1

Autopsy of a 70-year-old woman reveals a papillary growth within the left ventricular chamber. The
growth consists of a small mass of finger-like projections attached to the mitral valve,
without associated valvular or other cardiac abnormalities. Histologically, each papillary
structure is composed of a core of fibrous tissue lined by thickened endothelium. The patient
did not have any history of cardiac disease or evidence of thromboembolism. Which of the
following is the most likely diagnosis?

A. Acute mural thrombus

B. Cardiac myxoma

C. Infective endocarditis

D. Nonbacterial thrombotic endocarditis

E. Papillary fibroelastoma

Explanation:

The correct answer is E. Gross and microscopic features of this small mass in the left
ventricle are entirely consistent with papillary fibroelastoma. This lesion is not neoplastic,
despite the sound of the name. It probably results from organized thrombi forming on the
endocardial surfaces of the mitral valve or left ventricular cavity. Papillary fibroelastomas
are usually clinically silent and are discovered at autopsy as an incidental finding.

An acute mural thrombus (choice A) would not have a core of fibrous tissue. Acute mural
thrombosis usually develops as a result of stasis in the ventricular cavities, in association
with ventricular enlargement, myocardial infarction, or ventricular aneurysm, for example.
Thrombosis often develops in the atria when there is atrial fibrillation.

Cardiac myxoma (choice B) is the most frequent primary cardiac neoplasm. It is benign and
consists of stellate mesenchymal cells within a myxoid background. Since the left atrium is the
most frequent location, this tumor can produce mitral stenosis by a ball-valve effect.

Both forms of endocarditis are associated with formation of vegetations attached to the surface
of the atrioventricular valves. Vegetations of infective endocarditis (choice C) are bulky and
composed of fibrin, bacteria, and inflammatory cells. Since nonbacterial thrombotic
endocarditis (choice D) is caused by hypercoagulable states, the vegetations consist of
aggregates of fibrin but few inflammatory cells and no bacteria.

Note that all of the above conditions may lead to systemic embolization. Fragments of
vegetations, thrombi, myxoma, and papillary fibroelastoma may detach and be released into the
bloodstream, causing infarcts.

A 45-year-old man presents to his physician with hematuria. Renal biopsy demonstrates a focal
necrotizing glomerulitis with crescent formation. The patient has a history of intermittent
hemoptysis and intermittent chest pain of moderate intensity. A previous chest x-ray had
demonstrated multiple opacities, some of which were cavitated. The patient also has chronic
cold-like nasal symptoms. Which of the following is the most likely diagnosis?

A. Aspergillosis

B. Polyarteritis nodosa

C. Renal carcinoma metastatic to the lung

 2

D. Tuberculosis

E. Wegener's granulomatosis

Explanation:

The correct answer is E. While in real life, other diseases (or combinations of diseases) may
occasionally cause concurrent pulmonary, sinus, and renal involvement, if you see this pattern
on a test question, you should immediately think of Wegener's granulomatosis. This is a rare
focal necrotizing vasculitis of still unclear etiology, which also features prominent
granulomas, some of which are centered on the vascular lesions. The vasculitis and granulomas
can involve the entire respiratory tract, and an easily obtained nasal biopsy may sometimes
yield the diagnosis. The renal involvement is usually in the form of a necrotizing
glomerulonephritis. The disease typically affects middle aged men, and its formerly poor
prognosis has been improved by corticosteroid and cyclophosphamide therapy.

Aspergillosis (choice A) can cause prominent lung disease, but does not usually have renal
involvement.

Polyarteritis nodosa (choice B) is a possibility, but usually spares the lungs.

Renal cell carcinoma (choice C) might cause lung nodules, but there is no evidence of tumor in
the kidney.

Tuberculosis (choice D) can cause prominent lung disease, but does not usually have renal
involvement.

A 55-year-old man presents to a physician with jaundice. Ultrasonography demonstrates a 5 cm mass in the
head of the pancreas. Endoscopic retrograde cholangiopancreatography with cytologic sampling
demonstrates cells with large hyperchromatic nuclei and a high nuclear/cytoplasmic ratio. A few
small glands composed of these cells are also seen in the cytologic preparation. The overall
prognosis for this man will be most similar to that of a patient with which of the following
malignancies?

A. Adenocarcinoma of the breast

B. Adenocarcinoma of the colon

C. Adenocarcinoma of the esophagus

D. Adenocarcinoma of the prostate

E. Primary gastric lymphoma

Explanation:

The correct answer is C. The patient probably has pancreatic adenocarcinoma. This cancer
carries one of the worst prognoses, with a 3.5% overall 5 year survival rate despite all
attempts at aggressive management. The prognosis is also bleak with adenocarcinoma of the
esophagus, with a 10% overall 5 year survival rate.

Adenocarcinoma of the breast (choice A) now has an overall 5 year survival rate of 60-70%.

Adenocarcinoma of the colon (choice B) now has an overall 5 year survival rate of 50-60%.
 3

Adenocarcinoma of the prostate (choice D) now has an overall 5 year survival rate of 50-70%.

Primary gastric lymphoma (choice E) has an overall survival 5 year survival rate of 75-85%.

Biopsy of a persistent exophytic area on the vulva of a 60-year-old woman demonstrates a squamous
epithelial lesion. No koilocytes are seen. The lesions show papillary projections composed of
disordered, squamous epithelium with well-differentiated cells. The basement membrane at the
dermal-epidermal junction is focally disrupted by squamous cell groups extending deep into the
dermis. Which of the following diagnoses is most accurate?

A. Condyloma acuminatum

B. Extramammary Paget's disease

C. Vulvar intraepithelial neoplasia

D. Vulvar melanoma

E. Vulvar squamous cell carcinoma

Explanation:

The correct answer is E. The disruption of the basement membrane with cell groups extending
deep into the dermis indicates that this is invasive squamous cell carcinoma of the vulva,
which may arise in vulvar intraepithelial neoplasia, in condyloma, or spontaneously. The latter
type (which is likely here) tends to be well differentiated, while the former two are often
poorly differentiated.

Condyloma acuminatum (choice A) would contain koilocytes and would not cross the basement
membrane.

Extramammary Paget's disease (choice B) would probably contain individual tumor cells that
stain for mucin.

The lesion of vulvar intraepithelial neoplasia (choice C) does not cross the basement membrane.

Vulvar melanoma (choice D) is composed of melanocytes that would mark with S100 or HMB-45.

Which of the following conditions is associated with overexpression of bcl-2?

A. Acute lymphoblastic leukemia

B. Burkitt lymphoma

C. Follicular lymphoma

D. Multiple myeloma

E. Small lymphocytic lymphoma

Explanation:

The correct answer is C.bcl-2 inhibits apoptosis; a (14;18) translocation resulting in

overexpression of the bcl-2 protein in B lymphocytes causes apoptosis of neoplastic cells to be
permanently inhibited, producing follicular lymphoma. Follicular lymphoma involves the lymph
nodes and bone marrow of older people and is characterized by slow, but relentless, growth.
 4

Thus, this lymphoma allows a long survival even without any treatment. Indeed, follicular
lymphoma is resistant to aggressive therapy because of its low mitotic activity.

Acute lymphoblastic leukemia (ALL) (choice A) is a neoplasm of pre-B cells that affects
children. Different molecular mechanisms probably account for different cases. Hyperdiploidy,
the Philadelphia chromosome, t(12;21), and t(4;11) are variably found in patients with ALL.

Burkitt lymphoma (choice B) occurs in different clinical settings, including the African
endemic, sporadic nonendemic, and AIDS-associated forms. Histologically, all these forms are
identical and are derived from neoplastic transformation of B cells expressing surface IgM.
Common to all forms are translocations involving the c-myc oncogene (chromosome 8) and Ig loci
(chromosome 14). These translocations lead to overexpression of c-myc, which encodes a nuclear
transcription protein, resulting in sustained cell replication. The African form is associated
with Epstein-Barr virus infection.

Multiple myeloma (choice D) is a neoplasm of terminally differentiated B lymphocytes that

secrete large amounts of monoclonal Ig or its fragments (light or heavy chains). Approximately
25% of cases have translocations that lead to overexpression of FGFR3, a receptor for
fibroblast growth factor implicated in control of cell proliferation.

Small lymphocytic lymphoma (choice E), a B cell neoplasm, is equivalent to chronic lymphocytic
leukemia. Neoplastic cells resemble a normal subset of circulating mature B cells that express
CD5. Various types of chromosomal abnormalities have been found in small lymphocytic
lymphoma/chronic lymphocytic leukemia, but none affecting the bcl-2 locus.

A 10-year-old boy with history of epilepsy and mental retardation is brought to a specialty clinic for
evaluation. Physical examination is remarkable for several ovoid hypopigmented areas on the
trunk and large numbers of red and yellow papules on the face, particularly near the mouth.
Biopsy of the papules demonstrates angiofibromata. This patient is most likely to have which of
the following central nervous system pathologies?

A. Acoustic neuromas

B. Capillary hemangioblastomas

C. Herniation of cerebellar tonsils into foramen magnum

D. Large cortical hamartomas

E. Leptomeningeal angiomatosis

Explanation:

The correct answer is D. The disease is tuberous sclerosis. The facial angiofibromata are also
called adenoma sebaceum, and the hypopigmented patches on the trunk are called ash-leaf spots.
This disease is one of the neurocutaneous disorders called phacomatoses. Tuberous sclerosis is
inherited as an autosomal dominant trait, and epilepsy and mental retardation are commonly seen
in this disorder. Large, firm, white hamartomatous nodules (tubers) are seen in the cortex and
in subependymal sites. The tubers consist of aberrantly arranged neurons and/or glia. Patients
may also have pancreatic cysts, renal angiomyolipomas, and cardiac rhabdomyomas. Rarely, an
astrocytoma will arise in a tuber.

Acoustic neuromas (choice A) are a feature of neurofibromatosis Type II.

Capillary hemangioblastomas (choice B) are a feature of Von Hippel-Lindau syndrome.

 5

Herniation of cerebellar tonsils (choice C) is a feature of Arnold-Chiari malformation.

Leptomeningeal angiomatosis (choice E) is a feature of Sturge-Weber disease.

A 30-year-old African American woman has a chest x-ray that shows hilar lymphadenopathy and diffuse
abnormalities of the lung parenchyma. Biopsy reveals non-caseating granulomas. Acid fast,
silver, and PAS stains on the granulomas are negative. Which of the following is the most likely
diagnosis?

A. Coccidioidomycosis

B. Histoplasmosis

C. Leprosy

D. Sarcoidosis

E. Tuberculosis

Explanation:

The correct answer is D. Sarcoidosis is a common granulomatous disease, the etiology of which
remains unclear. It is a diagnosis of exclusion, and mycobacterial (acid fast) and fungal
(silver stain, PAS) are used to rule out infectious etiologies. The granulomas are
characteristically small, non-caseating (hard) granulomas that may contain giant cells.
Sarcoidosis has an initial predilection for the lungs and the hilar lymph nodes, but with time
may spread to involve many organs. In the United States, sarcoidosis is much more common in
people of African ancestry. In Europe, it mainly affects whites. There is a slight female
preponderance. Patients can have a progressive course or experience exacerbations and
remissions. Some patients recover with little residual damage; those who die typically do so
from pulmonary fibrosis and cor pulmonale.

The causative agent of coccidioidomycosis (choice A), Coccidioides immitis, or the causative
agent of histoplasmosis (choice B), Histoplasma capsulatum, would stain with PAS and silver
stain.

The causative agent of leprosy (choice C), Mycobacterium leprae, or the causative agent of
tuberculosis (choice E), Mycobacterium tuberculosis, would stain with acid fast stain.

A patient presents with a severe form of atopic asthma. Which of the following changes would most likely
be found in this patient's blood?

A. Basophilic leukocytosis

B. Eosinophilic leukocytosis

C. Lymphocytosis

D. Monocytosis

E. Neutrophilic leukocytosis

Explanation:

The correct answer is B. An increased number of eosinophils (AKA eosinophilia) occurs in

association with several conditions, the most frequent of which are immune-mediated diseases
 6

(e.g., asthma, hay fever, and pemphigus vulgaris) and parasitic infestations. This is due to an
absolute increase in the number of circulating eosinophils, brought about by IL-5, which
stimulates differentiation of eosinophilic precursor cells in the bone marrow.

Basophilic leukocytosis (choice A) is a rare event that is sometimes observed in association

with chronic myelogenous leukemia. It is not seen in patients with asthma.

Lymphocytosis (choice C) may result from a vast array of conditions, but it is not typical of
asthma or other allergic diseases. Lymphocytosis may develop in response to a number of
infections (e.g., brucellosis, whooping cough, hepatitis, infectious mononucleosis, and
tuberculosis) or manifest as part of chronic lymphocytic leukemia.

Monocytosis (choice D) refers to an increase in number of monocytes, which are circulating

macrophages. Chronic infections (e.g., tuberculosis, rickettsiosis, and malaria) and chronic
inflammatory conditions (e.g., collagen vascular diseases and inflammatory bowel disease) are
the most common underlying causes.

Neutrophilic leukocytosis (choice E) is a typical systemic reaction to acute and chronic

infections, especially those due to bacteria. The increase in neutrophil number is mediated by
IL-1 and TNF, which induce a rapid release of neutrophils from the bone marrow in acute
infections and stimulate proliferation of bone marrow precursors in chronic infections.

A patient with long term severe hypertension develops progressive dementia. CT scan of the head
demonstrates a diffuse loss of deep hemispheric white matter. Which of the following terms best
describes the pathological process that is occurring?

A. Anemic infarcts

B. Hemorrhagic infarcts

C. Hypertensive encephalopathy

D. Lacunae

E. Subcortical leukoencephalopathy

Explanation:

The correct answer is E. This patient has subcortical leukoencephalopathy (Binswanger's

disease), which is one of the neurologic syndromes associated with hypertension. It is
uncommon, but obviously devastating. The histologic findings are diffuse, irregular loss of
axons and myelin accompanied by widespread gliosis. Small infarcts may be seen in the frontal
lobes. The pathologic mechanism may be damage caused by severe arteriolosclerosis. None of the
other choices would produce diffuse subcortical white matter involvement.

Anemic infarcts (choice A) can be seen in hypertensive patients as a consequence of

atherosclerotic thromboembolic events.

Hemorrhagic infarcts (choice B) can also be seen in hypertensive patients as a consequence of

atherosclerotic thromboembolic events followed by reperfusion. They tend to occur in gray
matter or at the gray-white junction.

Hypertensive encephalopathy (choice C) is an acute generalized dysfunction of the brain that

can occur in malignant hypertension or other very severe hypertensive processes. The primary
pathology is seen in cerebral vessels, although cerebral edema may be present.
 7

Lacunae (choice D) are small necrotic foci in deep gray matter (especially basal ganglia and
thalamus) seen in some hypertensive patients.

What percentage of Down's syndrome patients also have congenital cardiovascular disease?

A. 0.1%

B. 3%

C. 20%

D. 50%

E. 90%

Explanation:

The correct answer is C. This fact is worth remembering: one-fifth of Down's syndrome patients
have congenital cardiovascular disease, most commonly an ostium primum type of ASD and/or a
ventricular septal defect. This is a sufficiently high incidence to justify at least one
echocardiogram in each of these children's lives. Affected children are also particularly
vulnerable to seizures, and as adults may develop an Alzheimer-like dementia in their mid 40s.

A 50-year-old man presents with renal colic and an intravenous pyelogram demonstrates "clumps" of
contrast medium limited to the medulla. Multiple small stones are also seen. Blood chemistries
are all within normal limits. What is the most likely explanation for these findings?

A. Adult polycystic renal disease

B. Horseshoe kidney

C. Infantile polycystic renal disease

D. Medullary sponge kidney

E. Renal dysplasia

Explanation:

The correct answer is D. This is a classic presentation for medullary sponge kidney, which has
a male predominance and typically presents at 40-60 years of age. Histologically, medullary
sponge kidney shows multiple small cysts lined by columnar or cuboidal epithelium localized to
the medullary collecting tubules. The cysts can contain laminated concretions of calcium
phosphates. Renal failure is rare in patients with medullary sponge kidney and the pathogenesis
for the lesion has not been clarified. The rare uremic medullary sponge kidney is distinguished
from the more common form by occurrence in 20-30 year-olds, salt-losing nephropathy, and
progression to renal failure.

The kidney of adult polycystic disease (choice A) is massively enlarged and filled throughout
with round cysts of varying sizes. Adult polycystic kidney disease often presents with
hypertension rather than renal failure or stones.

Horseshoe kidney (choice B) involves fusion of the upper or lower (most common) pole of the
kidney. It is fairly common (as high as 1:500), and is typically an incidental finding at
autopsy.
 8

Infantile polycystic kidney (choice C) produces a small kidney with round medullary cysts and
"radiating" linear cortical cysts.

Renal dysplasia (choice E) can also cause cystic change in a kidney, but typically involves
only the medulla and cortex of part of the kidney.

A 75-year-old female presents to the doctor with a chief complaint of vaginal spotting. She has been
post-menopausal for 25 years and does not take hormones. An ultrasound is performed, and shows a
mass in the uterine fundus. A hysterectomy is performed, and pathologic examination of the
removed uterus reveals a malignant tumor of the endometrial glands and stroma. Which of the
following is the most likely diagnosis?

A. Endolymphatic stromal myosis

B. Endometrial carcinoma

C. Endometrial stromal sarcoma

D. Leiomyosarcoma

E. Malignant mixed mllerian tumor

Explanation:

The correct answer is E. Malignant mixed mllerian tumor is a tumor with 2 components, stromal
and epithelial (endometrial glands), both of which are malignant. This is a rare and highly
aggressive tumor that has a 25% 5-year survival rate. It usually affects older patients and
presents with post-menopausal bleeding. The stromal component can contain metaplastic
components such as cartilage and bone. Interestingly, usually only the epithelial component
metastasizes.

Endolymphatic stromal myosis (choice A) is a type of endometrial stromal tumor of intermediate

malignancy. It appears as small pieces of stroma between myometrial bundles that infiltrate
lymph channels. Patients may have pain or bleeding, or may be asymptomatic. Recurrences happen
late in the course of the disease (years) in half of patients and metastasis occurs in 15%.
There is no epithelial component, so this is an incorrect choice.

Endometrial carcinoma (choice B) is a malignancy of the epithelial glandular component of the

endometrium. Abnormal bleeding is the usual presentation. High estrogen states cause this
tissue to proliferate. There is no stromal component of this tumor, so this is an incorrect
choice.

Endometrial stromal sarcoma (choice C) is a true sarcoma arising from the endometrial stroma
that infiltrates the myometrium and invades vessels. There is no epithelial component.

Leiomyosarcoma (choice D) is a true sarcoma arising from the uterine smooth muscle. It commonly
has satellite lesions within the uterus. Leiomyosarcomas usually recur after removal; survival
is greater with well differentiated lesions. Poorly differentiated lesions have a 10 to 15% 5-
year survival rate. Distant metastasis is via blood vessels. There is no epithelial component.

An 80-year-old man has low back pain. An x-ray of the lower back and pelvis shows sclerotic changes in
the lower vertebrae and in focal areas throughout the pelvis. The radiologist's report states
that the sclerotic changes may represent osteoarthritis; however, metastatic prostate cancer
cannot be excluded. Which of the following is most cost-effective in the initial work-up of this
patient?
 9

A. Bone marrow aspirate and biopsy

B. Digital rectal exam

C. Prostate-specific antigen

D. Radionuclide bone scan

E. Serum alkaline phosphatase

Explanation:

The correct answer is B. Osteoarthritis is the most common rheumatologic disease, the
prevalence of which increases with age. It primarily involves weight-bearing joints, hence its
distribution in the lower vertebrae, pelvic bones, and proximal femur. Sclerotic bone,
representing reactive bone formation, develops as a reaction to injury and is responsible for
the slightly elevated serum alkaline phosphatase levels that normally occur in much of the
elderly population. If prostate cancer with osteoblastic (bone-forming) metastases to the
vertebral column and pelvis were present in this patient (stage D disease), a digital rectal
exam would be the most cost-effective initial step in the work-up. With advanced prostate
cancer, the gland would very likely be enlarged and hard ("stony").

A bone marrow aspirate and biopsy (choice A) is not usually part of the normal work-up of
possible metastatic prostate cancer and has no place in the evaluation of osteoarthritis.

A prostate-specific antigen (PSA; choice C) level should be ordered in this patient, but not as
the initial step in the work-up, since it does not distinguish hyperplasia from cancer and is
fairly expensive. In known cases of prostate cancer, the PSA is a measure of tumor burden and
is used to monitor recurrences when following patients who have been treated for prostate
cancer.

A radionuclide bone scan (choice D) is commonly used to rule out metastasis in patients with
prostate cancer. It is expensive and is not used as a screening test for prostate cancer.

The serum alkaline phosphatase (choice E) is typically elevated in metastatic prostate cancer
due to osteoblastic activity in the metastatic foci. However, an elevated serum alkaline
phosphatase is non-specific, since it may be slightly increased in osteoarthritis (reactive
bone formation) as well as in liver disease.

A 40-year-old woman presents to the emergency department with severe abdominal pain localized to the
right upper quadrant. A urine sample is taken for rapid dipstick reagent strip analysis. A
positive result for which of the following substances would most strongly suggest gallstone
disease as a possible cause of her abdominal pain?

A. Bilirubin

B. Glucose

C. Nitrite

D. Protein

E. Urobilinogen

Explanation:
 10

The correct answer is A. A small gallstone passing into the common bile duct can cause
obstructive jaundice with conjugated hyperbilirubinemia. The conjugated bilirubin will spill
into the urine, causing the bilirubin square on the reagent strip to react. This strip may also
react with other causes of intrahepatic or extrahepatic obstructive jaundice, so it is not
completely specific. It is worth becoming very familiar with the strengths and weaknesses of
reagent strip technology, however, since this information may be available hours before serum
chemistry values are reported.

High glucose (choice B) in urine suggests diabetes mellitus.

High nitrite (choice C) in urine suggests urinary tract infection.

High protein (choice D) in urine suggests renal disease or myeloma.

Urobilinogen levels (choice E) in obstructive jaundice can be normal, raised, or lowered;

consequently, they are not diagnostically helpful in the setting described in the question stem
unless urinary bilirubin is negative.

A 60-year-old man presents to his physician after a routine screening test indicates hyperlipidemia.
Physical examination reveals raised, irregular, yellow papules in the skin of the soft tissues
below the eyes. Biopsy of these lesions would most likely show which of the following?

A. Benign nevus cells

B. Malignant nevus cells

C. Microscopic blisters

D. Munro microabscesses

E. Multinucleated giant cells

Explanation:

The correct answer is E. The lesions are xanthomas, which are tumor-like dermal collections of
foamy histiocytes containing cholesterol and lipids. The lesions may also contain
multinucleated giant cells (Touton giant cells) with clustered nuclei and foamy cytoplasm.
Xanthomas may be idiopathic or may be related to hyperlipidemia or lymphoproliferative
malignancies (e.g., leukemias and lymphomas).

Nevus cells are a type of melanocyte. Benign nevus cells (choice A) are a feature of the common
nevus, or mole. Malignant nevus cells (choice B) are a feature of malignant melanoma.

Microscopic blisters (choice C) at the dermal/epidermal junction are a feature of dermatitis

herpetiformis.

Munro microabscesses (choice D), small collections of neutrophils in the cornified epidermis,
occur in psoriasis.

A 17-year-old male develops a painless, firm mass beneath the nipple of his left breast. The mass is
mobile, and no fluid can be expressed from the breast. The right breast is normal to
examination. Which of the following conditions does this mass most likely represent?

A. Fibrocystic changes

B. Gynecomastia
 11

C. Intraductal papilloma

D. Invasive duct carcinoma

E. Invasive lobular carcinoma

Explanation:

The correct answer is B. The most common breast mass in men, especially under 25 years of age,
is gynecomastia-a benign proliferation of ductal and stromal elements of the breast. It is
generally an idiopathic condition, probably related to pubertal hormonal changes.

Fibrocystic changes (choice A) in the breast, which reflect physiological responses in the
breast to cyclical levels of sex hormones, are not observed in men. Fibrocystic changes are
most common in the late reproductive years and include fibrosis, cyst formation, and a variety
of epithelial changes such as hyperplasia and apocrine metaplasia.

Intraductal papillomas (choice C) are benign neoplasms commonly evolving in the major
lactiferous ducts beneath the nipple. They most commonly present with a bloody nipple discharge
and are rare in men.

Carcinoma of the male breast (choices D and E) is rare, and almost always develops in the
breasts of elderly men. Male breast carcinomas have a somewhat worse prognosis than their
female counterpart. Grossly and microscopically they resemble ductal carcinoma in the female.

Physical examination of a 45-year-old man who looks much older than his stated age demonstrates thin
arms and legs, a swollen abdomen, red tongue, dry, thin, and slightly yellow skin, gynecomastia,
testicular atrophy, multiple spider angiomas, tremor, yellow discoloration of sclera, and short-
term memory loss. Which of the following conditions is most strongly suggested by these
findings?

A. Bronchogenic carcinoma

B. Colon carcinoma

C. Congestive heart failure

D. Glomerulonephritis

E. Hepatic cirrhosis

Explanation:

The correct answer is E. The physical examination is typical for an advanced alcoholic with
hepatic cirrhosis. It is important to recognize these symptoms, as these patients are notorious
for "underestimating" and even denying their alcohol use.

Bronchogenic carcinoma (choice A) typically presents with cough and/or respiratory changes, but
can present with mass effects in the chest or involvement of mediastinal nerves or vessels.

Colon cancer (choice B) typically presents with changes in the stool or bowel habits.

Congestive heart failure (choice C) is typically heralded by shortness of breath or peripheral

edema, or both.
 12

Glomerulonephritis (choice D) typically presents with changes in quality or quantity of urine,

and, possibly, fluid retention.

A 54-year-old white male presents with gradual onset of mild dementia, ataxic gait, and startle
myoclonus. An MRI scan is normal, and an examination of his cerebrospinal fluid reveals no
abnormalities, but the patient's EEG is remarkable for recurrent bursts of high-voltage slow
waves. Over the next 6 months, the patient's dementia rapidly worsens, accompanied by general
hypertonicity and profound dysarthria. The patient dies shortly thereafter. Which of the
following is the mostly likely neuropathological finding on autopsy?

A. Cerebellar hyperplasia

B. Diffuse spongiform change

C. Multiple lacunar infarcts

D. Negri bodies

E. Neurofibrillary tangles

Explanation:

The correct answer is B. The rapidly progressive dementia in this case is characteristic of
Creutzfeldt-Jakob disease (CJD). The dementia is usually accompanied by motor dysfunction and
abnormal EEG activity, as described in the question stem. The pathological hallmark of this
disease is spongiform change in the gray matter. Death usually occurs within 6-12 months of
disease onset.

At autopsy, the cerebellum in CJD appears atrophic, not hyperplastic (choice A).

Multiple lacunar infarcts (choice C) are seen with vascular dementia, and patients typically
present with focal neurological signs. Additionally, vascular dementia typically presents with
a more gradual decline in cognitive function, measured in years rather than months.

Negri bodies (choice D) are pathognomic for rabies, which does not cause dementia.

Neurofibrillary tangles (choice E) are often seen in patients with Alzheimer's disease.
Alzheimer's disease primarily affects the higher order association cortex; motor dysfunction is
not generally observed. Additionally, in Alzheimer's disease, there is a more gradual decline
in cognitive function, measured in years rather than months.

A 38-year-old woman is in her first pregnancy, which has been uneventful until the 34th week, when she
develops swelling of feet and hands. An obstetric check-up reveals that she also has
hypertension and proteinuria. Laboratory analysis shows elevated aspartate aminotransferase
(AST) and alanine aminotransferase (ALT) and slightly decreased platelets. The initial event in
the pathogenesis of her condition is thought to be which of the following?

A. Chorioamnionitis

B. Disseminated intravascular coagulation

C. Maternal hypertension

D. Maternal renal ischemia

E. Placental ischemia
 13

Explanation:

The correct answer is E. This patient's condition is a classic third trimester complication
referred to as toxemia of pregnancy, or preeclampsia. It occurs in 6% of all pregnancies but is
more frequent in primiparas. Although the pathogenesis is still unclear, the first event
appears to be placental ischemia, probably due to abnormalities in the trophoblast and
alterations in the maturation of placental vessels. The trophoblast of invading placental
vessels fails to acquire the characteristics of normal endothelial cells, with subsequent
alterations in blood flow. Placental ischemia then triggers the release of thromboplastic
substances, increases renin synthesis, and reduces prostaglandin E levels.

Chorioamnionitis (choice A) is an infection of chorioamnionic membranes due to bacteria that

ascend through the vaginal canal. This is an important cause of spontaneous abortion in the
second and third trimester, but it plays no role in the pathogenesis of toxemia of pregnancy.

The release of thromboplastic substances may cause disseminated intravascular coagulation (DIC)
(choice B).

Increased renin and reduced prostaglandin E mediate increased sensitivity to angiotensin,

leading to maternal hypertension (choice C).

Ischemic damage to maternal organs, including brain, liver, and kidneys (choice D), results
from thrombotic occlusion of arterioles and capillaries as a consequence of DIC.

Overall, the clinical picture of toxemia is due to DIC-mediated ischemic damage to brain
(changes in mental status and convulsions), liver (elevated liver enzymes), and kidneys
(proteinuria, leading to peripheral edema). A manifestation of toxemia is HELLP syndrome, which
stands for hemolysis, elevated liver enzymes, and low platelets.

Molecular studies on an abdominal lymph node containing lymphoma demonstrate t(2;8)(p12;q24)

translocation. This is most compatible with which of the following diseases?

A. Burkitt's lymphoma

B. Mantle cell lymphoma

C. Multiple myeloma

D. Small cell lymphoma

E. Small cleaved cell lymphoma

Explanation:

The correct answer is A. Burkitt's lymphoma is actually associated with three translocations.
The common variant t(8;14)(q24;q32), involving the oncogene myc on chromosome 8, and the heavy
immunoglobulin chain on chromosome 14. The other two variants are: t(8;22)(q24;q11), involving
myc and the lambda light chain immunoglobulin site, and t(2;8)(p12;q24), involving the kappa
light chain and myc.

Mantle cell lymphoma (choice B), multiple myeloma (choice C), and small (not cleaved) cell
lymphoma (choice D) are associated with the t(11;14)(q13;q32) translocation involving bcl -1
and the heavy chain site.

Small cleaved cell lymphoma (choice E) is associated with t(14;18)(q 32;q21), involving the
 14

immunoglobulin chain site and bcl-2.

A newborn infant is noted to have numerous, light brown macules dispersed across her skin. The
significance of this feature is due to its strong association with the development of which of
the following tumors?

A. Basal cell carcinoma

B. Neuroblastoma

C. Neurofibroma

D. Retinoblastoma

E. Wilms' tumor

Explanation:

The correct answer is C. Congenital "cafe au lait" spots are present in more than 90% of
patients with neurofibromatosis. This autosomal dominant disorder is characterized by multiple
neural tumors, especially neurofibromas, pigmented hamartomas of the iris (Lisch nodules), and
cafe au lait spots, which usually occur over nerve trunks. Although the majority of
neurofibromas in this disease are benign, the tumors can be quite disfiguring and
psychologically damaging.

Basal cell carcinoma (BCC; choice A) is a common, slow-growing tumor of sun-exposed skin. It
develops in adulthood after years of chronic sun damage. Although malignant melanoma may arise
from large congenital nevi, BCC does not.

Neuroblastoma (choice B) is a common childhood tumor that arises anywhere along the sympathetic
chain, and most commonly in the adrenal medulla. The tumor usually presents as an abdominal
mass and is not associated with skin findings.

The ocular neoplasm associated with neurofibromatosis is the Lisch nodule, not the
retinoblastoma (choice D). Retinoblastoma is a neuroepithelial tumor usually identified by
funduscopic examination of a child with visual changes.

Wilms' tumor (choice E) is a neoplasm of primitive renal blastema that may be associated with
congenital malformations of visceral organs, notably the adrenals and gonads, but not skin. It
also presents as an abdominal mass, and is highly survivable with modern treatment modalities.

A neonate develops bile-stained vomiting and progressive abdominal distention, and does not pass
meconium over the first two days of life. The anus is patent, and the bowel loops are palpable.
Plain radiograph shows bubbly meconium in the right lower quadrant. No localized areas of
constriction or other abnormalities are noted. Which of the following is most likely
etiologically related to this infant's condition?

A. Cystic fibrosis

B. Hirschsprung's disease

C. Meckel's diverticulum

D. Omphalocele

E. Polycystic kidney disease

 15

Explanation:

The correct answer is A. The baby has meconium ileus, which is a manifestation of cystic
fibrosis due to the abnormally viscid pancreatic secretions which "get stuck" in the small
bowel. Meconium ileus can cause gut perforation with peritonitis and intraperitoneal
calcifications (that may be visible on plain film). Meconium ileus complicated by intestinal
perforation or formation of fistulas to the bladder or vagina must be treated surgically.
Medical treatments for uncomplicated meconium ileus are now available, which use enemas,
mucolytic agents, or pancreatic enzymes.

Hirschsprung's disease (choice B) is a cause of congenital constipation related to absence of

ganglion cells in a segment of bowel. The aganglionic bowel segment is narrowed because the
lack of peristalsis keeps stool from moving into the segment. The distal rectum is always
involved, and the lesion may extend proximally as far as the small intestine. The bowel
proximal to the lesion is usually dilated.

A Meckel's diverticulum (choice C) can form due to the persistence of the vitelline duct, which
connects the developing gut to the yolk sac. They are classically located in the distal ileum
within 30 cm of the ileocecal valve, and may contain ectopic pancreatic tissue or gastric
mucosa.

Omphalocele (choice D) is characterized by herniation of abdominal viscera through the

abdominal wall near the umbilicus.

In polycystic kidney disease (choice E), cysts of the liver and pancreas may occur; meconium
ileus is not associated with this disorder.

A 69-year-old woman is brought to the emergency room after falling off a step stool and fracturing her
hip. Her past medical history is significant for several bouts of pneumonia during the past
year. Laboratory results indicate a normal white blood cell count, but platelets are decreased,
and the erythrocyte sedimentation rate (ESR) is elevated. X-rays reveal multiple lytic bone
lesions. Serum electrophoresis demonstrates an M-protein spike. Which of the following is the
most likely diagnosis?

A. Chronic lymphocytic leukemia

B. Monoclonal gammopathy of uncertain significance

C. Multiple myeloma (plasma cell myeloma)

D. Plasmacytoma

E. Waldenstrm's macroglobulinemia

Explanation:

The correct answer is C. The patient is suffering from multiple myeloma, a neoplastic
proliferation of plasma cells (or their precursors) found within the bone marrow. These
malignant cells are responsible for the production of excessive amounts of immunoglobulin
(usually IgG or IgA), producing an M- protein spike, and increasing the ESR. The decreased
platelet count probably reflects infiltration of the bone marrow by myeloma cells. It is not
unusual for patients with malignant myeloma to have recurring bacterial infections,
particularly pneumococcal pneumonia, because the overall production of normal immunoglobulins
of all isotypes is decreased. Lytic bone lesions due to infiltration by myeloma cells may lead
to pathological fractures. All of the other disorders listed can be associated with an M-
 16

protein spike, but this is a nonspecific finding.

Chronic lymphocytic leukemia (CLL; choice A) is ruled out by the normal white count, since this
type of leukemia is generally associated with an absolute lymphocytosis.

Patients with monoclonal gammopathy of undetermined significance (choice B) are generally

asymptomatic, although they have a predisposition for subsequently developing myeloma,
lymphoma, amyloidosis, or Waldenstrm's macroglobulinemia.

Plasmacytoma (choice D) (solitary myeloma) is a rare, isolated plasma cell neoplasm in bone or
soft tissues. If the primary cancer is in bone, it is likely to disseminate; extraosseous
tumors tend to remain localized. Since this patient had multiple lytic bone lesions, multiple
myeloma is the correct diagnosis.

Waldenstrm's macroglobulinemia (choice E) is a disorder involving neoplasms of lymphocytoid

plasma cells that produce monoclonal IgM. Hypergammaglobulinemia produces hyperviscosity of the
blood which, along with infiltration by tumor produce the characteristic signs and symptoms.
Weakness, weight loss, bone pain, hepatosplenomegaly, and lymphadenopathy occur commonly.

A 55-year-old woman complains to her physician that the skin of her armpits and groin "keeps getting
darker and darker." Physical examination demonstrates velvety brown and warty skin in the axilla
and groin. Biopsy of these lesions shows a variably hyperplastic epidermis with many sharp peaks
and valleys. Aside from cosmetic considerations, which of the following is the primary medical
significance of these lesions?

A. They may be a sign of immunosuppression

B. They may be a sign of visceral carcinoma

C. They may be easily superinfected

D. They may be malignant

E. They may be premalignant

Explanation:

The correct answer is B. The lesions are acanthosis nigricans, which looks somewhat like a mole
or wart, but is actually due to epidermal hyperplasia. Acanthosis nigricans can be seen in
obesity, diabetes, and in patients with underlying cancers, often adenocarcinomas of the chest
or abdomen.

The lesions are not characteristic of immunosuppression (choice A) and are not easily
superinfected (choice C). They are also neither malignant (choice D) nor premalignant (choice
E).

A 47-year-old woman undergoes endometrial biopsy because she has had repeated episodes of irregular
spotting between periods lately. The biopsy shows strips of endometrium bearing long, narrow,
coiled glands lined by a single layer of columnar epithelium showing regular, uniform, small
nuclei and clear apical vesicles. Which of the following is the most likely diagnosis?

A. Atypical hyperplasia

B. Complex hyperplasia without atypia

C. Proliferative endometrium
 17

D. Secretory endometrium

E. Simple hyperplasia

Explanation:

The correct answer is D. Endometrial biopsies are often performed to evaluate patients with
menstrual bleeding abnormalities, particularly in perimenopausal or postmenopausal patients.
While the biopsies are done to rule out hyperplasias or cancer, most of the specimens actually
show only proliferative or secretory (as in this patient) endometrium. Secretory endometrium
has the features noted in the question stem.

Atypical hyperplasia (choice A) is characterized by complex glands lined by cells showing

features of atypia, such as cytomegaly, increased nuclear cytoplasmic ratio, prominent
nucleoli, and increased mitotic index.

Complex hyperplasia without atypia (choice B) is characterized by complex, branching glands

without cellular atypia.

Proliferative endometrium (choice C) is characterized by smaller, noncoiled, glands lined with

columnar epithelium without apical (secretory) vesicles.

Simple (cystic) hyperplasia (choice E) is characterized by cystically dilated glands without

cellular atypia.

Which of the following conditions is the most frequent cause of spontaneous abortion in the first
trimester of pregnancy?

A. Abruptio placentae

B. Chorioamnionitis

C. Chromosomal abnormalities

D. Placenta previa

E. Trauma

Explanation:

The correct answer is C. At least 10% to 15% of normally fertilized and implanted ova are lost
in the first trimester of pregnancy because of spontaneous abortion. Studies using immunoassay
of human chorionic gonadotropin (hCG) for early diagnosis of pregnancy suggest that the
percentage of fertilized ova lost in the first trimester might be even higher. The great
majority of these cases are attributable to chromosomal abnormalities. Chromosomal studies are
not routinely performed in such cases, but they are recommended when a malformed fetus has been
identified or when habitual or recurrent abortions occur.

Abruptio placentae (choice A), a complication of the third trimester, occurs when the placenta
detaches prematurely from its implantation site. Retroplacental hemorrhage develops within the
space between placenta and uterine wall, leading to interruption or severe reduction in the
blood supply to the fetus.

Chorioamnionitis (choice B), a complication of the second and third trimesters, results from
ascending infections through the vaginal canal. Infection of chorioamnionic membranes may lead
 18

to premature rupture of membranes and abortion or premature labor.

Placenta previa (choice D) is a placenta implanted in the lower segment of the uterus. When
dilatation of this segment begins in late pregnancy, a placenta previa may cause severe
bleeding and lead to premature labor.

Surprisingly, trauma (choice E) is a rare cause of spontaneous abortion.

A 65-year-old woman has a long-standing dementing disorder characterized by deterioration in

personality, neglect of personal hygiene, impaired judgment, and disinhibited behavior. MRI
demonstrates severe cortical atrophy limited to the frontal lobes and anterior two thirds of the
temporal lobes, while the remaining cortex is preserved. No evidence of recent or remote
infarcts is found. Which of the following diagnoses is most consistent with these pathologic and
clinical features?

A. Alzheimer disease

B. Creutzfeldt-Jacob disease

C. Dementia with Lewy bodies

D. Frontotemporal dementia

E. Vascular dementia

Explanation:

The correct answer is D. Not all dementing disorders manifest with the same clinical features.
Although there is considerable overlap in clinical symptomatology among different types of
dementias, making clinical diagnosis somewhat problematic, there are classic presentations that
allow identification of a specific form of dementia with a high degree of confidence. In this
case, the patient has symptoms due to frontal lobe damage, eg, disinhibition, impaired
judgment, and personality changes. Furthermore, MRI demonstrates a specific pattern of cortical
atrophy, restricted to the frontal lobes and anterior portion of the temporal lobes. This
combination points toward a group of dementias called frontotemporal dementia, the most
frequent form of which is Pick disease. Other forms of frontotemporal dementia are very
infrequent. Remember: frontal symptoms in conjunction with frontotemporal atrophy =
frontotemporal dementia/Pick disease.

Alzheimer disease (choice A) is the most frequent form of dementia in industrialized countries.
Although symptoms due to frontal damage may be present in Alzheimer disease, they are usually
associated with a more generalized impairment of higher neurologic functions, eg, language,
memory, and learned movements. In addition, cortical atrophy in Alzheimer disease is widespread
and not limited to the frontal and anterior temporal lobes.

Creutzfeldt-Jacob disease (choice B) represents the prototype of prion diseases. Cortical

atrophy is not a prominent feature of Creutzfeldt-Jacob disease, which manifests with
personality changes, memory loss, and seizures, leading to death after a rapid clinical course
(a few months to 1 year).

Dementia with Lewy bodies, also known as diffuse Lewy body disease (choice C), is one of the
most common forms of dementia in Western countries, possibly more common than vascular
dementia. It is characterized by widespread formation of Lewy bodies in the substantia nigra,
limbic cortex, and subcortical nuclei, such as the basal nucleus of Meynert. Extrapyramidal
symptoms similar to Parkinson disease manifest in this form of dementia as a result of
degeneration of dopaminergic pathways.
 19

Vascular dementia (choice E) is an umbrella term encompassing dementing conditions that arise
from pathology of large or small cerebral vessels. It manifests with memory loss associated
with focal neurologic symptoms depending on the location of damage. MRI would identify old or
recent infarcts, as well as white matter disease. Conditions associated with vascular dementia
include the following: Multi-infarct dementia, which is caused by multiple, scattered brain
infarcts secondary to atherosclerosis of large arteries of the circle of Willis and/or carotid
arteries. Binswanger disease, which involves rarefaction of cerebral white matter and is caused
by hypertension-related arteriolosclerosis. Lacunar infarcts, which consist of small (< 1 cm)
infarcts in the striatum and thalamus; this condition is related to arteriolosclerosis.

Biopsy of a reasonably well-demarcated mass of the nasopharynx demonstrates a plasma cell proliferation.
Serum electrophoresis shows a small monoclonal IgG spike. Bone marrow evaluation fails to
demonstrate plasma cell proliferation and no lesions are seen on extensive skeletal x-rays.
Which of the following is the most likely diagnosis?

A. Heavy chain disease

B. Monoclonal gammopathy of undetermined significance

C. Multiple myeloma

D. Plasmacytoma

E. Waldenstrm's macroglobulinemia

Explanation:

The correct answer is D. Plasmacytoma (solitary myeloma) involving soft tissue (lungs,
nasopharynx, nasal sinuses) is a plasma cell proliferation resembling multiple myeloma but
without significant metastatic potential. In contrast, some plasmocytomas involving bone
eventually (up to 10 to 20 years) develop into frank multiple myeloma.

Heavy chain diseases (choice A) constitute a group of rare lymphoplasmacytic malignancies in

which excessive amounts of a defective heavy immunoglobulin chain are produced. They may take
the form of gamma heavy-chain disease (from IgG), alpha heavy-chain disease (from IgA) or mu
heavy-chain disease (from IgM); malignant cells are usually present in marrow in all of these
conditions.

Monoclonal gammopathy of undetermined significance (choice B) is a disease of elderly patients

with a monoclonal spike on serum or urine electrophoresis, but no identifiable mass or bone
marrow lesion; 20% of these patients eventually develop one of the other diseases listed in the
answer choices.

Multiple myeloma (choice C) is a malignancy derived from a single plasma cell clone with
significant metastatic potential. Multiple lytic bone lesions are usually seen.

Waldenstrm's macroglobulinemia (choice E) is a malignancy of lymphoplasmacytic cells that

secrete IgM. In this disorder, the bone marrow is diffusely rather than focally infiltrated by
lymphocytes, plasma cells, and hybrid forms.

A 65-year-old woman presents with a 30-lb weight loss and malaise. Cancer is suspected. Which of the
following is the correct list, starting with the most prevalent, of the three most common
causes of cancer in women?

A. Breast, lung, colon and rectum

 20

B. Breast, uterus, lung

C. Colon and rectum, lung, ovary

D. Lung, breast, ovary

E. Ovary, uterus, lung

Explanation:

The correct answer is A. The correct female incidence sequence is breast (32%), lung (13%),
and colon and rectum (13%). The two major causes of cancer death in women are lung (23%) and
breast (18%). In men, the incidence sequence is prostate (32%), lung (16%), and colon and
rectum (12%). The two leading causes of male cancer deaths are lung (33%) and prostate (13%).

The uterus and ovary (choices B, C, D, and E) are not among the three organs most frequently
affected by cancer in women.

A 50-year-old woman presents with a 5-year history of headaches, generalized tonic-clonic seizures, and
bilateral leg weakness. Skull films reveal hyperostosis of the calvarium. Biopsy of the
responsible lesion shows a whorling pattern of the cells. Which of the following is the most
likely diagnosis?

A. Arachnoid cyst

B. Glioblastoma multiforme

C. Meningioma

D. Metastatic breast cancer

E. Oligodendroglioma

Explanation:

The correct answer is C. The most likely diagnosis is an intracranial meningioma. Meningiomas
are slow-growing, benign tumors comprising 15% of intracranial tumors; they are most common in
the elderly. They originate from either dura mater or arachnoid and are sharply demarcated from
brain tissue. Meningiomas often incite an osteoblastic reaction in the overlying cranial bones.
Microscopically, the meningioma cells have a tendency to encircle one another, forming whorls
and psammoma bodies. Clinically, they present as mass lesions; seizures may occur. The superior
parasagittal surface of the frontal lobes is a favorite site of origin. This can often produce
leg weakness, since the leg motor fibers that pass down through the internal capsule originate
in parasagittal cortical regions. Treatment of meningiomas is usually surgical.

Arachnoid cysts (choice A) are formed by splitting of the arachnoid membrane; most arachnoid
cysts arise near the Sylvian fissure. They may present with mass effect, but would be unlikely
to produce seizures, prominent focal signs, or reactive hyperostosis.

Glioblastoma multiforme (choice B) is an aggressive malignant astrocytoma that would likely

have killed the patient long before 5 years had elapsed.

Metastatic breast cancer (choice D) would generally look different microscopically (the
whorling cell pattern is characteristic of meningioma). It would be unlikely for metastatic
cancer to cause a reaction in the overlying bone, or to be present long enough to cause
 21

symptoms for 5 years.

Oligodendrogliomas (choice E) are glial tumors that could produce the described clinical
picture, but usually do not cause hyperostosis of the calvarium or exhibit the characteristic
whorling cell pattern microscopically.

When a histologic section is taken of an abscess, many of the observed neutrophils show a degenerative
change in which the nucleus has undergone fragmentation. This process is known as

A. caseous necrosis

B. coagulative necrosis

C. karyolysis

D. karyorrhexis

E. pyknosis

Explanation:

The correct answer is D. Karyorrhexis refers to a pattern of nuclear degradation in which a

pyknotic or partially pyknotic nucleus undergoes fragmentation followed by complete lysis. This
pattern is common in the neutrophils present in acute inflammation.

The type of necrosis seen in an abscess is liquefactive necrosis. Caseous necrosis (choice A)
is seen in tuberculosis and some other granulomatous diseases; coagulative necrosis (choice B)
is seen following infarctions of many organs (other than the brain).

Karyolysis (choice C) is also a degenerative change affecting nuclei. In this case, however, it
is seen as a decrease in nuclear basophilia, which is presumably the result of DNAse activity.

Pyknosis (choice E) is characterized by nuclear shrinking and basophilia, apparently as a

result of DNA condensation.

A 52-year-old woman has recently undergone a breast resection for carcinoma. Based on the statistics for
breast cancer incidence, which of the following types of carcinoma does this patient most
likely have?

A. Colloid (mucinous)

B. Invasive ductal

C. Invasive lobular

D. Medullary

E. Metastatic bronchogenic

Explanation:

The correct answer is B. Invasive ductal carcinoma is the most likely candidate. Of the various
types of breast adenocarcinoma, invasive ductal carcinoma is by far the most common variant,
accounting for approximately 75% to 80% of all invasive breast carcinomas. Invasive ductal
carcinoma develops from epithelial cells of the terminal duct. Histologically, it is composed
of small, glandular, ductlike structures, lined by variably anaplastic cells. The most common
 22

mode of presentation is a palpable mass in the breast. Its prognosis depends mostly on staging
(spread of cancer) rather than grading (degree of differentiation).

The colloid (mucinous) variant (choice A) is relatively rare (about 1% to 2%) and occurs more
frequently in older women. Histologically, this carcinoma is characterized by abundant mucin
secretion. It is associated with a better prognosis than the ductal type.

Invasive lobular carcinoma (choice C) is the second most frequent histologic type of breast
adenocarcinoma, accounting for approximately 10% of all cases. Its presumed cell of origin is
the lobular cell. The most typical histologic characteristic is the presence of cancer cells
lined up in orderly rows ("single-file").

Medullary carcinoma (choice D) tends to occur in younger women and is associated with a
slightly better prognosis. Although a malignant tumor, medullary carcinoma is well
circumscribed and surrounded by a florid lymphoplasmacytic reaction. The name is due to its
soft consistency.

Metastatic cancer may involve the breast like any other organ. Bronchogenic carcinoma (choice
E) may also spread to the breast by lymphatic route or by contiguity, but this would be less
likely than primary breast cancer.

A 55-year-old man is brought to his physician's office with a 3-month history of progressive mental
deterioration in the form of memory loss, mood changes, and errors in judgment. His gait is
unsteady, and he requires assistance to prevent falling. He has no history of seizures, head
trauma, or incontinence. Computed tomography (CT) scan and lumbar puncture are unremarkable.
Physical examination reveals hypertonicity of all extremities, bilateral equivocal plantar
response, ataxic gait, and myoclonic jerks in the lower extremities. What is the mechanism by
which this infectious agent causes its pathology?

A. Amyloid deposition

B. Autoimmune destruction

C. Chronic inflammation

D. Embolization and infarction

E. Toxin production

Explanation:

The correct answer is A. This is the classic presentation of Creutzfeldt-Jacob disease (CJD).
Although the pathogenesis is incompletely understood, these patients develop extracellular
deposition of abnormal fibrillar proteins in the brain, ie, amyloid.

Autoimmune destruction (choice B) is not indicated because there is no immunologic response to

the deposition of these extracellular proteins; thus there is no chronic inflammation (choice
C)

Although embolization and infarction (choice D) could complicate the presentation in the age
group typically afflicted with CJD, these processes are not believed to have any direct role in
this pathology.

No toxin is produced (choice E) to account for the presentation in CJD.

A patient consults a dermatologist about a skin lesion on her neck. Examination reveals a 1-cm diameter,
 23

red, scaly plaque with a rough texture and irregular margins. Biopsy demonstrates epidermal and
dermal cells with large, pleomorphic, hyperchromatic nuclei. Which of the following conditions
would most likely predispose this patient to the development of this lesion?

A. Actinic keratosis

B. Compound nevus

C. Dermal nevus

D. Junctional nevus

E. Melanoma

Explanation:

The correct answer is A. The lesion is a squamous cell carcinoma of the skin. Actinic
keratosis, which is a hyperplastic lesion of sun-damaged skin, predisposes for squamous cell
carcinoma. Another predisposing condition to remember is xeroderma pigmentosum, which
predisposes for both squamous cell and basal cell carcinomas of skin.

A nevus is a mole, containing characteristic cells called nevocellular cells. If the

nevocellular cells are located at the dermal-epidermal junction (junctional nevus, choice D),
in the dermis (dermal nevus, choice C), or both (compound nevus, choice B), they do not
predispose for squamous cell carcinomas of the skin. Malignant melanoma (choice E), however,
can arise in pre-existing nevi.

A 24-year-old woman gives birth to an apparently normal infant. The neonate begins feeding well by the
second day, then at ten days, suddenly develops gastrointestinal obstruction. Which of the
following is the most likely cause of this presentation?

A. Adhesions

B. Congenital pyloric stenosis

C. Hirschsprung's disease

D. Intussusception

E. Volvulus

Explanation:

The correct answer is D. All of the conditions listed can cause gastrointestinal obstruction,
but the clinical presentation is most suggestive of intussusception. In intussusception, there
is telescoping of one bowel segment into another, more distal segment. The disorder is
relatively common in infants and children due to the poor support offered by their thin
mesentery. Intussusception produces intestinal obstruction, and it may produce bowel ischemia
or infarction by trapping mesenteric vessels along with the affected segment. In some cases,
the intussusception may be reduced by diagnostic barium enema.

Adhesions (choice A) can cause bowel obstruction following surgery or inflammatory bowel
diseases.

Congenital pyloric stenosis (choice B) typically presents as projectile vomiting in a 3-4 week
old baby.
 24

Hirschsprung's disease (choice C), caused by absence of ganglion cells in the distal bowel, is
usually diagnosed in the first few days of life when there is a failure to pass meconium.

Volvulus (choice E) is due to rotation of bowel segments. This is usually a disease of the
elderly.

A middle-aged man with a long history of sexual activity slowly develops testicular enlargement. Needle
biopsy demonstrates the presence of obliterative endarteritis with perivascular cuffing of
lymphocytes and plasma cells. A diffuse interstitial inflammation with edema and prominent
plasma cell infiltrate is also present. Which of the following is the most likely diagnosis?

A. Gonorrhea

B. Mumps

C. Nonspecific orchitis

D. Syphilis

E. Tuberculosis

Explanation:

The correct answer is D. This is one presentation of syphilis, which can involve the testis and
epididymis in both the acquired and congenital types of the disease. Characteristically, the
testis is usually involved before the epididymis. Microscopically, the testis may show either
gumma formation or the findings described in the question stem.

Gonorrhea (choice A) usually causes an acute epididymitis and orchitis with prominent
neutrophils.

Mumps orchitis (choice B) would usually be accompanied by parotitis.

Nonspecific orchitis (choice C) is characterized by prominent neutrophils.

Tuberculosis orchitis (choice E) is characterized by granulomas with acid-fast bacteria.

A 70-year-old woman dies in a nursing home after a heart attack. The time of onset of her clinical
symptomatology and the cause of death are uncertain; furthermore, the possibility of neglect is
being considered. Therefore, an autopsy investigation is arranged. The forensic pathologist
discovers acute thrombosis involving the posterior descending branch of the right coronary
artery with resultant myocardial infarction (MI) in the posterior third of the interventricular
septum. Histologically, there is coagulation necrosis with associated abundant neutrophilic
infiltration. Histiocytes and lymphocytes are scanty. Which of the following is the approximate
period between the onset of pain (ie, beginning of ischemic injury) and death?

A. 1 hour

B. 12 hours

C. 2 days

D. 5 days

E. 10 days
 25

Explanation:

The correct answer is C. Following irreversible ischemic injury, the heart (and any other
organ) displays an orderly sequence of events that progresses from necrosis of parenchymal
cells to inflammatory reaction, granulation tissue, and scar healing.

Although ischemic injury manifests with pain almost immediately following vascular occlusion,
histologic evidence of necrosis lags behind the clinical symptoms. At 1 hour (choice A) after
ischemia, there is no morphologic change indicative of necrosis. The first signs of necrosis
appear 12 hours (choice B) after irreversible ischemia: myocytes appear intensely eosinophilic
and wavy, but there is no inflammatory reaction yet. Acute inflammatory cells (neutrophils)
infiltrate the infarcted area beginning 1 day and peaking at approximately 2-3 days after
injury. This acute inflammatory response partially overlaps with the subsequent influx of
lymphocytes and histiocytes. Reabsorption of necrotic myofibers by histiocytes, as well as
proliferation of small blood vessels, marks early formation of granulation tissue at around 5
days (choice D). Granulation tissue is advanced at 10 days (choice E) and consists of
fibroblasts, small blood vessels, and residual chronic inflammatory cells within a matrix of
young collagen matrix.

A 54-year-old man presents with a chief complaint of "burning" abdominal pain in the epigastric region.
Endoscopy demonstrates a well-defined, regular gastroesophageal junction located 3 cm above the
esophageal hiatus in the diaphragm. Biopsy of the distal side of the junction demonstrates
normal gastric mucosa. This lesion is best classified as which of the following?

A. Achalasia

B. Esophageal ring

C. Esophageal web

D. Paraesophageal hernia

E. Sliding hernia

Explanation:

The correct answer is E. This patient has a sliding hiatal hernia, which is the most common
(90%) form of hiatal hernia. This condition is frequently associated with gastric reflux.

Achalasia (choice A) is actually a physiologic, rather than an anatomic variation. In this

disorder, the lower esophageal sphincter fails to relax adequately, and esophageal peristalsis
is often abnormal.

Esophageal rings (choice B) are mucosal folds in the esophagus. They are called esophageal webs
(choice C) in the upper esophagus. Schatzki rings are mucosal rings in the lower esophagus, at
the gastroesophageal junction.

In a paraesophageal hernia (choice D), an area of gastric cardia rolls along with the esophagus
through an incompetent hiatus into the thorax. In a paraesophageal hernia, the gastroesophageal
junction would not be displaced.

Which of the following pulmonary conditions is associated with widespread formation of hyaline
membranes
in the alveolar cavities?
 26

A. Asthma

B. Bacterial pneumonia

C. Desquamative interstitial pneumonitis

D. Diffuse alveolar damage

E. Hemodynamic pulmonary edema

Explanation:

The correct answer is D. Diffuse alveolar damage, clinically referred to as adult respiratory
distress syndrome (ARDS), is characterized by diffuse damage to the alveolar/capillary barrier,
which may result from diverse acute conditions. The four most frequent causes are trauma,
sepsis, shock, and gastric aspiration. The pathogenesis is not entirely clear, but influx of
neutrophils and release of cytokines, eicosanoids, and free radicals seem to be crucial in
promoting alveolar damage. The most characteristic histopathologic hallmark of diffuse alveolar
damage is formation of hyaline membranes within the alveolar cavities. These consist of
proteinaceous material of plasma origin and necrotic debris from desquamated epithelium. The
condition has a 60% mortality and manifests with acute respiratory failure.

The pathologic features of asthma (choice A) are relatively nonspecific and are similar, for
example, to those of chronic bronchitis, including chronic inflammatory infiltration,
hyperplasia of mucous glands, and hypertrophy of smooth muscle. The presence of numerous
eosinophils, however, is more characteristic of asthma.

Bacterial pneumonia (choice B) is characterized by intra-alveolar exudation of neutrophils,

fibrin, and erythrocytes. Bacteria are also present within the alveolar cavities.

Desquamative interstitial pneumonitis (DIP) (choice C) is a form of interstitial disease

referred to as idiopathic pulmonary fibrosis. In contrast to usual interstitial pneumonitis
(another form of idiopathic pulmonary fibrosis), DIP is more responsive to steroid treatment.
Histopathologically, DIP leads to hyperplasia of pneumocytes and accumulation of histiocytes
that fill the alveolar cavities.

Hemodynamic pulmonary edema (choice E) is caused by increased hydrostatic pressure, as occurs

in acute left ventricular failure. It is due to escape of fluid from the intravascular
compartment into the alveoli.

A baby is born with a flat facial profile, prominent epicanthal folds, and simian crease. She vomits
when fed, and upper GI studies demonstrate a "double bubble" in the upper abdomen. Which of the
following cardiovascular abnormalities might this child also have?

A. Atrial septal defect

B. Berry aneurysm

C. Coarctation of the aorta

D. Endocardial cushion defect

E. Tetralogy of Fallot

Explanation:
 27

The correct answer is D. The disease is Down syndrome (trisomy 21). In addition to mental
retardation and the characteristic physical findings described in the question stem, duodenal
atresia is fairly common, as evidenced by the "double bubble" sign on x-ray. These children are
also likely to have various cardiac anomalies; endocardial cushion defect is the most common.

Atrial septal defect (choice A) is one of the most common genetic defects in the general
population, but is less common than endocardial cushion defect in patients with Down syndrome.

Berry aneurysms (choice B), also known as saccular aneurysms, are typically located in the
circle of Willis on the ventral surface of the brain. They occur more frequently in patients
with adult polycystic disease. Rupture can produce subarachnoid hemorrhage.

Coarctation of the aorta (choice C) occurs more commonly in females with a 45, XO genotype
(Turner syndrome).

Tetralogy of Fallot (choice E) is the most common cause of early cyanosis, consisting of a
ventricular septal defect, right ventricular outflow tract obstruction, an overriding aorta,
and right ventricular hypertrophy.

A 47-year-old man presents to the emergency room with sudden onset of severe upper abdominal pain with
vomiting. The pain is focused in the epigastrium with radiation to the back. Serum amylase
levels are 2000 U/L. Which of the following are the most commonly encountered predisposing
factors for this patient's condition?

A. Alcohol use and gallstones

B. Helicobacter pylori infection and excess gastric acid secretion

C. Hepatitis B infection and iron overload

D. Obesity and high serum cholesterol

E. Stress and cigarette use

Explanation:

The correct answer is A. The clinical scenario is typical of acute pancreatitis. The
overwhelmingly most important contributing factors for development of acute pancreatitis are
gallstones (particularly small ones) and alcohol abuse.

Helicobacter pylori infection and excess gastric acid secretion (choice B) are predisposing
factors for peptic ulcer disease of the stomach and duodenum, respectively.

Hepatitis B infection and iron overload (choice C) predispose for cirrhosis.

Predisposing factors for myocardial infarction include obesity, high serum cholesterol (choice
D), stress, and cigarette smoking (choice E).

A 37-year-old woman complains to her gynecologist of discomfort during intercourse and placement of a
tampon. Physical examination demonstrates a flocculent swelling below the skin of the
posterolateral part of one labium majora.Which of the following is the most likely diagnosis?

A. Bartholin's gland cyst

B. Condyloma acuminatum
 28

C. Lichen sclerosis

D. Vestibular adenitis

E. Vulvar squamous hyperplasia

Explanation:

The correct answer is A. This is a Bartholin's gland cyst, which is a relatively common lesion
occurring when Bartholin's duct becomes obstructed, typically a sequela to a previous
infection. The cysts can enlarge to 3 to 5 cm in diameter. They are lined by either
transitional epithelium or metaplastic squamous epithelium. Treatment is by excision or
marsupialization (permanent opening).

Condyloma acuminatum (choice B) usually produces a papillary lesion (venereal wart).

Lichen sclerosis (choice C) usually produces a gray, parchment-like thinned epidermis.

Vestibular adenitis (choice D) usually produces an exquisitely tender posterior introitus with
focal ulcerations.

Vulvar squamous hyperplasia (choice E) usually produces a white plaque.

Which of the following types of hepatitis is associated with an immune-mediated vasculitis characterized
by p-ANCA antibodies?

A. Hepatitis A

B. Hepatitis B

C. Hepatitis C

D. Hepatitis D

E. Hepatitis E

Explanation:

The correct answer is B. Hepatitis B is associated with polyarteritis nodosa (PAN), a

necrotizing vasculitis of small- and medium-sized muscular arteries involving all organ
systems. A significant percentage of patients with PAN have hepatitis B antigenemia. They also
have circulating immune complexes containing hepatitis B antigen. Hepatitis B antigen, IgM, and
complement can be demonstrated in blood vessel walls. P-ANCA (perinuclear-antinuclear
cytoplasmic antibody) is a marker for polyarteritis nodosa.

Hepatitis A (choice A) is not associated with a vasculitis.

Hepatitis C (choice C) accounts for 50-70% of chronic hepatitis. Chronic hepatitis C can be
associated with immune-complex mediated extrahepatic complications, but is less common than
hepatitis B. Hepatitis C does have a significant association with essential mixed
cryoglobulinemia, which presents with glomerulonephritis, arthralgias, hepatosplenomegaly, and
lymphadenopathy, in addition to a vasculitis. However, there is no association with p-ANCA.

Hepatitis D (choice D) requires that the patient be co-infected with hepatitis B. As such, it
does not independently cause disease, but it can produce a worsening of the liver disease.
 29

Hepatitis E (choice E) resembles hepatitis A due to its primarily enteric mode of spread. It is
not associated with chronic hepatitis and does not have a predisposition for vasculitis.

Testicular biopsy of an infertile man demonstrates a complete absence of sperm or sperm precursors in
spermatic tubules that have a regular, round cross-section and are closely packed together. The
most probable etiology is

A. diabetes mellitus

B. maturation arrest

C. seminoma

D. Sertoli-only syndrome

E. tuberculosis

Explanation:

The correct answer is D. All of the conditions listed can cause infertility due to a low or
absent sperm count. Only in Sertoli-only syndrome is there a complete absence of sperm
precursors in an undamaged tubule. There is no known method to correct Sertoli-only syndrome
(or maturation arrest) that is not due to a treatable chronic disease.

Chronic diseases such as diabetes mellitus (choice A) or tuberculosis (choice E) can arrest the
maturation of sperm, but do not usually show a complete absence of sperm precursors.

In maturation arrest (choice B), mature sperm are absent, but precursors are found.

Tumors such as seminomas (choice C) cause infertility by occluding the flow of semen or by
replacing the seminiferous tubules. Sampling of a seminiferous tubule not replaced by tumor
would probably still demonstrate sperm.

A 50-year-old woman who works as a paralegal in a law firm comes to her local doctor because of
problems
with sleep. The patient says that over the past several weeks, she hasn't slept well, feels
tired, and has had headaches. She does not smoke or drink alcohol, except on special occasions,
and does not take any medications. The patient's pupils are 5 mm in size, equal and reactive,
with both the direct and consensual light reflexes intact. Accommodation is unimpaired.
Examination of the visual fields and funduscopy are unremarkable. Extraocular movements reveal
normal conjugate, oblique, and downward movement, but she is unable to look upwards. No other
abnormalities are found on the neurological examination. Which of the following is the most
likely diagnosis?

A. Acoustic neuroma

B. Astrocytoma in the cerebellum

C. Craniopharyngioma

D. Parasagittal meningioma

E. Pinealoma

Explanation:
 30

The correct answer is E. This patient has a pinealoma. Tumors of the pineal gland compress the
vertical gaze center in the tectum of the midbrain. The pineal gland manufactures melatonin
from its precursor serotonin; an inadequate supply of melatonin results in insomnia. Tumors of
the pineal gland will not compress the cerebral cortex or the rest of the brainstem.
Frequently, the only physical sign noted is failure of upward gaze.

An acoustic neuroma (choice A) is a schwannoma of the eighth cranial nerve. It results in

deafness, ataxia, and dysarthria. Nystagmus may be present. The gaze centers are not affected.

Astrocytomas of the cerebellum (choice B) are usually seen in children. These tumors present
with headache, nausea, vomiting, papilledema, and cerebellar signs such as ataxia, dysarthria,
nystagmus, and intention tremor. The gaze centers are not affected.

Craniopharyngiomas (choice C) are usually seen in children. There is failure of growth,

headaches, and bitemporal hemianopia.

Parasagittal meningiomas (choice D) usually result in headache, spastic paresis, and urinary
incontinence.

A 25-year-old man experiences the gradual onset of intermittent diarrhea, which over years, progresses
to severe diarrhea, alternating with constipation, rectal bleeding, and passage of mucus. On
physical examination, the abdomen is tender over the colon. Stool examination fails to reveal
parasites. Colonoscopy demonstrates inflammation limited to the rectum, with no higher lesions.
Which of the following diseases would most likely be seen in a close relative of the patient?

A. Celiac disease

B. Crohn's disease

C. Hirschsprung's disease

D. Tropical sprue

E. Whipple's disease

Explanation:

The correct answer is B. The presentation is classic for ulcerative colitis. Family members
have an increased incidence of both ulcerative colitis and Crohn's disease, supporting the idea
that these two diseases are actually different ends of the same spectrum. In contrast to
Crohn's disease, in which the lesions may be patchy and involve the distal ileum and even the
esophagus, in ulcerative colitis, the lesions involve the rectum and may extend continuously
proximally for varying distances up to the cecum and very distal end of the ileum.

Celiac disease (choice A) is a small intestinal disease related to gluten intolerance.

Flattening of villi, elongated crypts and marked inflammation in the lamina propria are noted
histologically.

Hirschsprung's disease (choice C) is a congenital cause of severe constipation and megacolon

due to a lack of ganglion cells in the distal colon.

Tropical sprue (choice D) clinically resembles celiac disease, but may be related to infection.

Whipple's disease (choice E) is an intestinal diarrheal disease that has been shown to be due
to a bacterial infection.
 31

A surgeon operating on a 47-year-old woman finds cystic masses in both ovaries. Each mass consists of a
unilocular cyst containing clear fluid. The entire wall is covered with papillary excrescences.
Which of the following is the most likely diagnosis?

A. Endometrioid adenocarcinoma

B. Granulosa cell tumor

C. Mature cystic teratoma

D. Mucinous cystadenocarcinoma

E. Serous cystadenocarcinoma

Explanation:

The correct answer is E. Similar to testicular tumors, ovarian tumors can be classified
according to cell of origin. There are three main categories: tumors of surface epithelium,
tumors of germ cell origin, and tumors of sex cord-stromal origin. Ovarian surface epithelium
(coelomic mesothelium) may differentiate along tubal (serous), cervical (mucinous), or
endometrial lines, giving origin to serous cystadenoma/cystadenocarcinoma, mucinous
cystadenoma/cystadenocarcinoma and endometrioid tumors, respectively. Serous tumors represent
40% of all ovarian tumors, and serous cystadenocarcinoma is the most frequent serous tumor.
Serous cystadenocarcinomas occur primarily in women aged 40 to 65 years. About two thirds of
these tumors are bilateral. As the name suggests, it is a cystic tumor containing clear fluid.
The cystic wall is lined by malignant epithelial cells forming papillary fronds.

Less frequent than serous cystadenocarcinoma, endometrioid adenocarcinoma (choice A) and

mucinous cystadenocarcinoma (choice D) also derive from surface epithelium. Endometrioid
carcinoma is histologically similar to endometrial adenocarcinoma, whereas mucinous
cystadenocarcinoma is composed of mucin-producing cells similar to cervical epithelium. Both
these neoplasms have solid and cystic areas (mucinous cystadenocarcinoma more so than
endometrioid carcinoma) and may be bilateral (endometrioid carcinoma more frequently than
mucinous cystadenocarcinoma).

Granulosa cell tumors (choice B) originate from ovarian stroma and consist of variable mixtures
of granulosa cells and theca cells. Since they frequently produce large amounts of estrogens,
these tumors manifest with precocious puberty in preadolescent girls. On the contrary, mature
women with granulosa cell tumors develop endometrial hyperplasia and fibrocystic change of
breast. Histologically, these neoplasms are composed of uniform cuboidal cells, forming
structures reminiscent of ovarian follicles (Call-Exner bodies).

Mature cystic teratoma (choice C) is the most frequent neoplasm derived from germ cells.
Teratomas can be further classified into mature cystic, immature, and monodermal teratomas. The
great majority of teratomas are mature cystic. Since they originate from more than one germ
layer, these neoplasms contain an amazing mixture of mature tissue components, often including
skin, teeth, neural epithelium, thyroid, cartilage, and intestinal tissue, for example.

A 24-year-old woman is seen by her family practitioner. Her urine sample has a stable, frothy white foam
on top. Which of the following substances is likely to be present in her urine in significant
amounts?

A. Bilirubin

B. Blood
 32

C. Glucose

D. Ketones

E. Protein

Explanation:

The correct answer is E. Reagent strips of various types are commonly used both in physicians'
offices and in hospital laboratories for rapid semiquantitative urinalysis. The Multistix
strip, which is one of the more commonly used strips, contains reagent squares for glucose,
bilirubin, ketones, specific gravity, blood, pH, protein, urobilinogen, nitrite, and
leukocytes. Each of these squares undergoes a chemical change when dipped in urine, causing the
color of the square to change. The result is "read" by comparing the new color to reference
colors on the bottle. In this case, you need to know that a stable froth on urine is usually
due to proteinuria (more than several grams per 24 hr); therefore, the protein indicator would
be positive on the dipstick.

High levels of bilirubin (choice A) in urine can cause an unusual yellow foam.

Blood in the urine (choice B) might be present in some forms of renal disease, but would not
explain the stable foam.

High levels of glucose (choice C) in urine can cause it to develop a sweet smell and taste;
smelling and tasting urine was an ancient method of diagnosing diabetes mellitus, but is no
longer recommended for obvious reasons.

Ketones (choice D) may give urine an acetone-like odor, but testing for ketones in this manner
is no longer recommended for obvious reasons.

A patient with a long-standing intrauterine contraceptive device develops chronic pelvic pain. The
device is removed, and a biopsy of the endometrium is performed. The biopsy specimen shows a
prominent infiltrate composed of lymphocytes, plasma cells, and histocytes. Which of the
following is the most likely diagnosis?

A. Acute endometritis

B. Adenomyosis

C. Chronic endometritis

D. Endometriosis

E. Simple hyperplasia of endometrium

Explanation:

The correct answer is C. This is chronic endometritis, evidenced by the chronic inflammatory
infiltrate of lymphocytes, plasma cells, and histiocytes. This disorder may be idiopathic but
is more often associated with an obvious predisposing factor, such as chronic pelvic
inflammatory disease, tuberculosis, retained gestational tissue, or, as in this case, an
intrauterine contraceptive device. Chronic endometritis can cause abnormal bleeding, pain, and
infertility.

Acute endometritis (choice A) is characterized by a prominent neutrophilic infiltrate and

usually occurs after delivery or miscarriage.
 33

Adenomyosis (choice B) refers to endometrium abnormally located in myometrium.

Endometriosis (choice D) refers to abnormally located patches of endometrium (except in the

myometrium, where it would be called adenomyosis).

Simple hyperplasia of endometrium (choice E) causes cystically dilated glands in endometrium.

Autopsy of a 72-year-old man demonstrates the presence of deep venous thrombosis of the legs and
multiple acute brain infarcts due to thromboembolic occlusion of penetrating arteries. Which of
the following pathologic conditions would most likely account for these findings?

A. Atherosclerosis of penetrating cerebral arteries

B. Endocarditis of the tricuspid valve

C. Patent foramen ovale

D. Pulmonary thromboembolism

E. Trousseau syndrome

Explanation:

The correct answer is C. Persistence of patent foramen ovale is found in a significant

proportion of healthy subjects. A widely patent foramen ovale may allow emboli originating from
the veins in the legs to bypass the pulmonary circulation and reach the systemic arteries,
thereby producing infarcts (paradoxical embolism) in the brain as well as in other organs.
Interatrial or interventricular defects can have the same effect. None of the other answer
choices would explain the development of embolic infarcts in the cerebral parenchyma.

Atherosclerotic changes are frequently found in the circle of Willis and its major branches,
but not in the small-caliber penetrating arteries of the brain (choice A).

Endocarditis of the tricuspid valve (choice B) may give rise to emboli resulting from
fragmentation of valvular vegetations. Emboli from the tricuspid valve, however, would enter
the pulmonary circulation, possibly leading to infarcts of the lungs.

Pulmonary thromboembolism (choice D) frequently occurs as a result of deep venous thrombosis,

especially after immobilization, bed rest, obstetric delivery, and surgery. However,
thromboemboli that become lodged in the pulmonary arteries cannot pass through the pulmonary
capillary filter and cause systemic embolization.

Trousseau syndrome (choice E), also known as migratory thrombophlebitis, occurs in association
with disseminated cancers, especially mucinous adenocarcinomas.This condition is probably due
to release of procoagulant factors by the tumor and manifests with recurrent episodes of
thrombosis affecting veins (but not arteries) in both limbs and visceral organs.