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A pregnant woman presents at 22 weeks gestation for a routine prenatal visit. Physical examination
demonstrates ankle edema and new onset hypertension. Urinalysis reveals marked proteinuria.
Development of which of the following would justify a diagnosis of eclampsia?
A. Diabetes mellitus
B. Hyperuricemia
C. Seizures
D. Systemic lupus erythematosus
E. Thrombocytopenia
Explanation:
The correct answer is C. A pregnant patient is considered to be in preeclampsia if she develops
hypertension, proteinuria, and edema. Eclampsia includes the addition of seizures to the triad.
Approximately 7 percent of pregnant women develop preeclampsia, typically between 20 weeks
gestation to 6 weeks postpartum. Predisposing conditions include pre-existing hypertension,
diabetes (choice A), and autoimmune diseases such as lupus (choice D). Laboratory features can
include hyperuricemia (choice B) and thrombocytopenia (choice E), but these are not used to
define the presence of eclampsia.
A 65-year-old woman presents to the emergency room with a pathologic fracture of the shaft of her
humerus. X-ray studies demonstrate multiple lytic and blastic bone lesions. Biopsy of one of
these lesions shows adenocarcinoma. Which of the following is the most likely source of the
primary tumor?
A. Breast
B. Colon
C. Kidney
D. Lung
E. Thyroid
Explanation:
The correct answer is A. Breast cancer is unusual in that it produces both lytic and blastic
metastases to bone. Breast and prostate cancers are the most common sources of bone metastases,
but prostate metastases are usually blastic.
Colon cancer (choice B) does not usually metastasize to bone.
Kidney cancer (choice C), lung cancer (choice D), and thyroid cancer (choice E) produce lytic
lesions when they metastasize to bone.
Physical examination of a 14-year-old boy demonstrates six coffee-colored skin macules up to 3 cm in
diameter. No other skin lesions are noted, but a small mass lesion is felt in the subcutaneous
tissues below two of the macules. These masses are most likely closely associated with which of
the following structures?
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A. Arrector pili
B. Hair follicles
C. Peripheral nerves
D. Sebaceous glands
E. Sweat glands
Explanation:
The correct answer is C. The lesions are café au lait spots. Isolated café au lait spots are
common in the general population, but more than 3 or 4 café au lait spots suggests the
possibility of neurofibromatosis. Apparently, the peripheral nerve tumors (neurofibromas) that
are part of this syndrome sometimes induce hyperpigmentation of the overlying skin, producing
the café au lait spots.
The arrector pili (choice A) are the small muscles of the hair follicle that give rise the
sensation of "goose-bumps"; it is thought that some leiomyomas of the skin may arise from these
tiny muscles.
Hair follicles (choice B), sebaceous glands (choice D), and sweat glands (choice E) can give
rise to a variety of benign and, very rarely, malignant tumors of the skin that do not usually
involve subcutaneous tissues.
During a routine physical examination, a 45-year-old woman is noted to have a ruddy complexion. Her
hematocrit is 52%. Her lungs are clear and she does not smoke. Serum erythropoietin levels are
elevated. Cancer of which of the following organs is the most likely cause of her increased
hematocrit?
A. Breast
B. Colon
C. Kidney
D. Stomach
E. Thyroid
Explanation:
The correct answer is C. The kidney normally produces erythropoietin, which stimulates the
erythroid cell line in the bone marrow. Renal cell carcinoma can lead to overproduction of
erythropoietin and thereby cause secondary polycythemia. Other causes of secondary polycythemia
are diseases that impair oxygenation, including pulmonary diseases (including smoking) and
congestive heart failure.
Breast cancer (choice A) can present as an axillary mass or as Paget's disease of the nipple.
Colon cancer (choice B) and stomach cancer (choice D) can present with anemia secondary to
blood loss.
Thyroid cancer (choice E) can present with hypothyroidism.
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A patient with respiratory symptoms undergoes bronchoalveolar lavage. Which of the following findings
would be most suggestive that congestive heart failure is the cause of the symptoms?
A. Ciliated bronchial epithelial cells
B. Encapsulated pairs of small cocci
C. Hemosiderin-laden macrophages
D. Rhomboid-shaped crystals
E. Single hat-shaped structures that stain with silver stains
Explanation:
The correct answer is C. Hemosiderin-laden macrophages are sometimes called "heart failure
cells" because they are so often seen in congestive heart failure. The congestive heart failure
causes increased pulmonary capillary pressure with tiny hemorrhages. The pulmonary alveolar
macrophages phagocytize the dead erythrocytes and retain the iron from the hemoglobin in the
form of hemosiderin.
Ciliated bronchial epithelial cells (choice A) are a normal finding.
The cocci described in choice B are pneumococcus, and can cause pneumonia.
Choice D describes Charcot-Leyden crystals, found in allergic asthma.
Choice E describes the Pneumocystis organism, which can infect AIDS patients.
A 78-year-old woman is brought to the emergency department because of slowly developing confusion
over
the past ten days. Careful physical examination demonstrates a relatively small laceration of
the scalp. CT of the head would be most likely to reveal which of the following?
A. Epidural hematoma
B. Mixed parenchymal and subarachnoid hemorrhage
C. Multiple tiny hemorrhages of the putamen
D. Subarachnoid hemorrhage
E. Subdural hematoma
Explanation:
The correct answer is E. This history is fairly typical for subdural hematoma. Usually, the
patient is elderly or alcoholic and has some degree of brain atrophy, causing the brain to pull
slightly away from the skull. This stretches the bridging (penetrating) veins that cross the
skull to connect to the cranial venous sinuses, leaving them very vulnerable to rupture after
minor head trauma. This type of hematoma is due to venous, rather than arterial, hemorrhage and
thus tends to develop rather slowly.
Epidural hematoma (choice A) is seen following severe head trauma causing laceration of the
middle meningeal artery.
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Mixed parenchymal and subarachnoid hemorrhage (choice B) can be seen with bleeding from AV
malformations.
Multiple tiny hemorrhages of the putamen (choice C) are intraparenchymal hemorrhages associated
with severe hypertension.
Subarachnoid hemorrhage (choice D) can be seen with bleeding from ruptured berry aneurysms.
A liver biopsy from a 54-year-old man shows many Mallory bodies. This finding is most suggestive of
which of the following diseases?
A. Alcohol abuse
B. Alpha1-antitrypsin deficiency
C. Hepatitis A
D. Hepatitis B
E. Wilson's disease
Explanation:
The correct answer is A. Mallory bodies are eosinophilic cytoplasmic inclusions ("alcoholic
hyaline") that are found in the largest numbers in alcoholic hepatitis. They were originally
considered to be pathognomic of alcohol abuse, but have since been found (in much smaller
numbers) in many other liver conditions.
Alpha1-antitrypsin deficiency (choice B) involvement of the liver is characterized by periodic
acid Schiff (PAS)-positive cytoplasmic granules in hepatocytes.
Hepatitis A (choice C) and hepatitis B (choice D) infections are definitively established with
serologic markers.
In Wilson's disease (choice E), there is excess copper deposition in the liver.
A pathologist examining electron micrographs of glomeruli sees prominent deposits between the podocytes
and the basement membrane of the glomerular capillaries. These findings are most likely related
to prior infection with which of the following genera?
A. Escherichia
B. Klebsiella
C. Neisseria
D. Pseudomonas
E. Streptococcus
Explanation:
The correct answer is E. The disease is post-infectious glomerulonephritis, which is usually
related to prior sore throat or skin infection by Streptococcal species; Staphylococcus also
causes some cases. The prominent deposits are also known as subepithelial humps, and consist of
immunoglobulin and complement.
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Gram-negative rods such as Escherichia(choice A), Klebsiella (choice B), and Pseudomonas
(choice D) have not been implicated as significant causes of post-infectious
glomerulonephritis.
The gram-negative cocci Neisseria(choice C) have not been implicated in post-infectious
glomerulonephritis.
About one week after birth, a premature infant develops acute abdominal distress with gastrointestinal
bleeding, large intestinal perforation, and sepsis. Which of the following conditions should be
suspected?
A. Crohn's disease
B. Diverticulosis
C. Necrotizing enterocolitis
D. Pseudomembranous colitis
E. Ulcerative colitis
Explanation:
The correct answer is C. This question illustrates the typical presentation of necrotizing
enterocolitis. This frequently fatal condition is unfortunately fairly common in premature and
low-birth-weight infants and appears to have a multifactorial origin, with intestinal ischemia,
microbial agents, and a poor gastrointestinal immune response being major contributing factors.
None of the other conditions listed in the choices would usually be seen in a neonate.
Crohn's disease (choice A), also known as regional enteritis, is a type of inflammatory bowel
disease that affects the colon and small intestine. It usually manifests in the teens or early
twenties, but milder cases may not be diagnosed until later in life.
Diverticulosis (choice B) is prevalent in older individuals.
Pseudomembranous colitis (choice D) is seen in the setting of broad-spectrum antibiotic use.
Ulcerative colitis (choice E) is a form of inflammatory bowel disease typically diagnosed in
young adults.
An infant born to German-American parents presents with mild anemia, jaundice, and splenomegaly. A
complete blood count with differential reveals spherocytosis; the reticulocyte count is
elevated. The parents state that several relatives have also suffered from a similar illness.
The infant's condition is most likely caused by defective
A. clathrin
B. connexon
C. dynein
D. spectrin
E. tubulin
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Explanation:
The correct answer is D. The infant is suffering from hereditary spherocytosis, a disease that
can result from defective erythrocyte cytoskeletal proteins such as spectrin or ankyrin.
Spectrin is a cytoskeletal protein in the erythrocyte that binds to the ankyrin/band 3 protein
complex. It also binds to a protein 4.1/actin complex to form a stable supporting cytoskeletal
network just below the plasma membrane. This helps to maintain the biconcave shape of the cell.
Defective spectrin can lead to a destabilization of this network and a tendency of the affected
cells to assume a spherical shape and become osmotically fragile. Such cells often become
trapped in the splenic cords, and are subsequently destroyed by phagocytes. This can lead to
hemolytic anemia, jaundice and splenomegaly.
Clathrin (choice A) is a protein found on the cytoplasmic side of the plasma membrane. It is
located within the coating of the so-called coated pits seen in electron micrographs of cells
engaged in receptor-mediated endocytosis.
Connexon (choice B) is a protein found in gap junctions, usually aggregated around the aqueous
pores within the junctional area.
Dynein (choice C) is an ATPase protein responsible for the interaction and sliding of
microtubule doublets, resulting in the bending of cilia and flagella.
Tubulin (choice E) is a protein that exists in alpha and beta forms that polymerize to form
microtubules.
A 43-year-old man presents to his physician with complaints of fatigue. Physical examination is
remarkable for hypertension. Laboratory examination reveals anemia, elevated blood urea nitrogen
(BUN), and elevated creatinine. Which of the following conditions would best account for this
presentation?
A. Adult polycystic kidney disease
B. Lipoid nephrosis
C. Poststreptococcal glomerulonephritis
D. Renal cell carcinoma
E. Wilms' tumor
Explanation:
The correct answer is A. Adult polycystic disease is characterized by kidneys that
progressively enlarge as a consequence of multiple renal cysts. Presenting signs (typically
beginning when patients are in their 40s), include hypertension (secondary to renin
production), renal failure (with elevated BUN and creatinine), and anemia (secondary to a
failure of renal erythropoietin production). This autosomal dominant condition also causes
cysts in other organs (liver, pancreas, spleen, gonads), berry aneurysms (the rupture of which
may cause death), and abnormalities of cardiac valves.
Lipoid nephrosis (choice B), or minimal change disease, is the most common cause of nephrotic
syndrome in children, and is not usually associated with renal failure.
Poststreptococcal glomerulonephritis (choice C) usually presents with hematuria following a
bout of streptococcal pharyngitis.
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Renal tumors typically present either as a mass or with hematuria. Renal cell carcinoma (choice
D) generally affects adults, while Wilms' tumor (choice E) is an early childhood tumor.
A hospital laboratory is sent blood samples from six patients with six different diagnoses. A blood
smear from one sample shows a reduced number of normochromic, normocytic erythrocytes, with
numerous schistocytes. This blood sample has been probably drawn from the patient with
A. acute blood loss
B. chronic autoimmune gastritis
C. disseminated intravascular coagulation
D. immune-mediated hemolysis
E. iron deficiency
F. thalassemia minor
Explanation:
The correct answer is C. Simply put, schistocytes are fragments of red blood cells of different
shapes and sizes. They are derived from mechanical damage to circulating erythrocytes, which
results in a form of anemia referred to as microangiopathic hemolytic anemia. There are two
main causes of this form of anemia: disseminated intravascular coagulation (DIC) and prosthetic
valves. DIC is due to widespread and uncontrolled activation of the coagulation cascade,
leading to formation of microthrombi throughout the circulation. Erythrocytes become fragmented
as they squeeze through narrowed arterioles and capillaries.
Acute blood loss (choice A) is followed by reduced circulating blood volume. In the acute
phase, a sample of blood may appear entirely normal. Only following hemodilution does a
normocytic normochromic anemia becomes apparent.
Chronic autoimmune gastritis (choice B) is associated with autoantibodies that block the
binding of intrinsic factor to vitamin B12, leading to deficient B12 absorption and
megaloblastic anemia. Abnormally large (macrocytic) red blood cells and hypersegmented
neutrophils are the diagnostic features of this form of anemia.
Immune-mediated hemolysis (choice D) is due to agglutinins that can be classified as warm (IgG
type) or cold (IgM type) according to whether the Coombs test is positive at 37 C or 0-4 C.
Agglutinins binding red blood cells may cause acute or chronic anemia by intravascular or
extravascular coagulation. Unconjugated hyperbilirubinemia is usually present, and the anemia
is normochromic and normocytic. Schistocytes are not observed.
Any form of iron-deficiency anemia (choice E), whether due to decreased absorption or to
chronic blood loss, is characterized by small (microcytic) and pale (hypochromic) erythrocytes.
Thalassemia (choice F) is a genetic condition caused by mutations of the genes coding for the
globin chains. Patients homozygous for mutations in the β-globin genes are affected by a
severe form of chronic anemia, referred to as thalassemia major, because of severely reduced or
absent β-globin synthesis. Heterozygous individuals have the β-thalassemia trait and
manifest a clinical picture known as thalassemia minor. They are usually asymptomatic, but the
peripheral blood smear shows microcytic erythrocytes, similar to those observed in irondeficiency anemia.
A 45-year-old man presents to a clinician because of a "bulge in his neck." Physical examination
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demonstrates an enlargement of the patient's thyroid gland. Needle aspiration of the thyroid
demonstrates cell clusters that are suspicious for papillary carcinoma of the thyroid. Which of
the following findings would most strongly support this diagnosis?
A. Anitschkow cells
B. Auer rods
C. Psammoma bodies
D. Reed-Sternberg cells
E. Roth's spots
Explanation:
The correct answer is C. Features of papillary carcinoma of the thyroid on aspiration include
papillary clusters, "Orphan Annie" nuclei, and psammoma bodies. Psammoma bodies are laminated,
concentric, calcific spherules seen most frequently in papillary adenocarcinoma of the thyroid,
serous papillary cystadenocarcinoma of the ovary, meningioma, and malignant mesothelioma.
Anitschkow cells (choice A) are activated histiocytes found in rheumatic heart disease.
Auer rods (choice B) are cytoplasmic inclusions found in promyelocytic leukemia cells.
Reed-Sternberg cells (choice D) are typically binucleate (or contain bilobed nuclei) with
prominent "owl's eyes" nucleoli cells found in Hodgkin's disease.
Roth's spots (choice E) are pale retinal spots surrounded by hemorrhage seen in endocarditis.
A blood sample from a patient with polycythemia vera is sent for complete blood count. Which of the
following blood components is most likely to be reported within normal limits?
A. Lymphocytes
B. Neutrophils
C. Platelets
D. Red blood cells
E. White blood cells
Explanation:
The correct answer is A. Polycythemia vera is an example of a myeloproliferative disorder, a
neoplastic disease of multipotential myeloid stem cells with the capacity to differentiate into
erythrocytes, megakaryocytes, or granulocytes. The only hematologic cell line which is not
increased in polycythemia vera is the lymphocytic line, and the lymphocyte count is generally
normal. The complications of polycythemia vera are generally due to increased blood viscosity
and a tendency toward thrombosis. Without regular phlebotomy, death usually occurs within
months of diagnosis.
Increased megakaryocyte production often produces platelet counts (choice C) above 500,000
cells/ml.
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Dramatic increases in erythroid cell production (choice D) dominate the hematologic picture in
polycythemia vera, and patients may have hematocrits as high as 60%.
Clonal expansion of granulocyte precursors leads to markedly increased neutrophil counts
(choice B) and white blood cell counts (choice E).
A patient presents to an ophthalmologist complaining of difficulty reading in the afternoons and
evenings because his eyelids get "too heavy" and he gets double vision. The ophthalmologist is
concerned about a paraneoplastic syndrome because the patient also has a recent unexplained 20
lb weight loss. Which of the following tumors would be most likely to produce this patient's
symptoms?
A. Breast carcinoma or renal cell carcinoma
B. Bronchogenic carcinoma or intracranial neoplasm
C. Lymphoma or myeloma
D. Renal cell carcinoma or parathyroid adenoma
E. Thymoma or bronchogenic carcinoma
Explanation:
The correct answer is E. The patient is suffering from myasthenia gravis, which is caused by an
autoimmune attack on the nicotinic acetylcholine receptor of the skeletal muscle motor end
plate. Symptoms include early muscle fatigue, often beginning with the small, active muscles
around the eyes. Myasthenia gravis can be associated with thymoma and bronchogenic carcinoma.
Hypercalcemia can be produced as a paraneoplastic effect in lytic bony metastases, squamous
cell lung cancer, breast cancer (choice A), renal cell carcinoma (choices A and D), multiple
myeloma (choice C), and parathyroid adenomas (choice D).
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) can be produced by
bronchogenic carcinoma and intracranial neoplasms (choice B).
Which of the following cardiac complications may develop in a 33-year-old woman with systemic lupus
erythematosus (SLE) because of her underlying condition?
A. Hemorrhagic pericarditis
B. Infective endocarditis
C. Libman-Sacks endocarditis
D. Mitral valve prolapse
E. Myocardial fibrosis
Explanation:
The correct answer is C. Libman-Sacks endocarditis affects patients with systemic lupus
erythematosus (SLE). Small granular vegetations consisting of fibrin develop on the
undersurface of the leaflets of mitral and aortic valves. Fragments of vegetations may detach,
resulting in embolism. Eventually, vegetations heal by organization of fibrin and subsequent
fibrosis, leading to distortion of valve leaflets and resultant insufficiency or stenosis. The
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pathogenesis is unclear but is probably related to thrombotic diathesis.
Hemorrhagic pericarditis (choice A) is usually a consequence of tuberculosis or metastatic
spread of cancer to the pericardium. An exudate containing blood accumulates in the pericardial
sac, producing pain and a characteristic auscultatory phenomenon known as a pericardial rub.
SLE is associated instead with fibrinous pericarditis, which also manifests with chest pain and
pericardial rub.
Infective endocarditis (choice B) is prevalent in patients with damaged or prosthetic valves
and in intravenous drug abusers. It is associated with formation of bulky, friable vegetations
that consist of masses of fibrin, neutrophils, and bacteria. Such vegetations cause extensive
destruction of valve leaflets and may release fragments into the bloodstream, with resultant
septic embolism.
There is no association between SLE and mitral valve prolapse (choice D), which is a frequent,
usually asymptomatic, valvular abnormality that occurs in 2% to 3% of the general population.
Mitral valve prolapse is also associated with Marfan syndrome. Complications include sudden
death, thromboembolism, and mitral regurgitation.
Myocardial fibrosis (choice E) does not occur in SLE. It develops in progressive systemic
sclerosis, a collagenopathy characterized by extensive fibrosis in many organs, especially
skin, lungs, and gastrointestinal tract. The heart is involved in 30% of cases. Myocardial
fibrosis may cause arrhythmias.
A 27-year-old female feels a lump in her breast and schedules an appointment with her doctor for
examination. A tissue biopsy is taken and examined, with multiple areas showing only benign
features. Which of the following findings implies an increased risk of subsequently developing
invasive carcinoma?
A. Apocrine metaplasia
B. Blue-domed cysts of Bloodgood
C. Duct ectasia
D. Intraductal papilloma
E. Sclerosing adenosis
Explanation:
The correct answer is E. Sclerosing adenosis is a type of proliferative fibrocystic disease
that is often seen with other variants of fibrocystic disease. It is a proliferation of small
ducts and myoepithelial cells near the terminal duct lobular unit. It also is characterized by
fibrosis that distorts the glands and lobules into a whorled pattern. The demonstration of this
on biopsy, as with other proliferative fibrocystic changes, implies an increased risk for
subsequent invasive breast cancer.
Apocrine metaplasia (choice A) is the term used to describe a transformation of ductal
epithelial cells to eosinophilic cells resembling apocrine sweat gland epithelium. This is a
benign, common, non-proliferative change that is not associated with increased cancer risk.
A blue-domed cyst of Bloodgood (choice B) is a fluid-filled cyst, sometimes up to 5 cm in size,
that appears blue grossly before it is incised. When incised, the fluid is serous and darkcolored. These cysts are part of benign non-proliferative fibrocystic disease and do not carry
increased cancer risk.
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Duct ectasia (choice C) is characterized by a large dilated duct with inspissated material. It
is associated with periductal inflammation and fibrosis of the large collecting ducts under the
areola. It is common in elderly women, although the cause is not clear. There is no increased
risk of cancer.
Intraductal papilloma (choice D) is a benign tumor that occurs in the large subareolar ducts.
It is usually solitary and found in middle-aged-to-elderly females. Clinically, it mimics
cancer and may be associated with nipple discharge. It is covered with benign epithelium and
attached to the duct by a fibrovascular stalk. A solitary lesion is not precancerous nor is it
a risk for subsequent cancer.
A 40-year-old man develops progressive weakness culminating in paralysis. Both upper and lower motor
neurons are lost in this man's disease. Over the course of a decade, the disease progresses to
complete paralysis of all voluntary muscles, and he dies in respiratory failure. At autopsy,
which CNS sites would show the most marked neuronal loss?
A. Caudate
B. Cerebellum
C. Globus pallidus
D. Spinal cord
E. Substantia nigra
Explanation:
The correct answer is D. Amyotrophic lateral sclerosis (ALS) is a devastating disease
characterized by degeneration of both upper and lower motor neurons. Depending on the stage of
this disease, patients may primarily experience either upper motor symptoms (hyperreflexia,
spasticity, Babinski reflex) or lower motor symptoms (weakness, muscular atrophy,
fasciculations). The upper motor neurons are located in the motor area of the cerebral cortex;
the lower motor neurons are located in the anterior horn of the spinal cord. The physicist
Steven Hawking has the disease. There is as yet no effective therapy.
The caudate (choice A) is damaged in Huntington disease, characterized by choreiform movements.
The cerebellum (choice B) is damaged in spinocerebellar degenerative diseases, including
Friedreich ataxia and olivopontocerebellar atrophy, both of which have ataxia as a prominent
symptom.
The globus pallidus (choice C) degenerates in striatonigral degeneration, which resembles
Parkinson disease.
The substantia nigra (choice E) is damaged in Parkinson disease, characterized by tremor and
difficulty initiating movements.
A 35-year-old retarded man with a strong history of mental retardation among male relatives undergoes
genetic testing. His lymphocytes are cultured in a medium containing methotrexate and 4% of the
metaphase chromosomes in the lymphocytes show a breakpoint at q27.3 on the X chromosome. This
man is at increased risk for which of the following cardiovascular disorders?
A. Aortic stenosis
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B. Atrial septal defect
C. Mitral valve prolapse
D. Tricuspid atresia
E. Ventricular septal defect
Explanation:
The correct answer is C. The disease is Fragile X Syndrome, which is a familial form of mental
retardation that is roughly as common as Down's syndrome. The phenotype has a variable
expression, but can include large head circumference at birth, perinatal complications
(premature birth, asphyxia, seizures), and possibly increased incidence of sudden infant death
syndrome. Later, mental retardation, particularly involving language, and symptoms suggestive
of attention deficit disorder and/or autism may appear. Features suggestive of connective
tissue disorder (lax skin and joints, flat feet, large ears) are common. After puberty, there
may be a long narrow face with prominent jaw and nasal bridge. Macro-orchidism is also common
after puberty. Mitral valve prolapse and aortic root dilatation, which may appear in late
adolescence or adulthood, are among the most serious complications of this disorder.
Aortic regurgitation related to aortic root dilatation, not stenosis (choice A), can be a
problem in this population.
Common congenital cardiac malformations such as atrial septal defect (choice B) or ventricular
septal defect (choice E) are not features of Fragile X syndrome, but can be seen with Down's
syndrome.
Tricuspid atresia (choice D) is a serious congenital cardiac malformation limiting flow into
the right ventricle, but it is not part of Fragile X syndrome.
A 52-year-old woman complains of generalized itching. On examination, she has mild jaundice, and
laboratory evaluation reveals elevated conjugated bilirubin and increased alkaline phosphatase.
A liver biopsy shows granulomatous inflammation centered on small bile ducts within the portal
spaces. Which of the following findings would support the diagnosis of primary biliary
cirrhosis?
A. Antimitochondrial autoantibodies
B. Decreased serum ceruloplasmin
C. Elevated liver enzymes
D. Hypoalbuminemia
E. Prolonged prothrombin time
Explanation:
The correct answer is A. Primary biliary cirrhosis is characterized by chronic granulomatous
inflammation leading to destruction of medium-sized intrahepatic bile ducts. A cholestatic
picture develops, with conjugated hyperbilirubinemia and increased alkaline phosphatase.
Itching is due to elevated levels of circulating bile salts. The disease predominantly affects
middle-aged women and typically progresses to cirrhosis. Ninety percent of patients have
circulating antimitochondrial autoantibodies, which may play a pathogenetic role.
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Decreased serum ceruloplasmin (choice B) suggests Wilson disease, an inherited condition
characterized by accumulation of copper in the liver, brain, and eye. Increases in hepatic
copper content and urinary copper excretion are diagnostically important findings.
Elevated liver enzymes (choice C) result from any condition causing damage to hepatocytes, with
release of enzymes (such as AST and ALT) into the bloodstream. Thus, this finding is not
specific for any particular type of cirrhosis or liver disease.
Hypoalbuminemia (choice D) is caused by liver failure of any etiology and results from
decreased hepatocyte protein synthesis.
Prolonged prothrombin time (choice E) is also an effect of liver failure of any cause.
Coagulopathy is attributable to impaired synthesis of clotting factors II, VII, IX, and X.
A 45-year-old woman develops abdominal and pelvic discomfort. Physical examination reveals a large
mass
in the right lower quadrant, which is surgically resected. The mass consists of a large (25 cm)
cystic sac containing thick mucinous fluid within a thin wall. On careful inspection, the
pathologist finds an area of increased thickness in the cyst wall, which is sampled for
histology. Microscopically, the tumor appears to be composed mostly of a single layer of
nonciliated columnar cells arranged in papillary projections. The thickened area, however,
displays stratification of epithelial cells, increased cytologic atypia, and high mitotic
activity. Nevertheless, no stromal invasion is found. Which of the following is the most likely
diagnosis?
A. Borderline mucinous tumor
B. Mucinous cystadenocarcinoma
C. Mucinous cystadenoma
D. Serous cystadenocarcinoma
E. Serous cystadenoma
Explanation:
The correct answer is A. Classification of ovarian tumors, like testicular tumors, is based on
putative cell of origin. Thus, ovarian tumors can be divided into neoplasms of germ cells,
surface epithelium, or stromal origin. Two thirds of all ovarian neoplasms derive from the
surface (coelomic) epithelium. These cystic tumors may contain clear serous fluid or turbid
mucinous fluid. Depending on whether a tumor is benign or malignant, surface epithelium tumors
can be differentiated into serous cystadenoma or cystadenocarcinoma, and mucinous cystadenoma
or cystadenocarcinoma. How about borderline tumors? These are intermediate cases in which the
epithelial lining shows malignant features (cytologic atypia and architectural disorganization)
in the absence of stromal invasion. Thus, microscopic features of the ovarian tumor in this
case are consistent with a borderline mucinous tumor.
Mucinous cystadenocarcinoma (choice B) shows obvious signs of malignancy, including foci of
invasion of the stroma within the cystic wall.
Mucinous cystadenoma (choice C) is a cystic tumor with a mucin-rich fluid content. The
epithelial lining is similar to intestinal or cervical epithelium, ie, a single layer of
columnar cells with apical mucin and no cilia.
Serous cystadenocarcinoma (choice D) is the most frequent malignant ovarian tumor. Its
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epithelial lining is composed of columnar cells showing atypia and crowding. By definition,
stromal invasion is present.
Serous cystadenoma (choice E) is the benign counterpart of serous cystadenocarcinoma. Ciliated
columnar epithelial cells line the neoplasm in an orderly single layer.
CT scan of the head in a patient who had been in an automobile accident fails to demonstrate a pituitary
gland. Endocrine evaluation demonstrates serum hormones are all within normal limits. Which of
the following is the most likely diagnosis?
A. Craniopharyngioma
B. Empty sella syndrome
C. Hypothalamic suprasellar tumor
D. Large pituitary adenoma
E. Pituitary microadenoma
Explanation:
The correct answer is B. Empty sella syndrome is an uncommon but dramatic condition in which
the pituitary radiologically appears to be completely missing from the sella turcica, which is
instead filled with cerebrospinal fluid (CSF). The most common cause is herniation of the
arachnoid through the diaphragm sella. This leads to excess local CSF production, in turn
causing pressure atrophy of the pituitary. Other causes include Sheehan's syndrome, infarction
of an adenoma followed by scarring of the remaining pituitary, and surgery or radiation
therapy. Most patients with empty sella syndrome have sufficient residual pituitary parenchyma
to prevent hypopituitarism.
Craniopharyngiomas (choice A) can produce a mass that involves the pituitary.
Hypothalamic suprasellar tumors (choice C), including craniopharyngiomas, can produce a mass
that involves the pituitary.
Large pituitary adenomas (choice D) usually produce a mass lesion. They can infarct and produce
empty sella syndrome, but this is rare.
Pituitary microadenoma (choice E) would produce no visible radiographic changes.
A patient presents to a physician complaining of recurrent episodic diarrhea, triggered by eating too
much or drinking alcohol. His wife states that "he turns as red as a beet, starts wheezing, and
looks just ghastly" during these episodes. Chest x-ray demonstrates a lung mass. Which of the
following would be most likely to be present on biopsy of the lesion?
A. Bronchioloalveolar carcinoma
B. Carcinoid tumor
C. Primary tuberculosis
D. Recurrent tuberculosis
E. Squamous cell carcinoma
15
Explanation:
The correct answer is B. The patient has carcinoid syndrome, in which vasoactive mediators
secreted by carcinoid tumors (typically of the lung or small bowel) produce recurrent diarrhea,
flushing, wheezing, and carcinoid heart disease. Although many substances may be produced by
these tumors, serotonin is one of the more important mediators produced, probably accounting
for the observed diarrhea.
Bronchioloalveolar carcinomas (choice A) are not particularly likely to secrete hormones.
Primary (choice C) and recurrent (choice D) tuberculosis can be uncommonly associated with
finger clubbing, or hypertrophic osteopathy, but not with carcinoid syndrome.
Squamous cell carcinoma (choice E) can cause hypercalcemia by producing circulating hormones
(humoral hypercalcemia of malignancy).
A patient develops a persistent macrocytic anemia. Serum folate levels are normal, but serum vitamin B12
levels are low. Oral vitamin absorption studies demonstrate that the patient is unable to
absorb vitamin B12 in adequate amounts. Cancer of which of the following organs is most
strongly associated with this patient's condition?
A. Colon
B. Duodenum
C. Esophagus
D. Ileum
E. Stomach
Explanation:
The correct answer is E. Megaloblastic anemia with poor vitamin B12 absorption suggests
pernicious anemia. In this condition, an autoimmune attack on gastric parietal cells leads to
atrophic gastritis with deficient synthesis of the intrinsic factor needed for vitamin B12
absorption. Vitamin B12 is required for DNA synthesis in blood cell precursors; deficiency
produces megaloblastic anemia. Chronic atrophic gastritis predisposes an individual to the
development of gastric carcinoma.
Predisposing factors for colon cancer (choice A) include familial polyposis syndromes,
inflammatory bowel disease, isolated adenomatous polyps, and diet.
Duodenal (choice B) and ileal (choice D) cancers are uncommon.
Predisposing factors for esophageal cancer (choice C) include Barrett's esophagus and PlummerVinson syndrome.
A diabetic mother gives birth to a baby who dies in the first week of life. Autopsy reveals a severe
cardiac malformation. Which of the following is the most likely diagnosis?
A. Atrial septal defect
B. Coarctation of the aorta
C. Eisenmenger's syndrome
16
D. Tetralogy of Fallot
E. Transposition of the great arteries
Explanation:
The correct answer is E. Maternal diabetes is best known for causing large but immature-for-age
babies. There is also a specific association between maternal diabetes and transposition of the
great vessels. In transposition of the great vessels, the aorta takes off from the anterior
part of the right ventricle and the pulmonary trunk takes off from the posterior part of the
left ventricle. This produces a complete separation of the systemic and pulmonary circulations.
Without surgical correction, most affected infants die within the first months of life,
although a patent ductus arteriosus, patent foramen ovale, or ventricular septal defect may
allow enough mixing of blood to temporarily sustain life.
In atrial septal defect (choice A) blood can pass from one atrium to the other.
Associate coarctation of the aorta (choice B) with Turner syndrome.
Eisenmenger's syndrome (choice C) is a shift from a left-to-right shunt to a right-to-left
shunt secondary to developing pulmonary hypertension.
Tetralogy of Fallot (choice D) consists of a ventricular septal defect, an overriding aorta,
pulmonic stenosis, and right ventricular hypertrophy. It is the most common cause of early
cyanosis.
A 10-year-old child with new onset of visual field abnormalities and diabetes insipidus undergoes a head
CT. The CT scan demonstrates a 3 cm mass lesion with focal calcification involving the area
above the sella turcica. Needle biopsy of this mass shows that the tumor is composed of tissue
resembling tooth enamel. Which of the following diagnoses is most likely?
A. Craniopharyngioma
B. Glioblastoma multiforme
C. Large pituitary adenoma
D. Medulloblastoma
E. Pituitary microadenoma
Explanation:
The correct answer is A. The tumor is a craniopharyngioma, alternatively known as an
adamantinoma or ameloblastoma. Craniopharyngiomas may arise in, or more commonly above, the
sella turcica. The histological pattern recapitulates the enamel organ of the tooth, with nests
or cords of stratified squamous or columnar epithelium embedded in a loose fibrous stroma.
Calcification (and even metaplastic bone formation) is common in these benign tumors, which are
thought to arise from vestigial remnants of Rathke's pouch.
Glioblastoma multiforme (choice B) characteristically shows at least some enlarged cells with
bizarre nuclei.
Large pituitary adenomas (choice C) contain nests of uniform glandular cells.
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Medulloblastoma (choice D) is made of small basophilic cells with relatively large nuclei for
their size.
Pituitary microadenomas (choice E) contain nests of uniform glandular cells.
A 25-year-old-man presents with weight loss, abdominal pain, and bloody diarrhea.
Sigmoidoscopy/colonoscopy reveal mucosal erythema and ulceration extending in a continuous
fashion proximally from the rectum. Which of the following pathologic findings would also be
characteristic of this patient's illness?
A. Bowel wall thickening
B. Cobblestone appearance of mucosa
C. Fistulas
D. Pseudopolyps
E. Transmural lesions
Explanation:
The correct answer is D. This is a question that tests your ability to distinguish between
ulcerative colitis (UC) and Crohn's disease. First, you need to figure out which one this
patient has. The key clues here are the bloody diarrhea (much more common in UC), the rectal
involvement, and especially, the continuous nature of the mucosal damage. Once you've figured
out that the patient has ulcerative colitis, you need to identify the answer choice that is
characteristic of UC. The correct answer is pseudopolyps, which are inflammatory polyps found
in ulcerative colitis and not Crohn's disease.
All of the other choices are features of Crohn's disease. Especially diagnostic is the
transmural nature of the inflammation, which can lead to the development of fissures and
fistulas. Remember also that while Crohn's can involve any part of the GI tract, it typically
does not involve the rectum and is usually found in the terminal ileum and/or colon. In
contrast to UC, the lesions are discontinuous (skip lesions).
Biopsy of a skin lesion shows marked intercellular edema that splays apart adjacent cells, leaving only
thin dark lines between the cells. What is this process called?
A. Acantholysis
B. Acanthosis
C. Hyperkeratosis
D. Parakeratosis
E. Spongiosis
Explanation:
The correct answer is E. Spongiosis is the name used for intercellular edema of the epidermis.
Fluid accumulates between the cells, pulling them apart. However, the intercellular connections
(desmosomes) remain largely intact. This produces a distinctive microscopic appearance in which
each cell is surrounded by a broad white band with tiny dark cross-stripes, somewhat
reminiscent of a closed zipper. The basic terms that describe skin lesions are a favorite
18
target on examinations.
Acantholysis (choice A) is the process of cell separation seen in some blistering diseases. The
intercellular connections are broken in acantholysis, producing "rounded-up" cells that are
dissociated from each other.
Acanthosis (choice B) is a marked thickening of the epidermis due to an increase in the number
and size of the epithelial cells.
Hyperkeratosis (choice C) is an increase in the thickness of the superficial keratin layer of
the epidermis.
The term parakeratosis (choice D) is used when nuclei are present in the normally anuclear
superficial keratin layer.
An elderly woman with a history of multiple oral ulcers presents with flaccid bullae on her scalp, face,
and trunk. Manual pressure on the skin produces separation of the upper layer of the epidermis,
followed by eventual sloughing of the skin. The patient has been in relatively good health
until recently, and denies taking any medications. A biopsy of one of the skin lesions reveals
separation of epithelial cells above the basal layer. Autoantibodies to which of the following
components would most likely be found in this patient?
A. Epidermal basement membrane proteins
B. Glycoprotein IIb/IIIa
C. Intercellular junctions of epidermal cells
D. Intrinsic factor
E. Type IV collagen
Explanation:
The correct answer is C. Bullae with the cleavage plane above the basal layer of the epidermis
suggests pemphigus vulgaris, which is caused by autoantibodies to intercellular junctions of
epidermal cells. The autoantibodies decrease the ability of the keratinocytes to adhere to one
another, permitting formation of vesicles and bullae. Oral involvement is common, and often
precedes the characteristic skin lesions. Separation of the epidermis upon manual stroking of
the skin is known as Nikolsky's sign. This sign is present in other disorders such as StevensJohnson syndrome, but we are told the woman is not taking any medications, a typical cause of
Stevens-Johnson syndrome in the adult population.
Antibodies to epidermal basement membrane proteins (choice A) are seen in bullous pemphigoid,
which is a bullous disease characterized by blisters with a cleavage line between the epidermis
and dermis.
Antibodies to glycoprotein IIb/IIIa (choice B) are seen in autoimmune thrombocytopenic purpura.
Antibodies to intrinsic factor (choice D) are seen in pernicious anemia.
Antibodies to Type IV collagen (choice E) are seen in Goodpasture's syndrome.
A 60-year-old man who is being evaluated for abdominal pain and a 30-pound weight loss undergoes
endoscopy, which demonstrates a broad region of the gastric wall in which the rugae are
flattened. Biopsy of this area shows infiltration by numerous polygonal tumor cells with small,
19
dark, round or ovoid nuclei pushed to the margin of the cell by large, clear, cytoplasmic
structures. These cells might be expected to have which of the following properties?
A. Keratohyalin granules observed by electron microscopy
B. Melanosomes and premelanosomes by electron microscopy
C. Positive staining for gastrin by light microscopy
D. Positive staining for leukocyte common antigen by light microscopy
E. Positive staining for mucin by light microscopy
Explanation:
The correct answer is E. The tumor described is the linitis plastica form of gastric
adenocarcinoma, in which individual mucin-producing tumor cells diffusely infiltrate the mucosa
and muscularis propria to produce a rigid, thickened, "leather-bottle" gastric wall. This tumor
is poorly differentiated and has a poor prognosis.
Keratohyalin granules (choice A) are a feature of squamous cell carcinoma, which does not
usually occur in the stomach.
Melanosomes and premelanosomes (choice B) are observed with electron microscopy in melanocytic
lesions, including melanoma.
Positive immunostaining for gastrin (choice C) would be a feature of gastrin-secreting
carcinoids, which typically form small, yellow nodules composed of nests or cords of small
cells with centrally located, round-to-oval, stippled nuclei.
Positive immunostaining for leukocyte common antigen (choice D) is associated with lymphoma,
which can also affect the stomach, appearing similar to linitis plastica grossly.
Microscopically, however, the individual malignant lymphocytes usually have centrally located
nuclei, and lack the large, clear, cytoplasmic vacuoles described in this question.
Which of the following is the most frequent underlying cause of sudden cardiac death (SCD)?
A. Aortic valve stenosis
B. Congenital anomalies
C. Dilated cardiomyopathy
D. Hereditary anomalies of conduction system
E. Hypertrophic cardiomyopathy
F. Hypertrophy of heart, isolated or hypertensive
G. Ischemic heart disease
H. Mitral valve prolapse
I. Myocarditis
J. Pulmonary hypertension
20
Explanation:
The correct answer is G. About 300,000 to 400,000 individuals succumb to sudden cardiac death
(SCD) each year in the U.S. SCD is defined as any unexpected death of proven cardiac origin,
occurring either within 1 hour after the onset of symptoms or without the onset of symptoms. By
far the most common cause of SCD is ischemic heart disease (IHD), which is most frequently
related to atherosclerosis of the coronary arteries. In younger populations, the
nonatherosclerotic causes listed above are proportionately more frequent.
Aortic valve stenosis (choice A) is most commonly due to senile calcification of the valve
leaflets or a congenitally bicuspid valve.
Congenital anomalies (choice B and D) of the heart, whether involving the cardiac chambers and
valves or the conduction systems, should be strongly suspected in cases of SCD of a young
person.
Dilated cardiomyopathy (choice C) has numerous etiologies, whereas hypertrophic cardiomyopathy
(choice E) is more often familial.
Hypertrophy of the heart (increased cardiac mass) (choice F) is an independent risk factor for
SCD and may be associated with hypertension or increased physical activity (athletes).
Mitral valve prolapse (choice H) is a frequent anomaly in the general population and, although
usually asymptomatic, has been found in young victims of SCD.
Myocarditis (choice I) is usually caused by viral infections and may be asymptomatic, manifest
with slowly progressive heart failure, or lead to SCD.
Patients with pulmonary hypertension (whether primary or secondary) (choice J) are at increased
risk for SCD.
In summary, although IHD is the underlying cause in the majority of SCD cases,
nonatherosclerotic causes should be suspected in young victims or patients without evidence of
significant coronary artery disease.
A 40-year-old man with adult polycystic kidney disease is brought to the emergency room in a coma. CT
scan of the head demonstrates a subarachnoid hemorrhage without parenchymal hemorrhage. Which of
the following is the most likely source of the bleeding?
A. AV malformation
B. Bridging veins
C. Charcot-Bouchard aneurysm
D. Circle of Willis
E. Middle meningeal artery
Explanation:
The correct answer is D. Two relationships are useful in solving this problem. The first
relationship is that adult polycystic kidney disease has a specific association with berry
aneurysms involving the circle of Willis and its branches. The second relationship is that
spontaneous subarachnoid hemorrhages are most often the result of bleeding from berry
21
aneurysms. The berry aneurysms develop at sites of congenital weakness (near branch points) of
the relatively unsupported vessels of the circle of Willis.
AV malformations (choice A) tend to produce mixed parenchymal and subarachnoid hemorrhages.
Rupture of bridging veins (choice B) produces a subdural hematoma.
Rupture of Charcot-Bouchard aneurysms (choice C) can be seen with hypertension (which may
complicate adult polycystic kidney disease). Such rupture produces intraparenchymal hemorrhage,
which if severe, may spread to the subarachnoid space.
Rupture of the middle meningeal artery (choice E) produces epidural hematoma.
Following a weekend alcoholic binge, a patient is brought to the emergency room covered with vomit.
While there, he complains of severe pain of the chest and upper abdomen with radiation to the
left shoulder. The initial chest radiograph is normal. Despite an unremarkable EKG, the patient
is admitted for a presumptive or developing myocardial infarction. Over the next 24 hours, his
condition deteriorates and he goes into shock. Repeat x-ray shows extensive haziness in the lung
fields. Which of the following conditions is the most likely cause of the man's illness?
A. Boerhaave's syndrome
B. DiGeorge syndrome
C. Dressler's syndrome
D. Dubin-Johnson syndrome
E. Osler-Weber-Rendu disease
Explanation:
The correct answer is A. Boerhaave's syndrome is the eponymic name for lower esophageal
rupture. This condition is uncommon, but can follow straining and vomiting. The rupture allows
a high volume of gastric contents to enter the pleural space, and has a very high mortality
rate if the diagnosis is delayed beyond 24 hours (which is unfortunately rather common). The
pain involves the chest and upper abdomen, and can radiate to the back, left chest, or left
shoulder. The initial chest radiograph is often normal. Shock eventually develops. Treatment is
with surgical repair and drainage.
DiGeorge syndrome (choice B) is a failure of development of the third and fourth pharyngeal
pouches, which leads to absence of the parathyroid glands and thymus.
Dressler's syndrome (choice C) is pericarditis following a myocardial infarction.
Dubin-Johnson syndrome (choice D) is an inherited cause of conjugated hyperbilirubinemia.
In Osler-Weber-Rendu disease (choice E), also known as hereditary hemorrhagic telangiectasia,
multiple, small aneurysmal telangiectasias are present from birth in the skin, oral cavity,
alimentary tract, respiratory tract, urinary tract, liver, brain, and spleen.
A 60-year-old woman presents to a physician because her right knee is painful, swollen, and red.
Aspiration of the joint space demonstrates basophilic rhomboid crystals. Which of the following
is the most likely composition of the crystals?
A. Calcium pyrophosphate
22
B. Cholesterol
C. Cystine
D. Monosodium urate
E. Struvite
Explanation:
The correct answer is A. The disease is pseudogout, which is caused by deposition of calcium
pyrophosphate (basophilic rhomboid) crystals within the joint space. The disease tends to
affect older patients of both sexes and typically involves the knee or other large joints.
There is no entirely satisfactory treatment available, although colchicine administration may
protect against attacks and corticosteroids may be of some benefit.
Cholesterol (choice B) can form gallstones in association with obesity, high estrogen states,
multiparity, Crohn's disease, rapid weight loss, clofibrate therapy, and Native American
origin.
Cystine (choice C) and struvite (choice E) can form kidney stones.
Monosodium urate (choice D) is deposited in gout as needle shaped, negatively birefringent
crystals.
A 22-year-old patient presents with multiple neural tumors, Lisch nodules, and café au lait spots. He
informs the physician that his father, as well as one uncle and his paternal grandfather, had a
similar condition. This patient likely suffers from
A. ependymoma
B. Huntington's disease
C. Marfan's syndrome
D. neuroblastoma
E. neurofibromatosis type I
Explanation:
The correct answer is E. Neurofibromatosis type 1, or von Recklinghausen's disease, is an
autosomal dominant disorder with high penetrance, but variable expressivity. The disease has
three major features: (1) multiple neural tumors anywhere on or in the body; (2) numerous
pigmented cutaneous lesions (café au lait spots); and (3) pigmented iris hamartomas (Lisch
nodules). Electron micrographic studies show that the tumors are the result of the
proliferation of fibroblasts or Schwann cells in the peripheral nerves, possibly due to ras
inactivation. There is no treatment, except for surgical resection of symptomatic tumors.
Ependymoma (choice A) can occur wherever ependymal cells are found. They are more common in
children, and most often originate in the fourth ventricle. They are the most common
intramedullary glioma of the spinal cord.
Huntington's disease (choice B), an autosomal dominant disorder, is characterized by severe
degeneration of the caudate nucleus along with degenerative changes in the putamen and cortex.
23
In addition to chorea, these patients frequently suffer from athetoid movements, progressive
dementia, and behavioral disorders.
Marfan's syndrome (choice C) is due to a defect in the gene for fibrillin. The major clinical
findings involve the skeleton, cardiovascular system, and the eye. Affected individuals tend to
be tall with long extremities and long, tapering appendages. Mitral valve prolapse and
dilatation of the aortic valve ring or aortic dissection due to cystic medial degeneration are
common.
Neuroblastoma (choice D) is a rare tumor derived from ganglion cell precursors. It may arise
anywhere in the cerebral hemispheres and is typically encountered in children ranging in age
from 2 months to 9 years.
A 65 year-old man develops periumbilical pain which then localizes to the right lower quadrant. On
physical examination, his temperature is 100.5 degrees F rectally, and his abdomen is tender.
Which of the following is the most likely diagnosis?
A. Acute appendicitis
B. Diverticulitis
C. Gallstones
D. Pancreatitis
E. Pyelonephritis
Explanation:
The correct answer is B. Diverticulitis is a disease of the elderly, and usually involves the
distal colon. However, in severe cases, the diverticula may extend throughout the colon and up
to the cecum. Inflammation of a cecal diverticulum can closely mimic acute appendicitis.
Acute appendicitis (choice A) is usually a disease of young adults (and sometimes children).
Pancreatitis (choice D), pyelonephritis (choice E), and gall bladder disease (choice C), refer
pain to the mid back, lateral back, and right upper quadrant, respectively.
A baby is born with a large defect in the occipital bone through which the posterior portion of the
brain has herniated. Which of the following terms best describes this lesion?
A. Encephalocele
B. Meningocele
C. Myelocele
D. Spina bifida
E. Syringomyelia
Explanation:
The correct answer is A. The central neurons system and its overlying bones are subject to a
variety of malformations and developmental diseases. The defect described in the question stem
is a cranial encephalocele, in which brain herniates through a defect in the skull bones. The
24
most common site for such a herniation is the occipital bone. Small defects in the occipital
bone can be treated surgically, but large defects are very problematic, particularly if
significant herniation has occurred, since the brain becomes very vulnerable to trauma and
infection.
Meningocele (choice B) is the term used when the meninges, but not the brain or spinal cord,
herniate through a defect in the bony cranium or spinal column.
Myelocele (choice C) is the term used when the spinal cord herniates through a defect in the
spinal column.
Spina bifida (choice D) refers to vertebral defects through which the spinal cord or meninges
may herniate.
Syringomyelia (choice E) is a tubular, fluid-filled cavity within the spinal cord.
A 77-year-old smoker with hemoptysis and weight loss undergoes a left upper lobectomy for squamous cell
carcinoma. The uninvolved lung tissue shows destruction of the alveolar septae around the
respiratory bronchioles, with marked enlargement of the airspaces. Anthracotic pigment is
deposited heavily in the walls of these tissues. These findings are most compatible with
A. asthma
B. chronic bronchitis
C. emphysema
D. pulmonary hypertension
E. silicosis
Explanation:
The correct answer is C. Emphysema is a pulmonary disease characterized by enlargement of the
alveolar airspaces due to destruction of the septae without consequent fibrosis. The gross
appearance of emphysematous lungs is characteristic: alveoli are sufficiently dilated to allow
visualization with the naked eye, and destruction of structural support to lymphatic vessels
produces heavy pigment deposition in the tissue. Microscopic findings that confirm the
diagnosis include enlarged, round airspaces with club-like ends of broken septae sticking into
the alveoli.
Asthma (choice A) is a disease of airway hyperreactivity, and is characterized by hypertrophy
of the bronchial basement membranes and smooth muscle, with glandular hyperplasia and thick
mucus plugs in the bronchi.
Chronic bronchitis (choice B) produces marked hypersecretion of mucus in the large airways, and
can be identified by hypertrophy of mucous glands in the bronchi and goblet cell hyperplasia in
the smaller airways.
Pulmonary hypertension (choice D) affects neither the airways nor the alveoli. It is
characterized by thickening of the arterial smooth muscle with intimal hyperplasia and
fibrosis. Atherosclerotic changes in the normally plaque-free larger pulmonary arteries may be
seen.
Silicosis (choice E), one of the forms of pneumoconiosis, is an interstitial fibrosing disease
that produces thick pleural scars and dense nodules of collagen that may calcify. The silica
25
particles may be visualized within the nodules using polarized light.
A patient with chronic reflux esophageal symptoms undergoes endoscopy, which demonstrates islands of
red
tissue above the gastroesophageal junction. Biopsy of several of these lesions demonstrates
glandular epithelium with no atypical nuclei, with no invasion into the adjacent tissue. For
which of the following cancers does this lesion predispose?
A. Adenocarcinoma of the esophagus
B. Adenocarcinoma of the stomach
C. Sarcoma of the esophagus
D. Sarcoma of the stomach
E. Squamous cell carcinoma of the esophagus
F. Squamous cell carcinoma of the stomach
Explanation:
The correct answer is A. The lesion is Barrett's esophagus, which is related to chronic reflux
of gastric contents into the esophagus, and which predisposes for the development of
adenocarcinoma of the distal esophagus.
Conditions predisposing for adenocarcinoma of the stomach (choice B) include chronic atrophic
gastritis, pernicious anemia, and post-surgical gastric remnants.
Sarcoma of the esophagus (choice C) or stomach (choice D) is rare.
Plummer-Vinson syndrome predisposes for squamous cell carcinoma of the esophagus (choice E).
Squamous cell carcinoma of the stomach (choice F) is virtually non-existent.
A 63-year-old male with a 75-pack-year history of smoking and marked chronic obstructive pulmonary
disease (COPD) develops fevers and a persistent cough frequently tinged with blood. Chest x-ray
reveals a complex cavitary lesion in the right upper lobe. Bronchoscopic examination identifies
a large lung abscess from which pure Fusobacterium nucleatum is cultured. What is the most
likely source of the Fusobacterium?
A. Blood
B. Infected aerosols
C. Oral cavity
D. Stomach
E. Upper respiratory tract
Explanation:
The correct answer is C. Anaerobic lung abscesses commonly arise from aspirated oral secretions
in patients with compromised neurological status (e.g., anesthesia, coma, intoxication), or in
individuals with a depressed cough reflex. The most common anaerobic organisms isolated from
26
lung abscesses include Bacteroides, Fusobacterium, and Peptococcus species, all of which are
typical oral flora.
Blood-borne pathogens (choice A) producing lung abscesses probably originate as emboli from
vegetations on the right heart. The most likely pathogens in endocarditis are Staphylococcus
and Streptococcus species; Fusobacterium would be very unusual.
Fusobacterium usually is not pathogenic and lives in a commensal relationship with the host.
Infective aerosols (choice B) generally contain organisms that are intrinsically pathogenic
(e.g., mycobacteria, influenza virus).
It is the acidity of the gastric aspirate that most seriously injures the lung, not the gastric
bacteria. Fusobacterium do inhabit the gastrointestinal tract, but viable bacteria are much
more likely to be transmitted from the oral secretions than from the stomach (choice D).
The upper respiratory tract (choice E) is generally sterile, although COPD is frequently
complicated by chronic bronchitis. Numerous bacterial and viral pathogens can be involved in
chronic bronchitis; however, Fusobacterium is not an upper respiratory tract pathogen.
A 39-year-old female presents to her gynecologist for a checkup. An adnexal mass is palpated and an
ultrasound shows a 10 cm right ovarian cyst. Surgery is scheduled and the tumor is removed. The
patient is informed that the tumor is not overtly malignant, but is a "borderline" malignancy
and that a future complication may be pseudomyxoma peritonei. Which of the following types of
ovarian tumors was removed?
A. Brenner tumor
B. Clear cell tumor
C. Endometrioid tumor
D. Mucinous cystadenoma
E. Serous cystadenoma
Explanation:
The correct answer is D. Mucinous cystadenoma is a tumor that arises from the ovarian surface
epithelium and can be benign, borderline, or malignant. It occurs in middle-aged females and
contains mucin-secreting epithelial cells. If it is a borderline or malignant tumor then a rare
complication is pseudomyxoma peritonei. This is a condition in which large amounts of
gelatinous, sticky, myxoid material fills the abdominal cavity and causes adhesion and
obstruction of viscera. The myxoid material itself is not malignant, but the complications from
its presence are usually fatal.
Brenner tumors (choice A) can be benign, borderline, or malignant. They are composed of
epithelial nests that look like bladder epithelium. There is also a stromal component that
looks like ovarian stroma. Mucin may be produced in the center of the epithelial cells. They
are sometimes associated with mucinous cystadenomas, but alone are not associated with
pseudomyxoma peritonei.
Clear cell tumor (choice B) is a malignant ovarian epithelial tumor that has clear-appearing
cytoplasm due to glycogen content. It is rare and is usually associated with endometriosis and
coexistent endometrial carcinoma. They do not lead to pseudomyxoma peritonei.
Endometrioid tumor (choice C) is a neoplasm of ovarian surface epithelium that appears
27
histologically like endometrial glands and is almost always malignant. It is associated with
endometriosis and coexistent endometrial carcinoma. These do not lead to pseudomyxoma
peritonei.
Serous cystadenoma (choice E) is the most common tumor of ovarian surface epithelium. It is
usually cystic and filled with serous fluid. It may be benign, borderline, or malignant and
occur mostly between 20-50 years of age. Malignant tumors are called serous cystadenocarcinomas
and show more papillary structures with invasion. They do not lead to pseudomyxoma peritonei.
A 7-year-old girl contracts chicken pox from her sister. Five days after the onset of the rash, she
begins vomiting and becomes lethargic. She is seen in the emergency room, and admitted to the
hospital, after which she becomes comatose. Laboratory examination is significant for elevated
liver enzymes and ammonia. Which of the following is the most likely diagnosis?
A. Crigler-Najjar syndrome
B. Dubin-Johnson syndrome
C. Gilbert syndrome
D. Reye syndrome
E. Rotor syndrome
Explanation:
The correct answer is D. Reye syndrome (fatty liver with encephalopathy) is an acute (and
potentially fatal) post-viral injury that is characterized by severe mitochondrial damage
affecting the liver, brain, skeletal muscle, heart, and kidneys. Most patients are children,
although adult cases have been described. Varicella and influenza A and B are the most common
precipitating illnesses. Aspirin use has been linked to the development of this disorder, but
cases occur in the absence of salicylate ingestion.
Crigler-Najjar (choice A) syndrome is a rare, mild-to-severe form of inherited unconjugated
hyperbilirubinemia.
Dubin-Johnson syndrome (choice B) is an inherited conjugated hyperbilirubinemia associated with
a darkly pigmented liver.
Gilbert syndrome (choice C) is a relatively common, benign form of inherited unconjugated
hyperbilirubinemia.
Rotor syndrome (choice E) resembles Dubin-Johnson syndrome, but is associated with a normalcolored liver.
A 30-year-old man with a 15-year history of ulcerative colitis develops intermittent cholestatic
jaundice. Ultrasonographic examination fails to reveal gallstones. Liver biopsy demonstrates a
large bile duct obstruction. Which of the following would most likely be seen on endoscopic
retrograde cholangiopancreatography (ERCP)?
A. Beading of intrahepatic bile ducts
B. Markedly dilated common bile duct containing irregular radiolucent masses
C. Mass at the ampulla of Vater
28
D. Moderately dilated intrahepatic bile ducts and stricture in the bile duct at the
porta hepatis
E. Very dilated biliary tree terminating in a blunt, nipple-like obstruction at the
lower end of the common bile duct
Explanation:
The correct answer is A. The most likely diagnosis is primary sclerosing cholangitis, a
disorder with a probable autoimmune component that is associated with ulcerative colitis (2/3
of primary sclerosing cholangitis patients have a history of ulcerative colitis). The disease
is characterized by inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts,
producing alternating strictures and dilatation of the structures. These changes are seen as
"beading" on endoscopic retrograde cholangiopancreatography.
Gallstones in the biliary tree produce irregular radiolucent masses (choice B).
Choice C describes the findings associated with carcinoma of the ampulla of Vater.
Choice D describes the findings associated with carcinoma of the extrahepatic bile ducts.
Choice E describes the findings associated with carcinoma of the pancreas.
A 17-year-old girl in the 4th month of pregnancy presents with vaginal bleeding, accompanied by passage
of grapelike tissue fragments. Plasma human chorionic gonadotropin (hCG) is very high.
Following ultrasound evaluation, dilatation and curettage is performed. Histologic examination
shows diffuse trophoblastic proliferation and edema in all chorionic villi. Cytogenetic studies
demonstrate 46, XY karyotype. Clinical studies show that this condition progresses to
choriocarcinoma at a rate of
A. 0.2%
B. 2%
C. 20%
D. 50%
E. 90%
Explanation:
The correct answer is B. The condition described is a complete hydatidiform mole. Hydatidiform
mole is a spectrum of conditions due to abnormal proliferation of trophoblast and ranging from
entirely benign conditions (complete and partial mole) to very aggressive neoplasms
(choriocarcinoma). Partial moles have a triploid karyotype (69,XXY) and derive from
fertilization of an ovum with one or two sperm; fetal parts are frequently seen. Complete moles
have a diploid karyotype (46,XX or 46,XY) and derive from fertilization of an empty ovum by a
single sperm (androgenesis); no fetal parts are found. Ten percent of moles acquire a more
aggressive behavior and invade deeper parts of the myometrium, degenerating into invasive
moles. Two percent of complete moles may transform into choriocarcinoma, a very aggressive
neoplasm that spreads rapidly through the blood stream. Fortunately, choriocarcinomas of
placental origin are highly responsive to chemotherapy, affording up to 100% cure or remission.
Nongestational choriocarcinoma, in contrast, is poorly responsive to chemotherapy.
Remember the following important points:
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-Complete mole, usually diploid karyotype: results from androgenesis (sperm fertilization of an
empty egg), no fetal parts are identified, 2% progress to choriocarcinoma.
-Partial mole, usually triploid karyotype: results from fertilization of normal egg by one or
two sperm; fetal parts are often identified; rarely progresses to choriocarcinoma.
A 4-year-old girl is brought to a specialty clinic by her foster parents because of a limp in her right
leg and a serum alkaline phosphatase (ALP) that is 10 times the adult upper limit of normal for
the test. The child is withdrawn and clinging to her foster mother. Physical examination is
remarkable for a blue-green discoloration of the skin overlying a tender, 3-cm mass on the
anterior portion of the right mid-thigh. An x-ray of the right thigh reveals a dense mass within
the femur that extends into the surrounding tissue. Which of the following best describes the
increased alkaline phosphatase and physical findings in this case?
A. ALP is abnormal for her age and the bone lesion represents an area of aseptic
necrosis
B. ALP is abnormal for her age and the bone lesion represents repair of a femoral
fracture
C. ALP is abnormal for her age and is unrelated to the bone lesion
D. ALP is normal for her age and the bone lesion is an osteogenic sarcoma
E. ALP is normal for her age and is unrelated to the bone lesion
Explanation:
The correct answer is B. The reference intervals for serum alkaline phosphatase (ALP) and serum
phosphate are higher in children than in adults. Growing bone in children requires alkaline
phosphatase secreted by osteoblasts and an increase in serum phosphate to provide a proper
solubility product ([calcium] x [phosphorus]) for mineralization of bone. However, the normal
serum ALP in children is no greater than 5-times the upper limit of normal for adults, hence
this patient's ALP is abnormally elevated. The most likely scenario is that the child is a
victim of abuse and has suffered a femoral fracture that is healing. Bone repair further
increases the serum ALP owing to the increase in osteoblastic activity.
Aseptic necrosis of bone in the leg (choice A) is more likely to occur in the femoral head
(Legg-Calve-Perthes disease). This disease is more common in boys than girls and occurs in the
3- to 10-year-old age bracket. Although aseptic necrosis is associated with dense bone
formation, it does not extend out into the soft tissue nor would it produce skin discoloration
directly over the lesion (due to trauma in this case).
Since the elevation in serum ALP is increased for age and related to the bone lesion, choice C
is incorrect.
Since the serum ALP is not normal for the age of this patient, choices D and E are incorrect.
Furthermore, osteogenic sarcoma (choice D) does not normally occur in the first decade and
favors the metaphysis of the distal femur or proximal tibia.
A six-month-old baby girl who was normal at birth, begins to show signs of motor retardation. While she
could sit up at 5 months, she can no longer do so. As time goes on, the child continues to
deteriorate, and eventually becomes unresponsive to visual or auditory stimuli. Funduscopic
examination reveals cherry-red macular spots in both eyes. Which of the following genetic
abnormalities is most often related to the development of this disease?
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A. Confined placental mosaicism
B. Expanded trinucleotide repeat
C. Frameshift mutation
D. Nondisjunction
E. Translocation
Explanation:
The correct answer is C. Most cases of Tay-Sachs disease are caused by insertion of four
nucleotides into the coding region of the gene for the alpha-subunit of the hexosaminidase A
gene. This produces a frameshift mutation, resulting in the creation of a premature stop codon
downstream from the inserted nucleotides. The disease presents as described in the question,
and is more common in Ashkenazi Jews. The carrier rate in this population is 1 in 25. There is
presently no effective treatment and survival beyond four years of age is rare.
Confined placental mosaicism (choice A) is caused by a genetic aberration (e.g., a trisomy)
occurring in the trophoblast or extraembryonic progenitor cells in the inner cell mass of the
embryo. This leads to abnormal placental development and intrauterine growth retardation.
Expansion of tandem nucleotide repeats (choice B) is thought to be etiologically involved in
Fragile X syndrome and Huntington disease.
Nondisjunction (choice D) during meiosis is a common cause of trisomy, e.g., trisomy 21, or
Down syndrome.
Translocations (choice E) are frequently involved in leukemias, lymphomas, and solid tumors. A
minority of cases of Down syndrome are actually due to a translocation, rather than trisomy.
A 54-year-old African-American female patient undergoes a routine insurance physical examination. Chest
x-ray reveals bilateral hilar masses. Biopsy of the masses shows granulomata, but acid-fast and
fungal stains are negative for organisms. Which of the following diseases should be suspected?
A. Caroli's disease
B. Raynaud's disease
C. Sarcoidosis
D. Scleroderma
E. Systemic lupus erythematosus
Explanation:
The correct answer is C. Sarcoidosis is a multisystem disease characterized by non-caseating
granulomata in a variety of organs. The disease may be symptomatic (respiratory and
constitutional symptoms) or may be discovered incidentally when chest x-ray or autopsy reveals
bilateral hilar adenopathy. Definitive diagnosis is based on biopsy, which reveals noncaseating granulomata that are negative for fungi or acid-fast bacilli. Sarcoidosis is more
common in individuals of African descent.
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Caroli's disease (choice A) is a congenital malformation of the bile duct system.
Raynaud's disease (choice B) is a vasospasm of vessels that causes temporary ischemia in the
hands.
Scleroderma (choice D), or progressive systemic sclerosis, is characterized by progressive
fibrosis of skin and internal organs.
Systemic lupus erythematosus (choice E) is an autoimmune disease characterized by vasculitis
(which may produce a variety of symptoms depending on the site of the lesion), rash, renal
disease, hemolytic anemia, and neurologic disturbances.
During laparoscopy performed for other reasons, a surgeon is startled to see a uniformly black liver.
Which of the following is the most likely diagnosis?
A. Angiosarcoma
B. Dubin-Johnson syndrome
C. Hemochromatosis
D. Malignant melanoma
E. Wilson's disease
Explanation:
The correct answer is B. Dubin-Johnson syndrome is a relatively mild, hereditary conjugated
hyperbilirubinemia that has the distinctive feature of causing the liver to turn black. The
same black pigment can be seen in microscopic sections. The origin of the black pigment is not
fully understood, but the genetic defect responsible for Dubin-Johnson syndrome has recently
been identified, and appears to involve a defect in the canalicular organic anion transporter.
Patients homozygous for Dubin-Johnson syndrome may also have significant amounts of
unconjugated bilirubin in the serum, presumably due to deconjugation of conjugated bilirubin in
the hepatobiliary system.
Angiosarcoma (choice A) can produce a dark red liver due to increased blood and hemorrhage.
Hemochromatosis (choice C) can produce a dark red to brown liver.
Malignant melanoma (choice D) can produce black nodules in the liver, but would not be expected
to produce a uniformly black liver.
The liver in Wilson's disease (choice E) can be cirrhotic but does not have a distinctive
color.
A 64-year-old man begins to show behavioral changes and irritability, and is found wandering in the park
near his home. On neurological examination, there is evidence of mild aphasia and cognitive
dysfunction, but motor function is preserved. CT scan of the head demonstrates selective
atrophy of the cortex of the frontal lobes. Which of the following is the most likely
diagnosis?
A. Alzheimer's disease
B. Friedreich's ataxia
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C. Huntington's disease
D. Parkinson's disease
E. Pick's disease
Explanation:
The correct answer is E. Pick's disease is a condition that is clinically similar to
Alzheimer's disease. It differs from Alzheimer's disease in that the pronounced brain atrophy
characteristically involves the frontal and temporal lobes, with sparing of the posterior
aspects of the cortex. Microscopically, the affected cortex contains characteristic ballooned
neurons (Pick cells) or cytoplasmic inclusions (Pick bodies). Clinically, there is a slowly
progressive dementia with language disturbances and behavioral changes that may eventually lead
to mutism. The progressive nature of the dementing process has been termed a "descent into a
sea of mindlessness."
Alzheimer's disease (choice A) is characterized by dementia, but with diffuse brain atrophy.
Friedreich's ataxia (choice B) characteristically affects the spinal cord, brainstem, and
cerebellum, rather than cortex.
Huntington's disease (choice C) characteristically affects the caudate nucleus and putamen.
Motor symptoms such as choreoathetosis are prominent.
Parkinson's disease (choice D) characteristically affects the substantia nigra, and produces
prominent motor symptoms, including cogwheel rigidity, a resting tremor, and a festinating
gait.
A neonate has a 10-cm neck mass. She is diagnosed with a cystic hygroma of the neck. The physician is
concerned that she may also have which of the following abnormalities?
A. Aneurysm of the ascending portion of the aortic arch
B. Aortic dissection
C. Coarctation of the aorta
D. Cystic medial necrosis of the aorta
E. Early severe aortic atherosclerosis
Explanation:
The correct answer is C. You need to know that cystic hygromas (lymphatic malformations
resembling hemangiomas) are a feature of Turner syndrome that later contributes to the better
known "webbed neck." Turner syndrome is also associated with coarctation of the aorta, and to a
lesser extent, pulmonary stenosis.
Aneurysms involving the proximal aorta (choice A) suggest tertiary syphilis. The clues given in
a question about tertiary syphilis might be sexually transmitted disease or chronic
neurological signs.
Aortic dissection (choice B) and cystic medial necrosis of the aorta (choice D) would probably
be presented in a question giving you a clue about Marfan's syndrome, such as a patient with
tall stature and hyperextensible joints.
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Early severe aortic atherosclerosis (choice E) can be a feature of either diabetes mellitus
(clues would include high fasting blood glucose, thirst, excessive urination, etc.) or familial
hyperlipidemias (clues include xanthomas or elevated serum lipids).