1

A patient presents to a physician because of troubling "heartburn" and difficulty swallowing. Esophageal
motility studies demonstrate a near absence of smooth muscle peristalsis and lower esophageal
sphincter tone. No mass lesions are noted and the esophagus is not dilated. Which of the
following findings would most likely also be present?

A. Anemia

B. Atrophic glossitis

C. Hourglass-shaped stomach on barium swallow

D. Massively dilated colon

E. Thick skin

Explanation:

The correct answer is E. Near complete absence of muscle tone and peristalsis is characteristic
of involvement of the esophagus with scleroderma, which causes replacement of muscle by dense
connective tissue. Similar changes in the dermis cause the skin to be thickened. The thickened,
shiny skin of the hands may cause them to resemble claws.

Anemia (choice A) and atrophic glossitis (choice B) are associated with esophageal webs in
Plummer-Vinson syndrome.

An hourglass-shaped stomach within the thoracic cavity (choice C) is a feature of a sliding

hiatal hernia.

A massively dilated esophagus (megaesophagus) can be caused by Chagas' disease, a trypanosomal

disease that can also cause massive dilation of the colon (choice D).

A strict vegetarian is not getting sufficient vitamin D in his diet, and he develops osteomalacia. This
disease is characterized by which of the following changes in his bones?

A. Decreased osteoblasts

B. Increased osteoclast activity

C. Increased osteoid

D. Marrow fibrosis

E. Sparse bony trabeculae

Explanation:

The correct answer is C. The hallmark of osteomalacia is widened osteoid seams. Although the
trabeculae are normal in number and size, they do not mineralize effectively, and the rim of
uncalcified osteoid is much larger than normal.

Osteoclast activity is normal in osteomalacia. Increased osteoclast activity (choice B) is

typical of hyperparathyroidism and Paget's disease of bone.

There are increased numbers of osteoblasts in osteomalacia (compare to choice A), which lay
down increased quantities of osteoid in an effort to strengthen the bone. Unfortunately, the
increased osteoid is not mineralized and the bone remains soft and weak.
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The bone marrow space is normal in osteomalacia. Marrow fibrosis (choice D) is more typical of
hematopoietic disorders, although hyperparathyroidism may also lead to bone marrow fibrosis.

Although poorly mineralized, the bony trabeculae are of normal abundance in osteomalacia.
Sparse trabeculae (choice E) is characteristic of osteoporosis.

A 35-year-old woman notices a change in the appearance of a mole on her neck. Physical examination
reveals that the lesion is an irregular, nodular, superficial mass with a variegated
appearance. Biopsy demonstrates a primary malignant tumor. Which of the following factors is
most predictive of the patient's long term prognosis?

A. Circumference of lesion

B. Darkness of lesion

C. Degree of color variation

D. Depth of lesion

E. Sharpness of border between lesion and adjacent skin

Explanation:

The correct answer is D. The lesion is a malignant melanoma. Melanomas can develop either de
novo or in an existing mole. Sunlight exposure is a significant risk factor and fair-skinned
persons are at increased risk of developing melanoma. The most significant factor for long term
prognosis is the depth of the lesion, since the superficial dermis lies about 1 mm under the
skin surface, and penetration to this depth is associated with a much higher incidence of
metastasis than is seen with a more superficial location.

The circumference of the lesion (choice A) is much less important than depth, since one form of
melanoma (superficial spreading) can still have good prognosis despite large size, if it has
not extended to the depth of the superficial dermal lymphatic bed.

The darkness (choice B) or degree of variation in color (choice C) do not have prognostic
significance once melanoma is diagnosed.

Irregularity, or fuzziness at the border (choice E) of a mole-like lesion is a good clue to

potential malignancy, but does not affect prognosis once a melanoma is diagnosed.

A 45-year-old man presents to a physician with flank pain and hypertension. Serum chemistries
demonstrate slightly increased blood urea nitrogen and creatinine. Hematuria is noted on
urinalysis. Ultrasound studies demonstrate markedly enlarged kidneys with irregular margins and
many fluid-filled spaces of varying sizes. Excessive secretion of which of the following
hormones would most likely account for the patient's hypertension?

A. ACTH

B. Cortisol

C. Parathormone

D. Renin

E. Thyroxine
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Explanation:

The correct answer is D. The disease is adult polycystic kidney disease, which is an autosomal
dominant condition that typically manifests in middle age. While the kidneys appear very badly
deformed, they function surprisingly well because the cystic spaces actually only affect 10% or
less of the nephrons. Pressure exerted by the cysts can somewhat compromise blood flow to some
glomeruli, which is probably why hypertension, as a consequence of renin secretion, is such a
problem for these patients.

ACTH (choice A) can stimulate cortisol (choice B) secretion, and the cortisol (in high amounts)
can have enough mineralocorticoid activity to cause hypertension. However, this would be more
likely with a pituitary tumor, adrenal tumor, or with exogenous corticosteroid use.

Parathormone (choice C) regulates calcium metabolism and does not usually affect blood
pressure.

Thyroxine excess (choice E) can cause hypertension as a consequence of its effects on the heart
and vasculature; this might be seen in the setting of hyperthyroidism due to thyroid disease.

A 45-year-old woman with a history of thyroid disease presents to her physician with a anterior neck
mass. Biopsy demonstrates non-Hodgkin's lymphoma. Which of the following thyroid conditions
most likely preceded the development of lymphoma in this patient?

A. Follicular thyroid carcinoma

B. Graves disease

C. Hashimoto's thyroiditis

D. Nodular goiter

E. Papillary thyroid carcinoma

Explanation:

The correct answer is C. Hashimoto's disease (autoimmune thyroiditis) confers a 60- to-80 fold
increased risk of developing thyroid lymphoma compared to normal controls. This increased risk
is not surprising, considering the histology exhibited in Hashimoto's, in which sheets of
benign but activated lymphocytes infiltrate and eventually destroy the thyroid gland, producing
eventual thyroid failure.

Neither follicular (choice A) nor papillary (choice E) thyroid carcinomas predispose for
lymphoma.

Lymphoma is not particularly related to Graves disease (choice B) or benign nodular goiter
(choice D).

A patient with intestinal malabsorption is found to markedly improve when flour products (bread,
noodles, etc.) are removed from his diet. At the height of the patient's disease, marked
histologic changes would be seen at which of the following sites?

A. Distal large bowel

B. Distal small bowel

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C. Entire large bowel

D. Entire small bowel

E. Proximal small bowel

Explanation:

The correct answer is E. The patient has celiac disease, which is apparently an acquired
hypersensitivity to the gluten (such as gliadin) in wheat. Unlike tropical sprue (which may be
related to enterotoxigenic E. coli infection), which involves the entire small bowel, celiac
sprue is usually limited to the proximal small bowel. This may occur because the gluten
antigens have not yet been digested at this point in their journey through the bowel. A gluten-
free diet usually restores the small bowel mucosa.

Accumulation of which of the following substances indicates aging at a cellular level?

A. Beta-carotene

B. Bilirubin

C. Hemosiderin

D. Lipofuscin

E. Melanin

Explanation:

The correct answer is D. Lipofuscin is a brown pigment that accumulates with aging. It is
believed to be produced from the peroxidation of lipids. Lipofuscin accumulation does not
necessarily impair the ability of the cell to function, and can be found in the hearts and
livers of healthy elderly patients.

Beta-carotene (choice A) is a carotenoid ingested in the diet (found in yellow vegetables such
as squash, pumpkins, and carrots) and converted to vitamin A. Excessive beta-carotene can cause
a benign yellow-orange discoloration of the skin in a condition known as carotenemia.

Bilirubin (choice B) is a pigment derived from the metabolism of the heme group of hemoglobin.
As hemoglobin is broken down, it first forms biliverdin, which is subsequently converted to
bilirubin. Bilirubin can be conjugated (to glucuronide) or unconjugated. The conjugated form
(also called the direct reacting portion) accumulates in biliary obstructions. The unconjugated
form of bilirubin (indirect-reacting) accumulates in hemolytic processes.

Hemosiderin (choice C) is the storage form of iron and stains blue with Prussian blue.
Hemosiderin accumulation from breakdown of red cells is seen in chronic passive congestion of
the lung (inside hemosiderin-laden macrophages called "heart failure cells"). Hemosiderin
deposition is also seen in hemochromatosis, a disorder characterized by abnormal iron storage.
Hemochromatosis is seen in patients with increased iron uptake from the GI tract, and in
patients receiving repeated blood transfusion therapy.

Melanin (choice E) is a brown-black pigment made by melanocytes in the skin. Melanin is also
found in the iris, giving the eye its color. Neuromelanin is a type of melanin found in
catecholamine neurons in the brain.

A 25-year-old man presents to a physician because of multiple small nodules on his lips. The clinician
 5

notes that the patient has a marfanoid habitus. Biopsy of one of these nodules demonstrates a
mucosal neuroma. Which of the following screening tests is indicated?

A. Pentagastrin-stimulated calcitonin

B. Serum gastrin

C. Serum insulin

D. Serum parathyroid hormone

E. Serum vasoactive intestinal peptide

Explanation:

The correct answer is A. The presence of mucosal neuromas, particularly when multiple and when
the patient has a marfanoid syndrome, is a marker for multiple endocrine neoplasia type IIb (MEN
IIb). MEN IIb predisposes for medullary carcinoma of the thyroid and pheochromocytoma.
Pentagastrin-stimulated calcitonin studies may suggest the presence of thyroid C cell
hyperplasia, which may precede frank medullary carcinoma.

High serum gastrin (choice B) suggests pancreatic or duodenal gastrinomas, which may be a
component of MEN I.

High serum insulin (choice C) or vasoactive intestinal peptide (choice E) also suggest
pancreatic endocrine tumors, which may be a component of MEN I.

Parathyroid hyperplasia or adenomas with parathyroid hormone secretion (choice D) can be seen in
MEN I and MEN IIa, but are not part of MEN IIb.

An adult patient presents with persistent headaches. A CT scan of the head demonstrates a 2-cm spherical
mass at the junction of the white and gray matter of the lateral aspect of the cerebral
hemisphere. Which of the following would most likely produce this lesion?

A. Astrocytoma

B. Ependymoma

C. Glioblastoma multiforme

D. Meningioma

E. Metastatic carcinoma

Explanation:

The correct answer is E. 70% of adult brain tumors occur above the tentorium (70% of childhood
tumors occur below the tentorium). Statistically, metastases > astrocytomas (including
glioblastoma) > meningioma > pituitary tumor. Location at the junction of cortical gray and
white matter is also typical for metastatic disease, as is the round shape.

Astrocytomas (choice A) typically arise in the white matter and have an irregular shape.

Ependymomas (choice B) are uncommon and arise from the ependymal lining of the ventricles.

Glioblastoma multiforme (choice C) is an aggressive form of astrocytoma that can cause a

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"butterfly lesion", crossing between the cerebral hemispheres.

Meningiomas (choice D) can cause spherical lesions, and are usually located on the surface of
the brain.

A 62-year-old female is evaluated for uterine bleeding. In the course of her workup, an endometrial
biopsy reveals marked endometrial hyperplasia. A left ovarian mass is identified, which appears
to be solid and about 4 cm in diameter on ultrasound. The ovarian tumor is most likely to be
a(n)

A. corpus albicans

B. endometrioid carcinoma

C. endometriotic cyst

D. granulosa cell tumor

E. teratoma

Explanation:

The correct answer is D. Granulosa cell tumors arise from the granulosa cells of the ovarian
follicle. Typically occurring in postmenopausal women, granulosa cell tumors are solid, yellow
masses that frequently produce estrogens. Consequently, granulosa cell tumors often present
with abnormal uterine bleeding, and they are considered a risk factor for endometrial
carcinoma.

Corpora albicantia (choice A) are the fibrotic remnants of corpora lutea. The corpus albicans
is small, usually less than 1 cm, and does not produce an ovarian mass or hormonal changes that
might cause bleeding.

Endometrioid carcinoma (choice B) of the ovary is an epithelial malignancy that resembles

endometrial carcinoma by light microscopy. It is a solid and/or cystic tumor that arises (like
serous or mucinous carcinoma) in the absence of any appreciable hormonal imbalance.

An endometriotic cyst (choice C) is a focus of endometriosis within an organ other than the
uterus. Endometriotic cysts are commonly called "chocolate" cysts due to the appearance of
brown, semi-solid hemorrhage with the lining wall of endometrial glands and stroma.
Endometriotic cysts do not appear solid, and they commonly regress after menopause.

Teratomas (choice E) usually appear solid and cystic on diagnostic studies, due to the multiple
tissue components present within. Most teratomas contain hair and sebaceous material among
other things, but they do not produce estrogens. There are rare cases of teratomas containing
predominantly thyroid tissue or carcinoids that may be hormonally active.

A 79-year-old man complains of pain in the upper portion of his neck on swallowing. He occasionally
regurgitates undigested food shortly after eating. Which of the following is the most likely
etiology of his problems?

A. Mallory-Weiss tears

B. Plummer-Vinson syndrome

C. Schatzki rings
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D. Traction diverticula

E. Zenker's diverticulum

Explanation:

The correct answer is E. This is the classic presentation of Zenker's diverticulum, which is a
false diverticulum formed by herniation of the mucosa at a point of weakness at the junction of
the pharynx and esophagus in the posterior hypopharyngeal wall. Zenker's diverticulum is also
associated with halitosis, and if the diverticulum fills completely with food, it can cause
dysphagia or obstruction of the esophagus.

Mallory-Weiss tears (choice A) are mucosal tears at the gastroesophageal junction secondary to
repeated, forceful vomiting. They are often seen in alcoholics.

Plummer-Vinson syndrome (choice B) is the triad of dysphagia (due to esophageal webs in the
upper esophagus), atrophic glossitis, and iron-deficiency anemia.

Schatzki rings (choice C) are mucosal rings found in the distal esophagus at the squamocolumnar
junction.

In contrast to a Zenker's diverticulum, the usually asymptomatic traction diverticula (choice

D) are true diverticula involving all of the layers of the esophagus. They are typically caused
by adherence of the esophagus to a scarred mediastinal structure.

A 72-year-old woman complains of constipation and abdominal pain. Over a period of 48 hours, her
symptoms worsen, and she is transported to the hospital for laparoscopic evaluation of an acute
abdomen. At laparoscopy, a volvulus is noted. Which of the following is the most likely
location for the volvulus?

A. Appendix and cecum

B. Ascending colon

C. Descending colon

D. Sigmoid colon

E. Transverse colon

Explanation:

The correct answer is D. Typically, an elderly patient with a volvulus develops an "acute
abdomen", and is found at laparoscopy or laparotomy to have a twisted (and potentially
infarcted) segment of bowel, usually in the poorly supported sigmoid colon. Most other parts of
the colon are held in place by the posterior peritoneal membrane, and the transverse colon is
stretched so that it can not twist. In contrast, intussusception tends to occur either in
babies and young children or in patients with a mass lesion that gets dragged by peristalsis
into the adjacent section of large or small intestine.

A 7-year-old child with slowly developing cardiac outflow obstruction is found on echocardiographic
study to have a mass lesion in the left ventricle. Surgical removal of the mass demonstrates a
benign tumor composed of cells resembling striated muscle. This child should also be evaluated
for which of the following central nervous system lesions?

A. Berry aneurysm
 8

B. Glioblastoma multiforme

C. Infarction

D. Meningioma

E. Tubers

Explanation:

The correct answer is E. The child has a rhabdomyoma, which is the most common primary cardiac
tumor in children. These tumors are composed of cells that resemble skeletal muscle cells, and
are particularly common in children with tuberous sclerosis.

You should associate berry aneurysms (choice A) with adult polycystic kidney disease.

Glioblastoma multiforme (choice B) is a high-grade astrocytoma, and is a relatively common

childhood CNS malignancy. Glioblastoma is not associated with cardiac tumors.

Embolization of atrial myxomas, not rhabdomyomas, may cause CNS infarction (choice C).

Meningiomas (choice D) are not associated with cardiac tumors and are more common in adults.
These usually benign tumors tend to grow at the periphery of the brain, and may compress it,
but do not penetrate it.

A 57-year-old woman with a 30-year x 2 pack/day history of cigarette smoking undergoes bronchoscopy.
Biopsy of bronchial tissue shows replacement of the normal pseudostratified ciliated columnar
epithelium with stratified squamous epithelium. This change represents

A. dysplasia

B. hyperplasia

C. malignant transformation

D. metaplasia

E. necrosis and repair

Explanation:

The correct answer is D. Squamous metaplasia is a frequent airway response to chronic

irritation from cigarette smoking. It represents the replacement of one differentiated tissue
with another mature, differentiated tissue. It is believed that the squamous epithelium is more
resistant to injurious agents, and so represents an adaptive response.

Dysplasia (choice A) is characterized by pleomorphism (the individual cells may vary widely in
appearance) and by loss of normal tissue architecture, rather than by replacement with another
mature epithelium (squamous).

Hyperplasia (choice B) refers to growth of a tissue or organ by cellular proliferation.

Malignant transformation (choice C) is the multistep process by which normal cells progress to
the "cancer" phenotype. Metaplasia is not malignant transformation, although the stimuli
producing metaplasia may also be associated with the development of malignancy.
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Necrosis and repair (choice E) typically result in re-epithelialization and/or fibrosis, not
metaplasia.

A patient develops an ovarian mass that is picked up on pelvic examination. Resection of the mass
demonstrates a lymphoma composed of small lymphocytes with interspersed macrophages, producing
a starry sky pattern. This lesion would be most likely to be associated with which of the
following?

A. abl-bcr hybrid

B. bcl-2 activation

C. c-myc activation

D. t(9,22)

E. t(14,18)

Explanation:

The correct answer is C. The disease is Burkitt's lymphoma (the major clue is "starry sky"
pattern), which occurs as a jaw lesion in epidemic form in Africa (associated with Epstein-Barr
virus) and in a sporadic form that usually involves the pelvic or abdominal organs. Burkitt's
lymphoma is associated with c-myc activation due to a t(8,14) translocation that places the c-
myc-containing segment of chromosome 8 near an actively transcribed gene for immunoglobulin
heavy chains.

t(9,22) (choice D) and abl-bcr hybrid (choice A) are associated with chronic myeloid leukemia
(CML).

t(14, 18) (choice E) and bcl-2 (choice B) are associated with follicular lymphomas, not
Burkitt's lymphoma.

A 43-year-old man presents to a urologist because of a lesion on his penis. Physical examination reveals
an 8-mm opaque, gray-white, relatively flat penile plaque. A biopsy is performed on the lesion;
the pathology report indicates the presence of clearly dysplastic squamous epithelium. Which of
the following is the most likely diagnosis?

A. Bowenoid papulosis

B. Bowen's disease

C. Condyloma acuminatum

D. Erythroplasia of Queyrat

E. Giant condyloma

Explanation:

The correct answer is B. The lesion described is the form of in situ penile carcinoma known as
Bowen's disease. Bowen's disease is thought to carry a 10% risk of progressing to invasive
squamous cell carcinoma, if left untreated.

Bowenoid papulosis (choice A) is a form of in situ penile carcinoma that is characterized

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clinically by multiple, reddish-brown, papular lesions.

Condyloma acuminatum (choice C) is a benign lesion that resembles the common wart. Condylomata
are associated with papillomavirus infection.

Erythroplasia of Queyrat (choice D) is a form of in situ penile carcinoma that produces a soft,
red plaque.

Giant condyloma (choice E) is an uncommon variant of condyloma acuminatum that is locally

aggressive, but does not usually metastasize.

Which of the following types of breast cancer has the best prognosis?

A. Ductal carcinoma

B. Inflammatory carcinoma

C. Lobular carcinoma

D. Medullary carcinoma

E. Tubular carcinoma

Explanation:

The correct answer is E. Breast adenocarcinoma occurs in a variety of morphologic subtypes,

some of which have a significantly worse or better prognosis than the most common invasive
ductal carcinoma. Tubular carcinoma occurs in women younger than 50 and has an excellent
prognosis. It consists of well-formed tubules, which are so well differentiated that the tumor
is sometimes mistaken for a benign lesion. Axillary metastases are present in fewer than 10% of
cases at the time of diagnosis. Of the histologic types of breast cancer listed here, the
tubular variant is certainly associated with the best chances of survival.

Invasive ductal carcinoma (choice A) and invasive lobular carcinoma (choice C) are the main
morphologic types of breast carcinoma. Together, they constitute 80% to 90% of all cases. The
prognosis mainly depends on the staging, related to size of the primary cancer and evidence of
lymphohematogenous spread to regional nodes and distant organs. Grading (that is degree of
differentiation of primary tumor) has a minor influence on prognosis.

Whenever breast cancer of any histologic type grows very rapidly, infiltrating and occluding
the dermal lymphatics, acute swelling and redness of the breast may develop, leading to a
clinical picture referred to as inflammatory carcinoma (choice B). Inflammatory carcinoma,
therefore, is not a true morphologic subtype but a clinical definition. Any form of breast
cancer manifesting as “inflammatory carcinoma” is likely to be extremely
aggressive.

Medullary carcinoma (choice D) has a slightly better prognosis than ductal or lobular types. It
tends to occur in younger women, especially those with mutations of BRCA1. Grossly, this tumor
is soft and well circumscribed. Histologically, this carcinoma is surrounded by a marked
lymphoplasmacytic reaction, which may account for its propensity to grow more slowly than other
forms of cancer. Medullary carcinoma, however, has a worse prognosis than tubular carcinoma.

A 13-year-old girl is brought to pediatrician because her mother says "she just sits around." Physical
examination reveals akinesia and rigidity without other obvious neurologic deficits. Her eyes
are unusual, with thin greenish-brown rings around the outer edge of the cornea. Serum liver
enzymes are moderately elevated. Which of the following medications would likely be most
 11

effective in treating this patient?

A. Deferoxamine

B. Edetate (EDTA)

C. Lithium

D. Penicillamine

E. Phenobarbital

Explanation:

The correct answer is D. The disease is Wilson's disease. This is an autosomal recessive
abnormality of copper metabolism that can present with either neurologic (psychiatric symptoms,
bradykinesia and rigidity, tremors, or chorea) or hepatic (hepatitis, cirrhosis, or
asymptomatic liver function test abnormalities) findings. The corneal rings described in the
question stem are the pathognomic Kayser-Fleischer rings due to copper deposition. Treatment is
with life-long administration of the copper-chelating agent, penicillamine.

Deferoxamine (choice A) is used parenterally to chelate circulating iron.

EDTA (choice B) is an effective chelator of divalent (and trivalent) cations such as lead. It
is administered as the Na2CaEDTA salt to avoid hypocalcemia.

Lithium (choice C) is used to treat bipolar disorder.

Phenobarbital (choice E) is used to treat epilepsy.

A 35-year-old man with severe arthritis and a decrease in mobility of his lower back undergoes HLA
testing, which demonstrates HLA-B27. With which of the following diseases is the HLA-B27
haplotype strongly associated?

A. Budd-Chiari syndrome

B. Goodpasture's syndrome

C. Reiter's syndrome

D. Reye's syndrome

E. Sjgren's syndrome

Explanation:

The correct answer is C. The patient has ankylosing spondylitis, which is very strongly
associated with HLA-B27. HLA-B27 is also associated with Reiter's syndrome, which can be
remembered as the syndrome in which you "can't see (anterior uveitis conjunctivitis), can't pee
(urethritis), and can't climb a tree (arthritis)."

Budd-Chiari syndrome (choice A) is liver disease secondary to occlusion of the inferior vena
cava or hepatic veins.

Goodpasture's syndrome (choice B) is pulmonary hemorrhage and glomerular disease secondary to

antibodies to basement membrane.
 12

Reye's syndrome (choice D) is an often fatal liver disease that can follow viral infection.

Sjgren's syndrome (choice E) is an autoimmune disease that damages salivary glands and tear
glands.

A 63-year-old woman is seen in the emergency room after falling on an icy sidewalk and fracturing her
hip. She is found to have a low bone density, thought to be due to a malignant tumor. She also
has a history of recurrent pneumonia over the last 6 months. Lab work demonstrates a normal
white blood cell count, but decreased platelets and serum albumin with an elevated erythrocyte
sedimentation rate (ESR). Serum electrophoresis indicates an M-protein spike band of IgG kappa.
The urine will most likely show the presence of Bence-Jones proteins composed of

A. IgG heavy chains

B. kappa and lambda light chains of a 60:40 ratio

C. kappa light chains

D. lambda light chains

E. monomer IgG

Explanation:

The correct answer is C. The patient suffers from multiple myeloma, a neoplastic proliferation
of plasma cells (or their precursors) found within the bone marrow. These malignant cells are
responsible for the production of excessive amounts of immunoglobulin (usually IgG or IgA).
Plasma cells synthesize a greater amount of light chains than heavy chains. The intact
immunoglobulins are not excreted by the kidney, but light chains are filtered at the glomerulus
and found in the urine. In normal individuals, polyclonal light chains will be found in the
urine, reflecting the polyclonal population of plasma cells producing the light chains. In
monoclonal proliferations such as multiple myeloma, the light chains will be monoclonal. This
patient is making a monoclonal population of kappa light chains and excreting them in the urine
as Bence-Jones proteins. It is not unusual for patients with myeloma to have recurring
bacterial infections, particularly pneumococcal pneumonia. Remember, this patient is making
decreased levels of normal immunoglobulins of all isotypes, thus making her susceptible to the
bacteria to which she is exposed. Infiltration of bone by the myeloma cells may lead to
pathological fractures.

Bence Jones proteins are light chains, not heavy chains (choice A).

The serum protein electrophoresis showed a monoclonal spike of kappa chains, so the Bence-Jones
proteins will be monoclonal kappa chains. Rarely, a biclonal plasma cell dyscrasia can produce
Bence-Jones proteins composed of both kappa and lambda light chains (choice B), but this is not
the case here.

Bence-Jones proteins composed of lambda light chains (choice D) would not be produced by a
monoclonal myeloma producing kappa chains in the serum.

Bence-Jones proteins are light chains of the immunoglobulin molecule and not the intact monomer
IgG (choice E), which is composed of two light chains and two heavy chains.

Three to five days after a viral illness, a 4-year-old child develops pernicious vomiting, lethargy
progressing to coma, and hepatomegaly. A liver biopsy would likely show
 13

A. hemosiderin

B. microvesicular steatosis

C. normal histology

D. Periodic acid-Schiff (PAS)-positive cytoplasmic granules

E. rhodamine-positive cytoplasmic granules

Explanation:

The correct answer is B. The child has Reye syndrome, which is a postviral derangement of
metabolism associated with enlarged, distorted mitochondria in many tissues. Most significant
clinically are the effects on the liver and brain. In the liver, there is a reduction in the
activity of many key biochemical pathways, notably the citric acid cycle, urea cycle, and beta
oxidation of fatty acids. The disruption of these pathways produces the very extensive
microvesicular steatosis (fatty change) that is the characteristic liver finding. In the brain,
edema is a prominent feature, and the astrocytes show mitochondrial disruptions by electron
microscopy. Many of the first described cases of Reye syndrome occurred in children treated
with aspirin, but the role of salicylates in the pathogenesis of this condition has not been
clearly established. Seventy-five percent of patients have a mild clinical course; the
remainder develop coma, liver failure, or permanent neurologic impairments. Death may result
from either hepatic or CNS damage. Therapy is supportive.

Hemosiderin (choice A) is seen in hemochromatosis and other conditions with increased hepatic
iron stores.

PAS-positive cytoplasmic granules (choice D) are a feature of α-1-antitrypsin deficiency.

Rhodamine-positive cytoplasmic granules (choice E) reflect copper accumulation in patients with

Wilson disease.

During a bitterly cold winter, an elderly couple is found dead in their apartment. All of their windows
are closed and their leaky old furnace is on full. Which of the following is the primary
mechanism by which the toxin involved led to the death of this couple?

A. Decreasing intracellular calcium

B. Inhibition of cytochrome oxidase

C. Inhibition of Na+/K+ ATPase

D. Irreversibly binding to hemoglobin

E. Stimulation of cellular apoptosis

Explanation:

The correct answer is D. This couple died of carbon monoxide poisoning. Carbon monoxide has
approximately 240 times the affinity for hemoglobin than does oxygen. In a sense, the
hemoglobin-CO dissociation curve is shifted very far to the left compared to the hemoglobin-O2
dissociation curve. This means that the binding of hemoglobin to carbon monoxide is virtually
irreversible. (The carbon monoxide that cigarette smokers inhale is cleared only when senescent
red cells are phagocytized in the spleen and the hemoglobin is degraded.) In addition, the
carbon monoxide shifts the hemoglobin-O2 dissociation curve to the left, making the unloading
 14

of O2 to the tissues very difficult. When too much hemoglobin is tied up with carbon monoxide,
the person dies. The carbon monoxide-hemoglobin complex has a bright red color; a distinctive
feature of carbon monoxide poisoning that can be helpful either at autopsy or in living
patients is that this color makes the skin and organs also appear bright cherry red.

Generally, intracellular calcium levels increase, rather than decrease (choice A), with
cellular injury or death.

Cytochrome oxidase is inhibited by cyanide (choice B).

Ouabain is an example of a poison that inhibits Na+/K+ ATPase (choice C).

Apoptosis (programmed cell death) is stimulated (choice E) by certain genes (e.g., p53, ced
3,4), glucocorticoids, and aging.

A third-world patient develops muscle weakness and atrophy with fasciculations and hyporeflexia. The
patient's condition continues to deteriorate, and his legs are eventually permanently
paralyzed. The virus that can cause these problems is usually spread by which of the following
routes?

A. Dirt contact with open wound

B. Injection

C. Mosquitoes

D. Oral-fecal

E. Puncture wound of the foot

Explanation:

The correct answer is D. The disease is poliomyelitis, which is caused by the poliovirus, a
picorna virus. The virus is spread via the fecal-oral route and can then cause paralysis by
infecting the alpha-motor neurons of the anterior horn of the spinal cord. Early symptoms
include malaise, headache, fever, nausea, abdominal pain, and sore throat.

Bacterial and fungal infections can be spread by dirt contact with an open wound (choice A).

AIDS is an example of a disease spread by injection (choice B) or exchange of body fluids.

Malaria is an example of a disease spread by mosquitoes (choice C).

Tetanus is the classic example of disease spread by a puncture wound of the foot (choice E).

A 6-cm length of rectosigmoid colon containing a 2-cm diameter sessile polyp is surgically removed. On
sectioning, the lesion shows finger-like papillae with cores of scant lamina propria. The
surfaces of the papillae are covered by dysplastic columnar epithelium with considerable
nuclear pleomorphism. No glandular structures are seen in the base of the lesion or in the
adjacent muscle tissue. The margins of the specimen are free of dysplastic epithelium. What
further therapy does this person require?

A. Adjunct chemotherapy

B. Complete colectomy
 15

C. Radiation therapy

D. Resection of regional lymph nodes

E. No further therapy is required

Explanation:

The correct answer is E. The patient has a villous adenoma, which has been adequately treated
by complete resection. If dysplastic epithelium had been found at the surgical resection
margins, re-excision to remove the dysplastic epithelium would be required, since villous
adenomas are considered to be a premalignant condition.

Adjunct chemotherapy (choice A) or radiation therapy (choice C) are not indicated since villous
adenoma is a premalignant condition rather than an actual malignancy.

Complete colectomy (choice B) is typically performed for inflammatory bowel disease rather than
for carcinoma of the colon, and would certainly not be indicated for the treatment of villous
adenoma.

The presence of clearly invasive glands would have indicated that the patient had a true
adenocarcinoma and evaluation of regional lymph nodes (choice D), would be required to stage
the extent of the disease.

A 62-year-old man with a long history of cigarette smoking develops high blood pressure, a moon face,
and central obesity. Serum ACTH is increased, but MRI studies of the pituitary and hypothalamus
fail to demonstrate any tumors. A chest x-ray film reveals a small tumor in the right upper
lobe, and a biopsy is performed. Histologically, the tumor is composed of sheets of anaplastic
cells with a high nuclear/cytoplasmic ratio. The tumor is immunoreactive to antibodies directed
against ACTH. Which of the following is the most likely diagnosis?

A. Adenocarcinoma

B. Carcinoid tumor

C. Hamartoma

D. Small cell carcinoma

E. Squamous cell carcinoma

Explanation:

The correct answer is D. Small cell carcinoma of the lung is composed of extremely
undifferentiated (ie, anaplastic) cells, with high nuclear/cytoplasmic ratio. This neoplasm is
very aggressive and tends to metastasize so early in its course that even small tumors are
considered inoperable by the time of clinical diagnosis. One of the most interesting
characteristics of this type of tumor is the frequent association with paraneoplastic
syndromes, the most common of which is due to ectopic production of ACTH. Paraneoplastic
syndromes also occur with other types of lung tumors.

Adenocarcinomas of the lung (choice A) are composed of mucin-producing neoplastic cells

arranged in a glandular pattern. Its histologic features make this tumor easily distinguishable
from small cell carcinoma.

Carcinoid tumors of the lung (choice B) are histologically similar to carcinoid tumors of the
 16

gastrointestinal tract. They are composed of cords and islands of uniform cuboidal cells.
Carcinoid syndrome may be produced because of the ability of the tumor to produce and release
serotonin.

A hamartoma (choice C) is not a true neoplasm, but rather a malformative lesion consisting of
normal lung tissues arranged in haphazard manner. Hamartomas are often discovered incidentally
on chest x-ray films as "coin lesions" and contain cartilage, smooth muscle, and cystlike
spaces lined by bronchial epithelium.

Squamous cell carcinomas (choice E) are characterized by neoplastic squamous epithelium with
evidence of extracellular and/or intracellular keratin production. The most frequent
paraneoplastic syndrome accompanying pulmonary squamous cell carcinomas is hypercalcemia.

Finally, remember that cigarette smoking is a strong risk factor for all types of lung cancer,
especially squamous cell carcinoma and small cell carcinoma.

A patient presents to a physician with ill-defined complaints of malaise. The physician orders an
erythrocyte sedimentation rate, which yields a value lower than normal. Which of the following
conditions would most likely produce a decreased erythrocyte sedimentation rate?

A. Cancer

B. Infection

C. Polycythemia

D. Pregnancy

E. Systemic lupus erythematosus

Explanation:

The correct answer is C. The erythrocyte sedimentation rate (ESR) is a simple, cheap, but
nonspecific test based on the rate at which red cells will settle in blood. A decreased
erythrocyte sedimentation rate (cells settle out slower) can be seen in sickle cell anemia
(because of the altered cell shape), polycythemia (because there are many cells), and
congestive heart failure (the mechanism is not obvious).

Diseases associated with increased antibody formation tend to markedly increase the ESR by
causing the erythrocytes to stick to each other better and consequently settle faster.
Conditions with elevated ESR include cancer (choice A), infection (choice B), pregnancy (choice
D) and connective tissue diseases such as systemic lupus erythematosus (choice E).

A 42-year-old man previously diagnosed with kidney stones complains of gnawing, burning epigastric pain.
On questioning, he also notes moderate to severe diarrhea. Measurement of the patient's basal
gastric acid output reveals that it is markedly elevated. These symptoms are likely the result
of which of the following neoplastic syndromes?

A. Familial polyposis coli

B. MEN I

C. MEN IIA

D. MEN IIB
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E. MEN III

Explanation:

The correct answer is B. Pancreatic islet tumors, which may produce gastrin and secondarily
Zollinger-Ellison syndrome, are a feature of multiple endocrine neoplasia type I. Other
features of MEN I are tumors of the parathyroid (the resulting hypercalcemia and hypercalciuria
leads to kidney stones), adrenal cortex, and pituitary gland. In general, the tumors in the MEN
syndromes may be expressed at different times in a patient's life, and not all patients may
exhibit the full syndromes.

Endocrine tumors are not a feature of familial polyposis coli (choice A), which is instead
characterized by colonic polyps and colon cancer.

MEN type IIA (choice C) features tumors of the adrenal medulla (pheochromocytoma), medullary
carcinoma of the thyroid, and parathyroid hyperplasia or adenoma.

MEN type IIB (choice D) closely resembles type IIA but also includes mucosal neuromas, and less
often includes parathyroid diseases.

MEN type III (choice E) is now considered to be the same as MEN type IIB.

A 70-year-old woman has a bilateral hip replacement for osteoarthritis. Which of the following
pathological changes will the removed femoral heads most likely demonstrate?

A. Marked synovial proliferation with pannus formation

B. Multiple small fractures in the cartilage

C. Multiple white flecks in the synovium

D. No visible change

E. Pus covering the articular surface

Explanation:

The correct answer is B. Osteoarthritis is characterized by mechanical, rather than

inflammatory, damage to the joint. The damage usually begins as multiple small fractures of the
cartilage tips of the involved bones, which can lead to wearing down of the cartilage to expose
the underlying bone. In long-standing cases, the articular ends of the bones may develop a
mushroom-like or flattened deformation.

Synovial proliferation with pannus formation (choice A) suggests chronic inflammatory joint
disease such as rheumatoid arthritis.

White flecks (choice C) in a joint suggests the crystals of gout or pseudogout.

The presence of pus (choice E) would suggest an acute inflammatory (possibly infectious)
etiology.

Examination, at autopsy, of the brain of a man who died in an intensive care unit demonstrates
bilateral, linear, parasagittal areas of liquefactive necrosis in the junctional zone between
the anterior and middle cerebral arterial systems. Which of the following is the most likely
etiology?
 18

A. Bacterial infection

B. Fungal infection

C. Ischemia

D. Tumor

E. Viral infection

Explanation:

The correct answer is C. The distinctive areas of necrosis described in the question stem are
border zone (watershed) infarcts. They occur as the result of severe ischemia, which most
profoundly affects the relatively poorly perfused areas at the boundaries between major
arterial territories. The areas of necrosis described in the question stem are those most
commonly observed, although similar infarcts involving border zones in the brain stem are
sometimes also seen.

Bacterial infection (choice A) tends to produce either meningitis, cerebritis, or localized

infections such abscesses.

Fungal infection (choice B) tends to produce either meningitis, vasculitis, granulomas, or

abscesses.

Tumor (choice D) tends to produce localized masses.

Viral infection (choice E) may have a variety of patterns, including meningitis, diffuse
encephalitis, or localized necrosis, but would not be expected to produce a distinctive linear
pattern.

A 59-year-old woman with advanced, metastatic lung cancer develops profound fatigue and weakness and
alternating diarrhea and constipation. Physical examination demonstrates hyperpigmentation of
skin, even in areas protected from the sun. Tumor involvement of which endocrine organ is most
strongly suggested by this patient's presentation?

A. Adrenal gland

B. Endocrine pancreas

C. Ovaries

D. Pituitary gland

E. Thyroid gland

Explanation:

The correct answer is A. This is Addison disease, in which severe adrenal disease produces
adrenocortical insufficiency. Causes include autoimmune destruction, congenital adrenal
hyperplasia, hemorrhagic necrosis, and replacement of the glands by either tumor (usually
metastatic) or granulomatous disease (usually tuberculosis). The symptoms can be subtle and
nonspecific (such as those illustrated), so a high clinical index of suspicion is warranted.
Skin hyperpigmentation is a specific clue that may be present on physical examination,
suggesting excess pituitary ACTH secretion. (The ACTH precursor has an amino acid sequence
similar to MSH, melanocyte stimulating hormone.) Most patients have symptoms (fatigue,
 19

gastrointestinal distress) related principally to glucocorticoid deficiency. In some cases,

however, mineralocorticoid replacement may also be needed for symptoms of salt wasting with
lower circulating volume.

Except in the case of primary pancreatic cancer, complete tumor replacement of the endocrine
pancreas (choice B) would be uncommon. In any event, pancreatic involvement would be associated
with diabetes mellitus.

Involvement of the ovaries (choice C) by metastatic tumor (classically gastric adenocarcinoma)

would produce failure of menstruation.

Involvement of the pituitary gland (choice D) could produce Addisonian symptoms, but the
pigmented skin suggests a primary adrenal problem rather than pituitary involvement.

Replacement of the thyroid gland (choice E) by tumor would cause hypothyroidism with lesser
degrees of fatigue and cold intolerance; this is an unusual cause of hypothyroidism and is less
likely to be tested than Addison disease caused by bilateral adrenal metastasis.