1

A homeless man is brought in to the emergency room by the police after they observe him staggering down
the street in a disoriented state. He appears malnourished and smells like wine. The edge of
the liver is difficult to palpate, but feels nodular to the examiner. Also noted on physical
examination are multiple bruises, and a new bruise is produced by the blood pressure cuff.
Ocular examination reveals horizontal nystagmus on lateral gaze, and bilateral lateral rectus
palsies. Deficiency of which of the following vitamins is most likely responsible for the
neurological problems observed in this patient?

A. Folate

B. Thiamine

C. Vitamin B12

D. Vitamin C

E. Vitamin K

Explanation:

The correct answer is B. This is an example of Wernicke-Korsakoff syndrome, which is caused by

thiamine deficiency, usually secondary to chronic alcohol abuse. The acute symptoms are
referred to as Wernicke's encephalopathy and include confusion, ataxia, vestibular dysfunction,
sluggish pupillary light reflexes, anisocoria, and oculomotor dysfunction (the lateral rectus
palsies are caused by abducens nerve lesions). If untreated, chronic symptoms including
anterograde amnesia and confabulation may occur (Korsakoff's syndrome).

Deficiency of folate (choice A) can cause megaloblastic anemia, but is not usually associated
with neurological problems, with the possible exception of neuropathies.

Lack of vitamin B12 (choice C) could cause megaloblastic anemia and spinal cord damage,
producing ataxia, but would not produce the cranial nerve deficits observed in this individual.

Coexistent vitamin C (choice D) deficiency may be present in alcoholics, and contributes to

easy bruising because of small vessel fragility caused by poor collagen formation around small
blood vessels.
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Alcoholic patients with hepatic cirrhosis may have impaired ability to synthesize vitamin K
(choice E) dependent blood clotting factors, leading to increased bleeding and increased
prothrombin and partial thromboplastin times.

A 56-year-old male presents with complaints of gnawing pain in the midepigastrium, with occasional
radiation to the back. He also notes a 15 pound weight loss over the last 3 months. The
clinician suspects pancreatic carcinoma. Which of the following tumor markers would aid in
confirming this diagnosis?

A. AFP

B. CA-125

C. CEA

D. hCG

E. PSA

Explanation:

The correct answer is C. Tumor markers can be very helpful in narrowing the possible primary
sources for metastatic lesions. Carcinoembryonic antigen (CEA) can be seen in any tumor derived
from gut epithelium, notably colon cancer and pancreatic cancer. Tumor markers should not be
used as the primary tool for cancer diagnosis, but they have considerable utility in the
confirmation of the diagnosis, as well as for monitoring recurrence or response to therapy.

Alpha-fetoprotein (AFP; choice A) is seen in hepatocellular carcinoma, embryonal cell tumor of

the testis, and malignant teratoma.

CA-125 (choice B) is produced by ovarian cancer.

The beta subunit of human chorionic gonadotropin (hCG; choice D) is seen in choriocarcinoma,
hydatidiform mole, and germinoma.

Prostate-specific antigen (PSA; choice E) is seen in prostatic carcinoma.

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You should also remember that serum elevations of many of these markers can also be seen in
some benign conditions of similar tissues. HCG, for example, is elevated normally in pregnancy.

A patient has a lymphoproliferative disorder containing mature B cells that mark with weak kappa light
chain expression on the plasma membrane, strong CD5, strong CD23, and weak CD22. What is the
most likely diagnosis?

A. Chronic lymphocytic leukemia

B. Hairy cell leukemia

C. Non-Hodgkin's lymphoma

D. Prolymphocytic leukemia

E. Szary syndrome

Explanation:

The correct answer is A. The immunophenotype of chronic lymphocytic leukemia is distinctive

among clonal B-cell disorders. There is usually strong expression of both CD5 and CD23, and
weak expression of surface immunoglobulin (either kappa or lambda chain) and CD22.

In contrast, other disorders that contain mature B cells, such as hairy cell leukemia (choice
B), non-Hodgkin's lymphoma (choice C) (including follicular and mantle cell lymphomas), and
prolymphocytic leukemia (choice D), typically have strong expression of surface immunoglobulin
and CD22. There is usually absent expression of CD5 (may be seen in prolymphocytic leukemia and
some non-Hodgkin's lymphomas) and CD23 (may be seen in some non-Hodgkin's lymphomas).

Szary syndrome (choice E) is a form of T-cell lymphoma/leukemia.

A 70-year-old man comes to clinical attention with progressive memory loss, urinary incontinence, and
gait instability. MRI of the brain shows dilatation of the ventricular cavities, while the
cerebral cortex appears normal. No infarcts are seen. Repeated lumbar punctures reveal
occasional increases in cerebrospinal fluid (CSF) pressure. A biopsy of the frontal cortex
demonstrates the absence of neurofibrillary tangles and senile plaques. Which of the following
 4

is the most appropriate treatment?

A. Acetylcholinesterase inhibitors such as tacrine

B. Aspirin

C. L-DOPA

D. Ventricular shunt

E. Vitamin B1 (thiamine)

Explanation:

The correct answer is D. This is an "interdisciplinary" question, which begins with a clinical
scenario and ends by testing your knowledge of pathophysiology and pharmacology. The clinical
presentation has the classic triad of memory loss, urinary incontinence, and gait abnormalities
characteristic of normal pressure hydrocephalus (recently renamed intermittently raised
pressure hydrocephalus). This condition results from intermittent increases in CSF pressure,
leading to progressive damage to cerebral white matter and dilatation of the ventricles. No
significant cortical atrophy is present. The lack of Alzheimer-related changes in the biopsy
and the measurements of CSF pressure support the diagnosis. Relief of CSF pressure can be
obtained by placing a ventricular shunt, which usually improves clinical symptomatology.

Tacrine and other inhibitors of acetylcholinesterase (choice A) are used in the symptomatic
therapy of Alzheimer disease. The pathology of this disease includes degeneration of cerebral
cholinergic systems, such as the basal nucleus of Meynert, which project to the neocortex and
are involved in memory and learning. Acetylcholinesterase degrades acetylcholine after release
from presynaptic boutons. Acetylcholinesterase inhibitors therefore enhance the concentration
of acetylcholine and amplify cholinergic neurotransmission.

Aspirin (choice B) is used to prevent aggregation and adhesion of platelets in patients with
risk factors for cerebrovascular disease. Prophylactic aspirin treatment lowers the incidence
of transient ischemic attacks and brain infarcts.

L-DOPA (choice C) is a precursor of dopamine, the neurotransmitter of the nigrostriatal neurons

that degenerate in Parkinson disease. L-DOPA, especially in combination with a peripheral
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decarboxylase inhibitor, is therefore used in the treatment of this disorder.

Vitamin B1(choice E) is used in the treatment of Wernicke encephalopathy, which is caused by

thiamine deficiency. If untreated, Wernicke encephalopathy progresses to Korsakoff syndrome,
characterized by memory loss, confusion, and confabulation.

An immigrant from Brazil presents with difficulty swallowing, and is referred to a gastroenterologist
for evaluation of his dysphagia. Special studies demonstrate massive dilatation of the
esophagus. Which of the following other organs may also be seriously affected by the patient's
disease?

A. Bladder

B. Brain

C. Heart

D. Lungs

E. Small intestine

Explanation:

The correct answer is C. The disease is Chagas' disease, which is due to the intracellular
protozoan parasite, Trypanosoma cruzi. Chagas' disease is an important cause of cardiac failure
in some Latin American countries, and Brazilian cases can be associated with megaesophagus and
megacolon.

Involvement of other organs including bladder (choice A), brain (choice B), lungs (choice D)
and small intestine (choice E) is usually not clinically significant.

A 65-year-old man develops increased frequency of urination, nocturia, dysuria, and difficulty starting
and stopping the flow of urine. Serum prostate-specific antigen (PSA) is within normal limits,
and prostate biopsy demonstrates benign tissue. In which of the following sites is the patient's
lesion most likely located?

A. Bladder neck
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B. Penile urethra

C. Periurethral prostate

D. Posterior prostate

E. Ureters

Explanation:

The correct answer is C. The man most likely has benign prostatic hyperplasia, which is thought
to be related to the growth-promoting effects of dihydrotestosterone (DHT). This is possibly
coupled with an age-related increase in estradiol, which may potentiate the action of DHT on
the prostate. The growth characteristically involves the periurethral prostate. In contrast,
prostatic carcinoma (which, if extensive, would elevate the PSA) characteristically involves
the posterior lobe of the prostate (choice D).

Stones and tumors can also involve the bladder neck (choice A), causing difficulty in
urination, but these are less common than benign prostatic hypertrophy.

Lesions of the penile urethra (choice B) can cause dysuria, but do not usually cause difficulty
stopping and starting urine flow.

Lesions of the ureters (choice E) can cause renal failure, but would not cause difficulties
with urination.

An elderly patient dies with chronic dementia. At autopsy, the brain shows diffuse cortical atrophy with
relative sparing of primary motor and sensory areas. Which of the following would most likely
be a prominent feature on microscopic examination of her brain tissue?

A. Central chromatolysis

B. Lewy bodies

C. Gliosis of the caudate nucleus

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D. Loss of pigmented neurons

E. Neurofibrillary tangles

Explanation:

The correct answer is E. The clinical history and gross pathology suggest Alzheimer's disease.
Neurofibrillary tangles and senile plaques are found primarily in higher order association
cortex. Other microscopic features of Alzheimer's disease include granulovacuolar degeneration
and, sometimes, Hirano bodies.

Central chromatolysis (choice A) is a loss of histological staining seen in lower motor neurons
whose axons have been damaged, for example by injury to the ventral roots.

Gliosis of the caudate nucleus (choice C) is a feature of Huntington's disease, and certain
other degenerative diseases of the basal ganglia.

Lewy bodies (choice B) (eosinophilic intracytoplasmic spherules) and loss of pigmented neurons
(choice D) in the substantia nigra are features of Parkinson's disease.

A patient has severe arthritis involving the lower back. Before making a diagnosis of ankylosing
spondylitis, the patient should be questioned about which of the following diseases?

A. Carcinoid syndrome

B. Celiac disease

C. Crohn's disease

D. Peptic ulcer

E. Whipple's disease

Explanation:

The correct answer is C. 10-20% of patients with Crohn's disease and ulcerative colitis
develop an arthritis that resembles ankylosing spondylitis. Similar arthropathies are seen in
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psoriasis, Reiter's syndrome (arthritis, urethritis, conjunctivitis, and rash following

chlamydial infection, and related syndromes seen following Shigella, Salmonella, or Yersinia
enterocolitis). The other answers are distracters.

A child develops a tumor of the cerebellum. Biopsy reveals evidence of both neuronal and glial
differentiation. Which of the following is the most likely diagnosis?

A. Astrocytoma

B. Glioblastoma multiforme

C. Medulloblastoma

D. Meningioma

E. Oligodendroglioma

Explanation:

The correct answer is C. Medulloblastoma is the only tumor on the list characterized by both
neuronal and glial differentiation. This tumor tends to form gray-white masses in the
cerebellum of children and in the cerebral hemispheres of adults. Histologically, the tumor
forms sheets of densely packed, poorly differentiated small cells. Occasional cells show
spindle cell morphology and stain for the glial marker glial fibrillary acidic protein (GFAP).
Other occasional cells show neuronal differentiation and form rosettes. The tumor has a 50% 10-
year survival rate when treated with combined surgery and radiation.

Astrocytoma (choice A), glioblastoma multiforme (choice B), and oligodendroglioma (choice C)
are pure glial tumors.

Meningioma (choice D) is a tumor of the meninges.

A concerned mother brings her 6-year-old son to the pediatrician because he has developed a "puffy
face." On examination, the child has a blood pressure of 90/60, marked periorbital edema, and
pitting edema of both the hands and feet. His cardiac exam is unremarkable and he has no
splenomegaly or signs of liver disease. Laboratory values are notable for decreased serum
albumin and increased total cholesterol. A urinalysis reveals 4+ proteinuria but no red blood
 9

cells, white blood cells, or casts. The most likely cause of this child's disease is

A. Goodpasture's syndrome

B. minimal change nephropathy

C. poststreptococcal glomerulonephritis

D. systemic lupus erythematosus

E. Wegener's granulomatosis

Explanation:

The correct answer is B. This boy has nephrotic syndrome: edema, heavy proteinuria with a
benign urinary sediment, hypoalbuminemia, and hypercholesterolemia. Of the choices listed, only
minimal change nephropathy is a recognized cause of nephrotic syndrome. It is the most common
cause of nephrotic syndrome in children.

All the other choices are not consistent with the clinical history and are causes of nephritis,
not nephrosis. Remember that nephritic patients present with hypertension, moderate
proteinuria, hematuria, and an active urinary sediment with red blood cell casts.

A 30 year-old man comes to medical attention because of fevers and night sweats. CT scan reveals masses
involving the mediastinal nodes, abdominal nodes, and liver. Biopsy of one of the nodes
demonstrates a nodular lymphoma with nodular areas composed predominately of small (6-12
micrometer) lymphocytes with scanty cytoplasm and irregular, twisted, and indented nuclei. This
lymphoma is most closely linked to a translocation involving which of the following?

A. Immunoglobulin heavy chain and bcl-1

B. Immunoglobulin heavy chain and bcl-2

C. Immunoglobulin heavy chain and myc

D. Kappa immunoglobulin light chain and myc

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E. Lambda immunoglobulin light chain and myc

Explanation:

The correct answer is B. The lymphoma described in the question stem is the follicular type of
small cleaved cell (B cell) lymphoma, and its characteristic translocation is t(14;18)
(q32;q21). The site on chromosome 14 involves the heavy chain of immunoglobulins (IgH), while
that on chromosome 18 involves the bcl-2 oncogene. The translocation produces a hybrid
bcl-2/immunoglobulin heavy-chain transcript.

A t(11,14)(q13;q32) translocation involving bcl-1 and IgH (choice A) is seen in small non-
cleaved lymphocytic lymphoma, myeloma, and some mantle cell lymphomas.

Burkitt's lymphoma is usually associated with t(8;14) (myc and IgH; choice C), but sometimes
with t(2;8) (kappa immunoglobulin light chain and myc; choice D) or t(8;22) (lambda
immunoglobulin light chain and myc; choice E).

A baby is born with a testicular mass. Histologic sections made of the homogeneous yellow-white mass
after its removal demonstrate epithelial-lined spaces that have flattened-to-cuboidal epithelial
cells with vacuolated cytoplasm containing eosinophilic, hyaline-like globules. Scattered
structures resembling primitive glomeruli (endodermal sinuses) are also seen. If appropriate
immunohistochemical stains are performed, the eosinophilic cytoplasmic globules would most
likely contain which of the following?

A. Alpha-fetoprotein

B. Estrogen receptors

C. Human chorionic gonadotropin

D. Human papilloma virus

E. Melanin

Explanation:

The correct answer is A. The malignant tumor is a yolk sac tumor, also known as infantile
 11

embryonal carcinoma and endodermal sinus tumor. The biggest tip-off in the question stem is the
presence of endodermal sinuses that resemble primitive glomeruli. The cytoplasmic globules
described contain alpha-fetoprotein, indicating yolk cell differentiation, and alpha-1-
antitrypsin. Alpha-fetoprotein can also be used as a serum marker for recurrent disease. Yolk
sac tumors occur in pure form in infants and children and may be part of mixed tumors in
adults.

Estrogen receptors (choice B) are important markers in breast cancer because they predict tumor
response to hormonal manipulation.

Human chorionic gonadotropin (choice C) is found in the syncytial cells of embryonal carcinoma.

Human papilloma virus (choice D) can be found in condylomas, cervical cancer, penile cancer,
laryngeal polyps, and warts.

Melanin (choice E) can be found in melanomas.

Physical examination of a 45-year-old diabetic patient demonstrates a pulsatile abdominal mass.

Radiographic studies demonstrate a 10 cm diameter aneurysm of the abdominal aorta with foci of
calcification in the walls. Which of the following is the most likely etiology for this
aneurysm?

A. Atherosclerosis

B. Congenital weakness

C. Cystic medial necrosis

D. Syphilis

E. Vasculitis

Explanation:

The correct answer is A. This is a typical presentation of an abdominal aortic aneurysm, which
is almost always due to severe atherosclerosis. The foci of calcification described occur
within the atherosclerotic plaques, and indicate severe atherosclerotic disease.
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Congenital weakness of vessels (choice B) can produce berry aneurysms, especially in cerebral
vessels in the circle of Willis.

Cystic medial necrosis (choice C) can produce dissecting aneurysms, especially in Marfan's
syndrome.

Syphilitic aneurysms (choice D) typically involve the aortic root as it leaves the heart.

Vasculitis (choice E) can produce aneurysms in small arteries.

A nontender, enlarged lymph node develops in the neck of a 17-year-old girl. On biopsy, the lymph node
shows a diffuse effacement of its architecture, with presence of fibrous bands creating a
nodular pattern. Numerous lacunar cells and scattered Reed-Sternberg cells are present among a
mixed population of lymphocytes, eosinophils, macrophages, and plasma cells. Which of the
following is the most likely diagnosis?

A. Diffuse large cell lymphoma

B. Hodgkin disease, lymphocyte depletion

C. Hodgkin disease, lymphocyte predominance

D. Hodgkin disease, mixed cellularity

E. Hodgkin disease, nodular sclerosis

Explanation:

The correct answer is E. The presence of Reed-Sternberg (RS) cells is pathognomonic of Hodgkin
disease (HD). After long debate, RS cells have been recognized as the true neoplastic elements
of HD. A classic RS cell is a giant, usually binucleated cell, with large "inclusion-like"
nucleoli. The nuclei are similar to each other, giving the impression of mirror images. Classic
RS cells and lacunar cells are probably transformed B lymphocytes and are positive for CD15 and
CD30. Variants of RS cells are found in different subtypes of HD. Lacunar cells are
mononucleated and surrounded by a pericellular halo. The lymphohistiocytic (L+H) cell is a
variant of RS cell with a characteristic convoluted nucleus resembling a popcorn kernel
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("popcorn cell"). The nodular sclerosis subtype affects adolescents and young adults.
Histologically, it is characterized by the lacunar cell variant and the presence of broad bands
of fibrous tissue that divide the lymph node into nodules. Nodular sclerosis HD has an
excellent prognosis.

Lymphocyte depletion HD (choice B) is rare and controversial. Most cases are large cell
lymphomas, affecting older males with disseminated disease.

Lymphocyte predominance HD (choice C) accounts for 6% of all cases. This subtype is

characterized by the L+H variant of the RS cell. The cells are CD15- and CD30-, but CD20+. This
lymphoma is of follicular B-cell origin and mostly affects young males with cervical
lymphadenopathy.

The mixed cellularity (choice D) form of HD is characterized by frequent RS cells. There is a

biphasic incidence curve, with peaks affecting young adults and those older than 55. This
lymphoma presents at advanced stages.

Diffuse large cell lymphoma (choice A) is an aggressive B-cell lymphoma that represents 20% of
non-Hodgkin lymphomas. It affects older people. Neoplastic lymphocytes are large, with
prominent nucleoli. The histopathologic and clinical features of this case clearly rule out
this form of lymphoma.

A young adult has progressive intellectual deterioration, weakness, ataxia, and seizures. Reference
laboratory tests demonstrate an abnormality of an important mitochondrial enzyme. From which of
the following diseases is this person most likely suffering?

A. Adrenoleukodystrophy

B. Central pontine myelinolysis

C. Krabbe's disease

D. Leigh's disease

E. Metachromatic leukodystrophy

Explanation:
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The correct answer is D. Leigh's disease, also known as subacute necrotizing

encephalomyelopathy, is a very rare disease that most physicians will never encounter in real
life. However, it may show up on the USMLE because it is one of the few examples of diseases
involving defects in the mitochondrial DNA rather than the chromosomal DNA. The specific
defective enzyme, in at least some cases, is cytochrome oxidase, one of the components of the
electron transport system. Muscle and brain are particularly affected. Patients have the
presentation described in the question and typically die within several years.

Adrenoleukodystrophy (choice A) is an X-linked disease with abnormal lipid metabolism leading

to demyelination in the CNS.

Central pontine myelinolysis (choice B) is characterized by demyelination of the pons

(especially the basis pontis) seen after overlying rapid correction of hyponatremia.

Krabbe's disease (choice C) is an autosomal recessive accumulation of cerebrosides in

histiocytes in the CNS.

Metachromatic leukodystrophy (choice E) is an autosomal recessive accumulation of sphingolipids

in the CNS and elsewhere.

A 6-month-old child with sickle cell anemia has a chronically enlarged spleen. By 5 years of age, the
child's spleen is no longer palpable. The decrease in size is most likely related to which of
the following?

A. Chronic infection

B. Hodgkin's lymphoma

C. Infarctions

D. Non-Hodgkin's lymphoma

E. Portal hypertension

Explanation:
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The correct answer is C. Early in sickle cell anemia, affected children usually have an
enlarged spleen. The spleen enlarges because the children are in a state of hypersplenism, in
which the spleen vigorously phagocytizes any abnormally shaped erythrocytes. During the first
decade of life, sickling within the spleen occludes its blood flow, causing repeated small
infarctions, leading to "autosplenectomy." The autosplenectomy is actually helpful to the
patient hematologically, as it may ameliorate the chronic anemia. Unfortunately, the lack of a
functional spleen renders the patients susceptible to infections with Salmonella and
encapsulated organisms such as Streptococcus pneumoniae and Haemophilus influenzae.

Patients with sickle cell anemia are not particularly vulnerable to chronic infection (choice
A), although acute infections can trigger painful crises.

Patients with sickle cell anemia do not have an increased incidence of either Hodgkin's disease
(choice B) or non-Hodgkin's lymphoma (choice D).

Portal hypertension (choice E) causes an enlarged, rather than a small, spleen.

A 2-week-old child shows difficulty feeding, somnolence, failure to thrive, and constipation. An alert
pediatrician orders blood studies that demonstrate low T4 and high TSH. If appropriate therapy
is not promptly instituted, which of the following complications would most likely occur?

A. Bronchiectasis

B. Gigantism

C. Hepatic cirrhosis

D. Mental retardation

E. Renal failure

Explanation:

The correct answer is D. The disease is infantile hypothyroidism, which can produce the
syndrome of cretinism if left untreated. Early manifestations include those listed in the
question stem. Later manifestations of untreated disease include impaired skeletal growth,
protruding abdomen, dry skin, and, most seriously, neurologic problems that typically include
 16

deaf-mutism, spasticity, and profound mental retardation. Many hospitals routinely screen
neonates for hypothyroidism and institute appropriate thyroid hormone replacement therapy
immediately if necessary, thereby preventing the many problems these children would otherwise
have.

Associate bronchiectasis (choice A) with the inherited childhood disease cystic fibrosis.

Associate gigantism (choice B) with pituitary tumors, which can be congenital.

Associate hepatic cirrhosis in childhood (choice C) with the inherited disease alpha-1-
antitrypsin deficiency.

Associate renal failure in infancy (choice E) with congenital anomalies and renal cystic
diseases.

Physical examination of a perimenopausal woman demonstrates bony swellings in the distal

interpharyngeal
joints; no inflammation is apparent. The proximal interphalangeal joints, hands, and wrists are
not involved, and the patient is asymptomatic. Which of the following processes is
etiologically related to these findings?

A. Autoantibody formation

B. Bacterial infection

C. Crystal deposition

D. Joint trauma

E. Viral infection

Explanation:

The correct answer is D. The disease is osteoarthritis, and the bony swellings are called
"Heberden's nodes", which may or may not be symptomatic. Osteoarthritis is thought to be
related to repetitive joint trauma.
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Autoantibodies (choice A) are important in rheumatoid arthritis.

Bacterial infections (choice B) cause septic arthritis.

Crystal deposition (choice C) is important in gout and pseudogout.

Viral infections (choice E) can cause transient arthralgias and arthritis.

Physical examination of a two-year-old child reveals a large abdominal mass. CT studies show that the
mass arises in the kidney. Which of the following is most likely a distinctive feature of this
lesion?

A. Abundant clear cells

B. Embryonic glomerular structures

C. Eosinophilic cells packed with mitochondria

D. Hamartomatous blood vessels

E. Necrotic bacterial forms in macrophages

Explanation:

The correct answer is B. A two-year-old with a tumor of the kidney most likely has Wilms tumor.
This aggressive lesion (now with a 90% survival rate thanks to modern management) is
microscopically interesting because it contains embryonic glomerular and tubular structures
embedded in a spindle cell stroma which may also contain smooth muscle, striated muscle, bone,
cartilage, fat, and fibrous tissue.

Abundant clear cells (choice A) are a feature of renal cell carcinoma.

Eosinophilic cells packed with mitochondria (choice C) suggests oncocytoma.

Hamartomatous blood vessels (choice D) suggest angiomyolipoma.

Necrotic bacterial forms in macrophages (choice E) suggest malakoplakia, which can cause mass
 18

lesions in the kidney without being a true tumor.

A 51-year-old alcoholic male suddenly starts vomiting blood and eventually loses consciousness; his wife
finds him laying on the bathroom floor. He has no prior history of hematemesis and had not been
vomiting prior to the appearance of the blood. Which of the following conditions is the most
likely cause of this man's presentation?

A. Esophageal varices

B. Mallory-Weiss tear

C. Plummer-Vinson syndrome

D. Schatzki ring

E. Zenker's diverticulum

Explanation:

The correct answer is A. This is a classic presentation of life-threatening bleeding from

esophageal varices (tortuous, dilated, submucosal esophageal vessels). Sclerotherapy of the
vessels and pressure on the bleeding site with an "esophageal balloon" may temporarily control
the problem, but, unfortunately, bleeding often recurs and exsanguination is a frequent cause
of death in these patients.

In contrast, Mallory-Weiss tears (choice B) occur as a complication of repeated vomiting and do

not often result in this amount of blood loss.

The other esophageal conditions listed do not usually cause hematemesis.

Plummer-Vinson syndrome (choice C) consists of hypochromic, microcytic anemia, atrophic

glossitis, and esophageal webs.

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

Zenker's diverticulum (choice E) is an esophageal evagination at the junction of the pharynx

 19

and esophagus.

A patient with long-standing, moderately severe anemia dies in an automobile accident. He was driving,
and an autopsy is performed to determine the cause of death. Which of the following cardiac
changes will most likely be seen when the heart is examined?

A. Endocarditis

B. Fatty change of myocytes

C. Fibrinous pericarditis

D. Fibrosis of valve leaflets

E. Frank myocardial infarction

Explanation:

The correct answer is B. Chronic anemia is not simply a disease of the blood. Other changes
that can occur with long-standing, moderately severe anemia include skin atrophy and
koilonychia (spoon-shaped nails, particularly in iron-deficiency anemia). Fatty change of
cardiac myocytes, renal proximal convoluted tubule cells, and centrilobular hepatic cells, and
degeneration of neurons of the cerebral cortex and basal ganglia are also seen. With time, some
of these cells may die, producing a patchy cell loss.

Endocarditis (choice A) usually has an infectious etiology.

Fibrinous pericarditis (choice C) typically is seen following myocardial infarction.

Fibrosis of valve leaflets (choice D) can be seen with aging or as a complication of infective
endocarditis.

Frank myocardial infarction (choice E) can occur in very severe anemia, particularly if
superimposed by an additional hypoxic insult, such as hemorrhage, shock, or pneumonia, but is
not typical of long-standing moderately severe anemia.

A leukemia patient who has undergone multiple courses of chemotherapy develops herpes simplex
 20

encephalitis. Which of the following would you expect a CT scan of the patient's brain to show?

A. Generalized volume loss

B. Volume loss selectively in the basal ganglia

C. Volume loss selectively in the brainstem

D. Volume loss selectively in the cerebellum

E. Volume loss selectively in the temporal and frontal lobes

Explanation:

The correct answer is E. Herpes simplex can cause a necrotizing, hemorrhagic acute encephalitis
that may rapidly produce death. The encephalitis characteristically involves the lower portions
of the cerebral cortex, notably the temporal lobes and the base of the frontal lobes, possibly
because the infection spreads from the oropharynx.

A 32-year-old woman complains of a sore throat, increasing fatigue, and shortness of breath for the past
3 days. On physical examination, her temperature is 101.5 F and her heart rate is 100, with no
murmurs. A CBC with reticulocyte count shows 1500 white blood cells/mm3. The platelet count is
12 x 109/L. Bone marrow aspiration and biopsy demonstrates cellularity less than 25%, and the
corrected reticulocyte count is less than 1%. Which of the following is the most likely
diagnosis?

A. Anemia of chronic disease

B. Aplastic anemia

C. Myelodysplasia with myelofibrosis

D. Myelophthisic anemia

E. Pure red cell aplasia

Explanation:
 21

The correct answer is B. Aplastic anemia is characterized by pancytopenia. The bone marrow
biopsy typically reveals a normal architecture with a decrease in cellularity to levels less
than 25% of normal. The corrected reticulocyte count (i.e., reticulocyte count patient's
hematocrit/45) is often 1%. Platelet counts range from 20 to 60 109/L, and the absolute
neutrophil counts are often less than 0.5 109/L. Aplastic anemia may be either hereditary
(e.g., Fanconi's anemia) or acquired. Certain pharmacologic agents, such as busulfan and
vincristine, often produce severe marrow hypoplasia or aplasia. Chloramphenicol, some
anticonvulsant drugs, phenylbutazone, and a variety of other agents may produce aplastic anemia
in an idiosyncratic manner. Aplastic anemias have also been linked to exposure to environmental
toxins, such as benzene and insecticides, and are often found to be preceded by viral
infections from cytomegalovirus, parvovirus, and hepatitis. The fever and sore throat in the
patient described in the question are consistent with cytomegalovirus infection.

Anemia of chronic disease (choice A) produces an isolated deficit of red cell production and
may resemble iron deficiency.

The myelodysplastic syndromes (e.g., myelodysplasia with myelofibrosis, choice C) are

characterized by replacement of the bone marrow with abnormal (dysplastic) stem cells and
ineffective hematopoiesis.

Myelophthisic anemia (choice D) is caused by infiltration of the bone marrow by expansile

lesions (e.g., metastatic carcinoma) that distort the marrow architecture and generally depress
the production of all three types of formed blood elements.

Pure red cell aplasia (choice E) would produce a selective deficit of the erythrocytic lineage,
not all three lineages.

A concerned couple bring in a 2-year-old boy with gonadal dysgenesis to a clinic for a follow-up visit.
The physician notices a large abdominal mass during his physical examination. Which of the
following disorders does the patient most likely have?

A. Renal cell carcinoma

B. Renal hamartoma

C. Squamous cell carcinoma of the bladder

 22

D. Transitional cell carcinoma of the bladder

E. Wilms' tumor

Explanation:

The correct answer is E. The only childhood malignancy listed is Wilms' tumor, which commonly
presents in a toddler as a large abdominal mass. There is now a 90% survival rate for this
tumor with combined therapy with surgery, chemotherapy, and radiotherapy.

Renal cell carcinoma (choice A), squamous cell carcinoma of the bladder (choice C), and
transitional cell carcinoma of the bladder (choice D) are malignant tumors of adults.

Renal hamartoma (fibroma; choice B) causes a small, gray, benign module in the renal pyramids
and is usually only identified as an incidental finding at autopsy.

A 23-year-old African-American woman presents in the emergency room with severe abdominal pain and
evidence of dehydration. Her past medical history is significant for numerous pulmonary
infections and effusions of the knees. This patient's erythrocytes would be expected to exhibit

A. an absence of central pallor

B. deletion of all four alpha Hb genes

C. denaturation during deoxygenation

D. Heinz bodies on RBC staining

Explanation:

The correct answer is C. Whenever the Step 1 exam specifies a patient's ethnic background,
there is a good chance that it provides an important clue to the question. The patient
described is an African-American woman with symptoms and history suggestive of sickle cell
anemia. The woman is experiencing the most frequent type of vaso-occlusive crisis in sicklers
(infarctive). Crises may be precipitated by dehydration or infection. Hb electrophoresis is
used to diagnose the illness, which is caused by an amino acid substitution of valine for
 23

glutamate in position 6 of the beta Hb chain. The resulting abnormal hemoglobin (HbS) tends to
polymerize during low oxygen states, causing the red blood cells to assume a sickle shape.

Absence of central pallor (choice A) may be observed in patients with hereditary spherocytosis
(usually autosomal dominant) resulting from abnormal red cell membrane proteins (e.g.,
spectrin, ankyrin). Spherocytes will exhibit increased osmotic fragility because they have
decreased surface area per unit volume.

Deletion of all four alpha genes (choice B) occurs in the most severe form of alpha thalassemia
and is incompatible with life. It can result in hydrops fetalis and intrauterine death.

Heinz bodies (choice D) are clumps of Hb-degradation products seen when RBCs are stained with
methylene blue. They are found in the peripheral blood smears of people with G6PD deficiency,
especially common in males of Mediterranean or West African descent. Hemolysis occurs in
response to oxidant stress that may be caused by drugs (e.g., antimalarials, sulfonamides, or
nitrofurantoin) or the ingestion of fava beans.

A woman presents to a dermatologist because she has lost almost all the hair on her body, including
scalp hair, eye brows, eye lashes, arm pit and groin hair, and the fine hairs on her body and
extremities. She most likely has a variant of which of the following?

A. Alopecia areata

B. Androgenic alopecia

C. Chronic cutaneous lupus erythematosus

D. Lichen planopilaris

E. Trichotillomania

Explanation:

The correct answer is A. Alopecia areata is caused by an autoimmune attack on hair follicles.
It has a wide range of clinical severity, with most cases involving a localized patch of hair
(which regrows within 1 year in half of the patients). The hair that does regrow may be gray or
depigmented. More severe cases can involve the entire scalp (alopecia totalis) or, as in this
 24

patient, the entire body surface (alopecia universalis). These more severe cases are less
likely to resolve adequately. Treatment of alopecia areata is often unsuccessful, but topical
steroids are typically tried.

Androgenic alopecia (choice B) is common male pattern baldness.

Chronic cutaneous lupus erythematosus (choice C) can produce localized baldness.

Lichen planopilaris (choice D) can produce localized baldness.

Trichotillomania (choice E), also called traumatic alopecia, is alopecia due to trauma, such as
hair pulling or tight braids.

A 68-year-old female undergoes surgery to remove an abdominal tumor. Pathological examination shows
that
the mass contains a large number of blood vessels. An increase in which of the following is the
most likely stimulus for the proliferation of these vessels?

A. Angiostatin

B. Growth hormone

C. Thrombospondin

D. Tissue oxygen partial pressure

E. Vascular endothelial growth factor

Explanation:

The correct answer is E. Vascular endothelial growth factor (VEGF) is a heparin-binding

glycoprotein that increases endothelial cell proliferation in vitro and increases capillary
growth (i.e., angiogenesis) in vivo. Unlike most other growth factors, VEGF has unique target
cell specificity for vascular endothelial cells. VEGF is overexpressed in solid tumors as well
as in ischemic areas of the heart and retina. VEGF levels are also reversibly increased in a
variety of normal and transformed cells exposed to a hypoxic environment. These characteristics
of VEGF make it an ideal candidate as a regulator of angiogenesis in physiological and
 25

pathophysiological situations in which vessel growth is preceded by deficient perfusion of the

tissues.

Angiostatin (choice A) is an anti-angiogenic factor expressed by tumors that tends to inhibit

angiogenesis.

Growth hormone (choice B) has a general effect that causes growth of almost all tissues of the
body, but does not appear to stimulate angiogenesis to a significant extent in solid tumors.

Thrombospondin (choice C) is a multifunctional glycoprotein that interferes with tumor growth,

angiogenesis, and metastasis.

An increase in tissue oxygen partial pressure (choice D) is unlikely to be the stimulus for new
vessel growth because (1) solid tumors are invariably hypoxic or ischemic, i.e., the partial
pressure of oxygen is low; and (2) an increase in the partial pressure of oxygen in a tumor
would tend to decrease the expression of VEGF, thereby decreasing the amount of angiogenesis in
the tissues.

A neuropathologist is performing an autopsy on a 65-year-old man who had resting tremor, rigidity, and
akinesia. Histologic sections of the substantia nigra reveal neurons containing round
eosinophilic inclusions. Such inclusions most likely represent

A. granulovacuolar degeneration

B. Hirano bodies

C. Lafora bodies

D. Lewy bodies

E. Marinesco bodies

F. Negri bodies

G. neurofibrillary tangles

H. Pick bodies
 26

Explanation:

The correct answer is D. This item lists a number of characteristic inclusions found in
pathologic conditions of the CNS. The trick here is to first identify the classic triad of
Parkinson disease (namely, tremors, rigidity, and akinesia), then recognize its typical
histopathologic hallmark: round, eosinophilic, intracytoplasmic inclusions seen in neurons of
substantia nigra. Lewy bodies are filamentous inclusions that appear brightly eosinophilic on
hematoxylin and eosin stain and accumulate in the cytoplasm of dopaminergic neurons in the
substantia nigra in Parkinson disease. All the other inclusions listed in the answer choices
have different pathologic significance.

Granulovacuolar degeneration (choice A) and Hirano bodies (choice B) are intracytoplasmic

inclusions found in hippocampal pyramidal neurons of Alzheimer patients and intellectually
intact elderly people.

Lafora bodies (choice C) contain polyglucosans and are found in neurons, glial cells, sweat
glands, liver, and skeletal muscles in patients with the rare Lafora disease.

Marinesco bodies (choice E) are also present in the dopaminergic neurons of substantia nigra.
However, they are intranuclear and are not associated with Parkinson disease. These inclusions
are found occasionally in normal brains, and their significance is unknown.

Negri bodies (choice F), which develop in the brains of patients with rabies, are filled with
viral particles and are frequently seen in Purkinje neurons (cerebellar cortex) and hippocampal
pyramidal neurons.

Neurofibrillary tangles (choice G) are intracytoplasmic filamentous inclusions found in

Alzheimer disease and, to a lesser extent, in normal aging brains.

Pick bodies (choice H) are characteristic of Pick disease, a form of frontotemporal dementia.
These are present in cortical neurons and appear as round intracytoplasmic inclusions that
stain dark with silver impregnation.

A 12-year-old girl with history of a streptococcal sore throat several weeks ago presents to her doctor
with an erythematous macular skin rash in a "bathing suit" distribution. Which one of the
following signs would be necessary to make the diagnosis of rheumatic fever?
 27

A. Elevated erythrocyte sedimentation rate

B. Leukocytosis

C. Migratory polyarthritis

D. Prolonged PR interval on EKG

E. Temperature greater than 100.4 F

Explanation:

The correct answer is C. This patient's macular skin rash in a "bathing suit" distribution is
also known as erythema marginatum, one of the five major Jones criteria for diagnosing
rheumatic fever. The other four major criteria are migratory polyarthritis, Sydenham's chorea,
subcutaneous nodules, and pancarditis. In context of prior streptococcal infection, the
presence of two of five of the major criteria or one major plus two minor (choices A, B, D, E)
are sufficient to establish the diagnosis. Other minor criteria include previous rheumatic
fever and elevated C-reactive protein. A mnemonic for the major criteria is "CANCER" (not
pleasant, but it's easy to remember): Chorea, Arthritis, Nodules, Carditis, Erythema
marginatum, Rheumatic fever diagnosis.

A newborn baby who was apparently healthy at birth develops aspiration pneumonia in the first two days
of life. All attempts to feed the infant cause it to cough and choke. Which of the following
abnormalities is the most likely cause of the infant's difficulties?

A. Bronchogenic cysts

B. Congenital pulmonary cysts

C. Posterior deviation of the tracheoesophageal septum

D. Pulmonary immaturity

E. Pulmonary sequestration
 28

Explanation:

The correct answer is C. The infant probably has esophageal atresia, which is typically caused
by posterior deviation of the tracheoesophageal septum. Attempts at feeding cause fluid to
spill into the trachea, and secondarily cause aspiration pneumonia. Emergent surgical
correction is usually required.

Bronchogenic cysts (choice A) are centrally located cysts that are often asymptomatic and may
be associated with cysts of other organs.

Congenital pulmonary cysts (choice B) are often multiple and located in the lung periphery
without connection to the bronchi; they are vulnerable to infection and rupture complicated by
pneumothorax and/or hemoptysis.

Pulmonary immaturity (choice D) produces progressive difficulty in breathing beginning in the

first few hours of life.

Pulmonary sequestration (choice E) represents extrapulmonary lung tissue supplied by systemic

blood vessels rather than by pulmonary arteries.

An 8-year-old male with oliguria is sent by his pediatrician to the radiologist for a renal ultrasound.
The ultrasound shows large, smooth kidneys with radial fusiform cysts in the cortex and
medulla. Neither parent has a history of renal disease, but the father recalls a family history
of "kidney problems." Which of the following is the correct diagnosis?

A. Glomerulocystic disease

B. Infantile polycystic disease

C. Medullary cystic disease

D. Segmental dysgenesis

E. Uremic medullary cystic disease

Explanation:
 29

The correct answer is B. A disorder occurring in offspring of unaffected parents (in the
context of a family history of the disease) suggests autosomal recessive inheritance. Infantile
polycystic disease is the only disease listed in the choices with autosomal recessive
inheritance. This disease affects both infants and children and is usually bilateral. The cysts
are fluid-filled and lined by cuboidal epithelium. It is thought to result from failure of
communication between the nephron and pericaliceal system during development, leading to renal
failure.

Glomerulocystic disease (choice A) is a rare disease without a recognized hereditary component

that causes cortical cysts of the kidneys bilaterally, eventually producing renal failure.
Grossly, the kidneys are enlarged with 1- to 8-mm cortical cysts that develop from dilated
Bowman's spaces in the glomeruli. Newborns, infants, and children are affected.

Medullary cystic disease (choice C), or medullary sponge kidney, can affect all ages, but
typically affects adults. It is not thought to be inherited and the cause is not known. The
cysts are located at the tips of the papillae. It is usually asymptomatic, but can lead to
defective sodium reabsorption in the tubule.

Segmental dysgenesis (choice D) is not inherited and affects all ages. The kidneys show
irregular cysts with scarring. Symptoms depend upon the severity of disease. Patients may be
asymptomatic if one kidney is spared.

Uremic medullary cystic disease (choice E) is a rare disease of children and young adults that
causes multiple cysts of the medulla. There is also cortical tubular atrophy and intestinal
fibrosis. Pathogenesis is unknown. Chronic renal failure occurs and mortality is high.

X-ray of the leg of a 75-year-old man demonstrates linear calcifications along the distal course of the
femoral artery. Angiography shows no change in the luminal diameter of the artery. Which of the
following is the most likely diagnosis?

A. Atheromatous plaques

B. Hyaline arteriolosclerosis

C. Hyperplastic arteriolosclerosis

D. Hypersensitivity angiitis
 30

E. Mnckeberg's arteriosclerosis

Explanation:

The correct answer is E. Mnckeberg's arteriosclerosis, also called medial calcific sclerosis,
is a disease of the elderly in which ring-like calcifications form in the media of medium-sized
to small muscular arteries. The process is not a vasculitis, as no inflammation occurs. It is
clinically insignificant because no change in vessel luminal diameter occurs.

Atheromatous plaques (choice A) might be calcified, but would narrow the vessel lumen.

Hyaline arteriolosclerosis (choice B) and hyperplastic arteriolosclerosis (choice C) typically

do not calcify and involve arterioles, rather than arteries.

Hypersensitivity angiitis (choice D) does not calcify.

A patient experiences intermittent, severe pain in the right upper quadrant of the abdomen, especially
after fatty meals. Ultrasound demonstrates multiple small opacities in the gall bladder that
change with the patient's position. Which of the following is a risk factor for this patient's
disorder?

A. 20 years of age

B. Male sex

C. Native American origin

D. Nulliparity

E. Thin build

Explanation:

The correct answer is C. The patient has gallstones (cholelithiasis). A useful mnemonic to
remember the risk factors for gallstones is the 5 F's: female, fat, fertile, forty, and
flatulent. Gallstones are usually composed predominantly of cholesterol with lesser amounts of
 31

other components such as calcium salts, bile acids, and bile pigments. Exceptions to this rule
are nearly pure cholesterol stones and pigment (calcium bilirubinate) stones. The incidence of
mixed stones and cholesterol stones is also increased in association with Crohn's disease,
cystic fibrosis, clofibrate therapy, estrogen therapy, rapid weight loss, and Native American
origin. Risk factors for pigment stones include chronic hemolysis, alcoholic cirrhosis, and
biliary infection.

The typical age for gallstones is Forty years or older, not 20 years (choice A).

Female, not male (choice B) sex predisposes the individual for gallstones.

Many patients with gallstones are multiparous (Fertile), not nulliparous (choice D).

Gallstones are associated with obesity (Fat), not a thin build (choice E).

A 35-year-old woman presents to a gastroenterologist with a chief complaint of difficulty swallowing

solids and some liquids for the past several years. After detailed evaluation, the physician
suggests the possibility that the patient's esophageal condition is autoimmune in nature.Which
of the following findings on physical examination would help confirm the likely diagnosis?

A. Butterfly rash

B. Dry mouth

C. Enlarged thyroid

D. Thickened skin

E. Tumor-like nodules on tongue

Explanation:

The correct answer is D. The autoimmune disease to specifically associate with esophageal
dysfunction is scleroderma (progressive systemic sclerosis), which also causes thickening of
the dermis because of extensive collagen deposition. A similar type of fibrosis can involve the
gastrointestinal tract, particularly the distal two-thirds of the esophagus. The term "rubber-
hose" inflexibility is sometimes applied to an affected esophagus. Microscopically, excessive
 32

collagenization of the lamina propria and submucosa is seen. The overlying mucosa may be
thinned and ulcerated.

Butterfly rash (choice A) is associated with systemic lupus erythematosus, which is usually not
accompanied by esophageal dysfunction.

Dry mouth (choice B) is associated with Sjgren syndrome. While this could potentially affect
swallowing of dry food, the patient had problems with a wider range of foods.

The thyroid gland is enlarged (choice C) in the autoimmune disorders known as Graves disease
and Hashimoto disease.

Tumor-like submucosal nodules on the tongue (choice E) are seen in some cases of amyloidosis.
This disorder can also affect the gastrointestinal tract, but more commonly involves the
intestines, rather than the esophagus.

A 67-year-old man is evaluated for persistent shooting pains, lower limb ataxia, and bladder
dysfunction. Physical examination demonstrates small irregular pupils that constrict with
accommodation but not in response to light. A VDRL test is positive. A CT scan of the spinal
cord would most likely demonstrate atrophy of which of the following structures?

A. Dorsal column

B. Dorsal horn

C. Lateral column

D. Ventral column

E. Ventral horn

Explanation:

The correct answer is A. The patient has tabes dorsalis, which is a form of neurosyphilis seen
10 to 25 years or longer after primary disease. The pupils described are Argyll Robertson
pupils, and are considered diagnostic for neurosyphilis. Characteristically, the dorsal
columns, which contain the ascending tracts for sensory information, become atrophic, probably
 33

as a result of damage to the dorsal root ganglion cells.

The dorsal gray horn (choice B) contains neurons that respond to sensory input.

The lateral column (choice C) contains both descending (e.g., lateral corticospinal,
rubrospinal) and ascending (e.g., spinocerebellar, spinothalamic) tracts.

The ventral column (choice D) contains both descending (e.g., anterior corticospinal,
tectospinal) and ascending (e.g., spinothalamic) tracts.

The ventral horn (choice E) contains lower motor neurons.

A 68-year-old man presents to his physician with complaints of fatigue and a dragging sensation in his
abdomen. Physical examination is remarkable for massive splenomegaly without lymphadenopathy.
The patient's hematocrit is 30%, his platelet count is 80,000/mm3, and his leukocyte count is
2500/mm3. Bone marrow biopsy shows "fried egg" cells expressing the pan B-cell markers CD19 and
CD20, and the monocyte marker CD11c. Positive staining for which of the following substances
would most likely verify the likely diagnosis?

A. CD4

B. GpIIb/IIIa

C. Myeloperoxidase

D. Nonspecific esterase

E. Tartrate-resistant acid phosphatase

Explanation:

The correct answer is E. Hairy cell leukemia is characterized by pancytopenia and splenomegaly.
Lymphadenopathy is unusual. The proliferating cells express the pan B-cell markers (CD19 and
CD20), the monocyte marker (CD11c), the interleukin-2 receptor (CD25), and plasma cell-
associated antigen-1 (PCA-1). Histologically, the cells display fine, hairlike projections when
viewed with phase-contrast microscopy. A "fried-egg" appearance on stained bone marrow biopsy
arises because of fixation artifacts that occur as a result of the hairlike projections on many
 34

of the cells. Tartrate-resistant acid phosphatase is virtually diagnostic of hairy cell

leukemia.

CD4 (choice A) is a cluster designation antigen that is displayed on the surfaces of T cells
and maturing thymocytes.

GpIIb/IIIa (choice B) is a platelet membrane receptor for fibrinogen, fibronectin, and von
Willebrand's factor.

Myeloperoxidase (choice C) is a marker for late myeloblasts and mature granulocytes. Monocytes
also stain to some extent.

Diffuse nonspecific esterase (choice D) staining is used to identify cells in the monocytic
lineage. Punctate nonspecific esterase staining is observed in T cells.

A 19-year-old sexually active female presents to urgent care with abdominal pain and nausea. Her last
menstrual period began seven days ago. Physical examination is remarkable for fever and lower
abdominal pain. Pelvic examination reveals a mucopurulent discharge, adnexal tenderness, and
tenderness with cervical motion. A pregnancy test is negative; the patient's white count is
elevated. Which of the following complications is associated with this disorder?

A. Ascites

B. Cervical carcinoma

C. Exsanguination

D. Infertility

E. Pseudomyxoma peritonei

Explanation:

The correct answer is D. The young woman is suffering from pelvic inflammatory disease (PID).
This disorder is classically caused by ascending infection with Neisseria gonorrhoeae or
Chlamydia trachomatis. Symptoms include a mucopurulent cervicitis (often producing a vaginal
discharge), abdominal pain, or abnormal vaginal bleeding. Fever, an elevated white count, and
 35

an elevated erythrocyte sedimentation rate may also be seen. Therapy consists of antibiotics
with activity against N. gonorrhoeae, C. trachomatis, vaginal anaerobes and facultative gram-
negative rods (e.g., cefoxitin plus doxycycline or clindamycin plus gentamicin). Infertility is
a feared complication of tubal scarring and adhesions following salpingitis in PID. Bacteremia,
peritonitis, and intestinal obstruction may also complicate this disorder.

Abdominal enlargement due to ascites (choice A) is observed in advanced cases of ovarian

carcinoma.

Cervical carcinoma (choice B) is related to infection with certain subtypes of human papilloma
viruses.

Exsanguination (choice C) is a feared complication of a ruptured ectopic pregnancy.

Pseudomyxoma peritonei (choice E) is a very serious complication of mucinous tumors of the

ovary or appendix.

A patient with large, penetrating vegetations on his mitral and aortic valves develops severe headaches.
Funduscopic examination reveals papilledema. CT scan of the brain demonstrates a ring-enhancing
lesion. Which of the following organisms is the most likely cause of the patient's disorder?

A. Herpesvirus

B. Mycobacterium tuberculosis

C. Staphylococcus aureus

D. Streptococcus pneumoniae

E. Treponema pallidum

Explanation:

The correct answer is C. The cardiac lesions described are characteristic of acute bacterial
endocarditis. The fact that the valvular vegetations are large and penetrating strongly
suggests that they are due to a virulent, pyogenic pathogen. Among the answer choices,
Staphylococcus aureus best fits this description, and is in fact the most common cause of acute
 36

bacterial endocarditis. Brain abscess, which produces ring-enhancing radiologic lesions, is a

known complication of bacterial endocarditis, occurring when the vegetations fragment and
release septic emboli.

Herpesvirus (choice A) can cause encephalitis, but is not a cause of vegetative endocarditis.

Mycobacterium tuberculosis(choice B) can cause brain masses, but does not usually cause
endocarditis.

Streptococcus pneumoniae(choice D) can cause acute pyogenic meningitis, but does not usually
cause endocarditis.

Treponema pallidum(choice E), the causative agent of syphilis, can cause aortic aneurysms and a
variety of neurologic problems, but does not usually cause endocarditis or brain abscess.

A 5-year-old boy who has been diagnosed with a mucopolysaccharidosis is given an IQ test and found to
have nearly normal intellectual functioning. Which of the following are possible diagnoses for
this patient?

A. Hunter syndrome or Hurler syndrome

B. Hunter syndrome or Scheie syndrome

C. Hurler syndrome or Sanfilippo syndrome

D. Morquio syndrome or Sanfilippo syndrome

E. Morquio syndrome or Scheie syndrome

Explanation:

The correct answer is E. All of the diseases listed are mucopolysaccharidoses, due to defective
degradation of mucopolysaccharides. Features typical of mucopolysaccharidoses include
hepatomegaly, skeletal abnormalities, and, often, mental retardation. The two exceptions to the
mental retardation are the milder conditions, Morquio syndrome and Scheie syndrome.

Autopsy of a hypertensive patient reveals a massive intracerebral hemorrhage filling the ventricles. A
 37

thorough search for the source of the hemorrhage is likely to demonstrate that the bleeding
began in which of the following sites?

A. Basal ganglia and internal capsule

B. Central white matter

C. Cerebellum and medulla

D. Pons

E. Thalamus and hypothalamus

Explanation:

The correct answer is A. Intraparenchymal hemorrhage is typically due to hypertension, and is

the most common cause of death from stroke. Such hemorrhages can occur at all of the sites
listed in the answer choices, but roughly half of such cases involve the basal ganglia and
internal capsule. Hypertensive hemorrhages are often massive and frequently dissect through the
brain parenchyma into the ventricular system. There is frequently nothing a physician can do to
prevent a fatal outcome in patients with massive intracerebral hemorrhage.

The other sites listed (choices B, C, D, and E) are important sites of intraparenchymal
hemorrhage, but they are less frequently involved than the basal ganglia and the closely
related internal capsule.

A 30-year-old woman undergoes her yearly gynecologic examination and is found to have microscopic
hematuria. The hematuria is again documented on several more occasions when she is seen for other
reasons. Because no etiology is obvious, renal biopsy is eventually performed; a photomicrograph
of a hematoxylin and eosin-stained section is shown above. Immunofluorescent staining of
histologic sections similar to the one shown demonstrates IgG, IgM, and complement in the
glomerular mesangium. Which of the following is the most likely diagnosis?

A. Amyloidosis

B. Goodpasture syndrome
 38

C. Henoch-Schnlein purpura

D. Lipoid nephrosis

E. Systemic lupus erythematosus

Explanation:

The correct answer is E. Systemic lupus erythematosus can produce a wide range of different
glomerular lesions; in some cases, the presenting symptoms may be associated with renal disease.
The pattern illustrated in the photomicrograph is mesangial expansion with cellular proliferation
and occurs in approximately 25% of lupus patients. Granular mesangial deposits of immunoglobulin
and complement are characteristically present and probably reflect the immune complex basis of the
problem.

Amyloidosis (choice A) is not usually associated with immune complex deposition.

Goodpasture syndrome (choice B) is characterized by linear IgG deposition along basement

membranes.

Henoch-Schnlein purpura (choice C) characteristically shows IgA deposits.

The glomeruli in lipoid nephrosis (choice D), also known as minimal change disease, appear normal
or very nearly normal.

A 66-year-old man develops low back pain, and radiologic investigations reveal multiple osteoblastic
lesions of the lumbar vertebrae. A hard, irregular nodule on the posterior surface of the
prostate is appreciated on rectal examination. Plasma levels of prostatic specific antigen (PSA)
are markedly increased. Which of the following is the most likely diagnosis?

A. Chronic prostatitis

B. Multiple myeloma

C. Prostatic adenocarcinoma

D. Prostatic hyperplasia
 39

E. Prostatic intraepithelial neoplasia (PIN)

Explanation:

The correct answer is C. This is the typical clinical presentation of carcinoma of the
prostate, which is probably the most frequent cancer in males (although lung cancer is the most
frequent neoplastic cause of death). Autopsy studies show that small foci of adenocarcinoma are
found in the prostate of up to 70% of men older than 80. Prostatic specific antigen (PSA) is
expressed by both normal prostatic tissue and adenocarcinoma of the prostate. A rise in PSA
plasma levels, therefore, simply results from any increase in the mass of prostatic tissue and
cannot be used to differentiate between cancer and hyperplasia. Cancer arises more frequently
in the peripheral zone of the gland, producing firm nodules on the posterior surface that can
be detected on rectal examination. Metastasis to the bone can be osteoblastic (with formation
of new bone) or osteolytic (with destruction of bone). Osteoblastic metastases in the vertebral
column are characteristic of prostatic adenocarcinoma.

Chronic prostatitis (choice A) presents with dysuria and perineal discomfort. The diagnosis
relies on finding at least 10 leukocytes per high-power field on microscopic examination of
expressed prostatic secretions. Chronic prostatitis is further classified into bacterial
prostatitis if cultures are positive for bacteria, or abacterial prostatitis if cultures are
negative. Increased plasma PSA is frequently seen.

Multiple myeloma (choice B) is a neoplasm of plasma cells that frequently manifests with
osteolytic (not osteoblastic) lesions in the vertebral column as well as other bones, such as
the cranial vault and ribs.

Prostatic hyperplasia (choice D) is an extremely common disorder in middle-aged and elderly

men. It involves the periurethral zone of the gland, leading to compression of the urethra,
difficulty in urination, urinary retention, and recurrent cystitis. PSA levels are increased in
a manner roughly proportional to the degree of prostatic enlargement.

Prostatic intraepithelial neoplasia (PIN; choice E) is the precursor of invasive prostatic

adenocarcinoma and consists of atypical proliferation of epithelial cells confined within the
basement membrane of prostatic acini. In one third of cases, PIN progresses to invasive cancer
within 10 years. By definition, PIN is not associated with metastasis. Other examples of cancer
precursors are CIN (cervical intraepithelial neoplasia) and VIN (vulvar intraepithelial
 40

neoplasia).

A 40-year-old, moderately obese man presents with a persistent productive cough. The cough has been
present for several weeks, but recently the man noted that his sputum has assumed a greenish
color. Further questioning elicits a history of productive cough, usually in the winter months,
over the past several years. He has smoked two packs of cigarettes per day since he was 16
years old. On examination, the man is febrile (100 F), and coarse rhonchi and wheezes can be
appreciated bilaterally. Which of the following is the most likely diagnosis?

A. Bronchogenic carcinoma

B. Chronic bronchitis with superimposed infection

C. Cystic fibrosis

D. Emphysema

E. Pulmonary tuberculosis

Explanation:

The correct answer is B. The diagnosis of chronic bronchitis requires the presence of chronic
productive cough over at least 3 months of the year for 2 successive years. The symptoms in
this patient (green productive sputum, fever) suggest that he has an acute infection
superimposed on chronic bronchitis (history of cigarette smoking, history of excessive mucus
production over many years). Histologically, the mucus-producing glands in the bronchi would
show hyperplasia and hypertrophy and extend to a greater depth in the bronchial wall, resulting
in a higher Reid index (ratio of thickness of mucus gland to thickness of bronchial wall).

Although the patient is a smoker and is at increased risk for bronchogenic carcinoma (choice
A), this is unlikely to be the cause of his symptoms. Hemoptysis and weight loss might also be
present if he had cancer.

Cystic fibrosis (choice C) presents earlier in life and may be associated with severe
production of mucus, especially if bronchiectasis supervenes. The age of the patient and the
relative late onset of disease preclude this diagnosis.
 41

This patient may also have emphysema (choice D), as chronic bronchitis and emphysema are often
coexistent. However, although pure emphysema might cause dyspnea, it would not be associated
with a fever or a productive cough.

Pulmonary tuberculosis (choice E) would typically present with a history of hemoptysis rather
than abundant green sputum. Weight loss, night anorexia, malaise, and weakness may also be
present.

A 55-year-old man with a history of recurrent calcium-containing renal stones presents to the emergency
room with excruciating flank pain and blood in the urine. This patient is likely to have which
of the following underlying disorders?

A. Anemia of chronic disease

B. Chronic Proteus infection

C. Factor VIII deficiency

D. Hyperaldosteronism

E. Hyperparathyroidism

Explanation:

The correct answer is E. This patient is experiencing the very painful passage of a renal
stone, which is often accompanied by hematuria. His history of recurrent urolithiasis with
calcium-containing stones implies a disorder in the regulation of calcium concentration.
Hyperparathyroidism is associated with increased parathormone (PTH) levels, which can produce
hypercalcemia, hypercalciuria, and, ultimately, renal stones.

Anemia of chronic disease (choice A) does not produce calcium stones. It is an attractive
distracter because the patient presents with a chronic condition and hematuria. Note that
urinary blood loss is not usually significant enough to produce an anemic state.

Chronic Proteus infection (choice B) would produce struvite (magnesium-ammonium phosphate), not
calcium stones. Staghorn calculi are also seen.
 42

Factor VIII deficiency (choice C) occurs in hemophilia, a hereditary clotting disorder. It is

not associated with calcium stones.

Hyperaldosteronism (choice D) results in potassium depletion, sodium retention, and

hypertension. Primary hyperaldosteronism (Conn's syndrome) is associated with adrenocortical
adenomas in 90% of patients and is characterized by decreased renin. Secondary
hyperaldosteronism results from excessive stimulation by angiotensin II that is caused by
excess renin production (plasma renin-angiotensin levels are high). Neither condition is
associated with renal stones.

A 36-year-old gravid female notes vaginal bleeding. Ultrasound reveals small grape-like cystic
structures without evidence of a developing embryo. A diagnosis of complete hydatidiform mole
is made at the hospital. Further analysis is most likely to reveal that

A. hCG levels are markedly decreased

B. serum levels of alpha fetoprotein are elevated

C. the genotype of the mole is 46, XX and is completely paternal in origin

D. the genotype of the mole is triploid

E. two or more sperm fertilized the ovum

Explanation:

The correct answer is C. A complete hydatidiform mole is characterized by elevated hCG and
grape-like cystic structures filling the uterus with no detectable embryo on ultrasound. The
genotype of a complete hydatidiform mole is purely paternal, caused by fertilization of an egg
that has lost its chromosomes. Hydatidiform mole is associated with increasing maternal age,
and may be a precursor to choriocarcinoma.

hCG levels are increased relative to normal values for dates, rather than decreased, in a molar
pregnancy (choice A).

Alpha fetoprotein (AFP; choice B) is a marker for endodermal yolk sac tumors, embryonal tumors
in men, and hepatocellular carcinoma. It is made by the fetus. In a complete hydatidiform mole,
 43

AFP is not detectable since there is no fetus.

Triploidy and even tetraploidy are characteristics of partial moles (choice D). Partial moles
are thought to be due to fertilization of an egg with two different sperm, one with an X and
one with a Y chromosome, typically leading to triploidy.

Two or more sperm may fertilize an ovum, leading to a triploid fetus and partial mole (choice
E).

A severely ill hospitalized patient develops a coagulopathy characterized by prolongation of the

prothrombin time (PT) and partial thromboplastin time (PTT) with a reduced platelet count.
Several hours later, acute anuria and uremia develop. The patient's blood pressure is initially
high normal, but then later falls as he is dying. Which of the following would most likely be
the major finding seen at autopsy?

A. Chronic cortical inflammation with tubular atrophy and interstitial fibrosis

B. Diffuse cortical necrosis

C. Patchy papillary necrosis

D. Small uric acid stones in the renal pelvis

E. Staghorn calculi

Explanation:

The correct answer is B. Prolongation of the PT and PTT with reduced platelets suggest
disseminated intravascular coagulation (DIC). DIC may be secondary to liberation of tissue
factors due to obstetric catastrophes, neoplasms, hemolysis, fat embolism, severe trauma,
endothelial damage, and infections. In DIC, widespread clotting and fibrinolysis occur
simultaneously throughout the body. Severe DIC can produce thrombosis in so many renal vessels
as to cause diffuse cortical necrosis.

Choice A describes chronic interstitial nephritis, which is by definition is a chronic process

that would not develop over hours.
 44

Patchy papillary necrosis (choice C) is seen in sickle cell renal disease, not DIC.

Uric acid stones (choice D) can be associated with gouty nephropathy and staghorn calculi
(choice E) occur with Proteus infections. In either case, the stones develop slowly, and are
not associated with DIC.

A pediatrician discovers a large mass in the abdomen of a 3-year-old child. Ultrasound examination
demonstrates that the mass appears to arise from the right kidney. Which of the following tumors
is most likely present?

A. Cortical adenoma

B. Hemangioma

C. Nephroblastoma

D. Oncocytoma

E. Renal cell carcinoma

Explanation:

The correct answer is C. Nephroblastoma (Wilms tumor) characteristically affects children

between 2 and 4 years of age and can form large spherical masses composed of variegated tissues
including primitive renal epithelial elements, a sarcomatous-appearing stroma, abortive
glomeruli and tubules, and heterologous tissues such as muscle, cartilage, fat, and bone.

Cortical adenoma (choice A) is a small (under 2 cm) benign tumor that is usually found
incidentally at autopsy.

Hemangiomas (choice B) can occur in the kidney, but would not usually produce a large mass.

Oncocytomas (choice D) are benign tumors that can be large but do not usually affect young
children.

Renal cell carcinoma (choice E) is usually a disease of older adults.

 45

A 58-year-old Japanese male with a 15-pound weight loss and guaiac-positive stools is found to have an
ulcerated gastric tumor on endoscopy. Which of the following mechanisms is thought to account
for the increased incidence of gastric carcinoma in the Japanese population?

A. Food preservatives

B. Helicobacter species

C. Inadequate screening

D. Menetrier's disease

E. Schistosoma species

Explanation:

The correct answer is A. The diet of the Japanese, with its increased concentration of
polycyclic hydrocarbons present in smoked fish, has been strongly implicated in the
pathogenesis of gastric adenocarcinoma. Nitrites are also potential carcinogens present in
preserved foods, and have been shown to cause gastric cancer in laboratory animals.

Helicobacter pylori(choice B) in the antral mucosa is highly associated with peptic ulcer
disease, gastric lymphoma, and gastric adenocarcinoma. There is no evidence, however, that this
bacterium is more prevalent in the Japanese population than in the American population.

The Japanese are routinely screened for gastric adenocarcinoma (compare with choice C), and as
such are more frequently treated when the tumor is at an earlier stage. Screening in the United
States is not routinely performed.

Menetrier's disease (or hypertrophic gastritis; choice D) is a condition characterized by

markedly thickened gastric rugal folds, accompanied by hyperplasia of mucous glands and
protein-losing enteropathy. Menetrier's disease is not associated with gastric carcinoma.

Schistosomiasis (choice E) may injure the liver, bladder, or intestines, depending upon the
species, but it is not a risk factor for gastric carcinoma. Schistosoma haematobium infection
is a risk factor for squamous cell carcinoma of the bladder.
 46

A 26-year-old man presents to his physician with a chronic cough. The man is a smoker, and states that
he also gets frequent headaches and aches in his legs when he exercises. Chest x-ray
demonstrates notching of his ribs. Which of the following undiagnosed congenital defects may be
responsible for these findings?

A. Coarctation of the aorta

B. Eisenmenger's syndrome

C. Tetralogy of Fallot

D. Transposition of great vessels

E. Ventricular septal defect

Explanation:

The correct answer is A. Coarctation of the aorta occurs in two patterns. In the infantile
type, the stenosis is proximal to the insertion of the ductus arteriosus (preductal); this
pattern is associated with Turner's syndrome. In the adult form, the stenosis is distal to the
ductus arteriosus (postductal) and is associated with notching of the ribs (secondary to
continued pressure from the aorta on them), hypertension in the upper extremities, and weak
pulses in the lower extremities. Headache, cold extremities, and lower extremity claudication
with exercise are typical if the patient is symptomatic (many adults with mild distal
coarctation may remain asymptomatic for years). Upper extremity hypertension with weak pulses
in the lower extremities, and a midsystolic (or continuous) murmur over the chest or back may
be the only obvious signs in some. Note that the chronic cough is probably related to the man's
smoking, and is not caused by the coarctation.

Eisenmenger's syndrome (choice B) is a shift from a left-to-right shunt to a right-to-left

shunt secondary to pulmonary hypertension.

Tetralogy of Fallot (choice C) and transposition of great arteries (choice D) cause cyanosis
and are usually diagnosed in infancy.

Ventricular septal defect (choice E) might remain undiagnosed until adulthood, but would not
cause notching of the ribs.
 47

A newborn child is noted to have a bulky abdominal tumor. CT scans reveal that the mass involves the
right abdomen and retroperitoneum. The tumor is resected, revealing ganglion cells and
primitive, small, round cells occasionally organized in rosettes, embedded in a fibrillary pink
matrix. Special studies confirm the likely diagnosis. Which of the following features of this
tumor is associated with a poorer prognosis?

A. Amplification of N-myc gene

B. Cellular aneuploidy

C. Diagnosis at birth

D. Numerous ganglion cells

E. Tumor spread into right kidney

Explanation:

The correct answer is A. Neuroblastoma is a childhood tumor of the sympathetic nerves, which
most commonly arises along the paravertebral chain or within the adrenal medulla. Neuroblastoma
has two characteristic genetic markers: a 1p deletion and an N-myc translocation. N-myc is an
oncogene that resides on chromosome 2p, and is amplified up to 300 times in neuroblastoma.
Amplification of this gene is associated with a poorer prognosis.

Cellular aneuploidy (choice B) and hyperdiploidy reflect a better prognosis for neuroblastoma,
whereas diploid and tetraploid tumors have an intermediate or poor prognosis.

Tumor presentation at a younger age predicts a better outcome for neuroblastoma. Children under
one year of age (choice C) have an excellent prognosis, regardless of tumor stage.

Ganglion cells (choice D) within the tumor are a reflection of focal differentiation of the
neuroblastoma into ganglioneuroma. Better differentiated tumors have a more favorable outcome.

In general, tumor stage is not very predictive of neuroblastoma survival. Nonetheless, higher
grades of tumor (III and IV) extend across the vertebral midline and into distal viscera or
nodes (choice E).