1

In the 25th week of pregnancy, a G1P0 woman develops increased blood pressure (160/95) and
proteinuria.
Physical examination demonstrates generalized edema, and serum chemistries demonstrate
hyperuricemia and
increased concentrations of liver enzymes. Which of the following usually provides definitive
therapy for this
patient's medical condition

A. Anti-hypertensive medical therapy

B. Delivery

C. Low dose aspirin

D. Oxygen supplementation

E. Renal dialysis
Explanation:

The correct answer is B. The woman has preeclampsia, the features of which include
proteinuria and increased
blood pressure. A wide variety of other features of preeclampsia can also be seen, including
excessive weight
gain, generalized edema, ascites, hyperuricemia, hypocalciuria, increased plasma concentration
of von
Willebrand factor and cellular fibronectin, reduced plasma concentration of anti-thrombin III,
thrombocytopenia,
increased hematocrit, increased liver enzymes, intrauterine growth retardation, and
intrauterine hypoxia.
Modern theories suggest that the true primary lesion may involve the endothelium, and that
medical control of
hypertension (choice A) actually only treats a small part of the syndrome. At present, the only
definitive therapy
is delivery of the baby, and obstetricians often play a delicate game trying to delay delivery for a
premature
baby's sake as long as possible while judging the severity of the preeclampsia and its immediate
risks to mother
and fetus.

Low dose aspirin (choice C) may have a modest effect in preventing pre-eclampsia, but this is
not yet well
established.

Oxygen supplementation (choice D) is used in some cases of cerebral hemorrhage secondary to

preeclampsia,
but does not constitute definitive therapy.

Renal dialysis (choice E) is usually not necessary in preeclampsia, although both renal cortical
necrosis and
renal tubular necrosis can occasionally occur in this disorder.
A baby is born with a large red, raised discoloration of the face that persists into adulthood. This type
of lesion ismost likely a component of which of the following syndromes?

A. Arnold Chiari malformation

 2

B. Dandy-Walker malformation

C. Neurofibromatosis

D. Sturge-Weber disease

E. Tuberous sclerosis
Explanation: The correct answer is D. The lesion is a port wine stain, which is a vascular lesion
that, unlike the more common strawberry nevus, does not usually regress with age. These lesions can
be a component of Sturge-Weber disease, which can also include similar vascular lesions of the
meninges (leptomeningeal angiomatosis) and sometimes cutaneous angiomatosis at other sites.

Arnold Chiari malformations (choice A) are a cluster of related brain and spinal cord
malformations in which
there is a downward displacement of the cerebellar vermis and tonsils into the foramen
magnum.

Dandy-Walker malformation (choice B) includes a distended fourth ventricle with a hypoplastic

(or absent) cerebellum.

Neurofibromatosis (choice C) includes benign and malignant peripheral nerve lesions and café au lait
spots.

Tuberous sclerosis (choice E) includes cortical tubers, adenoma sebaceum of the skin, pancreatic
cysts, renal angiomyolipomas, and cardiac rhabdomyomas.

Renal biopsy demonstrates concentric, laminated thickening of arteriolar walls due to proliferation
of smooth muscle cells. This process is best described by which of the following terms?

A. Atherosclerosis

B. Hyaline arteriolosclerosis

C. Hyperplastic arteriolosclerosis

D. Mönckeberg's arteriosclerosis

E. Polyarteritis nodosa

Explanation:

The correct answer is C. The "onion skinning" morphology of these arterioles is a feature of
hyperplastic
arteriolosclerosis. Affected vessels may also show necrotizing arteriolitis with acute vessel wall
necrosis
accompanied by fibrin deposition. This type of vessel change is a hallmark of severe (malignant)
hypertension,
and can damage arterioles throughout the body, notably in the kidneys, intestine, and gall
bladder.

Atherosclerosis (choice A) would produce luminal narrowing by plaques.

Hyaline arteriolosclerosis (choice B) would produce partial replacement of arterial walls by

homogeneous, pink
 3

material.

Mönckeberg's arteriosclerosis (choice D) is characterized by medial calcification of smaller

arteries.

Polyarteritis nodosa (choice E) is characterized by focal acute inflammation of smaller arteries.

Two bone marrow aspirates are studied under the microscope. One is taken from an adult with
Hemoglobin SS disease (sickle cell anemia) and the other is from an adult with normal Hemoglobin
A. The marrow aspirate from the patient with sickle cell anemia could be identified due to its
increased

A. fat

B. iron stores

C. medullary bone

D. megakaryocytes

E. myeloid:erythroid ratio
Explanation:
The correct answer is B. Adults with sickle cell disease have undergone decades of accelerated RBC
formation and destruction, leading to accelerated erythropoiesis in the bone marrow. Consequently
the bone marrow becomes hyperplastic, with marked increases in the number of normoblasts
(erythroblasts) at the expense of
marrow fat and marrow bone (choices A and C). Although the white cell and megakaryocyte
lines are
undiminished (choices D and E), there is a marked increase in RBC precursors and iron stores.
Iron storage
increases as a consequence of both chronic transfusions and increased dietary absorption; these
increased
iron stores can be appreciated with a Prussian blue stain.

Ultrasound examination of a developing fetus demonstrates a fluid-filled sac at the base of the fetus'
spine that connects to the spinal canal and apparently contains part of the spinal cord. A dietary
deficiency of which of the following is most strongly associated with this type of lesion?

A. Calcium

B. Folate

C. Iron

D. Vitamin C

E. Vitamin K
Explanation:
The correct answer is B. The lesion is a neural tube defect, probably a meningomyelocele, in which
both
meninges and spinal cord herniate through a bony vertebral defect. These defects most
commonly occur in the
 4

lumbosacral region, typically resulting in motor and sensory deficits in the lower extremities,
and bowel and
bladder dysfunction. This condition is now known to be associated with low maternal folate
during the first three
to four weeks of pregnancy, a time when many women may be unaware of their pregnancy. It is
now
recommended that all women of childbearing age consume at least 400 µg of folic acid daily.

Calcium deficiency (choice A) can cause osteoporosis and osteopenia.

Iron deficiency (choice C) can cause iron deficiency anemia.

Vitamin C deficiency (choice D) can cause scurvy.

Vitamin K deficiency (choice E) can cause a bleeding diathesis.

A 30-year-old patient presents to a clinician because of intermittent, severe headaches accompanied

by
perspiration, palpitations, and pallor. Blood pressure on the initial examination was within
normal limits, but, when the patient came in later with a headache, it was 180/135 mm Hg. Urinary
vanillylmandelic acid (VMA) levels were elevated. Roughly, what percentage of the tumors causing
this pattern is malignant?

A. 1%

B. 10%

C. 50%

D. 90%

E. 99%
Explanation:

The correct answer is B. The tumor is a pheochromocytoma that intermittently secretes

epinephrine and other vasoactive amines, producing episodes of elevated blood pressure
accompanied by headache. This is the tumor to associate with the rule of the 10's: 10% malignant,
10% bilateral, 10% extra-adrenal, 10% calcify, 10% occur in kids, and 10% are familial. It is also a
favorite target on examinations, although the incidence is quite low.

An 82-year-old man develops a round, fluid-filled cystic structure on the back of his knee that limits
the knee's
mobility. This most likely represents an enlargement of which of the following structures?

A. Deep infrapatellar bursa

B. Prepatellar bursa

C. Semimembranous bursa

D. Superficial infrapatellar bursa

E. Suprapatellar bursa
 5

Explanation:

The correct answer is C. The lesion is commonly called a Baker's cyst, and anatomically
represents an
enlarged semimembranous bursa. Baker's cysts are more commonly seen at the extremes of age.

The deep infrapatellar bursa (choice A) is on the anterior aspect below the knee.

The prepatellar bursa (choice B) is anterior to the patella.

The superficial infrapatellar bursa (choice D) is on the anterior aspect of the leg below the knee.

The suprapatellar bursa (choice E) is on the anterior aspect of the thigh above the knee.

Biopsy of a 4 mm rough, tan, and slightly raised skin lesion on the face of a 65-year-old man
demonstrates
atypical basal cells with eosinophilic cytoplasm but persistent intercellular bridges. The stratum
corneum is
thickened and parakeratosis is present; the remainder of the epidermis is thinned. Which of the
following features
would probably additionally be seen in the dermis?

A. Benign nevus cells

B. Blue-gray elastic fibers

C. Large numbers of spindle-shaped fibroblasts

D. Malignant nevus cells

E. Touton giant cells

Explanation:

The correct answer is B. The lesion described is an actinic keratosis, which is a common
premalignant lesion
caused by solar damage, which also characteristically damages the elastic fibers (changing their
color in
stained tissue to blue-gray) of the superficial dermis.

Benign nevocellular nevus cells (choice A) are found in common moles (nevocellular nevi).

Large numbers of spindle-shaped fibroblasts (choice C) are found in dermatofibromas.

Malignant nevus cells (choice D) are found in melanoma.

Touton giant cells (choice E) are found in xanthomas.

 6

A 50-year-old man consults a physician because of a lesion on his nose. On examination, a flesh-
colored lesion
about 1 cm in diameter, with a rolled edge and central ulceration, is observed. Which of the
following is the most
likely diagnosis?

A. Basal cell carcinoma

B. Eczema

C. Psoriasis

D. Urticaria

E. Verruca vulgaris

Explanation:

The correct answer is A. The description is typical for basal cell carcinoma. These skin cancers
typically occur
on sun-exposed areas of the head, neck, and upper trunk. Basal cell carcinoma only rarely
metastasizes, but
can become locally mutilating if neglected. When located on the face, it may be difficult to
adequately excise
without damaging facial structures.

Eczema (choice B) typically involves a larger area of skin and may cause dryness, discoloration,
and thickening
of the involved area. Blistering, erythema, or oozing may also be observed.

Psoriasis (choice C) is characterized by erythematous plaques with a silvery surface.

Urticaria (choice D) causes transient, nonpitting, erythematous wheals.

Verruca vulgaris (choice E), the common wart, causes well-demarcated verrucous papules, often
on the hands.

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

 7

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.

An adult presents to a physician because of repeated episodes of fainting. EKG fails to disclose an
arrhythmia.
Echocardiogram shows a mass in the left atrium that is acting like a "ball valve" to produce
intermittent
obstruction of flow. Which of the following would most likely be seen on microscopic
examination of the resected
mass?

A. Benign myxoid tumor

B. Benign tumor with gland formation

C. Benign tumor with striated muscle differentiation

D. Malignant tumor with gland formation

E. Malignant tumor with striated muscle differentiation

Explanation:

The correct answer is A. The most common primary cardiac tumor of adults is the benign atrial
myxoma. 90% of
these lesions involve the left atrium, where they can produce intermittent obstruction when they
flop onto the
mitral valve. Resection is curative.

Neither benign (choice B, adenomas) nor malignant (choice D, adenocarcinomas) primary

glandular tumors
usually involve the heart. If adenocarcinoma is seen, suspect metastatic disease.

The rhabdomyoma is the benign tumor with striated muscle differentiation (choice C) that can
involve the heart.
 8

This tumor is the most common cardiac tumor of children.

Rhabdomyosarcomas are malignant tumors with striated muscle differentiation (choice E) and
typically involve
the head and neck or uterus.

A patient with long-standing, progressive congestive heart failure dies in respiratory distress. The
lungs at
autopsy are 3 times their normal weight. Histologically, the alveoli show a proteinaceous
granular precipitate,
engorged alveolar capillaries, and hemosiderin-laden macrophages. Other inflammatory cells
are inapparent.
Which of the following is the most likely diagnosis?

A. Candida pneumonia

B. Pneumococcal pneumonia

C. Pneumocystis pneumonia

D. Pulmonary edema

E. Pulmonary infarction

Explanation:

The correct answer is D. These are the characteristic findings of pulmonary edema. The edema
fluid is
apparent as a proteinaceous granular precipitate after histologic processing of the tissue.
Hemosiderin-laden
macrophages in the tissue, called "heart failure cells," are the end result of ingestion of red
blood cells by
alveolar macrophages. Pulmonary edema develops in heart failure when the pulmonary venous
pressure rises
and the capacity for the tissue to reabsorb the fluid into the venous system is exceeded.

In Candida pneumonia (choice A), fungal hyphae and spores would be described.

In pneumococcal pneumonia (choice B), gram-positive cocci (Streptococcus pneumoniae) would

be described.

In Pneumocystis pneumonia (choice C), hat-shaped, silver-stained cysts would be described.

In pulmonary infarction (choice E), ischemic necrosis of alveoli would be described.

A 3-year-old child is brought to the emergency room by her concerned parents. They state the girl
has been
complaining of a severe headache and has had two episodes of vomiting. On physical
examination, there is bilateral papilledema and an impaired level of consciousness. Emergency
contrast CT scan demonstrates displacement of the ventricular system by a multilocular "mass" with
 9

well-defined white high-attenuation rings around black low-attenuation centers. The lesion involves
the cerebellum. To which of the following conditions i this lesion most likely related?

A. Bacteremia following tooth extraction

B. Bacterial meningitis

C. Lung abscess

D. Otitis media

E. Sinusitis

Explanation:

The correct answer is D. The child has a cerebellar abscess. Abscess of the brain can be caused
by any of the
choices listed, but about 60% are related to middle ear infection. Cerebellar abscess is
specifically associated
with middle ear infection.

Bacteremia following tooth extraction (choice A) and blood borne bacteria from lung abscess
(choice C) are
relatively uncommon causes of intracranial abscess.

Subdural empyema in infants is usually a complication of bacterial meningitis (choice B).

Both middle ear infections and sinusitis (choice E) can cause frontal and temporal lobe
abscesses.

Ophthalmoscopic examination of a 5-year-old child demonstrates a retinal angioma. This finding

should raise the possibility of which of the following syndromes?

A. Neurofibromatosis type I

B. Neurofibromatosis type II

C. Sturge-Weber disease

D. Tuberous sclerosis

E. Von Hippel-Lindau disease

Explanation:

The correct answer is E. Retinal angioma may be a "visible" manifestation of von Hippel-
Lindau disease. This
syndrome is characterized by tumors and/or cysts that can involve many structures: retinal
angiomas, capillary
 10

hemangioblastomas of the CNS (notably cerebellum, but also many other sites), renal
carcinoma (up to 30% of
cases, may occur at a young age or may be bilateral), and angiomatous or cystic lesions of many
other organs
(epididymis, kidneys, liver, pancreas, lung, skin).

Neurofibromatosis type I (choice A) is characterized by Lisch nodules of the iris, café-au-lait

macules, and
peripheral nerve tumors.

Neurofibromatosis type II (choice B) is characterized by acoustic neural tumors and café-au-lait

macules.

Sturge-Weber disease (choice C) is characterized by port-wine nevus of the head and

leptomeningeal
angiomatosis.

Tuberous sclerosis (choice D) is characterized by adenoma sebaceum of the skin and cortical
tubers.

A 45-year-old man presents to a physician with back pain and facial pain. Physical examination
demonstrates coarse facial features and kyphosis. Laboratory examination is remarkable for elevated
alkaline phosphatase.
X-ray studies demonstrate skull thickening with narrowing of foramina, and bowing of the femur
and tibia. Bone biopsy reveals a mosaic pattern of bone spicules with prominent osteoid seams.
Which of the following neoplasms occurs at an increased frequency in patients with this disorder?

A. Astrocytoma

B. Hodgkin's lymphoma

C. Meningioma

D. Non-Hodgkin's lymphoma

E. Osteosarcoma

Explanation:

The correct answer is E. The phrase "mosaic pattern" of newly formed woven bone is a specific
tip-off for
Paget's disease of bone, and is not seen in other bone conditions. The clinical and radiologic
presentation are
typical; an increased hat size may also be a clue. In its early stages, Paget's disease is
characterized by
osteolysis, producing patchwork areas of bone resorption with bizarre, large osteoclasts. In the
middle stage of
the disease, secondary osteoblastic activity compensates with new bone formation, producing
the mosaic
pattern. In late Paget's, the bones are dense and osteosclerotic. Paget's disease is suspected to be
related to
 11

prior viral infection, but the cause remains mysterious. Complications include myelophthisic
anemia, high output
cardiac failure, pain secondary to nerve compression, deformities secondary to skeletal changes,
and in about
1% of patients, osteosarcoma or other sarcoma, typically involving the jaw, pelvis, or femur.

An increased incidence of astrocytomas (choice A) is associated with tuberous sclerosis.

Hodgkin's lymphoma (choice B) is usually a disease of young adults, although older patients
may have the
lymphocyte-depleted form.

Meningiomas (choice C) are mostly benign tumors that affect adults, especially females. There
may be an
association with breast cancer, possibly related to high estrogen states.

Non-Hodgkin's lymphoma (choice D) is more common in AIDS and other immunodeficiency

states, although the
incidence in the immunocompetent is increasing.

A 28-year-old man discovers a mass in his neck while buttoning his shirt collar. Physical examination
reveals a 2
cm mass in one thyroid lobe, which is “cold” on scintiscan. Aspiration of the
nodule demonstrates
small “solid balls” of neoplastic follicular cells. Careful examination of these
tissue balls reveals that
they contain microscopic blood vessels and fibrous stroma in their centers. Which of the
following is the most
likely diagnosis?

A. Follicular carcinoma

B. Hashimoto's disease

C. Medullary carcinoma

D. Papillary carcinoma

E. Thyroid adenoma

Explanation:

The correct answer is D. The distinctive cell balls described are broken-off papillary clusters,
and are
considered pathognomic for papillary carcinoma of the thyroid. This is the most common form
of thyroid
carcinoma. It tends to present in the 3rd to 5th decade and shows a modest female
predominance. Despite its
propensity for local lymphatic intrusion (which may cause multifocality of tumor in the thyroid
or cervical lymph
node metastases), the tumor generally has an excellent prognosis with 90% 20-year survival.
 12

Follicular carcinoma (choice A) is characterized by follicular cells and colloid on aspiration, and
cannot be
reliably distinguished from thyroid adenoma.

Distinctive features of Hashimoto's disease (choice B) on aspiration are lymphocytes, plasma

cells, and
macrophages.

The most distinctive feature of medullary carcinoma (choice C) on aspiration is the presence of
amyloid.

Thyroid adenoma (choice E) shows follicular cells and colloid on aspiration, and cannot be
reliably
distinguished from follicular carcinoma.

A 1-year-old child with mental retardation, seizures, and facial angiofibromas develops repeated
episodes of
syncope. Echocardiogram reveals a mass in the left ventricle producing intermittent
obstruction. Pathologic
examination of the resected mass demonstrates a cardiac rhabdomyoma. Which of the following
lesions would
this patient most likely also have?

A. Acoustic neuromas

B. Berry aneurysm

C. Cortical tubers

D. Meningiomas

E. Neurofibromas

Explanation:

The correct answer is C. The disease is tuberous sclerosis, in which cortical hamartomas known
as tubers can
be associated with facial angiofibromas, cardiac rhabdomyomas (probably actually a skeletal
muscle
hamartoma), seizures, mental retardation, and astrocytomas.

Associate acoustic neuromas (choice A) with neurofibromatosis type II.

Associate berry aneurysms (choice B) with adult polycystic kidney disease.

Associate meningiomas (choice D) with breast cancer and, possibly, high estrogen states.

Associate neurofibromas (choice E) with neurofibromatosis type I.

 13

Endoscopy performed on a patient with persistent substernal pain despite antacid use demonstrates
irregular
erythematous patches several centimeters above the gastroesophageal junction. Biopsy of one of
these lesions
demonstrates epithelial metaplasia. Which of the following cell types was most likely observed
in the involved
areas?

A. Ciliated columnar epithelium

B. Cuboidal epithelium

C. Keratinizing squamous epithelium

D. Non-ciliated columnar epithelium

E. Non-keratinizing squamous epithelium

Explanation:

The correct answer is D. The medical condition is Barrett's esophagus, in which the normally
non-keratinizing
squamous epithelium (choice E) of the esophagus undergoes metaplasia to gastric or intestinal-
like epithelium
composed of non-ciliated columnar epithelial cells. Barrett's esophagus typically develops in the
setting of
chronic gastroesophageal reflux, and significantly increases the risk of later development of
adenocarcinoma of
the distal esophagus.

Ciliated columnar epithelium (choice A) is found in the respiratory tract.

Cuboidal epithelium (choice B) is found in the kidney, peritoneal lining, and pleural lining.

Keratinizing squamous epithelium (choice C) is found in skin.

Non-keratinizing squamous epithelium (choice E), in addition to being the normal epithelium of
the esophagus,
is found in mouth, nose, and vagina.

An elderly man comes to medical attention because of anemia and multiple infections. Physical
examination is
remarkable for hepatosplenomegaly. An automated blood count demonstrates pancytopenia.
Review of the
peripheral smear by a hematologist demonstrates rare, distinctive, neoplastic white cells covered
by fine, hairlike
projections. Which of the following characteristics would likely be associated with these cells?

A. Birbeck granules

B. Elevated leukocyte alkaline phosphatase

 14

C. Philadelphia chromosome

D. Positive tartrate-resistant acid phosphatase

E. Production of Bence-Jones proteins

Explanation:

The correct answer is D. The disease is hairy cell leukemia, which, unlike most forms of
leukemia, is
characterized by pancytopenia rather than increased numbers of circulating cells. This disease
tends to affect
older men and the characteristic cells (which are not always obviously “hairy”)
are positive for
tartrate-resistant acid phosphatase (TRAP).

Associate Birbeck granules (choice A) with Langerhans cell histiocytosis (histiocytosis X).

Associate elevated leukocyte alkaline phosphatase (choice B) with myeloid metaplasia.

Associate Philadelphia chromosome (choice C) with chronic myeloid leukemia (and occasionally
with acute
lymphocytic leukemia).

Associate production of Bence-Jones proteins (choice E) with multiple myeloma.

A pathologist reports the presence of koilocytotic atypia in a cervical biopsy from a 25-year-old
woman. On the
basis of this histopathologic finding, which of the following conditions does this patient most
likely have?

A. Chlamydia infection

B. Gonococcal infection

C. Herpes simplex virus infection

D. Human papillomavirus infection

E. Severe squamous dysplasia

F. Squamous cell carcinoma in situ

G. Trichomonas infection

Explanation:

The correct answer is D. Human papillomavirus (HPV) is the cause of condyloma, which may
occur on any
 15

mucocutaneous surface of the male or female external genitalia. Squamous epithelial cells
infected by HPV
show characteristic nuclear and cytoplasmic changes, referred to as koilocytosis or koilocytotic
atypia, on tissue
sections or Pap smears. These changes allow the diagnosis of HPV infection to be made. The
nuclei are
condensed and have irregular contours, acquiring a "raisin-like" appearance; cytoplasm
vacuolization creates a
perinuclear halo. HPV is a crucial etiopathogenetic factor in the development of squamous cell
carcinoma of the
cervix. Not all types of HPV, however, are associated with cervical carcinoma. High-risk types
are 16 and 18,
whereas the most frequent low-risk types are 6 and 11. HPV types 16 and 18 express proteins
(E6 and E7) that
inactivate p53 and Rb tumor suppressor genes, leading to neoplastic transformation. Although
HPV infection is
a risk factor for the development of squamous dysplasia and carcinoma, koilocytosis is not
equivalent to severe
squamous dysplasia (choice E) or carcinoma in situ (choice F). In the current Bethesda system
for diagnosing
and reporting Pap smears, koilocytosis is likened to a low-grade squamous intraepithelial lesion,
ie, mild atypia.
Remember that koilocytosis (koilocytotic atypia) = HPV infection, not severe
dysplasia/carcinoma.

Chlamydia infection (choice A) of the genital tract is due to Chlamydia trachomatis.

Approximately half a million
cases of Chlamydia urethritis (nongonococcal urethritis) are reported each year in the U.S. The
infection is
often symptomatic in men and clinically silent in women. In addition to urethritis and
lymphogranuloma
venereum, C. trachomatis causes trachoma, an eye infection endemic in some developing
countries.

Gonococcal infection (choice B), or gonorrhea, is due to Neisseria gonorrhoeae, a gram-negative

diplococcus.
There are about 700,000 cases of gonorrhea each year in the U.S.

Infection by herpes simplex virus (choice C) is the most common sexually transmitted disease in
the U.S. It is
generally due to herpes simplex type 2 virus and manifests with painless blisters, which
subsequently break
down, forming painful erosions.

Trichomonas infection (choice G) is also sexually transmitted. It is caused by Trichomonas

vaginalis, an
anaerobic flagellated protozoon, and manifests with itching and a frothy white discharge in
women. The infection
is usually asymptomatic in men. There are approximately 3 million cases of T. vaginalis
infection each year in
the U.S.

A 52-year-old woman has long-standing rheumatoid arthritis (RA) and is being treated with
corticosteroids and
 16

nonsteroidal anti-inflammatory drugs (NSAIDs). Which of the following cardiac complications

may arise in this
clinical setting?

A. Constrictive pericarditis

B. Dilated cardiomyopathy

C. Hypersensitivity myocarditis

D. Hypertrophic cardiomyopathy

E. Restrictive cardiomyopathy

Explanation:

The correct answer is E. What links rheumatoid arthritis (RA) to restrictive cardiomyopathy?
Amyloid!
Long-standing inflammatory conditions such as RA are associated with deposition of a form of
amyloid known
as AA (amyloid-associated protein), which may involve kidneys, heart, liver, skeletal muscle,
and skin, for
example. Amyloid deposition in the myocardium results in decreased compliance and impaired
diastolic filling,
i.e., restrictive cardiomyopathy. The myocardium has a rigid and waxy texture. This form of
amyloid, as well as
any other biochemical form, can be visualized on tissue section by staining with Congo red,
which acquires a
characteristic apple-green birefringence under polarized light.

Constrictive pericarditis (choice A) is due to any pathologic process that results in fibrous
thickening of the
pericardium, with resultant impaired compliance. Clinically, therefore, this condition manifests
with a picture
similar to restrictive cardiomyopathy because of impaired diastolic filling. Constrictive
pericarditis is usually
caused by previous episodes of acute pericarditis, especially hemorrhagic, suppurative, and
caseous
pericarditis.

Dilated cardiomyopathy (choice B) is characterized by massive ventricular dilatation and may

be caused by
genetic alterations, myocarditis, toxic insults (alcohol), metabolic disorders (hemochromatosis),
etc. Most cases
are idiopathic. The main pathophysiologic alteration is impaired contractility.

You may be tempted to think that this patient is prone to developing hypersensitivity
myocarditis (choice C), but
this form of myocardial disease has been reported after treatment with some antihypertensive
agents,
antibiotics, and diuretics -- not with corticosteroids or NSAIDs. Furthermore, myocarditis
manifests acutely with
arrhythmias and heart failure, and chronically with dilated cardiomyopathy and congestive
heart failure.
 17

Most cases of hypertrophic cardiomyopathy (choice D) are familial and due to mutations in one
of the genes
encoding proteins of the sarcomeres, most frequently β-myosin heavy chain. This form of
cardiomyopathy
leads to asymmetric hypertrophy of the left ventricle, with predominant thickening of the
interventricular septum.
In this case, too, impairment of ventricular compliance is the basic mechanism leading to
reduced diastolic filling
and heart failure.

Following an upper respiratory infection, a 7-year-old child develops multiple petechial hemorrhages
over her
entire body. Her mother takes her to the physician, who does a complete blood count, revealing
marked
thrombocytopenia. Which of the following diagnoses is most appropriate for this individual?

A. Bernard-Soulier syndrome

B. Idiopathic thrombocytopenic purpura

C. Thrombasthenia

D. Thrombotic thrombocytopenic purpura

E. Von Willebrand's disease

Explanation:

The correct answer is B. The process described is commonly called acute idiopathic
thrombocytopenic purpura
(ITP), even though the autoimmune basis has been clearly established (some authors use
"immune
thrombocytopenic purpura,” so that the initials still work). The thrombocytopenia in
this disorder appears
to be secondary to splenic destruction of opsonized platelets, and usually follows a viral upper
respiratory tract
infection or exanthem. The acute form of ITP is usually explosive, but self-limited; a chronic
form in adults may
respond to steroid therapy or splenectomy.

In Bernard-Soulier syndrome (choice A), platelets are unable to adhere to collagen.

Thrombasthenia (choice C), is associated with a functional defect in platelets (they do not
aggregate).

In thrombotic thrombocytopenic purpura (choice D), platelets are consumed in intravascular

platelet
microthrombi.

In von Willebrand's disease (choice E), deficient von Willebrand factor produces platelet
dysfunction, but
 18

thrombocytopenia is not prominent.

A 20-year-old man has a testicular mass, which on orchiectomy shows a malignant tumor with yolk
sac
differentiation. Which of the following tumor markers would probably be most useful in
monitoring the patient for
recurrent or metastatic disease?

A. Alpha-fetoprotein

B. Bombesin

C. Carcinoembryonic antigen (CEA)

D. Prostate-specific antigen (PSA)

E. S-100

Explanation:

The correct answer is A. Of the markers listed, alpha-fetoprotein is the best marker for non-
seminomatous germ
cell tumors of the testes, such as this patient's yolk sac tumor. Alpha-fetoprotein is also a good
marker for
hepatocellular carcinomas.

Bombesin (choice B) is a marker for neuroblastoma, small cell carcinomas, gastric carcinomas,
and pancreatic
carcinomas.

CEA (choice C, carcinoembryonic antigen) is a nonspecific marker, but has the advantage that
it is produced by
about 70% of colorectal and pancreatic cancers. It is also produced by some gastric and breast
cancers.

PSA (choice D, prostatic specific antigen) is a marker for prostatic carcinoma.

S-100 (choice E) is a marker for melanoma, neural tumors, and astrocytomas.

A 61-year-old woman with leukemia abruptly develops an intensely itchy rash. Physical examination
demonstrates multiple erythematous patches of the distal arms and legs, some of which involve
the palms and
soles. Some of the patches show central clearing with surrounding erythematous rings. Which of
the following is
the most likely diagnosis?

A. Erythema migrans chronicum

B. Erythema multiforme
 19

C. Kaposi's sarcoma

D. Psoriasis

E. Urticaria

Explanation:

The correct answer is B. The most specific clue in the description is the presence of
erythematous patches with
central clearing, known clinically as "target lesions," which are associated with erythema
multiforme. Both
erythema multiforme and its severe, life-threatening version, known as Stevens-Johnson
syndrome, are
produced by immune complex deposition in dermal blood vessels. In approximately 50% of
patients, no specific
precipitating cause is identified. In the remainder of patients, however, a variety of causes have
been
implicated, including certain infections (herpes simplex, enteroviruses, Mycoplasma
pneumoniae, Chlamydia,
histoplasmosis), drugs (penicillin, sulfonamides, phenytoin, aspirin, corticosteroids, cimetidine,
allopurinol, oral
contraceptives), neoplasia (leukemia, lymphoma, multiple myeloma, internal malignancy),
sarcoidosis, and
foods (notably emulsifiers in margarine).

Erythema migrans chronicum (choice A) also produces an annular erythematous rash with
central clearing, but
usually affects the thigh, groin, and axilla; it is associated with Lyme disease.

Kaposi's sarcoma (choice C) causes purple lesions with no target lesions.

Psoriasis (choice D) causes erythematous plaques with silvery scale but does not produce target
lesions.

Urticaria (choice E) causes wheals that are intensely pruritic, but does not produce target
lesions.

A jaundiced, 43-year-old alcoholic male presents to the emergency room complaining of bright red
blood in his
last two stools. He denies pain on defecation or changes in his bowel habits. Which of the
following would be the
most likely finding on sigmoidoscopic examination?

A. Colorectal carcinoma

B. Diverticulitis

C. Hemorrhoids

D. Hyperplastic polyps
 20

E. Ulcerative colitis

Explanation:

The correct answer is C. The patient's jaundice indicates that he has significant alcoholic liver
disease. Hepatic
fibrosis or cirrhosis both produce vascular injury and portal hypertension, which leads to the
development of
portosystemic shunts-most typically causing esophageal varices, caput medusae, and
hemorrhoids. Bright red
blood in stools is a classic presentation of hemorrhoids.

Colorectal carcinoma (choice A) generally develops in an older population, and produces occult
blood loss
rather than frankly bloody stools.

Although diverticulosis (choice B) may be an asymptomatic condition, diverticulitis is associated

with significant
abdominal distress, which may be accompanied by blood loss and diarrhea and/or constipation.

Hyperplastic polyps (choice D) are asymptomatic, non-neoplastic, polypoid growths, generally

less than 5mm in
diameter. They do not produce bleeding or any increased risk of carcinoma.

Ulcerative colitis (choice E) is an inflammatory bowel disease that produces mucoid diarrhea
accompanied by
lower abdominal pain and cramps. Painless bleeding is unlikely to be ulcerative colitis.

SPACE FOR PHOTO

The cells and related structures indicated by the arrow are reduced in number in which of the
following disorders?
 21

A. Hirschsprung's disease

B. Kwashiorkor

C. Polio

D. Schwannoma

E. Scurvy

Explanation:

The correct answer is A. These are autonomic motor ganglion cells and nerve fibers surrounded
by smooth muscle
of the muscularis externus. The close proximity of the smooth muscle and the orientation of the
fibers are keys to
deciding that this is a myenteric plexus. Ganglion cells usually have a spherical cell body, although
they are
considered multipolar, with a round nucleus and a prominent "owl's eye" nucleolus. The nerve
fibers typically appear
wavy in light microscopic views. The reduction in number of these cells and associated fibers leads
to the lack of
peristaltic control in the small and large bowel. The aganglionic bowel segment is narrowed
because the lack of
peristalsis keeps stool from moving into that segment. The distal rectum is always involved, and
the lesion can extend
proximally anywhere from a few centimeters past the rectum all the way up to the small intestine.
The bowel proximal
to the lesion is usually dilated.
 22

In kwashiorkor (choice B), a condition of extreme malnutrition, protein-secreting cells atrophy.

The cells in this figure
do not contain protein granules. In such cells, the rough endoplasmic reticulum would also be
abundant, and this is
not evident here.

In polio (choice C), motor neurons are lost from the anterior horn of the spinal cord.

Schwann cells produce schwannomas (choice D). Schwann cells are present among the nerve
fibers, but they are
not abundant, and they are not specifically affected in Hirschsprung's disease.

Vitamin C deficiency leads to scurvy (choice E), characterized by abnormal collagen

hydroxylation. The wavy fibers
do not have the typical bundle arrangement of collagen, but rather, have an appearance that is
characteristic of
nerve.

A 38-year-old female presents to the physician with complaints of excessive thirst and urination for
the past 4
weeks. Her appetite has been normal and she has not had diarrhea. Blood chemistry shows
mildly elevated
glucose and glucagon. Physical examination reveals tenderness in the left upper quadrant and
an erythematous
necrotizing skin eruption on her legs. Radiographic studies show a tumor in the pancreas.
Which of the following
cells is responsible for this lesion?

A. Acinar cell

B. Alpha cell

C. Beta cell

D. Delta cell

E. G cell

Explanation:

The correct answer is B. The symptoms described are typical for a patient with glucagon excess.
Glucagon is
secreted by alpha cells of the pancreatic islets of Langerhans. Increased levels are rare, usually
due to
carcinoma (70%) or adenoma (30%) of the islets. Two-thirds of patients with carcinoma have
liver metastasis at
the time of diagnosis. Increased glucagon causes a syndrome similar to diabetes mellitus, due to
antagonism of
insulin effects. Patients also have migratory skin rashes, alopecia, hyperpigmentation of the
skin, and glossitis.
Diagnosis is made by measuring glucagon.
 23

The acinar cell (choice A), the main exocrine cell of the pancreas, contains digestive enzymes.
Increases in the
release of these enzymes (especially amylase and lipase) occur with pancreatitis. Acute
pancreatitis is
considered an emergent medical condition. Chronic pancreatitis is associated with fibrosis and
atrophy of the
acinar structures.

Beta cells (choice C) are responsible for insulin release. An adenoma of beta cells (insulinoma)
would cause
hyperinsulinism. 70% are solitary and 10% are multiple. Insulinomas cause hypoglycemia,
dizziness, confusion,
and excessive sweating. Glucose needs to be given promptly to avoid coma and death. Diagnosis
is made by
finding increased insulin and hypoglycemia.

Delta cells (choice D) are islet cells that secrete somatostatin. Tumors producing increased
somatostatin are
usually malignant. Clinically, a diabetes mellitus-like syndrome occurs along with diarrhea.
Diagnosis is made
from elevated serum somatostatin levels, but can be difficult because of the hormone's short
half-life.

The G cell (choice E) is the islet cell that secretes gastrin. Gastrin excess is usually associated
with
gastrinomas, 70% of which are malignant. Zollinger-Ellison syndrome ensues, causing low
gastric and duodenal
pH, mucosal ulceration, and diarrhea. Diagnosis is made from high serum gastrin levels.

The patient shown in the pedigree above did poorly in school, then became increasingly forgetful
and irrational.
Over a period of years, he developed ataxia and began posturing. Eventually, he was demented
and unable to
care for himself. At autopsy, extensive cortical demyelination is observed. Microscopic
examination of the areas of
demyelination reveals numerous macrophages containing crystals that stain a light brown color
with toluidine
blue. This presentation is probably due to a deficiency of

A. arylsulfatase A

B. galactocerebroside β-galactosidase

C. glucocerebrosidase

D. hexosaminidase A

E. sphingomyelinase
 24

Explanation:

The correct answer is A. The presentation and autopsy findings are consistent with
metachromatic
leukodystrophy. The crystals in the macrophages that stained brown with toluidine blue are
sulfatides, which
accumulate in this disorder. The color shift seen in the toluidine blue stain is termed
metachromasia (hence the
term metachromatic leukodystrophy). The cause of metachromatic leukodystrophy is deficiency
of arylsulfatase
A.

Galactocerebroside β-galactosidase (choice B) deficiency produces Krabbe's disease. In

this disorder,
multinucleated cells derived from macrophages (globoid cells) are seen around blood vessels.
Electron
microscopy of the macrophages reveals the presence of linear inclusions.

Glucocerebrosidase (choice C) deficiency results in Gaucher's disease, characterized by

accumulation of
glucocerebrosides. Gaucher's cells are cells distended with material that resembles crumpled
tissue paper.

Hexosaminidase A (choice D) deficiency is associated with Tay Sachs disease, characterized by

accumulation of
GM2 ganglioside in the central and autonomic nervous systems.

Sphingomyelinase deficiency (choice E) produces Niemann-Pick disease, in which

sphingomyelin accumulates,
especially in cells of the mononuclear phagocytic system.

An IV drug abuser develops an aggressive form of nephrotic syndrome that does not respond to
steroids. A renal
biopsy is performed. Which of the following histological diagnoses will most likely be made from
the biopsy tissue?

A. Focal segmental glomerulosclerosis

B. IgA nephropathy

C. Lipoid nephrosis

D. Membranoproliferative glomerulonephritis

E. Membranous glomerulonephritis

Explanation:

The correct answer is A. You should be aware of a specific association between focal segmental
glomerulosclerosis and both IV drug abuse and HIV nephropathy. This disorder usually
presents as an
 25

aggressive form of nephrotic syndrome; the prognosis is generally poor, with rare cases
responding to steroid
therapy. Histologically, there is focal (affecting only some glomeruli) and segmental (affecting
only a portion of
each glomerular capillary tuft) sclerosis and hyalinization with focal deposits of IgM and C3.

In IgA nephropathy (choice B), there are mesangial deposits of IgA and mesangial proliferation.

Lipoid nephrosis (choice C), or minimal change disease, is the most frequent cause of nephrotic
syndrome in
children. Light microscopic changes are generally minimal or absent.

Membranoproliferative glomerulonephritis (choice D) is characterized by proliferation of

glomerular cells and
thickening of capillary loops. It is not particularly associated with drug abuse.

Membranous glomerulonephritis (choice E) is an important cause of nephrotic syndrome in

adults, characterized
by diffuse thickening of the walls of glomerular capillaries.

A 54-year-old man comes to the emergency room four hours after the onset of severe chest pain
radiating to the
left arm. Examination of the levels of which of the following serum markers would best aid in
the evaluation of this
individual's chest pain?

A. Aspartate aminotransferase (AST)

B. Creatine kinase-MB isozyme (CK-MB)

C. Lactate dehydrogenase-1 isozyme (LDH1)

D. Total creatine kinase

E. Troponin

Explanation:

The correct answer is E. Cardiac-specific forms of troponin-T and troponin-I are not normally
detectable in the
blood, but may increase 20-fold following a myocardial infarction. Slight amino acid differences
between cardiac
and skeletal muscle forms of troponin allow specific association of the troponin with heart
muscle damage,
rather than skeletal muscle damage. Troponin is the best serum marker for myocardial
infarction for the first
eight hours, and because levels of the cardiac troponins remain elevated for 7-10 days, it may be
useful for
evaluation of small, CK-negative infarctions for several days after the event.

AST (choice A) is a nonspecific marker for cardiac, liver, and skeletal muscle. Due to its lack of
specificity, it is
 26

much less useful as a marker of myocardial infarction than CK-MB or troponin .

Both total creatine kinase (choice D) and its more cardiac specific form CK-MB (choice B) are
most useful from
8 to 24 hours after infarction, typically with peaks at 12-18 hours.

LDH1(choice C), the cardiac specific form of lactic dehydrogenase, is the test of choice 2 to 7
days after a
suspected myocardial infarction.

A 37-year-old man presents with an unexplained 30 lb. weight loss and poorly-defined ill health over
the past six
months. The physician suspects cancer, but does not know which type of primary tumor is
involved. A panel of
tumor markers is ordered, demonstrating markedly elevated alpha-fetoprotein. Which of the
following tumors
would most likely produce an elevation of this substance?

A. Colorectal and pancreatic cancers

B. Liver and yolk sac tumors

C. Melanoma, neural tumors, and astrocytomas

D. Neuroblastoma, small cell carcinomas, gastric carcinomas, and pancreatic carcinomas

E. Prostatic carcinoma

Explanation:

The correct answer is B. Alpha-fetoprotein (AFP) is a normal fetal protein that can be produced
in the adult by
hepatocellular carcinomas and nonseminomatous germ cell tumors of the testes. The germ cell
tumors most
likely to be associated with elevated AFP are yolk sac tumors and mixed germ cell tumors with a
yolk sac
component.

CEA is associated with both colorectal and pancreatic cancers (choice A).

S100 is the tumor marker associated with melanoma, neural tumors, and astrocytomas (choice
C).

Bombesin is a tumor marker associated with neuroblastoma, small cell carcinomas, gastric
carcinomas, and
pancreatic carcinomas (choice D).

Prostate specific antigen is often markedly elevated in cases of prostatic carcinoma (choice E).
 27

A 75-year-old female with a long history of cigarette smoking is found to have a small tumor at the
periphery of
her right upper lobe. Initially, the tumor was believed to be a Stage I carcinoma (T1 NO MO),
but after surgery it
is found to be Stage II (T1 N1 MO). What is found at surgery that changed the staging?

A. Involvement of the chest wall

B. Positive bronchial lymph nodes

C. Small cell histology

D. Tumor at the carina

E. Tumor size greater than 3 cm

Explanation:

The correct answer is B. Although it is nearly impossible to memorize the staging rules for all
the different kinds
of tumors, there are several basic principles common to all. The TNM stage of a tumor is
determined by the
tumor size and extent (T for tumor), lymph node involvement (N for nodes), and metastasis (M
for metastasis).
N0 always means no lymph nodes are involved. An NI lesion has positive nodes, and only choice
B, positive
bronchial lymph nodes, changes the patient's nodal status.

Involvement of the chest wall is a feature of tumor size and extent-thus, it is a component of the
T in
TNM-staging. T2 lesions involve the chest wall (choice A).

Histological features of the tumor, such as small cell morphology (choice C), are not considered
in tumor stage,
but rather in tumor grade. Small cell tumors are considered high-grade carcinomas.

Tumor extending to the carina reflects the tumor size and extent-thus, it is a component of the T
in
TNM-staging: T3 lesions involve the carina (choice D).

Tumor size is a consideration in the T of TNM-staging. Tumors greater than 3 cm (choice E) are
at least T2
lesions.

A 30-year-old pregnant woman of Jewish descent presents to a physician with painful oral ulcers.
Physical
examination demonstrates widespread erosions of her mucous membranes. Close examination
reveals a friable
mucosa, but no well-defined aphthous ulcers. Biopsy of perilesional mucosa demonstrates
acantholysis; direct
immunofluorescence demonstrates an intraepidermal band of IgG and C3. Which of the
following is the most
 28

likely diagnosis?

A. Bullous pemphigoid

B. Dermatitis herpetiformis

C. Herpes simplex I

D. Herpes simplex II

E. Pemphigus vulgaris

Explanation:

The correct answer is E. This is pemphigus vulgaris, in which autoantibody directed against
transmembrane
cadherin adhesion molecules induces acantholysis (breakdown of epithelial cell-cell connections)
with resulting
intraepidermal blister formation. It may develop spontaneously or following triggers such as
drugs (thiols,
penicillamine), physical injury (burns), cancer, pregnancy, other skin diseases, and emotional
stress.
Pemphigus vulgaris is a relatively rare blistering disease; it is seen more commonly in patients
with Jewish or
Mediterranean heritage. In addition to the usually prominent oral ulcers, uncomfortable skin
erosions can also
occur when the blisters rupture rapidly and are not observed. The epidermis at the edge of
these erosions is
often easily disrupted by sliding pressure (Nikolsky sign).

Bullous pemphigoid (choice A) is characterized by deeper blisters, occurring at the dermal-

epidermal junction.

Dermatitis herpetiformis (choice B) is characterized by severe, intense pruritus and groups of

papules and
vesicles.

Herpes simplex I (choice C) or II (choice D) can show multinucleated giant cells on scrapings of
the ulcer base.

A 35-year-old woman with a ten-year history of vague arthralgias and fevers has antibody studies
performed that
demonstrate autoantibody directed against double-stranded DNA. Later, she develops a
photosensitive rash over
her nose and cheeks. Biopsy of the rash would most likely demonstrate which of the following?

A. Fibroblastic-like cells in a storiform pattern

B. Granular complement and IgG at the dermal-epidermal junction

C. Multiple horn cysts

 29

D. Pautrier microabscesses

E. Sawtooth dermal/epidermal junction

Explanation:

The correct answer is B. The disease is systemic lupus erythematosus; the most useful specific
clue to the
diagnosis is the presence of autoantibodies to double-stranded DNA (one type of antinuclear
antibody or ANA).
The characteristic "butterfly" facial rash of lupus is due to deposition of antibodies and
complement at the
dermal/epidermal junction.

Cells similar to fibroblasts growing in a storiform ("pinwheel") pattern (choice A) are

characteristic of
dermatofibrosarcoma protuberans, a slow-growing type of fibrosarcoma.

Horn cysts (choice C) are lamellated collections of keratin that occur in seborrheic keratoses, a
type of benign
epithelial tumor of the skin.

Pautrier microabscesses (choice D) are a feature of mycosis fungoides, a cutaneous T-cell

lymphoma.

A sawtooth dermal/epidermal junction (choice E) is a feature of lichen planus, an inflammatory

skin condition.

A demented elderly man is transferred from a nursing home to the emergency department because of
generalized edema. The patient is afebrile, and his blood pressure is within normal limits. Blood
samples are sent
to the laboratory for analysis, yielding a serum creatinine of 2.0 mg/dL and serum urea nitrogen
of 65 mg/dL.
Which of the following is the most likely diagnosis?

A. Acute tubular necrosis

B. Congestive heart failure

C. Low protein intake

D. Prostatic hyperplasia

E. Severe liver disease

Explanation:

The correct answer is D. This elderly patient with oliguria and edema has high serum creatinine
(normal 0.6-1.2
 30

mg/dL) and high serum urea nitrogen (normal 7-18 mg/dL). The serum urea nitrogen/serum
creatinine ratio is
32, greater than the normal 12 to 20 for individuals on a normal diet. High ratios with elevated
creatinine levels
can occur in postrenal obstruction (probably benign prostatic hyperplasia in this elderly man)
and in prerenal
azotemia that is superimposed on renal disease (but not pure prerenal azotemia, as would occur
in simple
congestive heart failure). The reason for the high ratio is that urine flow obstruction causes
back pressure on
the renal tubules, favoring back diffusion of urea into the blood from the tubules.

Acute tubular necrosis (choice A) is typically characterized by a low urea nitrogen/creatinine

ratio.

Congestive heart failure (choice B) generally causes prerenal azotemia. This is associated with a
high urea
nitrogen/creatinine ratio, mainly because of an increased plasma urea nitrogen, with the
creatinine level usually
near normal.

Low protein intake (choice C) and severe liver disease (choice E) can cause a low urea
nitrogen/creatinine
ratio.

A 30-year-old male presents to the dermatologist with silvery, scaling plaques on his elbows and
knees. His
mother has been afflicted with the same condition in the past. The most likely diagnosis is

A. acne rosacea

B. acne vulgaris

C. pemphigus vulgaris

D. pityriasis rosea

E. psoriasis vulgaris

Explanation:

The correct answer is E. Psoriasis vulgaris usually appears on the nails, knees, elbows, and
scalp. It does not
generally affect the mucous membranes. Lesions are well-demarcated coral-colored plaques
with a white or
silvery scale (classic clue). Histologically, epidermal hyperplasia causing thickening and
lengthening of the rete
ridges is apparent, as is thinning of the epidermis over the dermal papillae. There is a
recognized genetic
component to this condition. Peak incidence is at age 30.
 31

Here's a point-saving strategy: It is easy to get confused on this question because of the similar
looking answer
choices, especially under time pressure. Be extra careful in such cases to mark the proper choice
on your
answer grid.

Acne rosacea (choice A) affects the central face. Erythema, telangiectasias, acneform lesions
(papules, cysts,
pustules), and rhinophyma (telangiectasias and hyperplasia of nasal soft tissue) are found in
various
combinations. It is common from ages 30-50. Women are affected three times more frequently
than men, but
the syndrome is more severe in the latter.

Acne vulgaris (choice B) causes comedones, papules, and cysts. It may be related to hormones,
drugs, diet,
irritants, and genetic factors. Allergy to Propionibacterium acnes has been found to contribute
to this condition.

Pemphigus vulgaris (choice C) starts with small vesicles, usually on the oral or nasal mucosa,
then spreads to
other parts of the body. Bullae are delicate and flaccid. The condition is due to autoantibodies to
intercellular
junctions between keratinocytes. Nikolsky's sign (production of blistering by light stroking or
rubbing of the skin)
is positive. Pemphigus is most common from ages 40-60.

Pityriasis rosea (choice D) presents first with a red, scaling, "herald patch" approximately 4 cm
in diameter. It is
followed within days by eruption in a "short-sleeve turtleneck" distribution. The classic clue to
the diagnosis is
the appearance of crops of small, pink, oval patches in a "fir tree configuration" on the flexural
lines.

A 38-year-old man presents to the emergency room with multiple arm and leg fractures following a
minor fall.
Physical examination reveals a slight weakness of facial muscles on the left. A complete blood
count shows a mild
anemia. X-ray studies reveal a generalized bony widening with partial obliteration of marrow
spaces. The patient's
disorder is most likely due to abnormal function of which of the following cell types?

A. Granulocytic stem cells

B. Megakaryocytes

C. Plasma cells

D. Osteoblasts

E. Osteoclasts
 32

Explanation:

The correct answer is E. The disease is osteopetrosis (Albers-Schonberg disease), which is a

group of
hereditary diseases in which impaired osteoclast function leads to reduced bone resorption. The
abnormal
osteoclasts frequently are enlarged, with bizarre shapes. The bones become thick and brittle;
other features
include anemia secondary to marrow loss and cranial nerve deficits secondary to narrowing of
bony ostea. An
autosomal recessive, severe form of the disease produces death in childhood. A relatively benign,
autosomal
dominant form presents in adulthood.

Abnormal proliferation of granulocytic stem cells (choice A) can produce myelocytic leukemias.

Megakaryocyte abnormalities (choice B) can produce platelet disorders, but not deficient bone
resorption.

In multiple myeloma, neoplastic plasma cells (choice C) can cause lytic bone lesions
characterized by excessive
resorption of bone.

Abnormally low osteoclast, rather than osteoblast (choice D), function is apparently the problem
in
osteopetrosis.

A four-year-old child develops steroid-sensitive nephrotic syndrome. Renal biopsy studies

demonstrate normal
appearing glomeruli by light microscopy and fusion of foot processes by electron microscopy.
Which of the
following proteins would be present in the urine in the highest concentration?

A. Albumin

B. Ceruloplasmin

C. IgA

D. Kappa light chain

E. Lambda light chain

Explanation:

The correct answer is A. Severe, persistent, proteinuria is required to produce nephrotic

syndrome. The renal
histology described is that of minimal change disease, which produces a proteinuria that is
relatively selective
for albumin.
 33

Ceruloplasmin (choice B) is a copper-binding normal serum protein that could be spilled into
the urine in many
types of glomerulonephritis that cause nonselective proteinuria.

IgA (choice C) can also be spilled into urine in non-selective proteinurias.

Both kappa and lambda light chains (choices D and E) are freely filtered at the glomerulus, but
are usually
present in only trivial amounts in patients who do not have multiple myeloma or related
diseases.

A 24-year-old man has progressive, painless enlargement of neck lymph nodes. Routine chest film
followed by
CT scan demonstrates marked enlargement of mediastinal nodes. No nodules are seen in the
liver or lungs.
When evaluating the biopsy of one of the involved nodes, the pathologist should specifically look
for which of the following?

A. Abnormal plasma cells

B. Giant platelets

C. Immature neutrophil precursors

D. Melanin pigment

E. Reed-Sternberg cells

Explanation:

The correct answer is E. This is a classic presentation of Hodgkin's disease, which is a form of
lymphoma
characterized by neoplastic proliferation of Reed-Sternberg cells admixed with variable
numbers of reactive
lymphocytes, neutrophils, and eosinophils. The cell of origin of the Reed-Sternberg cells is still
disputed. These
cells have a distinctive appearance with a large double nucleus that contains paired, large,
nucleoli which are
often red, producing an "owl's eye" effect.

Abnormal plasma cells (choice A) would be a feature of multiple myeloma or some B-cell
leukemias and
lymphomas, which are not as likely in this patient.

Giant platelets (choice B) are a feature seen in several myeloproliferative disorders (notably
essential
thrombocytopenia), which do not cause lymphadenopathy.

Immature neutrophil precursors (choice C) would most likely be a feature of a myeloid

leukemia, which would not
cause a lymphadenopathy.
 34

Melanin pigment (choice D) would be a feature of malignant melanoma, which would probably
have caused lung
or liver metastases if it were at such an advanced stage as to have caused massive
lymphadenopathy.

A surgeon operates on a patient with a pheochromocytoma involving the adrenal gland. He requests
examination
of intraoperative frozen sections by the pathology laboratory. Which of the following criteria can
be used to determine if the lesion is benign or malignant?

A. Blood vessel invasion

B. Cannot be determined by microscopic examination

C. Hemorrhage and necrosis

D. Nuclear pleomorphism

E. Number of mitoses

Explanation:

The correct answer is B. Pheochromocytomas, and their related counterparts in extra-adrenal

sites called
paragangliomas, are notorious because the only reliable indicator of metastatic potential is the
presence of
distant metastases. Very malignant-appearing tumors may not metastasize and benign-
appearing tumors may
produce metastases. In practice, there is no way for the pathologist to make the decision on
frozen (or
permanent) section analysis unless metastasis has already occurred and can be documented.
These tumors
should all be considered "potentially malignant."