of these tumors are composed of sheets of uniform polyhedral cells with intervening
 12

fibrous septa of connective tissue, lymphocytes, and multinucleated giant cells. The number of
mitoses (choice B) per high-power field and ultrastructural appearance (choice E) do not differ
greatly between the two tumors.

These tumors in pure form are very radiosensitive (90% 5-year survival; choice D), but can be
much more aggressive (choice C) if foci of other germ cell tumors (notably embryonal carcinoma,
choriocarcinoma, and yolk sac tumors) are present.

A stenotic valve is removed from a 70-year-old man. The value demonstrates hard nodular masses heaped
up
within the sinuses of Valsalva. On microscopic section, the acellular masses stain darkly blue
with hematoxylin and eosin. Which of the following is the most significant constituent of the
masses?

A. Calcium oxalates

B. Calcium phosphates

C. Complexed iron

D. Magnesium phosphates

E. Uric acid

Explanation:

The correct answer is B. The valvular disease is calcific aortic stenosis, a disease of the
elderly in which nodules of calcium salts, notably calcium phosphate salts, form as a result of
dystrophic calcification. Dystrophic calcification can also be seen at sites of previous
necrosis of many etiologies (coagulative, caseous, liquefactive, or enzymatic fat necrosis) and
in advanced atherosclerosis.

Calcium oxalates (choice A) are found in some kidney stones.

Complexed iron (choice C) is seen in hemosiderin depositions, often at sites where there has
been previous hemorrhage or if there is a systemic overload of iron.
 13

Magnesium phosphates (choice D) are found in some kidney stones.

Uric acid (choice E) and urate deposits can be seen in gout and some kidney stones.

An elderly couple living in a very cold apartment turn on the oven, open the oven door, and go to sleep.
The next morning, the neighbors find the couple dead. The direct mechanism by which death was
produced most likely involves which of the following?

A. Damage to the plasmalemma

B. Decreased oxygen-carrying capacity of blood

C. Increased calcium transport into mitochondria

D. Poisoning of oxidative phosphorylation

E. Rupture of lysosomes

Explanation:

The correct answer is B. The scenario described in the question stem is unfortunately not at
all uncommon. The open oven door is a tip-off that carbon monoxide was involved. Carbon
monoxide has a very high affinity for hemoglobin, and binds, nearly irreversibly, to it in such
a manner that oxygen cannot bind, drastically decreasing the oxygen-carrying capacity of the
blood. Carbon monoxide also causes the oxygen-hemoglobin dissociation curve to shift to the
left, making oxygen more difficult to unload. Traditionally, patients with carbon monoxide
poisoning have been described as having "cherry red" blood and, consequently, skin, but this
change is somewhat unreliable in real life.

Choices A, C, and E list secondary changes that are commonly observed in injured cells, no
matter what the cause of the injury.

Cyanide acts by poisoning oxidative phosphorylation (choice D).

A 52-year-old alcoholic male develops chronic severe upper abdominal pain and maldigestion. Ultrasound
studies demonstrate pancreatic calcifications. Which of the following disorders will this
patient most likely develop?
 14

A. Diabetes mellitus

B. Hyperthyroidism

C. Hypothyroidism

D. Pheochromocytoma

E. Zollinger-Ellison syndrome

Explanation:

The correct answer is A. Pancreatic calcifications constitute strong radiologic evidence of

chronic pancreatitis. Up to 30% of patients with chronic pancreatitis eventually develop
secondary diabetes mellitus as a consequence of destruction of islets in addition to pancreatic
ducts. This form of diabetes mellitus may also eventually cause small vessel damage and
blindness.

Neither hyperthyroidism (choice B) nor hypothyroidism (choice C) are related to chronic

pancreatitis.

Pheochromocytoma (choice D) is unrelated to chronic pancreatitis.

Chronic pancreatitis does predispose for pancreatic carcinoma, but not for the gastrinomas that
cause Zollinger-Ellison syndrome (choice E).

A gastric biopsy is performed on a patient with suspected graft-versus-host disease following bone
marrow transplantation. The biopsy demonstrates many isolated dying epithelial cells in crypts
showing fragmented, hyperchromatic nuclei and small discrete blebs containing both cytoplasm and
nuclear fragments. The biopsy demonstrates which of the following?

A. Apoptosis

B. Caseous neurosis

C. Coagulative necrosis
 15

D. Gangrenous necrosis

E. Liquefactive necrosis

Explanation:

The correct answer is A. The changes described are those of apoptosis, which is a form of
programmed cell death. Apoptosis can be seen in a variety of settings. In this case, it is
occurring in the context of graft-versus-host disease, which is mediated by CD8+ and CD4+
cells. Apoptosis also occurs during embryogenesis, during hormone-dependent involution in the
adult (eg, during menstruation), during rapid proliferation of cell populations (eg, intestinal
crypt epithelia), and in the immune system (e.g., in developing thymus). It can also occur
after duct obstruction in organs such as pancreas and during some viral diseases. The hallmark
of this programmed method of cell death is the fragmentation of the cell with formation of
cytoplasmic blebs and apoptotic bodies that are phagocytized by other healthy cells.

Caseous necrosis (choice B), such as is seen in tuberculosis, shows necrotic, amorphous
granular debris surrounded by a granulomatous response.

Coagulative necrosis (choice C), such as is seen in myocardial infarction, shows coagulated,
anuclear cell "ghosts."

Gangrenous necrosis (choice D) is a commonly used surgical term (eg, in diabetic feet) that
does not have a precise pathologic counterpart.

Liquefactive necrosis (choice E) is usually seen in focal tissue-destructive bacterial

infection; a sterile liquefactive necrosis can also be observed in ischemic necrosis of the
brain.

A 60-year-old woman is seen at an emergency room after she fractures the neck of her right femur during
a minor fall. Radiologic studies demonstrate a generalized loss of bone mass. Exogenous therapy
with which of the following hormones would have been most likely to slow or prevent the
patient's bone disease?

A. Cortisol
 16

B. Epinephrine

C. Estrogen

D. Thyroxine

E. Vasopressin

Explanation:

The correct answer is C. The disease is osteoporosis, and estrogen replacement in post-
menopausal women appears to play an important role in preventing or limiting development of
osteoporosis in post-menopausal women.

Cortisol (choice A) excess, as in endogenous or exogenous Cushing's syndrome, is a contributing

cause of osteoporosis.

Epinephrine (choice B) levels appear to be unrelated to osteoporosis.

Thyroxine (choice D) excess (e.g., in thyrotoxicosis) may contribute to bone loss in some cases
of osteoporosis.

Vasopressin (choice E) levels appear to be unrelated to osteoporosis.

During a routine physical examination of a 74-year-old man, a physician palpates a large, pulsating mass
in the lower abdomen. To which of the following is this mass most likely etiologically related?

A. Atherosclerosis

B. Bacterial infection

C. Congenital anomaly

D. Cystic medial degeneration

E. Syphilis
 17

Explanation:

The correct answer is A. The mass is an abdominal aortic aneurysm, typically found in older
men. Such aneurysms are almost always related to the formation of complicated atherosclerotic
plaques in the aorta. Associated coronary artery disease is commonplace.

Bacterial infection (choice B) can cause "mycotic" aneurysms; these usually involve smaller
vessels.

The small berry aneurysms that can involve the circle of Willis are congenital anomalies
(choice C).

Cystic medial degeneration (choice D) is related to the development of dissecting aneurysms

(actually dissecting hematomas).

Tertiary syphilis (choice E) typically causes aneurysms of the root and arch of the aorta,
rather than the descending aorta.

At autopsy, a patient who had died with acute anuria and uremia is found to have ischemic necrosis of
the cortex of both kidneys with relative sparing of the medulla. These pathological findings
are most likely related to which of the following underlying conditions?

A. Disseminated intravascular coagulation

B. Multiple myeloma

C. Polycystic kidney disease

D. Pyelonephritis

E. Sickle cell anemia

Explanation:

The correct answer is A. Diffuse cortical necrosis, as described in this patient, is usually
seen in the setting of disseminated intravascular coagulation, typically in the context of
overwhelming sepsis. It can also be seen following hypotension combined with vasoconstriction.
 18

Multiple myeloma (choice B) is associated with renal deposition of amyloid protein and damage
to both glomeruli and tubules.

Adult polycystic kidney disease (choice C) would produce enlarged kidneys filled with cystic
masses.

Pyelonephritis (choice D) would produce inflammation, often most severe in the renal pelvis.

Sickle cell anemia (choice E) usually affects the medulla most severely, and can cause
papillary necrosis.

A 22-year-old female Asian immigrant presents with complaints of malaise, fever, arm pain, loss of
appetite, and visual problems. Her mother states that she fainted 1 week ago. The physician
cannot palpate the patient's lower extremity pulses and notes that the dial pulses are weak. The
erythrocyte sedimentation rate (ESR) is elevated. Which of the following is the most likely
diagnosis?

A. Buerger's disease

B. Kawasaki's disease

C. Takayasu's arteritis

D. Thrombophlebitis

E. Wegener's granulomatosus

Explanation:

The correct answer is C. Takayasu's arteritis is an uncommon disorder that is most prevalent in
young Asian women. In Takayasu's, an inflammatory process produces fibrous thickening of the
aortic arch, causing narrowing or near obliteration of the origins of arteries that branch from
the arch. Absent or diminished pulses are noted, especially in the upper extremities.
Involvement of the carotid circulation can produce ocular disturbances or other neurological
dysfunction (syncope or, less commonly, stroke).
 19

Buerger's disease (thromboangiitis obliterans; choice A) is a disease of young-to middle-aged

adult (predominantly males) smokers. It is characterized by segmental thrombosis of arteries
and veins, often in extremities.

Kawasaki's disease (choice B) is usually seen in children, and is characterized by rash, fever,
conjunctivitis, and lymphadenopathy. Coronary vasculitis and aneurysms may occur.

Thrombophlebitis (choice D) usually involves the deep veins of the legs and often occurs in
association with predisposing factors such as immobilization, clotting disorders, heart
disease, cancer, pregnancy, or tissue injury.

Wegener's granulomatosis (choice E) generally affects patients over 50 with vasculitis,

glomerulonephritis, and multiple granulomata of the upper and lower respiratory tract.

A 28-year-old female with a several-year history of intermittent diarrhea and abdominal pain is seen for
inflammatory bowel disease. Endoscopic evaluation of her terminal ileum, colon, and rectum is
undertaken. Which of the following endoscopic observations is more indicative of Crohn's
disease than of ulcerative colitis?

A. Discontinuous mucosal involvement

B. Mucosal atrophy

C. Mucosal ulceration

D. Pseudopolyps

E. Rectal involvement

Explanation:

The correct answer is A. Crohn's disease is frequently associated with "skip lesions,"
discontinuous areas of active disease in the colon and small intestine with intervening
segments that appear normal. This is in marked contrast to ulcerative colitis, which most
commonly shows continuous mucosal involvement.

Both ulcerative colitis and Crohn's disease can show mucosal atrophy (choice B). Chronic
 20

mucosal inflammation produces glandular atrophy, and a loss of mucosal folding.

Mucosal ulceration (choice C) is seen in both Crohn's disease and ulcerative colitis. The
ulcers of Crohn's disease are generally described as linear fissures, following the
longitudinal axis of the intestine. Ulcerative colitis typically produces broad, extensive
areas of ulceration.

Pseudopolyps (choice D) are most commonly associated with ulcerative colitis, and represent the
islands of spared mucosa between the broad ulcerations.

Rectal involvement (choice E) in inflammatory bowel disease is more typical of ulcerative

colitis than of Crohn's disease. Whereas ulcerative colitis is a "pancolitis," that is usually
most severe in the rectum and right colon, Crohn's disease is usually a disease of the small
intestine, and may involve the small intestine alone (40%) or both the small intestine and
colon (30%).

A renal biopsy is performed during a workup for renal insufficiency in a patient with a slightly reduced
renal size. The biopsy incidentally samples one of the arcuate arteries, which shows
reduplication of the elastic lamina and fibrosis of the media. These findings are most likely
associated with which of the following?

A. Amyloidosis

B. Escherichia coli enterotoxin

C. Hypertension

D. Lipoid nephrosis

E. Sickle cell disease

Explanation:

The correct answer is C. The lesion described is called fibroelastic hyperplasia, and it can
affect the media of larger interlobular and arcuate arteries. These changes are related to
benign nephrosclerosis, usually in hypertensive patients. Other changes seen in benign
nephrosclerosis include hyaline arteriolosclerosis and sometimes patchy ischemic atrophy.
 21

Amyloidosis (choice A) can cause deposition of amyloid material (homogeneous eosinophilic

extracellular deposits) around small blood vessels.

Escherichia coli enterotoxin (choice B) has been implicated in childhood hemolytic uremic
syndrome with microangiopathic hemolytic anemia related to vascular intimal hyperplasia,
fibrinoid necrosis, and thrombi.

Lipoid nephrosis (minimal change disease, choice D) has a normal or abnormal appearance by
light microscopy.

Sickle cell disease (choice E) can cause focal occlusions of the vasa recta (the hypertonic,
hypoxic milieu of the renal medulla favors sickling), leading to patchy papillary necrosis,
proteinuria, and sometimes cortical scarring.

A 51-year-old alcoholic man is admitted to the hospital after profuse upper gastrointestinal bleeding.
His wife states that she heard vomiting in the bathroom, then went to check on her husband
after he didn't emerge for 10 minutes, and found him in a pool of blood, unconscious. Which of
the following is the most likely cause of this man's bleeding?

A. Barrett's esophagus

B. Helicobacter gastritis

C. Mallory-Weiss tear

D. Schatzki ring

E. Zenker's diverticulum

Explanation:

The correct answer is C. This is the classic presentation of a Mallory-Weiss tear, which is a
mucosal tear at the gastroesophageal junction secondary to recurrent vomiting (the stomach
temporarily evulses through the esophagus, tearing the esophagus). The result can be massive
hematemesis, but the lesions usually heal without problems if the patient does not die from
exsanguination.
 22

Barrett's esophagus (choice A) is characterized by the replacement of normal esophageal

epithelium with gastric-type epithelium. Barrett's carries a high risk of adenocarcinoma, not
bleeding.

Helicobacter gastritis (choice B) does not usually cause profuse bleeding.

Schatzki rings (choice D) are benign mucosal rings at the squamocolumnar junction below the
aortic arch.

Zenker's diverticula (choice E) are esophageal evaginations at the junction of the pharynx and
esophagus. They are not typically associated with bleeding.

A patient presents to her hematologist with acute myeloblastic leukemia. A marrow smear contains many
promonocytes that stain positively for non-specific esterase. According to the French-American-
British (FAB) classification, this leukemia would be best classified as which of the following?

A. M1

B. M2

C. M3

D. M5

E. M7

Explanation:

The correct answer is D. Acute myeloblastic leukemia is subclassified based on the degree of
differentiation of the tumor cells. The cells described in the question stem are those of acute
monocytic leukemia-M5 according to the FAB classification.

M1 (choice A) is acute myelocytic leukemia without differentiation. A substantial proportion of

cells are myeloperoxidase-positive; few cells mature beyond the myeloblast stage.

M2 (choice B) is acute myelocytic leukemia with differentiation. Myeloblasts and promyeloblasts

 23

with a few Auer rods are typically seen.

M3 (choice C) is acute promyelocytic leukemia, characterized by promyelocytes with many Auer

rods.

M7 (choice E) is acute megakaryocytic leukemia. In this condition, blasts react with

antiplatelet antibodies.

Three days following a viral illness, a 3-year-old child develops severe vomiting and irritability,
followed by lethargy. The concerned parents take the child to the emergency room. Physical
examination is remarkable for hepatomegaly. The child is admitted to the hospital, but over the
next 24 hours, coma develops, and there is a marked elevation in serum ammonia levels. Electron
microscopy of brain or liver would most likely reveal profound alterations in which of the
following cellular organelles?

A. Centromeres

B. Cilia

C. Mitochondria

D. Peroxisomes

E. Ribosomes

Explanation:

The correct answer is C. The child has Reye's syndrome (fatty liver with encephalopathy), which
is an acquired mitochondrial abnormality (mechanism unknown) that can follow viral infections
in children under 15 years of age. The cause is unknown, and although aspirin use has since
been implicated, the syndrome may occur without exposure to salicylates. Reye's syndrome
usually follows an upper respiratory tract infection, especially influenza or chickenpox. The
mortality rate is near 50%, but if the child survives, full recovery is possible.

A 26-year-old female presents with a chief complaint of menstrual bleeding 10 days prior to the usual
onset of menses. She states that her last menstrual period was heavier that usual. The
physician examines her and performs a pregnancy test (which is negative) then concludes that
 24

she is probably experiencing dysfunctional bleeding due to anovulation. If an endometrial

biopsy were performed, which of the following would be the most likely histologic appearance of
this type of endometrium?

A. Asynchronous secretory endometrium

B. Decidualized stroma with inactive glands

C. Early proliferative endometrium

D. Late secretory endometrium

E. Menstrual endometrium

F. Proliferative endometrium with stromal breakdown

Explanation:

The correct answer is F. The most common cause of dysfunctional uterine bleeding is
anovulation. This is caused by excessive and prolonged estrogen effect without the
postovulatory progesterone effect. This occurs most often around menarche and menopause, when
subtle hormonal imbalances commonly occur. An estrogenic stimulation causes the endometrial
glands to proliferate. Persistent proliferation without a progesterone phase will eventually
break down and bleed even though there is no secretory change present and the stroma is not
menstrual. That is why this is called "anovulation bleed," because it is a non-ovulatory bleed
that may seem like normal menstruation.

Asynchronous secretory endometrium (choice A) refers to secretory endometrium that has a

mismatch of 2 or more days between the glands and the stroma. For example, the glands may be at
day 17 while the stroma shows more maturity, corresponding to day 22. This is a type of
dysfunctional ovulatory bleeding and clinically presents with infertility. It is usually due to
an inadequate luteal phase because the corpus luteum is not producing enough progesterone even
though ovulation has occurred.

Decidualized stroma with inactive glands (choice B) is the common histologic appearance of
patients taking oral contraceptives. These patients have asynchronous glands and stroma. The
glands are usually not active and the stroma appears to be ready for implantation. This reverts
 25

to normal with discontinuation of oral contraceptives.

Early proliferative endometrium (choice C) and late secretory endometrium (choice D) are
physiologic phases of the normal menstrual cycle.

Menstrual endometrium (choice E) histologically shows stromal and glandular breakdown with
bleeding following the full cycle. It follows the secretory phase and precedes the
proliferative phase.

A 27-year-old man with AIDS develops a reddish, slightly raised rash on his face, neck, and mouth,
consistent in appearance with Kaposi's sarcoma. Microscopically, the proliferating cells in this
malignancy most closely resemble which of the following?

A. Angiosarcoma

B. Carcinosarcoma

C. Lymphoma

D. Malignant fibrous histiocytoma

E. Melanoma

Explanation:

The correct answer is A. Kaposi's sarcoma is a spindle cell neoplasm that is highly associated
with AIDS and with the Herpes simplex virus type 8. The tumor has an appearance very similar to
that of angiosarcoma-proliferating stromal cells and endothelium creating vascular channels
that contain blood cells.

Carcinosarcoma (choice B) is a tumor that contains malignant epithelial cells and malignant
stromal cells. There is no epithelial element in Kaposi's sarcoma.

Although lymphoma (choice C) occurs with increased frequency in AIDS, it does not resemble
Kaposi's sarcoma. Lymphoma involves neoplastic lymphocytes, whereas Kaposi's sarcoma involves
neoplastic vascular structures.
 26

Malignant fibrous histiocytoma (MFH); (choice D) is an extremely poorly differentiated

(anaplastic) stromal malignancy. MFH does not produce any recognizable mesenchymal structures-
thus, the production of vascular structures by Kaposi's sarcoma differentiates the two tumors.

Melanoma (choice E) does produce colored skin lesions; however, the histological appearance of
the malignant melanocytes is quite unlike Kaposi's sarcoma. Melanoma in situ appears as small
nests of cells with large, red nucleoli in the dermis and epidermis; this lesion can progress
to a variety of forms, but none resemble Kaposi's sarcoma.

A 55-year-old man newly diagnosed with leukemia undergoes genetic studies that reveal a t(9;22)
translocation (the Philadelphia chromosome). Which of the following would a complete blood
count most likely show?

A. Increased lymphocyte count

B. Increased neutrophil count

C. Numerous lymphoblasts

D. Numerous myeloblasts

E. Pancytopenia

Explanation:

The correct answer is B. The Philadelphia chromosome is a hallmark of chronic myeloid leukemia
(CML). CML typically presents with markedly increased numbers of circulating neutrophils and
metamyelocytes, with lesser numbers of eosinophils and basophils and a small number of blasts.
The disease follows an indolent course, and usually progresses to an accelerated phase with
increased numbers of circulating blasts only after several years.

An increased lymphocyte count (choice A) would be seen in chronic lymphocytic leukemia (CLL),
another indolent leukemia.

Increased numbers of blasts (choices C and D) are seen in the late stages of CML and CLL, or in
the acute leukemias. The Philadelphia chromosome is occasionally associated with acute
lymphoblastic leukemia and acute myeloblastic leukemia, but these are diseases of children and
 27

young adults.

Pancytopenia (choice E) is most typical of the myelodysplastic syndromes (MDS), in which

ineffective hematopoiesis of a pluripotent stem cell produces abnormal development of all cell
types. No specific chromosomal abnormality is associated with MDS.

A 35-year-old man presents to his doctor with loss of appetite, nausea and vomiting, and fatigue.
Laboratory examination confirms the diagnosis of hepatitis B, and the man becomes icteric 2
weeks later. This patient may also be particularly vulnerable to the development of which of
the following disorders?

A. Berry aneurysm

B. Coronary artery aneurysm

C. Dissecting aneurysm

D. Giant cell arteritis

E. Polyarteritis nodosa

Explanation:

The correct answer is E. Thirty percent of patients with polyarteritis nodosa have hepatitis B
antigenemia. Polyarteritis is a systemic necrotizing vasculitis that can be difficult to
diagnose, since the vascular involvement is typically widely scattered, and the specific
symptoms depend on the specific vessels (small- to medium-sized arteries) involved. Patients
typically present with low-grade fever, weakness, and weight loss. Abdominal pain, hematuria,
renal failure, hypertension, and leukocytosis may occur. The disease is frequently fatal if
untreated.

Berry aneurysms (choice A) are congenital saccular dilatations of vessels associated with adult
polycystic kidney disease.

Coronary artery aneurysms (choice B) are associated with Kawasaki's disease in children.

Dissecting aneurysms (choice C) are associated with cystic medial necrosis (seen in Marfan's
 28

syndrome) and hypertension.

Giant cell arteritis (choice D) occurs in older adults; it is associated, in some cases, with
polymyalgia rheumatica.

A patient comes to medical attention because of a kidney stone. During the clinical evaluation, the
patient reveals that he has had a history of stomach ulcers. Which of the following diagnoses
should the physician consider?

A. Horner syndrome

B. Shy-Drager syndrome

C. Sipple syndrome

D. Turcot syndrome

E. Wermer syndrome

Explanation:

The correct answer is E. This patient may have Wermer syndrome (multiple endocrine neoplasia
type I; MEN type I). In this disorder: 1) parathyroid hyperplasia or adenomas can cause
hypercalcemia and kidney stones; 2) pancreatic neoplasms may secrete any of the islet hormones
or may secrete gastrin, producing Zollinger-Ellison syndrome with multiple peptic ulcers; and
3) pituitary adenomas may occur rarely.

Horner's syndrome (choice A) is characterized by ptosis, miosis, and in many cases,

hemianhidrosis. It is usually related to involvement of the cervical sympathetic plexus by
tumor (usually lung cancer).

In Shy-Drager syndrome (choice B), there is autonomic nervous system failure, leading to
orthostatic hypotension and parkinsonism.

Sipple syndrome (choice C) is MEN type II, characterized by medullary thyroid carcinoma,
pheochromocytoma, and parathyroid disease.
 29

28 In the very rare Turcot syndrome (choice D), adenomas of the digestive tract and central
nervous system gliomas (astrocytoma and medulloblastoma) occur.

A 34-year-old man presents with weight loss, diarrhea, and flatulence. Jejunal biopsy demonstrates
marked atrophy of villi. This patient's condition may improve with removal of which of the
following from the diet?

A. Beef

B. Eggs

C. Potatoes

D. Tomatoes

E. Wheat

Explanation:

The correct answer is E. The patient probably has celiac sprue, which is caused by an allergic,
immunologic, or toxic reaction to the gliadin component of gluten (from wheat). The symptoms
and pathologic changes usually reverse with complete removal of gliadin from the diet.
Therapeutic failures are frequently due to hidden wheat in the diet. Patients with celiac
disease have an increased risk of developing gastrointestinal lymphoma.