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1) A 31-year-old HIV-positive man develops a severe pneumonia. Lower respiratory tract secretions
obtained by fiberoptic bronchoscopy with bronchoalveolar lavage and stained with methenamine
silver stain demonstrate cup-shaped cysts with sharply outlined walls. Which of the following
organisms is the most likely pathogen in this case?
A. Candida albicans
B. Giardia lamblia
C. Haemophilus influenzae
D. Pneumocystis carinii
E. Streptococcus pneumoniae
Explanation:
The correct answer is D. The organism described is Pneumocystis carinii, which is an
opportunistic parasite that appears to be more closely related to fungi than to protozoa. Its
cyst form, when stained with silver stains, has the distinctive appearance described in the
question stem, and is typically found in frothy material that occupies the lumen of alveoli. The
trophozoites are smaller and much harder to recognize. Bronchoalveolar lavage is considered much
more reliable than induced sputum as a diagnostic specimen. Pneumocystis pneumonia is a common
infection among AIDS patients, and is very uncommon in other clinical settings. Formerly, many
AIDS patients died with Pneumocystis pneumonia, but the combination of early drug treatment
(with trimethoprim/sulfamethoxazole or pentamidine) and prophylaxis (usually with
trimethoprim/sulfamethoxazole) has decreased the number of fatal infections. In severe cases,
Pneumocystis infection can sometimes be demonstrated in extrapulmonary sites.
Candida albicans(choice A) can infect the lung and stain with methenamine silver, but the
description of the lavage material would probably include the terms fungal hyphae and yeast
forms.
Giardia lamblia (choice B) causes diarrhea, rather than pneumonia.
Haemophilus influenzae(choice C) and Streptococcus pneumoniae(choice E) are bacteria and would
not stain with silver stains.
2) A normal birthweight, term baby with high APGAR scores fails to pass meconium within 36 hours of
birth. The neonate also has a distended abdomen and has been vomiting and feeding poorly.
Digital rectal examination temporarily relieves the obstruction, but the baby fails to pass
stool thereafter. Barium enema examination demonstrates a very narrow distal segment of rectum
with proximal dilation. Abnormalities of which of the following are most likely etiologically
related to this baby's disorder?
A. Chloride channels
B. Ganglion cells
C. Mucosal cells
D. Smooth muscle cells
E. Vagus nerve
Explanation:
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The correct answer is B. The disease is Hirschsprung's disease, which is a congenital cause of
constipation caused by an absence of ganglion cells in both the submucosal and intermyenteric
plexus of 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 can extend proximally anywhere from a few centimeters past the rectum all the way up
to the small intestine. The bowel proximal to the lesion is usually dilated. In this patient's
case, rectal examination dilated the narrowed aganglionic bowel, temporarily allowing passage
of stool. Definitive treatment consists of surgical removal of the affected segment.
Failure to pass meconium is also characteristic of cystic fibrosis, a disorder of chloride
channels (choice A). The characteristic radiologic appearance of the bowel in this case
strongly suggests Hirschsprung's disease.
The mucosa (choice C) is not directly affected by Hirschsprung's disease, although a lifethreatening (20% mortality) secondary enterocolitis may develop.
Smooth muscle (choice D) changes are not usually apparent on biopsy of aganglionic segments of
bowel in Hirschsprung's disease.
Abnormalities of the vagus nerve (choice E) are not related to the aperistalsis in
Hirschsprung's disease.
3)A 20-year-old athlete dies suddenly during a basketball game. Autopsy reveals asymmetric thickening of
the interventricular septum at the level of the mitral valve. Microscopically, the myocytes in
the area are hypertrophied and arranged in a haphazard pattern. Which of the following is the
most likely diagnosis?
A. Alcoholic cardiomyopathy
B. Cardiac amyloidosis
C. Endocardial fibroelastosis
D. Idiopathic hypertrophic subaortic stenosis
E. Loeffler's endocarditis
Explanation:
The correct answer is D. The lesion described is hypertrophic cardiomyopathy, more specifically
known as idiopathic hypertrophic subaortic stenosis (IHSS). This lesion is usually seen in
young adults, although it can also be present in the elderly. A genetic predisposition
(autosomal dominant) may be present. Some patients with this condition may experience dyspnea,
angina, dizziness, or congestive heart failure. Other patients are asymptomatic until they
undergo sudden death, usually during strenuous exercise, possibly because the aortic outlet
becomes completely occluded as a result of muscle contraction. Infective endocarditis of the
adjacent (damaged) mitral valve and atrial fibrillation may also occur.
Alcohol abuse can produce a dilated cardiomyopathy (choice A).
Severe cardiac amyloidosis (choice B), endocardial fibroelastosis (choice C), and Loeffler's
endocarditis (choice E) can all produce a restrictive cardiomyopathy.
A 34-year-old man with AIDS suddenly falls to the floor and has a tonic-clonic seizure. His concerned
friends call paramedics, who take him to the hospital. On arrival at the hospital he is
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conscious, but confused. Physical examination is remarkable for cachexia and oral thrush.
Neurological examination reveals isolated weakness of lateral gaze on the right. MRI reveals
multicentric mass lesions in the brain and meninges. One of the masses is biopsied and
appropriate immunohistochemical stains are performed. From which of the following cell types did
the masses most likely derive?
A. Astrocyte
B. B lymphocyte
C. Ependymal cell
D. Melanocyte
E. Oligodendrocyte
Explanation:
The correct answer is B. Approximately one-third of AIDS patients will experience significant
morbidity from neurologic disease. Primary CNS lymphoma is rare in the general population, but
is a relatively common type of lymphoma in AIDS patients. Presenting symptoms include seizures,
headache, and cranial nerve deficits (e.g., the abducens nerve palsy in this patient). The
lesions are often multicentric, and may involve the leptomeninges in a significant number of
cases. Primary CNS lymphoma is typically a late manifestation of AIDS (median CD4 count 40/µl).
This lymphoma is usually an intermediate-to-high-grade B cell lymphoma; evidence of EpsteinBarr virus infection is commonly present.
Astrocytoma is a neoplasm derived from cells in the astrocyte (choice A) lineage. These are not
particularly associated with AIDS.
Ependymal cells line the ventricles. Tumors derived from ependymal cells (choice C), called
ependymomas, characteristically produce rosettes or perivascular pseudorosettes,
microscopically. The incidence of ependymoma is not increased in AIDS patients.
Melanoma is a neoplasm arising from transformation of melanocytic cells (choice D). Whereas the
brain is a favorite site for metastatic melanoma, the incidence of melanoma is not particularly
increased in AIDS patients.
Oligodendrocytes (choice E) are responsible for producing myelin in the central nervous system.
Neoplasms arising from cells in the oligodendrocyte lineage are called oligodendrogliomas.
Calcification is frequently present, and may be visible on CT scan. These neoplasms are not
more common in AIDS patients.
In which of the following ways does seminoma differ most significantly from dysgerminoma?
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:
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The correct answer is A. Both men and women can develop a distinctive germ cell lesion that is
called a seminoma if it involves a testis and a dysgerminoma if it involves an ovary. 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; and seminomas are relatively common in men while dysgerminomas are rare in women (1% of
ovarian tumors).
Both of these tumors are composed of sheets of uniform polyhedral cells with intervening
fibrous septa of connective tissue, lymphocytes and multinucleated giant cells. Both tumors are
similar ultrastructurally (choice E), and the number of mitoses (choice B) is comparable
between the two tumors. These tumors in pure form are very radiosensitive (choice D), with a
90% 5-year survival, but can be much more aggressive if foci of other germ cell tumors (notably
embryonal carcinoma, choriocarcinoma and yolk sac tumors) are present (choice C).
A 35-year-old woman consults a physician because of fatigue and "feeling cold all the time". On
examination, her thyroid gland is diffusely enlarged and rubbery. Thyroid studies show low T3
and T4 and high TSH. Thyroid aspiration demonstrates large numbers of lymphocytes of all
degrees of maturation, a few abnormal follicular cells with eosinophilic granular cytoplasm,
and only rare normal follicular cells. Hyperplasia and neoplastic proliferation of which of the
following tissues or organs may be associated with this patient's disorder?
A. Colon
B. Esophagus
C. Peripheral nerve
D. Skin
E. Thymus
Explanation:
The correct answer is E. The thyroid disease is Hashimoto's thyroiditis, an autoimmune disease
in which the thyroid parenchyma is destroyed by a lymphocytic infiltrate. The infiltrate
typically contains mature follicles; the remaining scanty follicular cells often have
eosinophilic granular cytoplasm and are called Hurthle cells or oncocytes. Clinically, patients
usually have hypothyroidism, although brief periods of hyperthyroidism ("Hashitoxicosis") may
also be seen. Like myasthenia gravis, Hashimoto's disease may be associated with thymic
disorders including thymic hyperplasia, benign thymomas, and malignant thymomas.
Colon (choice A) cancer is associated with ulcerative colitis and adenomatous polyps.
The risk of esophageal cancer (choice B) is increased with Barrett's esophagus and in PlummerVinson syndrome.
You should associate neurofibromas of peripheral nerve (choice C) with café au lait spots on
the skin.
Skin cancer (choice D) occurs with greater frequency in association with xeroderma pigmentosa
and actinic keratosis.
A 25-year-old man undergoes orchiectomy for a testicular tumor. Microscopically, the tumor shows a
variety of patterns, including lobules containing large cells with watery cytoplasm, structures
resembling primitive glomeruli, syncytiotrophoblast, and shafts of undifferentiated cells with
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focal glandular differentiation. Which of the following terms most accurately describes this
tumor?
A. Choriocarcinoma
B. Embryonal carcinoma
C. Mixed tumor
D. Seminoma
E. Yolk sac tumor
Explanation:
The correct answer is C. This is a mixed testicular tumor. Mixed patterns occur in 60% of
testicular tumors, with the most common pattern being teratoma (not present in this patient),
embryonal carcinoma, yolk sack tumor, and hCG-containing syncytiotrophoblast. This patient's
tumor also contains elements of seminoma. The prognosis of these tumors is determined by the
presence or absence of more aggressive elements, notably choriocarcinoma.
Choriocarcinoma (choice A) contains both syncytiotrophoblast and cytotrophoblast.
Embryonal carcinoma (choice B) is characterized by sheets of undifferentiated cells with focal
glandular differentiation.
Seminoma (choice D) shows lobules containing large cells with watery cytoplasm.
In about half the cases, yolk sac tumor (choice E) contains structures resembling primitive
glomeruli, known as endodermal sinuses.
A 71-year-old man has been in excellent health, and practicing competently as an attorney. He is brought
to the emergency room following a motor vehicle accident. A workup, including imaging of the
spine, thorax, and head, is negative, but the patient is admitted for overnight observation.
His injuries include several lacerations to the face and extremities as well as several
contusions to the thorax. Three weeks later, he is admitted to the hospital for confusion. A
neurologic exam is normal except that he is not oriented to time or place, and can recall only
1 out of 6 objects after 3 minutes. Which of the following is the most likely diagnosis?
A. Alzheimer's disease
B. Brain metastases
C. Epidural hematoma
D. Normal pressure hydrocephalus
E. Subdural hematoma
Explanation:
The correct answer is E. This is a classic history and presentation of a subdural hematoma,
which usually occurs several days to weeks following a traumatic head injury. Often the patient
will have had a hospital admission with a negative workup, including x-rays and CT scans of the
head. Either gradually or abruptly, the patient can experience decreasing mental status,
sleepiness, focal neurologic deficits, seizures, etc. The bleeding originates from the bridging
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veins of the meninges and blood collects beneath the dural layer. A CT or MRI of the brain will
show a semicircular, crescent-shaped opacity (blood) just below the cranium impinging on the
brain tissue.
Alzheimer's disease (choice A) usually develops more gradually, typically over several years
(although some cases can develop over a few months).
Brain metastases (choice B) could very well present like this, however, the patient will often
have constitutional symptoms of cancer such as fatigue and weight loss. In a patient with a
recent traumatic event, however, subdural hematoma is more likely.
An epidural hematoma (choice C) differs from a subdural hematoma in that it occurs much more
rapidly, usually over several hours or less. The bleed originates from the middle meningeal
artery, which runs right next to the anterolateral cranium and often gets injured with a skull
fracture in this location. A CT or MRI will show a circular opacity within the cranium
compressing the brain tissue.
Normal pressure hydrocephalus (choice D) occurs in the elderly and is associated with urinary
incontinence, new onset of confusion, and gait disturbances.
A biopsy of a brain tumor from a 42-year-old man reveals a glial neoplasm consisting of atypical
astrocytes with scattered mitoses. Besides mitotic activity, which of the following markers can
provide information about the neoplasm's proliferative activity?
A. bcl-2
B. Glial fibrillary acidic protein (GFAP)
C. Ki-67
D. p53
E. Ubiquitin
Explanation:
The correct answer is C. Ki-67 is a nuclear factor (of uncertain function) whose expression
correlates with neoplastic replicative activity. Its expression can be visualized by
immunostaining of formalin-fixed, paraffin-embedded sections. Ki-67 labeling correlates with a
neoplasm's rate of growth and, therefore, with prognosis.
The bcl-2 gene (choice A) suppresses apoptosis by different mechanisms. Its abnormal activation
is involved in the pathogenesis of low-grade lymphomas but not astrocytomas.
GFAP (choice B) is an intermediate cytoskeletal filament (analogue of keratin and vimentin)
expressed exclusively by certain types of glial cells, e.g., astrocytes and ependymal cells.
Immunohistochemistry for GFAP is used diagnostically to confirm an astrocytic origin of a
neoplasm, but gives no information about mitotic or proliferative rate.
The gene p53 (choice D) encodes a protein that blocks the cell cycle when damage to DNA occurs.
If the damage is successfully repaired, p53 allows the cell cycle to resume; if not, p53
induces apoptosis, thus eliminating dangerous DNA mutations. Mutations of p53 have been found
in the great majority of human neoplasms, including gliomas. However, its expression gives no
information concerning neoplastic replicative activity.
Ubiquitin (choice E) is a low-molecular-weight heat-shock protein. Its function is to tag
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aberrant proteins for degradation. It is present in many abnormal intraneuronal inclusions
associated with neurodegenerative disorders, such as Lewy bodies, Pick bodies, and
neurofibrillary tangles. It has no relationship with mitotic activity or growth rate.
Examination of a peripheral smear from a patient with a hematocrit of 30% demonstrates large numbers of
target cells. Further work-up of this patient would most likely reveal which of the following
abnormalities?
A. Abnormal hemoglobin synthesis
B. Abnormal red cell cytoskeleton
C. Cells that sickle when exposed to low oxygen tension
D. Mineral deficiency
E. Vitamin deficiency
Explanation:
The correct answer is A. Target cells are red cells with a peripherally dense rim of hemoglobin
enclosing a zone of pallor, often with a darker central punctum. They appear as a result of an
increase in the area of the red cell membrane, and/or a decrease in hemoglobin. Target cells
are most commonly seen in three conditions: thalassemia, hemoglobin C disease, and liver
disease. Of the choices given, only thalassemia involves abnormalities of hemoglobin synthesis
(either the alpha or the beta chain).
Hereditary spherocytosis is an abnormality of red cell cytoskeleton (choice B).
Sickle cell anemia and sickle cell trait are diseases characterized by sickling of cells when
exposed to low oxygen (choice C).
The microcytic anemia of iron deficiency is the best example of an anemia due to mineral
deficiency (choice D).
The macrocytic anemias of B12 and folate deficiencies are examples of anemias related to
vitamin deficiency (choice E).
A pathologist is examining five placentas from five different births. He notes the following
characteristics in the five placentas:
Patient A: fused dichorionic diamnionic
Patient B: dichorionic diamnionic
Patient C: circumvallate placenta
Patient D: monochorionic diamnionic
Patient E: bipartite placenta
Which of the patients unquestionably gave birth to identical twins?
A. Patient A
B. Patient B
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C. Patient C
D. Patient D
E. Patient E
Explanation:
The correct answer is D. Patient D is the lucky mother of identical (monozygotic) twins. The
chorion forms before the amnion, so the possible combinations are monoamnionic and
monochorionic; diamnionic and monochorionic; and diamnionic and dichorionic (either fused or
separated). The first two of these possibilities are seen only in identical twins. However, the
latter can be seen either in fraternal or identical twins. Exactly what happens in the case of
identical twins depends on the precise point at which twinning occurs: very early separation
produces completely separate membranes with duplication of both chorion and amnion; somewhat
later separation produces one chorion and two amnions; and very late separation produces one
chorion and one amnion. A dichorionic, diamnionic placenta develops if splitting occurs early
after fertilization, before the chorion forms. This type of placenta may occur with either
monozygotic or dizygotic twins. Thus, we are unable to determine whether Patient A (choice A)
or Patient B (choice B) had identical twins from the examination of the placentas.
Neither Patient C (choice C) nor Patient E (choice E) had a twin pregnancy. A circumvallate
placenta has an extrachorial portion outside the insertion of the amnionic membranes, creating
a circumferential groove (vallum in Latin). A bipartite placenta is composed of two equal
segments. Circumvallate and bipartite placentas are examples of placental abnormalities that
usually have no clinical significance.
A 42-year-old paraplegic woman has a neurogenic bladder and requires an indwelling urinary catheter. She
develops a urinary tract infection and is seen by a urologist, who orders abdominal x-rays and
an intravenous pyelogram. The radiographic studies demonstrate a very large stone that fills
and follows the contours of the renal pelvis. The stone is most likely composed of which of the
following?
A. Calcium salts
B. Cholesterol
C. Cystine
D. Magnesium ammonium phosphate
E. Uric acid
Explanation:
The correct answer is D. Staghorn calculi, such as described in the question, are associated
with infection by urea-splitting bacteria (notably Proteus species) and are composed of
magnesium ammonium phosphate (struvite). They are more common in women than men, and are far
more common in patients requiring chronic bladder catheterization.
Calcium-containing stones (choice A) are typically seen in patients with hypercalcinuria
without hypercalcemia; one-fifth of patients with this type of stone have hyperuricosuria.
Cholesterol (choice B) is found in gall stones, not kidney stones.
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Cystine stones (choice C) are rare; they may be seen in patients with cystinuria, an autosomal
recessive disorder of amino acid metabolism.
Uric acid stones (choice E) are seen in gout, leukemia, and in patients with acidic urine.
A radiologist notes the presence of fine, radiographically dense crystals in the tissues of a knee
joint. This patient most likely has which of the following types of arthropathy?
A. Gonococcal arthritis
B. Gouty arthritis
C. Osteoarthritis
D. Pseudogout
E. Rheumatoid arthritis
Explanation:
The correct answer is D. Radiographically dense calcium pyrophosphate dihydrate (CPPD) crystals
are deposited in cartilage and joint soft tissues in pseudogout, which can involve the knees,
wrists, elbows, shoulders, or ankles. If the patient is asymptomatic because the deposition is
primarily within cartilage, the condition is sometimes called chondrocalcinosis. In its more
severe form, the joint involvement can clinically resemble rheumatoid arthritis.
Neither gonococcal arthritis (choice A), osteoarthritis (choice C), nor rheumatoid arthritis
(choice E) are associated with crystal formation.
The monosodium urate crystals deposited in joints in gouty arthritis (choice B) are not radioopaque.
In a hindsight study, the progeny of woman who took diethylstilbestrol had an increased risk for
developing which of the following cancers?
A. Bladder cancer
B. Endometrial carcinoma
C. Ovarian carcinoma
D. Renal cell carcinoma
E. Vaginal clear cell adenocarcinoma
Explanation:
The correct answer is E. Diethylstilbestrol, or DES, is an estrogen analog that was prescribed
in the 1950s-1970s for prevention of spontaneous abortion. The progeny of woman taking DES were
often diagnosed with clear cell vaginal or cervical adenocarcinoma, which is rarely seen in
unexposed women.
Bladder cancer (choice A) is often seen in individuals exposed to beta-naphthalene dyes or
phenacetin.
Endometrial carcinoma (choice B) is seen in individuals on long-term estrogen therapy, but was
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not seen in the progeny of DES-treated women.
Ovarian carcinoma (choice C) is increased in nulliparous women, and in those with a family
history of the disorder.
Renal cell carcinoma (choice D) has been linked to such epidemiologic factors as smoking, and
the incidence is increased in patients with von Hippel-Lindau syndrome.
A 45-year-old man presents to the emergency department with severe headache and vomiting. A CT scan
shows a well-circumscribed cystic lesion within the 3rd ventricle; there is no calcium
deposition. The cyst is surgically removed. On histologic examination, the wall of the cyst
consists of a single layer of mucin-producing columnar epithelium with a ciliated apical
surface. Which of the following is the most likely diagnosis?
A. Colloid cyst
B. Craniopharyngioma
C. Cysticercosis
D. Echinococcus cyst
E. Pilocytic astrocytoma
Explanation:
The correct answer is A. This patient has symptoms of increased intracranial pressure, ie,
nausea, vomiting, and headache. This pressure is due to the location of the mass in the 3rd
ventricle, which is blocking the flow of cerebrospinal fluid from the lateral ventricles into
the 3rd ventricle through the foramen of Monro. All cysts and tumors listed here may be found
in the 3rd ventricle, but the histologic features are consistent with a colloid cyst. Colloid
cysts are thought to derive from embryologically misplaced endodermal epithelium, which
explains the presence of mucin-producing ciliated cells similar to respiratory epithelium. The
cyst contains mucinous fluid. It usually presents with these type of symptoms in adults,
especially middle-aged patients.
Craniopharyngioma (choice B) is a neoplasm arising in the suprasellar region of children and
young adults. It derives from misplaced odontogenic epithelium; indeed, the tumor is
histologically identical to the most common tumor of teeth, adamantinoma. Craniopharyngiomas
contain abundant calcium deposits. Although histologically benign, these tumors frequently
recur since complete surgical excision is rarely feasible.
A cysticercus is a cyst that develops following ingestion of Tenia solium eggs in undercooked
pork. The brain is one of the preferred sites of cysticercosis (choice C), and cysticerci may
develop within the brain (intraparenchymal), within the ventricles, or in the subarachnoid
space. The lining of a cysticercus, however, is entirely different from a colloid cyst: it
consists of three cell layers, the most superficial of which resembles dome-shaped urothelial
cells.
An Echinococcus cyst (choice D) is caused by infestation from another cestode parasite,
Echinococcus granulosus, which is acquired from dog feces. The defining feature of an
Echinococcus cyst is a tiny, hooklike projection called a scolex. Scolices detach from the
wall, accumulating within the cyst and producing a sandlike sediment. Liver and lungs are the
usual locations of echinococcosis.
Pilocytic astrocytoma (choice E) is a tumor of astrocytic origin that affects children and
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young adults. It usually develops either in the cerebellar hemispheres or in the hypothalamic
region. In the latter location, it may grow within the 3rd ventricle. Pilocytic astrocytomas
often have a cystic structure. Histologically, the tumor consists of elongated astrocytes
within an abundant fibrillary background and numerous Rosenthal fibers. The wall of the cystic
component is composed of glial (astrocytic) cells, usually of a reactive nature.
A 70-year-old man has smoked for years despite a chronic productive cough. One day, he notices blood in
his sputum and goes to see his physician. A chest x-ray reveals a mass in one lung, which is
biopsied during a fiberoptic bronchoscopy. Assuming that this patient's cancer is etiologically
related to his smoking, which of the following diagnoses are most likely to be returned by the
pathology laboratory?
A. Adenocarcinoma or bronchioloalveolar carcinoma
B. Adenocarcinoma or small cell carcinoma
C. Bronchioloalveolar carcinoma or small cell carcinoma
D. Bronchioloalveolar carcinoma or squamous cell carcinoma
E. Small cell carcinoma or squamous cell carcinoma
Explanation:
The correct answer is E. Smoking does not increase the risk of all types of lung cancers to the
same degree. Oat (small) cell carcinoma has a very strong association with smoking, with only
1% of cases occurring in nonsmokers. Squamous cell carcinoma is also strongly associated with
smoking, because smoking predisposes for squamous metaplasia, a precancerous condition. The
association of smoking with bronchogenic adenocarcinoma and with bronchioloalveolar carcinoma
is much weaker.
A 46-year-old female with rheumatoid arthritis develops progressively worsening renal failure. She
undergoes diagnostic renal biopsy, revealing thickening of the mesangial matrix and widened
capillary basement membranes due to deposition of an amorphous, eosinophilic material that
stains with Congo red. The material is shown to be composed of AA (amyloid-associated) protein
fibrils. In which of the following locations is this protein synthesized?
A. Bone marrow
B. Brain
C. Liver
D. Synovium
E. Thyroid
Explanation:
The correct answer is C. AA protein represents an enzymatically degraded form of SAA (serum
amyloid-associated) protein, which is synthesized in the liver. SAA is produced in response to
cytokines that are released in a number of inflammatory conditions, including chronic
infections, connective tissue disorders, and inflammatory bowel disease. It is not known why
only a minority of people with these conditions develop amyloidosis.
Bone marrow (choice A) and lymph nodes are the source of the AL (amyloid light chain) proteins,
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which cause amyloidosis in plasma cell and B-cell proliferations (e.g., multiple myeloma). This
is the most common form of amyloidosis in the U.S. today.
Beta 2-amyloid protein (Aβ2) is found in the brain (choice B) and forms the core of the
plaques in Alzheimer's disease.
The synovium (choice D) may be the site of chronic inflammation and pannus formation in
rheumatoid arthritis, but amyloid is not synthesized here.
In medullary carcinoma, excess calcitonin production leads to heavy amyloid deposition within
the thyroid gland (choice E), but this amyloid is not derived from AA protein.
A 62-year-old woman in the hospital for a hip fracture develops a deep venous thrombosis that embolizes.
The embolus lodges at the bifurcation of the pulmonary trunk, nearly completely occluding the
vessel. Which part of the heart would be most significantly and immediately affected by this
event?
A. Left main coronary artery
B. Left ventricle
C. Right atrium
D. Right main coronary artery
E. Right ventricle
Explanation:
The correct answer is E. A massive pulmonary embolus, such as this patient sustained, can
interrupt pulmonary blood flow, producing acute cor pulmonale with abruptly developing right
ventricular dilatation. Other parts of the heart are secondarily affected somewhat later.
Acute cor pulmonale is a surgical emergency requiring immediate correction of the underlying
problem, which is usually a pulmonary embolus lodged early in the pulmonary circulation. Acute
cor pulmonale is less common than chronic cor pulmonale, which is seen as a complication of
many chronic lung diseases.
The left main coronary artery (choice A) and right main coronary artery (choice D) would be
affected secondarily to the reduced blood flow to the left heart and aorta, from which the
coronary arteries arise.
The left ventricle (choice B) would be affected secondarily by reduced blood flow from the
pulmonary veins to the left atrium.
The right atrium (choice C) would be affected after the right ventricle since it is farther
from the circulatory block.
A 1-week-old, bottle-fed, low-birth-weight neonate develops severe abdominal pain with bloody diarrhea.
Several hours later, the neonate undergoes emergency surgery. A portion of small intestine is
resected, and pathologic examination demonstrates a perforation. Which of the following would
most likely be seen on microscopic examination of the involved bowel?
A. Inflammatory polyps
B. Multiple diverticula
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C. Neoplastic polyps
D. Thickened collagenous band
E. Transmural necrosis
Explanation:
The correct answer is E. The disease is necrotizing enterocolitis, which is a common cause of
gastrointestinal emergency in premature and low-birth-weight infants. Typically, the infants
are bottle-fed and develop severe abdominal distress in the first week of life. Contributing
factors include intestinal ischemia, poor neonatal immune response, and microbial agents. Both
the small and large bowel may be affected. Necrotizing enterocolitis may be complicated by
intestinal gangrene, gastrointestinal bleeding, intestinal perforation, and sepsis. Survivors
of severe necrotizing enterocolitis may have had significant lengths of bowel surgically
removed, and later suffer from malabsorption and stricture formation. Histologically, the
appearance varies with disease stage, but typically shows varying degrees of necrosis
(transmural if perforation has occurred), inflammation, hemorrhage, and edema. A pseudomembrane
composed of coagulated fibrin, neutrophils, and cellular debris may overlie the mucosa.
Inflammatory polyps (choice A) can be seen following reepithelialization of ulcers, typically
in ulcerative colitis, which would not be seen in the first week of life.
Multiple diverticula (choice B) are seen in diverticulosis, which does not usually develop
before middle age.
Neoplastic (precancerous) polyps (choice C), even in familial syndromes with a high colonic
cancer rate, would not be expected to cause an acute abdominal emergency in a neonate.
A thickened collagenous band (choice D) between surface epithelial cells and the lamina propria
is seen with episodic watery diarrhea, usually in adults.
A 20-year-old man with new onset of seizures and no history of hypertension is evaluated with a
contrast-enhanced CT scan of the head, which demonstrates a mixed parenchymal and subarachnoid
hemorrhage. The parenchymal hemorrhage is centered over one cerebral hemisphere. Which of the
following is the most likely source of the hemorrhage?
A. Arteriovenous malformation
B. Berry aneurysm
C. Bridging vein
D. Charcot-Bouchard aneurysm
E. Middle meningeal artery
Explanation:
The correct answer is A. Arteriovenous malformations are composed of complex tangles of
congenitally malformed vessels that typically involve the superficial or deep cerebral
hemispheres. There is a slight male predominance, and bleeding typically occurs in adolescence
or young adulthood. Symptoms may be those of subarachnoid hemorrhage (headache, increased
intracranial pressure) and/or seizures. Surgical resection is usually required for therapy.
Berry aneurysms (choice B) can produce both subarachnoid and parenchymal hemorrhage, but are
14
usually centered near the base of the brain.
Bleeding from bridging veins (choice C) causes subdural hematoma.
Charcot-Bouchard aneurysms (choice D) are small, intraparenchymal aneurysms that are related to
hypertension.
Rupture of the middle meningeal artery (choice E) causes epidural hematoma.
A 78-year-old woman has multiple long-standing lesions on her face and back. These well-circumscribed
lesions are tan to brownish, slightly raised with a rough surface, and typically 0.5 to 1.5 cm
in diameter. The clinician examining the patient is able to "peel away" parts of the lesion
with the dull side of a scalpel blade. Which of the following diagnoses is most likely?
A. Eczema
B. Melanoma
C. Psoriasis
D. Seborrheic keratoses
E. Verruca vulgaris
Explanation:
The correct answer is D. Seborrheic keratoses, as described in the question stem, are very
common lesions of the skin of middle-aged and older individuals. These benign growths
histologically show hyperplasia of the epidermis. While cosmetically disturbing to some
patients, the primary medical concern is that, occasionally, seborrheic keratoses may mimic the
clinical appearance of basal cell carcinomas or squamous cell carcinomas. Consequently, biopsy
should be performed on atypical appearing or rapidly changing "seborrheic keratoses" to exclude
the presence of cancer.
Chronic eczema (choice A) produces dry, thick, and sometimes discolored skin.
Melanomas (choice B) characteristically look like dark moles with irregular margins and
variations in the degree of pigmentation.
Psoriasis (choice C) produces erythematous plaques with a silvery scale.
Verruca vulgaris (choice E), the common wart, produces verrucous papules that are most commonly
found on the hands. The face and back would be unusual sites.
A 13-year-old male presents to the emergency room with a deep skin abrasion on his knee. He states that
it has not stopped bleeding since it happened during recess approximately 20-30 minutes ago.
Physical examination reveals a well developed, well nourished adolescent. There are multiple
purpura over his legs and arms, and a few scattered petechiae on his chest and gums. His
bleeding time is 22 minutes, platelets = 300,000/mm3, hemoglobin = 11g/dL. A trial of
cryoprecipitate transfusion does not improve his bleeding time. A normal platelet transfusion
does improve bleeding time. Which of the following is the correct diagnosis?
A. Bernard-Soulier syndrome
B. Henoch-Schönlein purpura
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C. Idiopathic thrombocytopenic purpura
D. Thrombotic thrombocytopenic purpura
E. Von Willebrand's disease
Explanation:
The correct answer is A. Bernard-Soulier syndrome is an autosomal recessive disease of platelet
adhesion which causes prolonged bleeding times in the presence of normal platelet counts. These
patients' platelets cannot bind to subendothelial collagen properly because of a deficiency or
dysfunction of the glycoprotein Ib-IX complex. Clinically the patients have impaired hemostasis
and recurrent severe mucosal hemorrhage. The only treatment for an acute episode is a
transfusion of normal platelets. This patient has a slightly decreased hemoglobin due to blood
loss.
Henoch-Schonlein purpura (choice B) is a self-limited autoimmune vasculitis that affects
children and young adults, usually following an upper respiratory infection. Affected
individuals develop purpuric rashes on the extensor surfaces of their arms, legs, and buttocks.
They also have abdominal pain and hematuria from glomerulonephritis. Despite the tendency
toward hemorrhage, the bleeding times and platelet count would be normal.
Idiopathic thrombocytopenic purpura (choice C) causes an increase in the bleeding time, but as
the name implies, platelet counts are decreased. There is bleeding from small vessels,
especially of the skin, gastrointestinal tract and genitourinary tract. Purpura and petechiae
frequently develop. It is considered a self-limited autoimmune disorder, typically affecting
children after a recent viral infection.
Thrombotic thrombocytopenic purpura (choice D) is characterized by an increased bleeding time,
but a decreased platelet count. It is a rare disorder of unknown etiology, thought to be
initiated by endothelial injury, which releases certain procoagulant materials into the
circulation, causing platelet aggregation. It causes purpura, fever, renal failure,
microangiopathic hemolytic anemia and microthrombi, generally in young women. In this disorder,
platelet transfusion is actually contraindicated, as it can precipitate thrombosis.
Von Willebrand's disease (choice E) causes increased bleeding times with normal platelet
counts. It is the most common inherited bleeding disorder, caused by a defect in von Willebrand
factor, which aids the binding of platelets to collagen. Even though the platelets themselves
are normal, binding is impaired, thus a platelet transfusion would not correct the problem.
Cryoprecipitate, a plasma fraction rich in von Willebrand factor, would help in the case of von
Willebrand's disease, but would not help with Bernard-Soulier syndrome.
Which of the following conditions may lead to development of an exudate within the pleural cavity?
A. Bacterial pleuritis
B. Cirrhosis of the liver
C. Congestive heart failure
D. Nephrotic syndrome
E. Protein-losing enteropathy
Explanation:
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The correct answer is A. An exudate results from leakage of protein-rich fluid from the plasma
into the interstitium. It is usually the result of increased vascular permeability caused by
inflammation. Exudates also contain numerous acute or chronic inflammatory cells, depending on
the inciting event. Of the above choices, only bacterial pleuritis would produce an exudate. If
pleuritis is caused by pyogenic organisms, the exudate is purulent (neutrophil-rich). If
pleural inflammation is due to mycobacterial infection or neoplastic infiltration, the
resulting exudate will contain chronic inflammatory cells.
In contrast, a transudate contains less protein and few inflammatory cells. There are two main
mechanisms of transudate formation: 1) decreased oncotic pressure, such as that which occurs in
cirrhosis of the liver, nephrotic syndrome, and protein-losing enteropathy (choices B, D, and
E); and 2) increased hydrostatic pressure, which may result from congestive heart failure
(choice C).
A 45-year-old man presents to a clinician because of chronic fatigue. He states that he has stopped
exercising, and feels tired after mild activity. A complete blood count reveals a hematocrit of
31, a white count of 1,950, and a platelet count of 90,000. Which of the following radiologic
findings would most likely lead to the correct diagnosis?
A. Bony overgrowth
B. Generalized decrease in bone mass
C. Large calcified growth on the tibia
D. Multiple exostoses
E. Single "punched out" lesion of upper femur
Explanation:
The correct answer is A. Trilineage failure of blood cell production, producing pancytopenia,
suggests a generalized decrease in marrow cavity size, which can be due to bony overgrowth in
processes such as osteopetrosis. The anemia observed in these patients is often very refractory
to treatment.
Osteomalacia produces a generalized decrease in bone mass (choice B), and is not associated
with pancytopenia.
A large calcified growth on the tibia (choice C) suggests a benign or malignant tumor of bone,
which would not usually replace enough marrow to cause anemia.
Multiple exostoses (choice D) would affect the outer surface, not the marrow cavity of the
bone.
A single “punched out” bony lesion (choice E) located in the upper femur suggests
monostotic fibrous dysplasia, an asymptomatic, benign, bony lesion.
A young woman presents to her family physician with complaints of numbness, tingling, and burning of
her
fingers. She states that these symptoms are typically accompanied by "blanching" of her
fingertips until they are nearly blue, followed by reddening as the episode resolves. The
condition described is the initial presenting complaint in over 70% of patients with which of
the following diseases?
A. Colonic polyposis
17
B. Congestive heart failure
C. Goodpasture's syndrome
D. Rheumatoid arthritis
E. Scleroderma
Explanation:
The correct answer is E. The finger color changes and pain are manifestations of Raynaud's
phenomenon, which is often idiopathic, but can be related to many connective tissue diseases,
notably progressive systemic sclerosis, also known as scleroderma (the initial complaint in
over 70% of patients).
Colonic polyposis (choice A) can be related to mucocutaneous pigmentation (Peutz-Jeghers
syndrome), and sebaceous cysts and other soft-tissue tumors of skin (Gardner's syndrome).
Congestive heart failure (choice B) can cause edema of subcutaneous tissues, but is not a cause
of Raynaud's phenomenon.
Goodpasture's syndrome (choice C) causes pulmonary hemorrhage and renal failure.
Raynaud's phenomenon can be seen in rheumatoid arthritis (choice D), but is not associated
nearly as frequently with this condition as with scleroderma.
A 25-year-old woman presents to her physician with complaints of easy bruising and excessive bleeding.
Physical examination demonstrates hepatosplenomegaly. A blood smear reveals pancytopenia and a
bone marrow biopsy demonstrates markedly enlarged cells containing a fine fibrillar material
resembling tissue paper. Leukocyte enzymatic studies demonstrate a deficiency of beta-Dglucosidase activity. Which of the following substances is most likely to accumulate in the bone
marrow cells?
A. Galactose
B. Glucosylceramide
C. Glycogen
D. Homocysteine
E. Mineralocorticoids
Explanation:
The correct answer is B. The disease is Gaucher disease, which is a glycolipid storage disease
in which glucosylceramide accumulates in spleen, liver, and bone marrow. The defective enzyme,
a lysosomal hydrolase known as acid beta-D-glucosidase, can be assayed in leukocytes separated
from the blood by centrifugation. Interestingly, the defective enzyme can now be supplied
intravenously, and strategies for transplantation of the cloned replacement gene are now being
developed.
Galactose (choice A) is a sugar. Deficiency of beta-D-glucosidase would not lead to
accumulation of galactose.
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Glycogen (choice C) is a storage polymer of glucose. It accumulates in various glycogen storage
diseases, but has a different appearance than the glycolipid in Gaucher disease.
Homocysteine (choice D) is an amino acid. It does not accumulate in Gaucher disease.
Mineralocorticoids (choice E) are lipids, but do not accumulate in bone marrow.
A pathologist is examining a poorly differentiated tumor that he suspects may be derived from muscle
tissue. Immunohistochemical stains for which of the following would be expected to yield
positive results if he is correct?
A. Cytokeratin
B. Desmin
C. Glial fibrillary acidic proteins
D. Neurofilaments
E. Vimentin
Explanation:
The correct answer is B. Muscle cells contain desmin, which is a component of the intermediate
filaments found in these cells.
Epithelial cells contain cytokeratin (choice A).
Neuroglia contain glial fibrillary acidic proteins (choice C).
Neurons contain neurofilaments (choice D).
Connective tissue contains vimentin (choice E).
A very ill 3-year-old child is brought into the emergency room with a fever. On physical examination,
the child has large cervical lymph nodes and a desquamating skin rash that involves the palms,
soles, and mouth. This child should be monitored for the development of which of the following
conditions?
A. Abdominal aortic aneurysm
B. Aneurysm of the aortic root
C. Berry aneurysm
D. Coronary artery aneurysm
E. Dissecting aneurysm
Explanation:
The correct answer is D. The child has Kawasaki's syndrome (mucocutaneous lymph node syndrome),
which is the leading cause of acquired heart disease in children in the United States. In this
disorder, small, medium, and large arteries are affected, with transmural inflammation and
variable necrosis. About 20% of affected children have damage to the coronary vessels; some
develop coronary artery aneurysms. In 1-2% of cases, sudden death may occur from aneurysm
19
rupture or thrombosis producing infarction.
Abdominal aortic aneurysms (choice A) are associated with atherosclerosis.
Aneurysms of aortic root (choice B) are usually associated with syphilis.
Berry aneurysms (choice C) are caused by congenital defects in the vessel wall, and are
associated with polycystic kidney disease.
Dissecting aneurysms (choice E) are associated with hypertension or cystic medial degeneration
(seen in Marfan's syndrome).
A 35-year-old woman consults her gynecologist because she has a blood-tinged discharge from one nipple.
Physical examination demonstrates a small, palpable, subareolar tumor. The tumor is surgically
resected and then pathologically examined. Which of the following features is most helpful in
establishing its benign, rather than malignant, character?
A. Abnormal mitotic figures
B. Intraductal location of tumor
C. Presence of both epithelial and myoepithelial cells
D. Presence of papillary fronds
E. Small size of tumor
Explanation:
The correct answer is C. Intraductal papillomas are small (usually less than 1 cm), benign
neoplastic papillary tumors found within the larger ducts of the breast. They are typically
located near the nipple under the areola. They can be frightening to the patient because they
may produce a serous or bloody nipple discharge. They have a malignant counterpart, papillary
ductal carcinoma of the breast, so it is important to be able to distinguish the benign from
the malignant lesion. Features favoring the diagnosis of ductal carcinoma, rather than benign
intraductal papilloma, include severe cytologic atypia, abnormal mitotic figures, and a
cribriform growth pattern. Features that are specifically reassuring are the consistent
presence of a fibrovascular core and both epithelial and myoepithelial cells in the papillary
fronds. The myoepithelial cells are small cells with a contractile function usually found
around breast ducts.
Abnormal mitotic figures (choice A) are a feature of malignancy.
Both benign and malignant papillary tumors can be located within ducts (choice B).
Both benign and malignant papillary tumors can have papillary fronds (choice D).
Both benign and malignant papillary tumors can be small (choice E).
A diabetic patient complains to a physician of a sensation of walking on pebbles with bare feet.
Physical examination demonstrates "clawing" of the toes with flexion of the interphalangeal
joints and extension of the metatarsophalangeal joints. Atrophy of which of the following
muscles is most likely responsible for the observed changes?
A. Flexor digitorum longus
20
B. Lumbricals and interossei
C. Peroneus longus
D. Tibialis anterior
E. Tibialis posterior
Explanation:
The correct answer is B. The condition described in the question stem is very common among
diabetics, and is due to atrophy of lumbricals and interosseus muscles secondary to diabetic
neuropathy. Another finding that may be seen is the presence of corns and callosities on the
dorsal surface of the feet overlying the protuberant interphalangeal joints. All of these
degenerative changes add to the diabetic's foot disease, predisposing for sores that heal
poorly in the poorly vascularized diabetic foot, often leading to gangrene, requiring
amputation of the distal foot.
Flexor digitorum longus (choice A) is an extrinsic muscle of the foot that flexes the distal
phalanges of the lateral four toes and assists in plantar flexion of the foot.
Peroneus longus (choice C) is an extrinsic muscle of the foot that plantar flexes and everts
the foot.
Tibialis anterior (choice D) is an extrinsic muscle of the foot that dorsiflexes and inverts
the foot.
Tibialis posterior (choice E) is an extrinsic muscle of the foot that plantar flexes and
inverts the foot.
A 39-year-old male with a 20-pack-year history of cigarette smoking presents with fever, chills, and
painful urination. On physical examination, his prostate is boggy, and exquisitely tender on
palpation. Urinalysis reveals white blood cells and gram-negative rods. This man's symptoms are
most likely due to which of the following?
A. Acute bacterial prostatitis
B. Chronic abacterial prostatitis
C. Chronic bacterial prostatitis
D. Nodular hyperplasia
E. Prostate cancer
Explanation:
The correct answer is A. Most prostatic conditions are painless; acute bacterial prostatitis
stands out as producing a very tender prostate. The etiologic agents are usually the same as
those that produce urinary tract infection, and include E. coli, Klebsiella, Proteus,
Pseudomonas, Enterobacter, Serratia, Enterococcus, and Staphylococcus.
Both chronic abacterial prostatitis (choice B) and chronic bacterial prostatitis (choice C) may
be asymptomatic, or either may cause low back pain, perineal tenderness, or dysuria. Suspected
pathogens in this form of prostatitis include Chlamydia and Ureaplasma, but the causative agent
is not known with certainty.
21
Nodular hyperplasia (choice D) produces difficulty in urination.
Prostate cancer (choice E) produces a firm mass that is generally palpable on rectal
examination.
A family suspected of child abuse because one of their children has had multiple fractures consults an
orthopedic specialist at a children's hospital. The specialist examines the child, who is now 5
years old, and notes that the child has blue-tinged sclera, hearing loss, and small, slightly
blue, misshapen teeth. Radiologic studies confirm the presence of numerous fractures of various
ages. No significant degree of bruising is seen over sites of recent fracture. The disease this
child most likely has is related to abnormal metabolism involving which of the following
substances?
A. Collagen
B. Glycogen
C. Mucopolysaccharides
D. Purines
E. Tyrosine
Explanation:
The correct answer is A. The suspected disease is osteogenesis imperfecta, which is a rare
genetic disorder that occurs in both recessive and dominant forms. The clinical presentation,
depending on the specific form, varies from death in utero, to that described in the question
stem, to very mild disease with only a modest increase in bone fragility. The different types
all have defects in the synthesis of type I collagen, often with insufficient or abnormal
pro-α1(1) or pro-α2(1) chains. These deficits produce an unstable collagen triple
helix that is not as strong as normal collagen.
Defective glycogen (choice B) metabolism is associated with the various glycogen storage
diseases, such as von Gierke disease and Pompe disease. These diseases tend to present with
profound hypoglycemia, hepatomegaly, or muscle weakness.
Defective mucopolysaccharide (choice C) metabolism is associated with the
mucopolysaccharidoses, such as Hurler and Hunter syndromes. These diseases tend to present with
abnormal facies ("gargoylism"), deformed ("gibbus") back, claw hand, and stiff joints.
Abnormalities of purine metabolism (choice D) are present in gout, which presents with joint
inflammation and often involves the great toe.
Abnormalities of tyrosine metabolism (choice E) are associated with phenylketonuria (pale hair
and skin, mental retardation, musty smelling urine), albinism (pale hair, skin, increased skin
cancer), cretinism (decreased T3 and T4), tyrosinosis (liver and kidney disease), and
alkaptonuria (chronic arthritis and urine that turns black upon standing).
A 53-year-old man develops acute, excruciating chest pain that radiates to his back. En route to the
emergency room, he becomes unresponsive, and is pulseless on arrival. Resuscitation attempts
are unsuccessful. Autopsy reveals massive hemoperitoneum due to a ruptured aortic dissection.
There is a jagged intimal tear in the ascending aorta, with a dissecting hematoma in the media,
extending from the aortic valve to the renal arteries. Which feature of this scenario most
strongly suggests hypertension as the cause of the aortic dissection?
22
A. Adventitial tear above renal arteries
B. Dissection through media
C. Involvement of major aortic branches
D. Origin at ascending aorta
E. Rapid exsanguination
Explanation:
The correct answer is D. The two most common causes of aortic dissection are hypertension and
atherosclerosis. An important distinction between the two is that hypertensive dissections
generally originate in the ascending aorta, at an intimal surface free of atherosclerosis.
Dissection secondary to atherosclerosis is typically the consequence of a ruptured aortic
aneurysm, which originates in the abdominal aorta at the iliac bifurcation. Dissections due to
both hypertension and atherosclerosis generally course through the wall within the media
(choice B). They both can involve the entire length of the aorta, and may rupture anywhere
along its course (choices A and C). Well recognized sequelae of dissections include rupture
through the adventitia, compromise of major arterial branches or the aortic valve, cardiac
tamponade, and rapid exsanguination (choice E).
A leukemic patient develops disseminated intravascular coagulation. Examination of the marrow reveals
hypergranular promyelocytes, some of which contain multiple Auer rods. The diagnosis of acute
promyelocytic leukemia is made. Which of the following translocations is associated with the
development of this disorder?
A. t(4;11)
B. t(6;9)
C. t(8;14)
D. t(8;21)
E. t(15;17)
Explanation:
The correct answer is E. Acute promyelocytic leukemia (M3 by the FAB classification) is
associated with a t(15;17) (q22;q11) translocation. Disseminated intravascular coagulation can
occur in this disorder due to the release of procoagulant substances from the leukemic cells,
especially during treatment.
The t(4;11)(q21;q23) translocation (choice A) is associated with acute lymphocytic leukemia
(ALL) and undifferentiated leukemia.
The t(6;9)(p23;q34) translocation (choice B) is found in subtypes of AML with basophilia (M1,
M2, M4).
Burkitt's leukemia, which is related to Burkitt's lymphoma, is associated with t(8;14) (q
24;q32) (choice C).
23
The t(8;21) (q22;q22) translocation (choice D) is seen in M2 leukemia, also known as acute
myeloid leukemia (AML) with maturation, and some M4 (AML with granulocytic and monocytic
maturation).
A patient presents to a dermatologist because of skin changes. The skin is hyperpigmented, thickened,
and feels velvety. Multiple skin tags are present. The changes are worst in the axillae, groin,
and anogenital area, but are very widespread. This patient should be specifically evaluated for
which of the following diseases?
A. Hepatic cirrhosis
B. Lung cancer
C. Polycystic renal disease
D. Systemic lupus erythematosus
E. Ulcerative colitis
Explanation:
The correct answer is B. The condition described is acanthosis nigricans. Mild forms are common
and may be associated with obesity and endocrine abnormalities. More extensive forms, such as
in this patient, may be associated with malignant disease: usually an adenocarcinoma (often
lung), less commonly a lymphoma. The pattern is important to recognize because the eruption may
precede other symptoms of the malignancy by several years.
A 25-year-old man with infertility is diagnosed with Kartagener syndrome. He has also been particularly
susceptible to recurrent pulmonary infections and bronchiectasis. Which of the following
cellular functions is most likely disrupted in this patient?
A. Chloride transport
B. Formation of phagolysosomes
C. Motility of cilia
D. Oxidative burst
E. Synthesis of IgA
Explanation:
The correct answer is C. To answer this question, you need not be acquainted with Kartagener
syndrome, a rare autosomal recessive condition caused by mutations of the gene encoding the
protein dynein. The information provided in the history is sufficient to find the right choice.
First, dynein is a protein that forms the side arms of microtubule doublets that allow motility
of cilia. Thus, a defect in this protein would affect ciliated cells such as spermatozoa and
respiratory epithelium. Consequently, poor sperm motility results in infertility, whereas
deficient mucociliary function in the respiratory system leads to defective bacterial clearance
and recurrent pulmonary infections. Bronchiectasis is a frequent complication, since recurrent
bouts of lung infections cause destruction and subsequent dilatation of the bronchial walls.
Chloride transport (choice A) is defective in cystic fibrosis, an inherited autosomal recessive
disease caused by mutations in the gene coding for a chloride channel protein. Respiratory
pathology is frequent and usually severe in cystic fibrosis, consisting of recurrent infections
24
and, consequently, bronchiectasis. Ninety-five percent of male patients are infertile as well
because of obstruction of the vas deferens and resultant azoospermia. Cystic fibrosis and
Kartagener syndromes have clinical similarities but entirely different etiologies.
Formation of phagolysosomes (choice B) is involved in the breakdown of phagocytosed material,
both extracellular (heterophagy) and intracellular (autophagy). Vacuoles containing material to
be digested fuse with lysosomes that form phagolysosomes. An example of deficient formation of
phagolysosomes is Chediak-Higashi syndrome, a rare hereditary condition characterized by
neutropenia and deficient microbial killing. In this disease, fusion of lysosomes with
phagocytic vacuoles is impaired, leading to defective microbial killing and recurrent
infections.
The oxidative burst (choice D) refers to the production of reactive oxygen species following
rapid activation of NADPH oxidase. NADPH is oxidized, and, in the process, oxygen is reduced to
superoxide anion. Superoxide is then converted into H2O2, which is involved in bacterial
killing. A defect in the oxidative burst causes chronic granulomatous disease, characterized by
susceptibility to recurrent bacterial infections.
Synthesis of IgA (choice E) is essential in immunologic defense at mucosal barriers, such as
respiratory, gastrointestinal, and urogenital tracts. Defective IgA synthesis occurs in
isolated IgA deficiency, a common disorder that renders patients susceptible to sinopulmonary
and gastrointestinal infections.
A 72-year-old man with a significant smoking history presents to the emergency room with complaints of
dyspnea and truncal, arm, and facial swelling for one week. Physical examination is remarkable
for facial erythema and facial, truncal, and arm edema with prominence of thoracic and neck
veins. On chest x-ray, there is a mass in the right mediastinum with adenopathy. Which of the
following is the most likely diagnosis?
A. Adenocarcinoma
B. Hodgkin's lymphoma
C. Large cell carcinoma
D. Non-small cell carcinoma
E. Small cell carcinoma
Explanation:
The correct answer is E. Superior vena cava (SVC) syndrome is characterized by obstruction of
venous return from the head, neck, and upper extremities. Over 85% of cases of SVC syndrome are
related to malignancy. Bronchogenic carcinomas (most commonly small cell cancer and squamous
cell cancer) account for over 80% of these cases. Among bronchogenic carcinomas, the most
common causes of SVC syndrome (in order of frequency) are small-cell carcinoma, epidermoid
carcinoma, adenocarcinoma (choice A), and large-cell carcinoma (choice C). Lymphomas such as
Hodgkin's disease (choice B) and non-Hodgkin's lymphoma are uncommon causes of SVC syndrome.
Rare tumors associated with SVC syndrome include primary leiomyosarcomas and plasmacytomas.
Infectious etiologies include tuberculosis, syphilis, and histoplasmosis. SVC syndrome can also
occur as a result of an enlarged goiter, and from thrombus formation caused by indwelling
intravenous lines or pacemaker wires.
Non-small cell carcinoma (choice D) is not commonly associated with SVC syndrome.
A 35-year-old man develops oliguria, peripheral edema, and shortness of breath over a two week period.
25
Serum chemistries show markedly elevated BUN and creatinine. Renal biopsy shows many glomerular
crescents, and fluorescent antibody studies demonstrate linear deposits of IgG along the
glomerular basement membrane. This patient is also at increased risk for developing
A. bladder carcinoma
B. meningioma
C. pulmonary hemorrhage
D. rheumatoid arthritis
E. testicular carcinoma
Explanation:
The correct answer is C. The clinical scenario is that of rapidly progressive
glomerulonephritis. Linear deposits of IgG along the basement membrane make the diagnosis of
anti-glomerular basement membrane disease, which may either occur as an isolated finding or as
part of Goodpasture's syndrome, which also features prominent pulmonary hemorrhage as a result
of antibody attack on the alveolar capillary basement membrane. Formerly, the prognosis of
patients with these conditions was dismal (most dying within 6 months of either renal failure
or pulmonary hemorrhage), but the patients can now often be successfully treated with
aggressive management including plasma exchange, renal dialysis, and high-dose
immunosuppression.
Predisposing factors for bladder carcinoma (choice A) include industrial chemical exposure,
cigarette smoking, and infection with Schistosoma haematobium. There is no link between bladder
carcinoma and glomerulonephritis.
Predisposing factors for meningiomas (choice B) include von Recklinghausen's neurofibromatosis
and probably small, inconsequential trauma to the meninges. There is no link between
meningiomas and glomerulonephritis.
Glomerulonephritis was previously considered to be almost nonexistent in rheumatoid arthritis
(choice D); it is now acknowledged that rheumatoid arthritis may occasionally be associated
with mesangial proliferation, membranous nephropathy, and rarely, rapidly progressive
glomerulonephritis.
Testicular carcinoma (choice E) is unrelated to glomerulonephritis. Predisposing factors for
testicular carcinoma include a failure of testicular descent.
A 22-year-old black female with sickle cell disease presents to her physician with intermittent right
upper quadrant abdominal pain. Ultrasound studies demonstrate multiple shadows within the gall
bladder. Which of the following is the most likely composition of these structures?
A. Calcium bilirubinate
B. Cholesterol
C. Cystine
D. Struvite
E. Uric acid
26
Explanation:
The correct answer is A. Pigment bile stones, derived from degradation of heme, are seen in
patients with chronic hemolytic disorders (such as this patient's sickle cell disease),
alcoholic cirrhosis, advanced age, and biliary tract infection. The stones consist largely of
calcium salts of bilirubin.
Cholesterol (choice B) gallstones are associated with obesity, high estrogen states,
multiparity, Crohn's disease, rapid weight loss, clofibrate therapy, and Native American
origin.
Cystine (choice C), struvite (choice D), and uric acid (choice E) stones are found in the
urinary tract, not the gall bladder.
A 15-year-old girl is evaluated for failure to begin menstruation. Physical examination demonstrates
short stature and a webbed neck. Chromosomal analysis demonstrates a lack of one X chromosome.
This patient should be specifically evaluated for which of the following cardiovascular
anomalies?
A. Coarctation of the aorta
B. Dextrocardia
C. Ostium primum septal defect
D. Pulmonary stenosis
E. Tetralogy of Fallot
Explanation:
The correct answer is A. The girl has Turner syndrome, which is specifically associated with
coarctation of the aorta. Even when coarctation has not been diagnosed in early childhood and
the patient appears to be doing well, surgical correction of any significant degree of
coarctation is recommended. Uncorrected coarctation can cause death after about age 40 due to a
variety of causes, including congestive heart failure, infective aortitis (analogous to
infective endocarditis), and hypertension-induced intracranial hemorrhage or rupture of the
damaged (pre-coarctation) aorta.
Associate dextrocardia (choice B) with Kartagener syndrome.
Associate ostium primum septal defect (choice C) with Down syndrome.
Pulmonary stenosis (choice D) and tetralogy of Fallot (choice E) are not specifically
associated with Turner syndrome.
A 66-year-old man with a long history of cigarette smoking and alcohol abuse has developed a protruding,
centrally ulcerated mass in his mouth, and he is concerned he has cancer. Which of the
following locations is most commonly the primary site of oral squamous cell carcinoma?
A. Base of tongue
B. Buccal mucosa
C. Floor of mouth
27
D. Palate
E. Tip of tongue
Explanation:
The correct answer is C. Oral cancers are highly associated with alcohol and tobacco use, and
HPV-16 (human papilloma virus type 16, which is also found in cervical carcinomas) is found in
nearly half of all oral cancers. The pattern of tumor development probably reflects exposurerelated factors. Oral cancers develop in the following locations (in order of decreasing
frequency): (1) floor of the mouth (choice C); (2) tip of the tongue (choice E); (3) hard
palate (choice D); (4) base of the tongue (choice A); and (5) others (choice B).
A 35-year-old woman dies suddenly. Autopsy findings are within normal limits except for the heart,
which is shown in the accompanying photograph. Which of the following is the most likely diagnosis?
A. Acute endocarditis
B. Calcification of the mitral anulus
C. Marantic endocarditis
D. Mitral valve prolapse
E. Rheumatic valvular disease
Explanation:
The correct answer is D. The floppy valve seen is characteristic of mitral valve prolapse. In this
still idiopathic condition, myxomatous degeneration of the zona fibrosa of the valve structurally
weakens the valve leaflets. The disorder has a female predominance, and a midsystolic click is
typically heard on auscultation. Most individuals are asymptomatic through life, but complications
can include infective endocarditis, valvular insufficiency, arrhythmias, and, rarely, sudden death
(as in this patient).
In acute endocarditis (choice A) valves typically show large vegetations.
Calcification of the mitral anulus (choice B) would appear as calcified nodules around the ring
surrounding the valve.
Marantic endocarditis (choice C) causes small, sterile vegetations along the line of closure of
the valve.
Rheumatic valvular disease (choice E) causes scarring of the valves with thickened, blunted
leaflets.
A 55-year-old female presents for an annual exam. Her right breast is swollen, red, and tender. The
physician palpates a firm area in the breast and suspects inflammatory breast cancer. Which of
the following best describes the histological changes observed in this disorder?
A. Acute inflammation in breast carcinoma
B. Chronic inflammation in breast carcinoma
C. Dermal lymphatic invasion by cancer cells
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D. Epidermal invasion by cancer cells
E. Fat necrosis in breast carcinoma
Explanation:
The correct answer is C. Inflammatory breast cancer is a pattern of invasive breast cancer in
which the neoplastic cells infiltrate widely through the breast tissue. The cancer involves
dermal lymphatics and therefore has a high incidence of systemic metastasis and a poor
prognosis. If the lymphatics become blocked, then the area of skin may develop lymphedema and
"peau d'orange," or orange peel appearance. The overlying skin in inflammatory breast cancer is
usually swollen, red, and tender.
Acute inflammation (choice A) is a rare finding in breast cancer and may be associated with
secondary infection or abscess.
Chronic inflammation in breast cancer (choice B) is a non-specific finding. In medullary breast
cancer, a type of invasive ductal carcinoma, there are a large number of lymphocytes around the
tumor and a desmoplastic reaction is often absent in the surrounding tissue. This type of
cancer carries a somewhat better prognosis.
Epidermal invasion by cancer cells (choice D) is a poor prognostic indicator. Intraepidermal
malignant cells are called Paget cells. Paget's disease of the nipple is a type of ductal
carcinoma that arises in large ducts and spreads intraepidermally to the skin of the nipple and
areola. There is usually an underlying ductal carcinoma.
Fat necrosis (choice E) is often seen following trauma to the breast, but is not specifically
associated with a particular type of breast cancer, although it may be confused with breast
cancer if areas of calcification are present.
An x-ray performed on a newborn infant shows enlargement of the left ventricle and left atrium as well
as dilatation of the aorta. Echocardiographic studies demonstrate volume-overloading of the
left ventricle. Cardiac auscultation reveals the presence of a continuous "machinery" murmur.
Which of the following is the most likely diagnosis?
A. Atrial septal defect
B. Patent ductus arteriosus
C. Pulmonic stenosis
D. Tetralogy of Fallot
E. Ventricular septal defect
Explanation:
The correct answer is B. Patent ductus arteriosus (PDA) is a congenital cardiac disorder in
which blood traveling in the aorta is shunted through the ductus arteriosus to the pulmonary
arteries. On x-ray, the left ventricle and left atrium may be enlarged, and pulmonary
hypertension may be observed. PDA is characterized by a continuous "machinery" murmur on
auscultation. If the ductus is widely patent, pulmonary hypertension may eventually develop,
and the initially left-to-right shunt is reversed, sending deoxygenated blood through the
descending aorta, and producing cyanosis (Eisenmenger syndrome). Since the deoxygenated blood
enters the descending aorta, the toes can be cyanotic, but the fingers are generally not.
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In atrial septal defect (choice A), left-to-right shunting causes volume overloading of the
right ventricle, the increased flow across the pulmonic valve producing a midsystolic pulmonary
ejection murmur. The second heart sound is widely split. A diastolic murmur may also be heard,
reflecting increased flow from the right atrium into the right ventricle.
Pulmonic stenosis (choice C) typically produces a harsh systolic ejection murmur best heard at
the upper left sternal border, often preceded by a systolic ejection sound.
Tetralogy of Fallot (choice D) is a form of cyanotic congenital heart disease characterized by
ventricular septal defect, right ventricular outflow tract obstruction, an overriding aorta,
and right ventricular hypertrophy. The heart is often described as "boot-shaped" on chest xray.
A ventricular septal defect (choice E) would produce an initial left-to-right shunt,
characterized by a holosystolic murmur, and increased pulmonary vascularity on chest x-ray. A
mid-diastolic rumble may also be heard.
A patient with chronic pelvic pain undergoes a hysterectomy. The resected uterus is filled with nodules
composed of benign smooth muscle cells. Which of the following terms best describes these
nodules?
A. Angiosarcoma
B. Leiomyoma
C. Leiomyosarcoma
D. Rhabdomyoma
E. Rhabdomyosarcoma
Explanation:
The correct answer is B. The lesions are the very common leiomyomas of the uterus. The lesions,
if numerous or large, may cause chronic pelvic pain, and infertility or pregnancy complications
(if they intrude on the uterine cavity). Malignant transformation to leiomyosarcoma (choice C)
is rare (and some authors suggest it may not occur, with uterine leiomyosarcoma being a de novo
lesion).
Angiosarcomas (choice A) are malignant tumors of blood vessels.
Rhabdomyomas (choice D) and rhabdomyosarcomas (choice E) are benign and malignant tumors of
skeletal muscle, respectively.
A 35-year-old woman has had type 1 diabetes mellitus for 20 years. She is now developing advanced
disease with visual complaints, foot ulcers, and renal disease. Which of the following features
that might be seen on renal biopsy is most specific for diabetic glomerulosclerosis?
A. Mesangial IgA deposits
B. Necrotic epithelial cells in tubules
C. Nests of cells with abundant clear cytoplasm
D. Numerous neutrophils in tubules
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E. Ovoid, periodic acid-Schiff (PAS)-positive, hyaline masses
Explanation:
The correct answer is E. The most specific lesion of diabetic glomerulosclerosis for the
purposes of the USMLE is the Kimmelstiel-Wilson nodule. These are ovoid, hyaline, PAS-positive
structures found in the mesangial core at the edge of the glomerulus. Although this lesion is
the most distinctive (pathognomonic) for diabetes, it is not seen in all renal biopsies from
diabetic patients. Other changes that may be present include glomerular capillary basement
membrane thickening, diffuse glomerulosclerosis, hyaline thickening of arteriolar walls,
tubular atrophy, interstitial fibrosis, and PAS-positive capsular drops in the parietal layer
of Bowman capsule.
Mesangial IgA deposits (choice A) are a feature of Berger disease (IgA nephropathy).
Necrotic epithelial cells in tubules (choice B) are a feature of acute tubular necrosis.
Nests of cells with abundant clear cytoplasm (choice C) are a feature of renal cell carcinoma.
Numerous neutrophils in tubules (choice D) are a feature of acute pyelonephritis.
A 45-year-old G2P2 presents with a chief complaint of pelvic pain that is worse immediately before and
during her period. A bimanual exam and Pap smear are performed and are unremarkable. An
ultrasound of her pelvic organs is performed and shows non-focal thickening of the myometrium
with unremarkable ovaries. Which of the following is most likely to be the cause of this
patient's complaint?
A. Adenomyosis
B. Endometrial polyps
C. Endometritis
D. Leiomyoma
E. Mittelschmerz
Explanation:
The correct answer is A. Adenomyosis is characterized by the presence of endometrial glands
within the myometrium of the uterus in addition to their normal location in the endometrium.
These glands undergo cyclic changes with the menstrual cycle in response to the same stimuli as
the normal endometrial glands. The cause of adenomyosis is not known but this condition may be
found in up to 20% of uteruses. Grossly, it may be inapparent if it is limited to a small
focus, or it may cause expansion of the uterine wall and have a glassy appearance.
Microscopically, the aberrant glands must be separated from the endometrium by 2-3 mm to be
diagnostic. Clinically pain is caused by the glands breaking down and bleeding within the
confines of the myometrium. The ultrasound shows non-circumscribed thickening.
Endometrial polyps (choice B), if symptomatic, could cause bleeding but not pain. The Pap smear
may show a few shed polyp cells, while an ultrasound would detect an intra-cavity polyp. It
could also be clinically silent. An endometrial curettage is needed for diagnosis.
Endometritis (choice C) is an infection of the endometrium that may present with pain or
bleeding. Diagnosis is made by endometrial biopsy. A Pap smear might not sample high enough to
detect infection in the uterine cavity. There is no uterine wall thickening and a bimanual exam
31
may elicit some pain.
Leiomyoma (choice D), a benign smooth muscle tumor of the myometrium also referred to as a
fibroid, may be asymptomatic even when it reaches a large size. Submucosal leiomyomas may cause
bleeding and infertility. Other problems include urinary frequency due to bladder pressure.
Pain is rare but may happen if the leiomyoma infarcts. Fibroids are usually detected with
bimanual exam if they are large or protuberant, and they are seen on ultrasound as wellcircumscribed masses.
Mittelschmerz (choice E) refers to mid-cycle ovulatory pain associated with normal physiologic
ovulation from the ovary. There are no ultrasound or clinical findings.
A 54-year-old woman presents to the emergency department after a fall. Skeletal roentgenograms show no
fractures. Serum chemistry studies reveal that her aspartate aminotransferase (AST) is markedly
elevated, while her alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), and
alkaline phosphatase are all within normal limits. Disease of which of the following organs
would be most likely to cause this serum enzyme pattern?
A. Colon
B. Duodenum
C. Heart
D. Pancreas
E. Stomach
Explanation:
The correct answer is C. Myocardial infarction (MI) can cause AST elevation without
accompanying elevation of ALT or other liver enzymes. This is an important fact to remember
because it may be the first clue for heart disease in a patient who has an atypical
presentation of MI (as is common in women with MI). MI can be confirmed with measurement of the
MB fraction of creatine phosphokinase (CPK-MB).
Unfortunately, diseases of the tubular organs of the gastrointestinal tract, including colon
(choice A), duodenum (choice B), and stomach (choice E), do not produce distinctive serum
enzyme patterns.
Damage to the pancreas (choice D) is associated with elevated amylase levels.
An elderly woman living at a nursing home is brought to the emergency room in shock. The nursing home
staff is very upset and stresses that the patient was completely well yesterday, and had only
complained of "feeling a little ill" several hours before being brought in. Physical
examination reveals a tense abdomen with guarding. Which of the following is the most likely
etiology for this patient's condition?
A. Acute appendicitis
B. Acute cholecystitis with gall bladder rupture
C. Gastric rupture
D. Rupture of a diverticulum
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E. Rupture of an ovarian cyst
Explanation:
The correct answer is D. Rupture of a colonic diverticulum, with resulting fecal peritonitis,
is a catastrophic complication of diverticulosis, particularly in the elderly, with a mortality
rate near 50%. The rupture frequently involves a diverticulum that is not inflamed (or only
minimally inflamed) and consequently the rupture may be inapparent, at least initially. Shock
secondary to septicemia develops rapidly, however. Vigorous resuscitation may be required to
stabilize the patient sufficiently for emergency surgery to resect the distal colon and form a
colostomy (Hartmann's operation).
Acute appendicitis (choice A), acute cholecystitis with gall bladder rupture (choice B),
gastric rupture (choice C), and rupture of an ovarian cyst (choice E) are all uncommon in this
age group.
A 10-week-old apparently healthy infant is laid down for a nap. The mother sits in a rocking chair
nearby reading. At one point, she hears the baby make a single small cry, but she keeps reading
because the baby quiets quickly. Later, she gets up to check on the child, whom she finds
dead.Careful autopsy would be most likely to reveal which of the following cardiac findings?
A. Endocarditis
B. Failure of development of the endocardial cushion
C. Large interventricular septal defect
D. Mitral valve stenosis
E. Right ventricular hypertrophy
Explanation:
The correct answer is E. The baby is probably a victim of sudden infant death syndrome (SIDS).
The etiology remains unknown. Rare cases have been witnessed, and some of the SIDS babies give
a single small cry, as described in the question stem. Some of these babies were premature at
birth and some have upper respiratory infections in the preceding few days before death.
Findings at autopsy are subtle and may be absent. The cardiovascular system may show right
ventricular hypertrophy, which is possibly secondary to smooth muscle hypertrophy in small
pulmonary arteries, and possibly cardiac conduction system abnormalities. Other features
include brainstem gliosis (suggesting chronic hypoxia), extramedullary hematopoiesis, and
retained periadrenal brown fat.
A baby with endocarditis (choice A) would be very obviously ill.
A serious congenital heart defect, such as failure of development of the endocardial cushion
(choice B), large interventricular septal defect (choice C), or a mitral value stenosis (choice
D) would have been picked up in the comprehensive physical examination at the child's birth.
A woman with swelling of the oral mucosa and dry mouth is found to have intense destructive
inflammation
of the salivary glands and antibodies against the ribonucleoprotein La. Which of the following
clinical findings would most likely be associated with this syndrome?
A. Conjunctivitis
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B. Goiter
C. Hemolytic anemia
D. Proximal muscle weakness
E. Urethritis
Explanation:
The correct answer is A. The patient has Sjögren's syndrome, an autoimmune disease
characterized by dry eyes (keratoconjunctivitis) and a dry mouth (xerostomia) due to
destruction of the lacrimal and salivary glands. Sjögren's syndrome is also characterized by
autoantibody production. The most diagnostic autoantibodies are those against
ribonucleoproteins Ro (SS-A) and La (SS-B), although coexisting rheumatoid factor and lupus
antibodies are not uncommon.
Goiters (choice B) are not typical of Sjögren's syndrome. Although autoimmune thyroiditis is
associated with Sjögren's syndrome, ocular involvement is much more characteristic than thyroid
involvement.
Hemolytic anemia (choice C) is not characteristic of Sjögren's syndrome. Primary
autoantibodies, drugs, and systemic lupus erythematosus may be associated with hemolytic
anemia, but the findings of anti-La and inflammation of the salivary glands indicate that this
patient has Sjögren's syndrome.
Proximal muscle weakness (choice D), in association with autoantibodies, is expected in
polymyositis or dermatomyositis. Although polymyositis may occur in association with Sjögren's
syndrome, keratoconjunctivitis would be much more common than muscle weakness.
Urethritis (choice E) in autoimmune disease is typical of Reiter's syndrome, not Sjögren's
syndrome.
A 3-year-old child develops headaches and is brought to the family doctor. Funduscopic examination
reveals papilledema; one retina also shows a very vascular tumor. CT of the head demonstrates a
cystic tumor of the cerebellum. This child has a high likelihood of later developing which of
the following?
A. Berry aneurysm of the basilar system
B. Bilateral renal cell carcinoma
C. Cancer of a peripheral nerve
D. Choreiform movements related to decreased GABA and acetylcholine
E. Serum cholesterol of greater than 700 mg/dL
Explanation:
The correct answer is B. The disease is von Hippel-Landau disease, which is associated with a
deletion involving the VHL gene on chromosome 3 (3p). Affected individuals develop vascular
tumors (hemangioblastomas) of the retina, cerebellum, and/or medulla. Roughly half of the
affected individuals later develop multiple, bilateral renal cell carcinomas.
Berry aneurysms (choice A) are unrelated to hemangioblastomas, but are instead associated with
34
adult polycystic disease.
Peripheral nerve cancers (choice C) are a feature of von Recklinghausen's disease
(neurofibromatosis type I).
Choreiform movements, related to decreased GABA and acetylcholine (choice D), are a feature of
Huntington's disease.
Extremely high serum cholesterol (choice E) suggests the homozygous form of familial
hypercholesterolemia.
A 2-year-old child with leukemia develops nephrotic syndrome. Light microscopic studies are normal.
Electron microscopic studies demonstrate fusion of epithelial foot processes. The current
hypothesis for the pathogenesis of this change is that it is secondary to which of the
following?
A. Consumption of complement factors
B. IgG directed against basement membrane
C. Immune complex deposition
D. Lymphokine production by T cells
E. Mesangial IgA deposition
Explanation:
The correct answer is D. The child is suffering from minimal change or nil disease (lipoid
nephrosis), which has a peak incidence at 2-3 years of age. Minimal change disease can be
associated with food allergies, medications, or hematologic malignancies, or it can occur
idiopathically. The pathology does not appear to involve complement, immunoglobulins, or immune
complex deposition. Rather, an altered cell-mediated immunologic response with abnormal
secretion of lymphokines by T cells is thought to reduce the production of anions in the
glomerular basement membrane, thereby increasing the glomerular permeability to plasma albumin
through a reduction of electrostatic repulsion. The loss of anionic charges is also thought to
favor foot process fusion. Some authors have noted that other conditions associated with T-cell
abnormalities, such as Hodgkin's disease and T-cell lymphoma, are sometimes associated with
minimal change disease.
Consumption of complement factors (choice A) is observed in many conditions in which complement
activation occurs, for example, membranoproliferative glomerulonephritis.
IgG directed against renal and pulmonary basement membranes (choice B) is found in
Goodpasture's syndrome, a cause of rapidly progressive glomerulonephritis and hemoptysis.
Immune complex deposition (choice C) is associated with type III hypersensitivity reactions,
including postinfectious glomerulonephritis, lupus nephritis, Henoch-Schönlein purpura,
cryoglobulinemia, and bacterial endocarditis.
Mesangial IgA deposition (choice E) is associated with Berger's disease, or IgA nephropathy, a
cause of glomerulonephritis.
A 65-year-old man presents to a physician because of a palpable mass immediately below the left
clavicle. Biopsy of the mass demonstrates metastatic adenocarcinoma in a lymph node. Which of
the following organs should be most strongly suspected as containing the primary tumor?
35
A. Bladder
B. Large bowel
C. Liver
D. Pancreas
E. Stomach
Explanation:
The correct answer is E. The supraclavicular nodes (Virchow's node) can be involved early in
mediastinal and neck cancers. A palpable mass in the left node can also be the presenting
finding of gastric carcinoma, which is worth remembering when you cannot find the primary in
the lungs or neck.
Bladder cancer (choice A) typically presents with hematuria or urinary symptoms.
Colon cancer (choice B) typically presents with blood in stool or changes in bowel habits.
Primary liver cancer (choice C) and pancreatic cancer (choice D) unfortunately tend to be
clinically silent until well advanced.
A one month-old baby develops vomiting of increasing severity after feeding, eventually developing
"projectile" vomiting. The vomitus contains milk and mucus, but not bile. The baby also fails to
gain weight and becomes constipated. Physical examination performed after feeding demonstrates
visible waves of peristalsis travelling from left to right in the epigastrium. An olive-sized
mass can be felt lying deep to the edge of the right rectus abdominis when the stomach is empty.
Which of the following techniques would be most useful in correcting the baby's problem?
A. Barium enema
B. Duodenoduodenostomy
C. Gastric resection
D. Pyloromyotomy
E. Surgical reduction of volvulus
Explanation:
The correct answer is D. The history is classic for "congenital" pyloric stenosis, which
typically presents from 3 to 6 weeks of life. The mass felt is the hypertrophied pylorus. This
problem can be easily surgically corrected with pyloromyotomy, in which the pyloric muscle is
partially cut, relieving the obstruction.
Barium enema (choice A) is occasionally effective in reducing childhood intussusception, but
would not be of value in pyloric stenosis.
Duodenoduodenostomy (choice B) is used to correct congenital duodenal obstruction, but is not
required for congenital pyloric stenosis.
Gastric resection (choice C) would be completely unnecessary in this case.
36
Volvulus (choice E) usually involves the small intestine and can produce an "acute abdomen"
secondary to infarction of the bowel.
A 14-year-old boy presents with a 1-month history of knee pain and a 6-pound weight loss. He is pale and
afebrile. An x-ray reveals a densely sclerotic lesion in the distal femur extending from the
growth plate into the diaphysis. The periosteum is lifted, forming an angle with the cortex. The
surrounding soft tissue resembles a "sunburst" on the radiograph. Which of the following is the
most likely diagnosis?
A. Nonossifying fibroma
B. Osteochondroma
C. Osteomyelitis
D. Osteosarcoma
E. Paget's disease
Explanation:
The correct answer is D. This patient has osteosarcoma, a malignant bone tumor that produces
osteoid and bone. Prognosis is poor. X-ray reveals bone destruction, soft tissue with
"sunburst" appearance, and Codman's triangle (periosteal elevation that forms an angle with the
cortex of the bone)—all classic clues to the diagnosis. Other hints were the patient's
weight loss and pallor, which should have raised your suspicion that a malignancy existed.
Choice D is the only malignant process among the answer choices. This tumor usually occurs in
the second or third decades of life. At the same time, it is the most common bone tumor in the
elderly and is often associated with Paget's disease (choice E). Histological findings classic
for osteosarcoma are anaplastic cells with osteoid (a pink amorphous material that is variably
mineralized).
Nonossifying fibroma (choice A) is also known as fibrous cortical defect. It is a common
developmental abnormality seen in the bones of the lower extremities of children. They are nonneoplastic lesions of bone cortex that are composed of fibrous connective tissue and that
usually resolve spontaneously. X-ray reveals irregular, well-demarcated radiolucent defects in
the bony cortex with an intact subperiosteal shell of bone. In the metaphysis, there are whorls
of connective tissue. These fibromas do not cross the epiphyses of bone, which distinguishes
them from giant cell tumors of bone.
Osteochondromas (choice B) are hereditary multiple exostoses (bony metaphyseal projections
capped with cartilage) that may be asymptomatic or may produce deformity and compromise the
blood supply of bone. Five percent of them progress to sarcomas. If a patient presents with
exostoses, sebaceous cysts, dermoid tumors, and colonic polyps, the likely diagnosis is
Gardner's syndrome.
Osteomyelitis (choice C) usually produces fever, localized pain, erythema, and swelling. The
patient in question is afebrile, which decreases the likelihood of this diagnosis. Though x-ray
may show periosteal elevation, more specific findings would be expected in a patient with this
condition, such as sequestrum (necrotic bone fragment), involucrum (new bone that surrounds the
area of inflammation), and Brodie's abscess (localized abscess formation in the bone).
Paget's disease (choice E), also known as osteitis deformans, is due to excessive bone
resorption with replacement by soft, poorly mineralized matrix (osteoid) in a disorganized
array. It generally affects the skull, pelvis, femur, and vertebrae. Skull involvement might
37
produce deafness by impinging on the cranial nerves. Malignant transformation to osteosarcoma
is seen in 1% of cases. X-ray reveals enlarged, radiolucent bones. Lab tests reveal extremely
elevated alkaline phosphatase. If you are given a patient over 40 with bone fracture, hearing
loss, and increased alkaline phosphatase, suspect Paget's disease. Note that this disease
rarely occurs in the young and could have been ruled out as a possible answer by virtue of the
patient's age.
A 38-year-old woman with multiple sclerosis (MS) has stable neurologic deficits resulting from old
demyelinated plaques. Which of the following histopathologic features would be prominent in
this patient's old plaques?
A. Complete loss of axons
B. Gliosis
C. Histiocytic infiltration
D. Lymphocytic infiltration
E. Myelin breakdown
Explanation:
The correct answer is B. Demyelinating plaques in MS mature through an orderly sequence of
events. Acute plaques show dense lymphohistiocytic infiltration and active digestion of myelin
byproducts. These features tend to disappear as plaques age. As inflammatory infiltration and
myelin breakdown abate, hyperplasia and hypertrophy of astrocytes transform the plaque into a
gliotic area, in which axons are relatively preserved but oligodendroglial cells are greatly
diminished. The term gliosis indicates proliferation of glial cells and is usually used as a
synonym of astrocytosis. Astrocytosis occurs as a nonspecific reaction to any damage to the
CNS, e.g., loss of neurons following hypoxic injury, inflammation due to infectious agents, and
neoplastic invasion. Hypertrophic astrocytes acquire abundant eosinophilic cytoplasm and are
known as gemistocytes.
Loss of axons occurs in MS plaques to some degree but is never complete (choice A). In fact,
axons can be remarkably spared, and loss of function in MS is thought to result from impaired
conduction along entirely denuded or incompletely remyelinated nerve fibers.
Histiocytic and lymphocytic infiltration (choices C and D) are prominent in the acute stage of
myelin destruction. Lymphocytes belong to both CD4 (helper lymphocytes) and CD8 (cytotoxic
lymphocytes) subgroups and are key players in MS immune-mediated pathogenesis. Histiocytes act
not only as scavengers that digest myelin debris, but also as important antigen-presenting
cells. As the acute stage of myelin destruction resolves, lymphocytes and histiocytes fade
away. Evidence of myelin breakdown (choice E), therefore, is minimal or absent in chronic
stages.
A patient who is being treated for leukemia develops unilateral flank pain. Radiologic studies
demonstrate a dilated renal pelvis and dilation of the upper one-third of the corresponding
ureter. A stone with which of the following compositions is most likely causing this patient's
problems?
A. Calcium salts
B. Cholesterol
C. Cystine
38
D. Struvite
E. Uric acid
Explanation:
The correct answer is E. Patients prone to develop uric acid stones include those with gout,
leukemia (particularly during chemotherapy, which releases large amounts of nucleic acids from
dying leukemia cells), and acidic urine.
Calcium-containing stones (choice A) are the most common kind in the general population.
Cholesterol stones (choice B) are found in the gall bladder.
Cystine stones (choice C) are a rare form of renal stone seen in patients with cystinuria.
Struvite (magnesium-ammonium phosphate) stones (choice D) are known for producing massive
staghorn stones that fill the renal pelvis.
A 5-year-old girl is thoroughly evaluated because of growth failure. The child has been complaining of
headaches, which are exacerbated when she tries to read. Funduscopic examination reveals
papilledema. CT scan demonstrates a mass involving the area above and within the sella turcica.
Surgical resection of the mass yields a multiloculated cystic and solid tumor containing dark
brown, oily fluid.This tumor is thought to arise from epithelial rests derived from which of the
following structures?
A. Hypothalamus
B. Pineal gland
C. Posterior pituitary gland
D. Rathke's pouch
E. Superior colliculus
Explanation:
The correct answer is D. The tumor described is a craniopharyngioma, which is one of the more
common brain tumors of children. These tumors arise from epithelial rests derived from Rathke's
pouch, which is an oral invagination that gives rise to the cells that form the anterior
pituitary gland. Histologically, craniopharyngiomas can resemble ameloblastomas, which are
tumors derived from dental epithelium.
Note that this question could also have been answered very simply by noting that the
hypothalamus, pineal gland, pituitary gland, and the superior colliculus are all adult
structures; only Rathke's pouch is an embryonic structure. Therefore, only Rathke's pouch could
be the source of epithelial rests, which are remnants of embryonic tissues that persist in the
adult.
While craniopharyngiomas often occur in close proximity to the hypothalamus (choice A) and
posterior portion of the pituitary gland (choice C), they do not arise from neural tissue.
The pineal gland (choice B) and superior colliculus (choice E) are found on the posterior
aspect of the brain stem.
39
A 15-year-old patient is taken to a physician because of severe episodic headaches, accompanied by
perspiration and palpitations. The patient is experiencing a headache at the time of the
examination and his blood pressure is 175/125 mm Hg with regular heart rate of 90. Treatment
with phenoxybenzamine relieves his symptoms. Which of the following studies would be most
helpful for establishing the likely diagnosis?
A. Serum albumin
B. Serum beta-hCG
C. Serum carcinoembryonic antigen (CEA)
D. Urinary Bence-Jones proteins
E. Urinary vanillylmandelic acid (VMA)
Explanation:
The correct answer is E. The suspected tumor is pheochromocytoma, 10% of which occur in
children. The symptoms (paroxysmal hypertension, palpitations, anxiety) are produced when the
tumor secretes epinephrine, norepinephrine, and other vasoactive amines into the circulation.
The diagnosis can be established with plasma catecholamine concentrations or concentrations of
the norepinephrine metabolite VMA in a 24-hour urine. The latter offers the advantage of
providing a longer time sample so that the intermittent secretion is more likely to be picked
up.
Serum albumin (choice A) can be low in liver and renal disease, but is unaffected in
pheochromocytoma.
beta-hCG (choice B) is a marker for choriocarcinoma and related lesions.
CEA (choice C) is a nonspecific marker that is positive in many cases of colorectal and
pancreatic cancer. Bence-Jones proteins (choice D) are a marker for multiple myeloma, representing
urinary excretion of myeloma light chains.
A 44-year-old man goes to his physician for an employment physical examination. The clinician notices
that the patient's fingers are clubbed. He also demonstrates tenderness over the distal ends of the
radius, ulna,and fibula. This patient should be explicitly evaluated to exclude which of the following?
A. Gastrointestinal cancer
B. Liver cancer
C. Lung cancer
D. Renal cancer
E. Testicular cancer
Explanation:
The correct answer is C. This patient has the finger clubbing and hypertrophic pulmonary
osteoarthropathy that can be associated with bronchogenic carcinoma (other than squamous cell
carcinoma), benign mesothelioma, and diaphragmatic neurilemmoma. X-ray of the bones generally
shows formation of new periosteal bone; arthritis may be present. The etiology of these changes
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remains a mystery. An alert clinician may identify a cancer at an earlier, potentially curable
stage by investigating a possible paraneoplastic syndrome.
After four days, a neonate has not passed meconium, and begins vomiting. Physical examination reveals
abdominal distension. Which of the following is the correct diagnosis?
A. Hirschsprung's disease
B. Meckel's diverticulum
C. Omphalocele
D. Renal agenesis
E. Tracheoesophageal fistula
Explanation:
The correct answer is A. The neonate is suffering from Hirschsprung's disease, which is caused
by an absence of ganglion cells in both the submucosal and the inter-myenteric plexus of a
segment of bowel. The aganglionic bowel segment is narrowed because the lack of peristalsis
keeps stool from moving into that segment. The distal rectum is always involved, but the lesion
extends proximally anywhere from a few centimeters all the way to the small intestine. The
bowel proximal to the lesion is usually dilated. Treatment is by surgical removal of the
affected segment.
A Meckel's diverticulum (choice B) is a small, usually asymptomatic pouch located near the
ileocecal valve.
An omphalocele (choice C) would present with an obvious sac filled with intestines at the site
of a defect in the ventral abdominal wall.
Renal agenesis (choice D) would present with failure to pass urine.
Tracheoesophageal fistula (choice E) would present with aspiration during feeding.
A 15-year-old male experiences sporadic episodes of severe muscle weakness. He has noticed that the
episodes occur after severe exercise and after large meals rich in carbohydrates. The patient
has also had nighttime attacks, from which he awoke nearly paralyzed. He notes that similar
problems have occurred in his father and brother. Serum chemistries performed during one of the
patient's attacks would most likely demonstrate which of the following?
A. Decreased bicarbonate
B. Decreased calcium
C. Decreased potassium
D. Increased glucose
E. Increased sodium
Explanation:
The correct answer is C. This is a classic presentation of the rare condition known as
hypokalemic periodic paralysis. There is often a family history suggesting autosomal dominant
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inheritance. Symptoms tend to appear late in the first decade or in the second decade of life
(when physical education instructors or other kids may criticize the child for being weak). In
addition to the triggers listed in the question stem, other precipitating factors include
tension, anxiety, and a habitual high-salt diet. The condition may be difficult to demonstrate,
since serum chemistries are normal between attacks. Muscle biopsy may demonstrate vacuolation
or damage to myofibrils. The pathophysiology of this condition was previously poorly
understood, but recent advances suggest that the primary defect is in calcium channels.
Treatment is with potassium supplementation during acute attacks, and prophylactic
acetazolamide, triamterene, amiloride or spironolactone.
Decreased serum bicarbonate (choice A) is a characteristic of metabolic acidosis.
Hypocalcemia (choice B) can cause muscle weakness (and more seriously, cardiac arrhythmias),
but this patient's history suggests a specific alternative etiology. Although calcium channels
may be involved in this disorder, the serum calcium level is generally normal.
Increased serum glucose (choice D) is seen in diabetes mellitus, not hypokalemic periodic
paralysis.
Hypernatremia (choice E) is usually caused by a failure to replace water lost from the body,
due to an inability to obtain or drink water, or rarely, by primary disorders of the thirst
mechanism or excessive ingestion of sodium.
A 50-year-old woman presents to her physician with fatigue and a 30 lb weight loss. A peripheral smear
and bone marrow biopsy demonstrate a leukemia composed of cells in the neutrophil, eosinophil,
and basophil lineages. No blast forms are seen. Which of the following is associated with this
leukemia?
A. bcl-2 activation
B. c-myc activation
C. t(8, 14)
D. t(9, 22)
E. t(14,18)
Explanation:
The correct answer is D. The disease is chronic myelogenous leukemia (CML), which usually
affects adults between 40 and 59 years of age. CML is associated with the Philadelphia
chromosome, which is actually a translocation involving chromosomes 9 and 22 that produces an
abl-bcr hybrid.
bcl-2 activation (choice A) and a t(14,18) (choice E) translocation are features of follicular
lymphomas.
c-myc activation (choice B) and a t(8,14) (choice C) translocation are features of Burkitt's
lymphoma.
Which of the following is the most frequent primary malignant tumor of the CNS?
A. Glioblastoma multiforme
B. Medulloblastoma
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C. Meningioma
D. Oligodendroglioma
E. Pituitary adenoma
Explanation:
The correct answer is A. Glioblastoma multiforme (GBM) is the most frequent primary malignant
tumor of the CNS. It usually affects middle-aged or elderly patients and most frequently arises
in the cerebral white matter. GBM is a malignant astrocytoma; it is referred to as grade IV
astrocytoma in the WHO classification and grade 4 astrocytoma in the St. Anne-Mayo grading
system. This tumor is very aggressive; median survival is approximately 12-14 months following
optimal treatment, ie, a combination of surgery and radiation therapy.
Medulloblastoma (choice B), a much less frequent malignant tumor, affects children; it arises
in the posterior fossa in this population. The histogenetic origin of this tumor is uncertain,
although it is thought to develop from immature cell precursors that give rise to glial and
neuronal cells.
Meningioma (choice C) and pituitary adenoma (choice E) are frequent but benign brain tumors
that arise from meningothelial cells and endocrine cells of the adenohypophysis, respectively.
Oligodendrogliomas (choice D) constitute 5% of all primary brain tumors. Although most
oligodendrogliomas have benign histologic features (e.g., low mitotic rate and mild nuclear
atypia), their complete surgical excision is virtually impossible owing to a diffuse, poorly
circumscribed pattern of growth. This tumor allows a much longer survival (up to 7-10 years)
than GBM, but eventually transforms into a malignant glioma indistinguishable from GBM.