05-12-2009, 04:24 PM
Molecular studies on an abdominal lymph node containing lymphoma demonstrate t(2;8)(p12;q24)
translocation. This is most compatible with which of the following diseases?
A. Burkitt's lymphoma
B. Mantle cell lymphoma
C. Multiple myeloma
D. Small cell lymphoma
E. Small cleaved cell lymphoma
Explanation:
The correct answer is A. Burkitt's lymphoma is actually associated with three translocations.
The common variant t(8;14)(q24;q32), involving the oncogene myc on chromosome 8, and the heavy
immunoglobulin chain on chromosome 14. The other two variants are: t(8;22)(q24;q11), involving
myc and the lambda light chain immunoglobulin site, and t(2;8)(p12;q24), involving the kappa
light chain and myc.
Mantle cell lymphoma (choice B), multiple myeloma (choice C), and small (not cleaved) cell
lymphoma (choice D) are associated with the t(11;14)(q13;q32) translocation involving bcl -1
and the heavy chain site.
Small cleaved cell lymphoma (choice E) is associated with t(14;18)(q 32;q21), involving the
14
immunoglobulin chain site and bcl-2.
A newborn infant is noted to have numerous, light brown macules dispersed across her skin. The
significance of this feature is due to its strong association with the development of which of
the following tumors?
A. Basal cell carcinoma
B. Neuroblastoma
C. Neurofibroma
D. Retinoblastoma
E. Wilms' tumor
Explanation:
The correct answer is C. Congenital "cafe au lait" spots are present in more than 90% of
patients with neurofibromatosis. This autosomal dominant disorder is characterized by multiple
neural tumors, especially neurofibromas, pigmented hamartomas of the iris (Lisch nodules), and
cafe au lait spots, which usually occur over nerve trunks. Although the majority of
neurofibromas in this disease are benign, the tumors can be quite disfiguring and
psychologically damaging.
Basal cell carcinoma (BCC; choice A) is a common, slow-growing tumor of sun-exposed skin. It
develops in adulthood after years of chronic sun damage. Although malignant melanoma may arise
from large congenital nevi, BCC does not.
Neuroblastoma (choice B) is a common childhood tumor that arises anywhere along the sympathetic
chain, and most commonly in the adrenal medulla. The tumor usually presents as an abdominal
mass and is not associated with skin findings.
The ocular neoplasm associated with neurofibromatosis is the Lisch nodule, not the
retinoblastoma (choice D). Retinoblastoma is a neuroepithelial tumor usually identified by
funduscopic examination of a child with visual changes.
Wilms' tumor (choice E) is a neoplasm of primitive renal blastema that may be associated with
congenital malformations of visceral organs, notably the adrenals and gonads, but not skin. It
also presents as an abdominal mass, and is highly survivable with modern treatment modalities.
A neonate develops bile-stained vomiting and progressive abdominal distention, and does not pass
meconium over the first two days of life. The anus is patent, and the bowel loops are palpable.
Plain radiograph shows bubbly meconium in the right lower quadrant. No localized areas of
constriction or other abnormalities are noted. Which of the following is most likely
etiologically related to this infant's condition?
A. Cystic fibrosis
B. Hirschsprung's disease
C. Meckel's diverticulum
D. Omphalocele
E. Polycystic kidney disease
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Explanation:
The correct answer is A. The baby has meconium ileus, which is a manifestation of cystic
fibrosis due to the abnormally viscid pancreatic secretions which "get stuck" in the small
bowel. Meconium ileus can cause gut perforation with peritonitis and intraperitoneal
calcifications (that may be visible on plain film). Meconium ileus complicated by intestinal
perforation or formation of fistulas to the bladder or vagina must be treated surgically.
Medical treatments for uncomplicated meconium ileus are now available, which use enemas,
mucolytic agents, or pancreatic enzymes.
Hirschsprung's disease (choice B) is a cause of congenital constipation related to absence of
ganglion cells in a segment of bowel. The aganglionic bowel segment is narrowed because the
lack of peristalsis keeps stool from moving into the segment. The distal rectum is always
involved, and the lesion may extend proximally as far as the small intestine. The bowel
proximal to the lesion is usually dilated.
A Meckel's diverticulum (choice C) can form due to the persistence of the vitelline duct, which
connects the developing gut to the yolk sac. They are classically located in the distal ileum
within 30 cm of the ileocecal valve, and may contain ectopic pancreatic tissue or gastric
mucosa.
Omphalocele (choice D) is characterized by herniation of abdominal viscera through the
abdominal wall near the umbilicus.
In polycystic kidney disease (choice E), cysts of the liver and pancreas may occur; meconium
ileus is not associated with this disorder.
A 69-year-old woman is brought to the emergency room after falling off a step stool and fracturing her
hip. Her past medical history is significant for several bouts of pneumonia during the past
year. Laboratory results indicate a normal white blood cell count, but platelets are decreased,
and the erythrocyte sedimentation rate (ESR) is elevated. X-rays reveal multiple lytic bone
lesions. Serum electrophoresis demonstrates an M-protein spike. Which of the following is the
most likely diagnosis?
A. Chronic lymphocytic leukemia
B. Monoclonal gammopathy of uncertain significance
C. Multiple myeloma (plasma cell myeloma)
D. Plasmacytoma
E. Waldenström's macroglobulinemia
Explanation:
The correct answer is C. The patient is suffering 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), producing an M- protein spike, and increasing the ESR. The decreased
platelet count probably reflects infiltration of the bone marrow by myeloma cells. It is not
unusual for patients with malignant myeloma to have recurring bacterial infections,
particularly pneumococcal pneumonia, because the overall production of normal immunoglobulins
of all isotypes is decreased. Lytic bone lesions due to infiltration by myeloma cells may lead
to pathological fractures. All of the other disorders listed can be associated with an M16
protein spike, but this is a nonspecific finding.
Chronic lymphocytic leukemia (CLL; choice A) is ruled out by the normal white count, since this
type of leukemia is generally associated with an absolute lymphocytosis.
Patients with monoclonal gammopathy of undetermined significance (choice B) are generally
asymptomatic, although they have a predisposition for subsequently developing myeloma,
lymphoma, amyloidosis, or Waldenström's macroglobulinemia.
Plasmacytoma (choice D) (solitary myeloma) is a rare, isolated plasma cell neoplasm in bone or
soft tissues. If the primary cancer is in bone, it is likely to disseminate; extraosseous
tumors tend to remain localized. Since this patient had multiple lytic bone lesions, multiple
myeloma is the correct diagnosis.
Waldenström's macroglobulinemia (choice E) is a disorder involving neoplasms of lymphocytoid
plasma cells that produce monoclonal IgM. Hypergammaglobulinemia produces hyperviscosity of the
blood which, along with infiltration by tumor produce the characteristic signs and symptoms.
Weakness, weight loss, bone pain, hepatosplenomegaly, and lymphadenopathy occur commonly.
A 55-year-old woman complains to her physician that the skin of her armpits and groin "keeps getting
darker and darker." Physical examination demonstrates velvety brown and warty skin in the axilla
and groin. Biopsy of these lesions shows a variably hyperplastic epidermis with many sharp peaks
and valleys. Aside from cosmetic considerations, which of the following is the primary medical
significance of these lesions?
A. They may be a sign of immunosuppression
B. They may be a sign of visceral carcinoma
C. They may be easily superinfected
D. They may be malignant
E. They may be premalignant
Explanation:
The correct answer is B. The lesions are acanthosis nigricans, which looks somewhat like a mole
or wart, but is actually due to epidermal hyperplasia. Acanthosis nigricans can be seen in
obesity, diabetes, and in patients with underlying cancers, often adenocarcinomas of the chest
or abdomen.
The lesions are not characteristic of immunosuppression (choice A) and are not easily
superinfected (choice C). They are also neither malignant (choice D) nor premalignant (choice
E).
A 47-year-old woman undergoes endometrial biopsy because she has had repeated episodes of irregular
spotting between periods lately. The biopsy shows strips of endometrium bearing long, narrow,
coiled glands lined by a single layer of columnar epithelium showing regular, uniform, small
nuclei and clear apical vesicles. Which of the following is the most likely diagnosis?
A. Atypical hyperplasia
B. Complex hyperplasia without atypia
C. Proliferative endometrium
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D. Secretory endometrium
E. Simple hyperplasia
Explanation:
The correct answer is D. Endometrial biopsies are often performed to evaluate patients with
menstrual bleeding abnormalities, particularly in perimenopausal or postmenopausal patients.
While the biopsies are done to rule out hyperplasias or cancer, most of the specimens actually
show only proliferative or secretory (as in this patient) endometrium. Secretory endometrium
has the features noted in the question stem.
Atypical hyperplasia (choice A) is characterized by complex glands lined by cells showing
features of atypia, such as cytomegaly, increased nuclear cytoplasmic ratio, prominent
nucleoli, and increased mitotic index.
Complex hyperplasia without atypia (choice B) is characterized by complex, branching glands
without cellular atypia.
Proliferative endometrium (choice C) is characterized by smaller, noncoiled, glands lined with
columnar epithelium without apical (secretory) vesicles.
Simple (cystic) hyperplasia (choice E) is characterized by cystically dilated glands without
cellular atypia.
Which of the following conditions is the most frequent cause of spontaneous abortion in the first
trimester of pregnancy?
A. Abruptio placentae
B. Chorioamnionitis
C. Chromosomal abnormalities
D. Placenta previa
E. Trauma
Explanation:
The correct answer is C. At least 10% to 15% of normally fertilized and implanted ova are lost
in the first trimester of pregnancy because of spontaneous abortion. Studies using immunoassay
of human chorionic gonadotropin (hCG) for early diagnosis of pregnancy suggest that the
percentage of fertilized ova lost in the first trimester might be even higher. The great
majority of these cases are attributable to chromosomal abnormalities. Chromosomal studies are
not routinely performed in such cases, but they are recommended when a malformed fetus has been
identified or when habitual or recurrent abortions occur.
Abruptio placentae (choice A), a complication of the third trimester, occurs when the placenta
detaches prematurely from its implantation site. Retroplacental hemorrhage develops within the
space between placenta and uterine wall, leading to interruption or severe reduction in the
blood supply to the fetus.
Chorioamnionitis (choice B), a complication of the second and third trimesters, results from
ascending infections through the vaginal canal. Infection of chorioamnionic membranes may lead
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to premature rupture of membranes and abortion or premature labor.
Placenta previa (choice D) is a placenta implanted in the lower segment of the uterus. When
dilatation of this segment begins in late pregnancy, a placenta previa may cause severe
bleeding and lead to premature labor.
Surprisingly, trauma (choice E) is a rare cause of spontaneous abortion.
A 65-year-old woman has a long-standing dementing disorder characterized by deterioration in
personality, neglect of personal hygiene, impaired judgment, and disinhibited behavior. MRI
demonstrates severe cortical atrophy limited to the frontal lobes and anterior two thirds of the
temporal lobes, while the remaining cortex is preserved. No evidence of recent or remote
infarcts is found. Which of the following diagnoses is most consistent with these pathologic and
clinical features?
A. Alzheimer disease
B. Creutzfeldt-Jacob disease
C. Dementia with Lewy bodies
D. Frontotemporal dementia
E. Vascular dementia
Explanation:
The correct answer is D. Not all dementing disorders manifest with the same clinical features.
Although there is considerable overlap in clinical symptomatology among different types of
dementias, making clinical diagnosis somewhat problematic, there are classic presentations that
allow identification of a specific form of dementia with a high degree of confidence. In this
case, the patient has symptoms due to frontal lobe damage, eg, disinhibition, impaired
judgment, and personality changes. Furthermore, MRI demonstrates a specific pattern of cortical
atrophy, restricted to the frontal lobes and anterior portion of the temporal lobes. This
combination points toward a group of dementias called frontotemporal dementia, the most
frequent form of which is Pick disease. Other forms of frontotemporal dementia are very
infrequent. Remember: frontal symptoms in conjunction with frontotemporal atrophy =
frontotemporal dementia/Pick disease.
Alzheimer disease (choice A) is the most frequent form of dementia in industrialized countries.
Although symptoms due to frontal damage may be present in Alzheimer disease, they are usually
associated with a more generalized impairment of higher neurologic functions, eg, language,
memory, and learned movements. In addition, cortical atrophy in Alzheimer disease is widespread
and not limited to the frontal and anterior temporal lobes.
Creutzfeldt-Jacob disease (choice B) represents the prototype of prion diseases. Cortical
atrophy is not a prominent feature of Creutzfeldt-Jacob disease, which manifests with
personality changes, memory loss, and seizures, leading to death after a rapid clinical course
(a few months to 1 year).
Dementia with Lewy bodies, also known as diffuse Lewy body disease (choice C), is one of the
most common forms of dementia in Western countries, possibly more common than vascular
dementia. It is characterized by widespread formation of Lewy bodies in the substantia nigra,
limbic cortex, and subcortical nuclei, such as the basal nucleus of Meynert. Extrapyramidal
symptoms similar to Parkinson disease manifest in this form of dementia as a result of
degeneration of dopaminergic pathways.
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Vascular dementia (choice E) is an umbrella term encompassing dementing conditions that arise
from pathology of large or small cerebral vessels. It manifests with memory loss associated
with focal neurologic symptoms depending on the location of damage. MRI would identify old or
recent infarcts, as well as white matter disease. Conditions associated with vascular dementia
include the following: Multi-infarct dementia, which is caused by multiple, scattered brain
infarcts secondary to atherosclerosis of large arteries of the circle of Willis and/or carotid
arteries. Binswanger disease, which involves rarefaction of cerebral white matter and is caused
by hypertension-related arteriolosclerosis. Lacunar infarcts, which consist of small (< 1 cm)
infarcts in the striatum and thalamus; this condition is related to arteriolosclerosis.
Biopsy of a reasonably well-demarcated mass of the nasopharynx demonstrates a plasma cell proliferation.
Serum electrophoresis shows a small monoclonal IgG spike. Bone marrow evaluation fails to
demonstrate plasma cell proliferation and no lesions are seen on extensive skeletal x-rays.
Which of the following is the most likely diagnosis?
A. Heavy chain disease
B. Monoclonal gammopathy of undetermined significance
C. Multiple myeloma
D. Plasmacytoma
E. Waldenström's macroglobulinemia
Explanation:
The correct answer is D. Plasmacytoma (solitary myeloma) involving soft tissue (lungs,
nasopharynx, nasal sinuses) is a plasma cell proliferation resembling multiple myeloma but
without significant metastatic potential. In contrast, some plasmocytomas involving bone
eventually (up to 10 to 20 years) develop into frank multiple myeloma.
Heavy chain diseases (choice A) constitute a group of rare lymphoplasmacytic malignancies in
which excessive amounts of a defective heavy immunoglobulin chain are produced. They may take
the form of gamma heavy-chain disease (from IgG), alpha heavy-chain disease (from IgA) or mu
heavy-chain disease (from IgM); malignant cells are usually present in marrow in all of these
conditions.
Monoclonal gammopathy of undetermined significance (choice B) is a disease of elderly patients
with a monoclonal spike on serum or urine electrophoresis, but no identifiable mass or bone
marrow lesion; 20% of these patients eventually develop one of the other diseases listed in the
answer choices.
Multiple myeloma (choice C) is a malignancy derived from a single plasma cell clone with
significant metastatic potential. Multiple lytic bone lesions are usually seen.
Waldenström's macroglobulinemia (choice E) is a malignancy of lymphoplasmacytic cells that
secrete IgM. In this disorder, the bone marrow is diffusely rather than focally infiltrated by
lymphocytes, plasma cells, and hybrid forms.
A 65-year-old woman presents with a 30-lb weight loss and malaise. Cancer is suspected. Which of the
following is the correct list, starting with the most prevalent, of the three most common
causes of cancer in women?
A. Breast, lung, colon and rectum
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B. Breast, uterus, lung
C. Colon and rectum, lung, ovary
D. Lung, breast, ovary
E. Ovary, uterus, lung
Explanation:
The correct answer is A. The correct female incidence sequence is breast (32%), lung (13%),
and colon and rectum (13%). The two major causes of cancer death in women are lung (23%) and
breast (18%). In men, the incidence sequence is prostate (32%), lung (16%), and colon and
rectum (12%). The two leading causes of male cancer deaths are lung (33%) and prostate (13%).
The uterus and ovary (choices B, C, D, and E) are not among the three organs most frequently
affected by cancer in women.
A 50-year-old woman presents with a 5-year history of headaches, generalized tonic-clonic seizures, and
bilateral leg weakness. Skull films reveal hyperostosis of the calvarium. Biopsy of the
responsible lesion shows a whorling pattern of the cells. Which of the following is the most
likely diagnosis?
A. Arachnoid cyst
B. Glioblastoma multiforme
C. Meningioma
D. Metastatic breast cancer
E. Oligodendroglioma
Explanation:
The correct answer is C. The most likely diagnosis is an intracranial meningioma. Meningiomas
are slow-growing, benign tumors comprising 15% of intracranial tumors; they are most common in
the elderly. They originate from either dura mater or arachnoid and are sharply demarcated from
brain tissue. Meningiomas often incite an osteoblastic reaction in the overlying cranial bones.
Microscopically, the meningioma cells have a tendency to encircle one another, forming whorls
and psammoma bodies. Clinically, they present as mass lesions; seizures may occur. The superior
parasagittal surface of the frontal lobes is a favorite site of origin. This can often produce
leg weakness, since the leg motor fibers that pass down through the internal capsule originate
in parasagittal cortical regions. Treatment of meningiomas is usually surgical.
Arachnoid cysts (choice A) are formed by splitting of the arachnoid membrane; most arachnoid
cysts arise near the Sylvian fissure. They may present with mass effect, but would be unlikely
to produce seizures, prominent focal signs, or reactive hyperostosis.
Glioblastoma multiforme (choice B) is an aggressive malignant astrocytoma that would likely
have killed the patient long before 5 years had elapsed.
Metastatic breast cancer (choice D) would generally look different microscopically (the
whorling cell pattern is characteristic of meningioma). It would be unlikely for metastatic
cancer to cause a reaction in the overlying bone, or to be present long enough to cause
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symptoms for 5 years.
Oligodendrogliomas (choice E) are glial tumors that could produce the described clinical
picture, but usually do not cause hyperostosis of the calvarium or exhibit the characteristic
whorling cell pattern microscopically.
When a histologic section is taken of an abscess, many of the observed neutrophils show a degenerative
change in which the nucleus has undergone fragmentation. This process is known as
A. caseous necrosis
B. coagulative necrosis
C. karyolysis
D. karyorrhexis
E. pyknosis
Explanation:
The correct answer is D. Karyorrhexis refers to a pattern of nuclear degradation in which a
pyknotic or partially pyknotic nucleus undergoes fragmentation followed by complete lysis. This
pattern is common in the neutrophils present in acute inflammation.
The type of necrosis seen in an abscess is liquefactive necrosis. Caseous necrosis (choice A)
is seen in tuberculosis and some other granulomatous diseases; coagulative necrosis (choice B)
is seen following infarctions of many organs (other than the brain).
Karyolysis (choice C) is also a degenerative change affecting nuclei. In this case, however, it
is seen as a decrease in nuclear basophilia, which is presumably the result of DNAse activity.
Pyknosis (choice E) is characterized by nuclear shrinking and basophilia, apparently as a
result of DNA condensation.
A 52-year-old woman has recently undergone a breast resection for carcinoma. Based on the statistics for
breast cancer incidence, which of the following types of carcinoma does this patient most
likely have?
A. Colloid (mucinous)
B. Invasive ductal
C. Invasive lobular
D. Medullary
E. Metastatic bronchogenic
Explanation:
The correct answer is B. Invasive ductal carcinoma is the most likely candidate. Of the various
types of breast adenocarcinoma, invasive ductal carcinoma is by far the most common variant,
accounting for approximately 75% to 80% of all invasive breast carcinomas. Invasive ductal
carcinoma develops from epithelial cells of the terminal duct. Histologically, it is composed
of small, glandular, ductlike structures, lined by variably anaplastic cells. The most common
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mode of presentation is a palpable mass in the breast. Its prognosis depends mostly on staging
(spread of cancer) rather than grading (degree of differentiation).
The colloid (mucinous) variant (choice A) is relatively rare (about 1% to 2%) and occurs more
frequently in older women. Histologically, this carcinoma is characterized by abundant mucin
secretion. It is associated with a better prognosis than the ductal type.
Invasive lobular carcinoma (choice C) is the second most frequent histologic type of breast
adenocarcinoma, accounting for approximately 10% of all cases. Its presumed cell of origin is
the lobular cell. The most typical histologic characteristic is the presence of cancer cells
lined up in orderly rows ("single-file").
Medullary carcinoma (choice D) tends to occur in younger women and is associated with a
slightly better prognosis. Although a malignant tumor, medullary carcinoma is well
circumscribed and surrounded by a florid lymphoplasmacytic reaction. The name is due to its
soft consistency.
Metastatic cancer may involve the breast like any other organ. Bronchogenic carcinoma (choice
E) may also spread to the breast by lymphatic route or by contiguity, but this would be less
likely than primary breast cancer.
A 55-year-old man is brought to his physician's office with a 3-month history of progressive mental
deterioration in the form of memory loss, mood changes, and errors in judgment. His gait is
unsteady, and he requires assistance to prevent falling. He has no history of seizures, head
trauma, or incontinence. Computed tomography (CT) scan and lumbar puncture are unremarkable.
Physical examination reveals hypertonicity of all extremities, bilateral equivocal plantar
response, ataxic gait, and myoclonic jerks in the lower extremities. What is the mechanism by
which this infectious agent causes its pathology?
A. Amyloid deposition
B. Autoimmune destruction
C. Chronic inflammation
D. Embolization and infarction
E. Toxin production
Explanation:
The correct answer is A. This is the classic presentation of Creutzfeldt-Jacob disease (CJD).
Although the pathogenesis is incompletely understood, these patients develop extracellular
deposition of abnormal fibrillar proteins in the brain, ie, amyloid.
Autoimmune destruction (choice B) is not indicated because there is no immunologic response to
the deposition of these extracellular proteins; thus there is no chronic inflammation (choice
C)
Although embolization and infarction (choice D) could complicate the presentation in the age
group typically afflicted with CJD, these processes are not believed to have any direct role in
this pathology.
No toxin is produced (choice E) to account for the presentation in CJD.
A patient consults a dermatologist about a skin lesion on her neck. Examination reveals a 1-cm diameter,
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red, scaly plaque with a rough texture and irregular margins. Biopsy demonstrates epidermal and
dermal cells with large, pleomorphic, hyperchromatic nuclei. Which of the following conditions
would most likely predispose this patient to the development of this lesion?
A. Actinic keratosis
B. Compound nevus
C. Dermal nevus
D. Junctional nevus
E. Melanoma
Explanation:
The correct answer is A. The lesion is a squamous cell carcinoma of the skin. Actinic
keratosis, which is a hyperplastic lesion of sun-damaged skin, predisposes for squamous cell
carcinoma. Another predisposing condition to remember is xeroderma pigmentosum, which
predisposes for both squamous cell and basal cell carcinomas of skin.
A nevus is a mole, containing characteristic cells called nevocellular cells. If the
nevocellular cells are located at the dermal-epidermal junction (junctional nevus, choice D),
in the dermis (dermal nevus, choice C), or both (compound nevus, choice B), they do not
predispose for squamous cell carcinomas of the skin. Malignant melanoma (choice E), however,
can arise in pre-existing nevi.
A 24-year-old woman gives birth to an apparently normal infant. The neonate begins feeding well by the
second day, then at ten days, suddenly develops gastrointestinal obstruction. Which of the
following is the most likely cause of this presentation?
A. Adhesions
B. Congenital pyloric stenosis
C. Hirschsprung's disease
D. Intussusception
E. Volvulus
Explanation:
The correct answer is D. All of the conditions listed can cause gastrointestinal obstruction,
but the clinical presentation is most suggestive of intussusception. In intussusception, there
is telescoping of one bowel segment into another, more distal segment. The disorder is
relatively common in infants and children due to the poor support offered by their thin
mesentery. Intussusception produces intestinal obstruction, and it may produce bowel ischemia
or infarction by trapping mesenteric vessels along with the affected segment. In some cases,
the intussusception may be reduced by diagnostic barium enema.
Adhesions (choice A) can cause bowel obstruction following surgery or inflammatory bowel
diseases.
Congenital pyloric stenosis (choice B) typically presents as projectile vomiting in a 3-4 week
old baby.
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Hirschsprung's disease (choice C), caused by absence of ganglion cells in the distal bowel, is
usually diagnosed in the first few days of life when there is a failure to pass meconium.
Volvulus (choice E) is due to rotation of bowel segments. This is usually a disease of the
elderly.
A middle-aged man with a long history of sexual activity slowly develops testicular enlargement. Needle
biopsy demonstrates the presence of obliterative endarteritis with perivascular cuffing of
lymphocytes and plasma cells. A diffuse interstitial inflammation with edema and prominent
plasma cell infiltrate is also present. Which of the following is the most likely diagnosis?
A. Gonorrhea
B. Mumps
C. Nonspecific orchitis
D. Syphilis
E. Tuberculosis
Explanation:
The correct answer is D. This is one presentation of syphilis, which can involve the testis and
epididymis in both the acquired and congenital types of the disease. Characteristically, the
testis is usually involved before the epididymis. Microscopically, the testis may show either
gumma formation or the findings described in the question stem.
Gonorrhea (choice A) usually causes an acute epididymitis and orchitis with prominent
neutrophils.
Mumps orchitis (choice B) would usually be accompanied by parotitis.
Nonspecific orchitis (choice C) is characterized by prominent neutrophils.
Tuberculosis orchitis (choice E) is characterized by granulomas with acid-fast bacteria.
A 70-year-old woman dies in a nursing home after a heart attack. The time of onset of her clinical
symptomatology and the cause of death are uncertain; furthermore, the possibility of neglect is
being considered. Therefore, an autopsy investigation is arranged. The forensic pathologist
discovers acute thrombosis involving the posterior descending branch of the right coronary
artery with resultant myocardial infarction (MI) in the posterior third of the interventricular
septum. Histologically, there is coagulation necrosis with associated abundant neutrophilic
infiltration. Histiocytes and lymphocytes are scanty. Which of the following is the approximate
period between the onset of pain (ie, beginning of ischemic injury) and death?
A. 1 hour
B. 12 hours
C. 2 days
D. 5 days
E. 10 days
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Explanation:
The correct answer is C. Following irreversible ischemic injury, the heart (and any other
organ) displays an orderly sequence of events that progresses from necrosis of parenchymal
cells to inflammatory reaction, granulation tissue, and scar healing.
Although ischemic injury manifests with pain almost immediately following vascular occlusion,
histologic evidence of necrosis lags behind the clinical symptoms. At 1 hour (choice A) after
ischemia, there is no morphologic change indicative of necrosis. The first signs of necrosis
appear 12 hours (choice B) after irreversible ischemia: myocytes appear intensely eosinophilic
and wavy, but there is no inflammatory reaction yet. Acute inflammatory cells (neutrophils)
infiltrate the infarcted area beginning 1 day and peaking at approximately 2-3 days after
injury. This acute inflammatory response partially overlaps with the subsequent influx of
lymphocytes and histiocytes. Reabsorption of necrotic myofibers by histiocytes, as well as
proliferation of small blood vessels, marks early formation of granulation tissue at around 5
days (choice D). Granulation tissue is advanced at 10 days (choice E) and consists of
fibroblasts, small blood vessels, and residual chronic inflammatory cells within a matrix of
young collagen matrix.
A 54-year-old man presents with a chief complaint of "burning" abdominal pain in the epigastric region.
Endoscopy demonstrates a well-defined, regular gastroesophageal junction located 3 cm above the
esophageal hiatus in the diaphragm. Biopsy of the distal side of the junction demonstrates
normal gastric mucosa. This lesion is best classified as which of the following?
A. Achalasia
B. Esophageal ring
C. Esophageal web
D. Paraesophageal hernia
E. Sliding hernia
Explanation:
The correct answer is E. This patient has a sliding hiatal hernia, which is the most common
(90%) form of hiatal hernia. This condition is frequently associated with gastric reflux.
Achalasia (choice A) is actually a physiologic, rather than an anatomic variation. In this
disorder, the lower esophageal sphincter fails to relax adequately, and esophageal peristalsis
is often abnormal.
Esophageal rings (choice B) are mucosal folds in the esophagus. They are called esophageal webs
(choice C) in the upper esophagus. Schatzki rings are mucosal rings in the lower esophagus, at
the gastroesophageal junction.
In a paraesophageal hernia (choice D), an area of gastric cardia rolls along with the esophagus
through an incompetent hiatus into the thorax. In a paraesophageal hernia, the gastroesophageal
junction would not be displaced.
Which of the following pulmonary conditions is associated with widespread formation of hyaline
membranes
in the alveolar cavities?
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A. Asthma
B. Bacterial pneumonia
C. Desquamative interstitial pneumonitis
D. Diffuse alveolar damage
E. Hemodynamic pulmonary edema
Explanation:
The correct answer is D. Diffuse alveolar damage, clinically referred to as adult respiratory
distress syndrome (ARDS), is characterized by diffuse damage to the alveolar/capillary barrier,
which may result from diverse acute conditions. The four most frequent causes are trauma,
sepsis, shock, and gastric aspiration. The pathogenesis is not entirely clear, but influx of
neutrophils and release of cytokines, eicosanoids, and free radicals seem to be crucial in
promoting alveolar damage. The most characteristic histopathologic hallmark of diffuse alveolar
damage is formation of hyaline membranes within the alveolar cavities. These consist of
proteinaceous material of plasma origin and necrotic debris from desquamated epithelium. The
condition has a 60% mortality and manifests with acute respiratory failure.
The pathologic features of asthma (choice A) are relatively nonspecific and are similar, for
example, to those of chronic bronchitis, including chronic inflammatory infiltration,
hyperplasia of mucous glands, and hypertrophy of smooth muscle. The presence of numerous
eosinophils, however, is more characteristic of asthma.
Bacterial pneumonia (choice B) is characterized by intra-alveolar exudation of neutrophils,
fibrin, and erythrocytes. Bacteria are also present within the alveolar cavities.
Desquamative interstitial pneumonitis (DIP) (choice C) is a form of interstitial disease
referred to as idiopathic pulmonary fibrosis. In contrast to usual interstitial pneumonitis
(another form of idiopathic pulmonary fibrosis), DIP is more responsive to steroid treatment.
Histopathologically, DIP leads to hyperplasia of pneumocytes and accumulation of histiocytes
that fill the alveolar cavities.
Hemodynamic pulmonary edema (choice E) is caused by increased hydrostatic pressure, as occurs
in acute left ventricular failure. It is due to escape of fluid from the intravascular
compartment into the alveoli.
A baby is born with a flat facial profile, prominent epicanthal folds, and simian crease. She vomits
when fed, and upper GI studies demonstrate a "double bubble" in the upper abdomen. Which of the
following cardiovascular abnormalities might this child also have?
A. Atrial septal defect
B. Berry aneurysm
C. Coarctation of the aorta
D. Endocardial cushion defect
E. Tetralogy of Fallot
Explanation:
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The correct answer is D. The disease is Down syndrome (trisomy 21). In addition to mental
retardation and the characteristic physical findings described in the question stem, duodenal
atresia is fairly common, as evidenced by the "double bubble" sign on x-ray. These children are
also likely to have various cardiac anomalies; endocardial cushion defect is the most common.
Atrial septal defect (choice A) is one of the most common genetic defects in the general
population, but is less common than endocardial cushion defect in patients with Down syndrome.
Berry aneurysms (choice B), also known as saccular aneurysms, are typically located in the
circle of Willis on the ventral surface of the brain. They occur more frequently in patients
with adult polycystic disease. Rupture can produce subarachnoid hemorrhage.
Coarctation of the aorta (choice C) occurs more commonly in females with a 45, XO genotype
(Turner syndrome).
Tetralogy of Fallot (choice E) is the most common cause of early cyanosis, consisting of a
ventricular septal defect, right ventricular outflow tract obstruction, an overriding aorta,
and right ventricular hypertrophy.
translocation. This is most compatible with which of the following diseases?
A. Burkitt's lymphoma
B. Mantle cell lymphoma
C. Multiple myeloma
D. Small cell lymphoma
E. Small cleaved cell lymphoma
Explanation:
The correct answer is A. Burkitt's lymphoma is actually associated with three translocations.
The common variant t(8;14)(q24;q32), involving the oncogene myc on chromosome 8, and the heavy
immunoglobulin chain on chromosome 14. The other two variants are: t(8;22)(q24;q11), involving
myc and the lambda light chain immunoglobulin site, and t(2;8)(p12;q24), involving the kappa
light chain and myc.
Mantle cell lymphoma (choice B), multiple myeloma (choice C), and small (not cleaved) cell
lymphoma (choice D) are associated with the t(11;14)(q13;q32) translocation involving bcl -1
and the heavy chain site.
Small cleaved cell lymphoma (choice E) is associated with t(14;18)(q 32;q21), involving the
14
immunoglobulin chain site and bcl-2.
A newborn infant is noted to have numerous, light brown macules dispersed across her skin. The
significance of this feature is due to its strong association with the development of which of
the following tumors?
A. Basal cell carcinoma
B. Neuroblastoma
C. Neurofibroma
D. Retinoblastoma
E. Wilms' tumor
Explanation:
The correct answer is C. Congenital "cafe au lait" spots are present in more than 90% of
patients with neurofibromatosis. This autosomal dominant disorder is characterized by multiple
neural tumors, especially neurofibromas, pigmented hamartomas of the iris (Lisch nodules), and
cafe au lait spots, which usually occur over nerve trunks. Although the majority of
neurofibromas in this disease are benign, the tumors can be quite disfiguring and
psychologically damaging.
Basal cell carcinoma (BCC; choice A) is a common, slow-growing tumor of sun-exposed skin. It
develops in adulthood after years of chronic sun damage. Although malignant melanoma may arise
from large congenital nevi, BCC does not.
Neuroblastoma (choice B) is a common childhood tumor that arises anywhere along the sympathetic
chain, and most commonly in the adrenal medulla. The tumor usually presents as an abdominal
mass and is not associated with skin findings.
The ocular neoplasm associated with neurofibromatosis is the Lisch nodule, not the
retinoblastoma (choice D). Retinoblastoma is a neuroepithelial tumor usually identified by
funduscopic examination of a child with visual changes.
Wilms' tumor (choice E) is a neoplasm of primitive renal blastema that may be associated with
congenital malformations of visceral organs, notably the adrenals and gonads, but not skin. It
also presents as an abdominal mass, and is highly survivable with modern treatment modalities.
A neonate develops bile-stained vomiting and progressive abdominal distention, and does not pass
meconium over the first two days of life. The anus is patent, and the bowel loops are palpable.
Plain radiograph shows bubbly meconium in the right lower quadrant. No localized areas of
constriction or other abnormalities are noted. Which of the following is most likely
etiologically related to this infant's condition?
A. Cystic fibrosis
B. Hirschsprung's disease
C. Meckel's diverticulum
D. Omphalocele
E. Polycystic kidney disease
15
Explanation:
The correct answer is A. The baby has meconium ileus, which is a manifestation of cystic
fibrosis due to the abnormally viscid pancreatic secretions which "get stuck" in the small
bowel. Meconium ileus can cause gut perforation with peritonitis and intraperitoneal
calcifications (that may be visible on plain film). Meconium ileus complicated by intestinal
perforation or formation of fistulas to the bladder or vagina must be treated surgically.
Medical treatments for uncomplicated meconium ileus are now available, which use enemas,
mucolytic agents, or pancreatic enzymes.
Hirschsprung's disease (choice B) is a cause of congenital constipation related to absence of
ganglion cells in a segment of bowel. The aganglionic bowel segment is narrowed because the
lack of peristalsis keeps stool from moving into the segment. The distal rectum is always
involved, and the lesion may extend proximally as far as the small intestine. The bowel
proximal to the lesion is usually dilated.
A Meckel's diverticulum (choice C) can form due to the persistence of the vitelline duct, which
connects the developing gut to the yolk sac. They are classically located in the distal ileum
within 30 cm of the ileocecal valve, and may contain ectopic pancreatic tissue or gastric
mucosa.
Omphalocele (choice D) is characterized by herniation of abdominal viscera through the
abdominal wall near the umbilicus.
In polycystic kidney disease (choice E), cysts of the liver and pancreas may occur; meconium
ileus is not associated with this disorder.
A 69-year-old woman is brought to the emergency room after falling off a step stool and fracturing her
hip. Her past medical history is significant for several bouts of pneumonia during the past
year. Laboratory results indicate a normal white blood cell count, but platelets are decreased,
and the erythrocyte sedimentation rate (ESR) is elevated. X-rays reveal multiple lytic bone
lesions. Serum electrophoresis demonstrates an M-protein spike. Which of the following is the
most likely diagnosis?
A. Chronic lymphocytic leukemia
B. Monoclonal gammopathy of uncertain significance
C. Multiple myeloma (plasma cell myeloma)
D. Plasmacytoma
E. Waldenström's macroglobulinemia
Explanation:
The correct answer is C. The patient is suffering 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), producing an M- protein spike, and increasing the ESR. The decreased
platelet count probably reflects infiltration of the bone marrow by myeloma cells. It is not
unusual for patients with malignant myeloma to have recurring bacterial infections,
particularly pneumococcal pneumonia, because the overall production of normal immunoglobulins
of all isotypes is decreased. Lytic bone lesions due to infiltration by myeloma cells may lead
to pathological fractures. All of the other disorders listed can be associated with an M16
protein spike, but this is a nonspecific finding.
Chronic lymphocytic leukemia (CLL; choice A) is ruled out by the normal white count, since this
type of leukemia is generally associated with an absolute lymphocytosis.
Patients with monoclonal gammopathy of undetermined significance (choice B) are generally
asymptomatic, although they have a predisposition for subsequently developing myeloma,
lymphoma, amyloidosis, or Waldenström's macroglobulinemia.
Plasmacytoma (choice D) (solitary myeloma) is a rare, isolated plasma cell neoplasm in bone or
soft tissues. If the primary cancer is in bone, it is likely to disseminate; extraosseous
tumors tend to remain localized. Since this patient had multiple lytic bone lesions, multiple
myeloma is the correct diagnosis.
Waldenström's macroglobulinemia (choice E) is a disorder involving neoplasms of lymphocytoid
plasma cells that produce monoclonal IgM. Hypergammaglobulinemia produces hyperviscosity of the
blood which, along with infiltration by tumor produce the characteristic signs and symptoms.
Weakness, weight loss, bone pain, hepatosplenomegaly, and lymphadenopathy occur commonly.
A 55-year-old woman complains to her physician that the skin of her armpits and groin "keeps getting
darker and darker." Physical examination demonstrates velvety brown and warty skin in the axilla
and groin. Biopsy of these lesions shows a variably hyperplastic epidermis with many sharp peaks
and valleys. Aside from cosmetic considerations, which of the following is the primary medical
significance of these lesions?
A. They may be a sign of immunosuppression
B. They may be a sign of visceral carcinoma
C. They may be easily superinfected
D. They may be malignant
E. They may be premalignant
Explanation:
The correct answer is B. The lesions are acanthosis nigricans, which looks somewhat like a mole
or wart, but is actually due to epidermal hyperplasia. Acanthosis nigricans can be seen in
obesity, diabetes, and in patients with underlying cancers, often adenocarcinomas of the chest
or abdomen.
The lesions are not characteristic of immunosuppression (choice A) and are not easily
superinfected (choice C). They are also neither malignant (choice D) nor premalignant (choice
E).
A 47-year-old woman undergoes endometrial biopsy because she has had repeated episodes of irregular
spotting between periods lately. The biopsy shows strips of endometrium bearing long, narrow,
coiled glands lined by a single layer of columnar epithelium showing regular, uniform, small
nuclei and clear apical vesicles. Which of the following is the most likely diagnosis?
A. Atypical hyperplasia
B. Complex hyperplasia without atypia
C. Proliferative endometrium
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D. Secretory endometrium
E. Simple hyperplasia
Explanation:
The correct answer is D. Endometrial biopsies are often performed to evaluate patients with
menstrual bleeding abnormalities, particularly in perimenopausal or postmenopausal patients.
While the biopsies are done to rule out hyperplasias or cancer, most of the specimens actually
show only proliferative or secretory (as in this patient) endometrium. Secretory endometrium
has the features noted in the question stem.
Atypical hyperplasia (choice A) is characterized by complex glands lined by cells showing
features of atypia, such as cytomegaly, increased nuclear cytoplasmic ratio, prominent
nucleoli, and increased mitotic index.
Complex hyperplasia without atypia (choice B) is characterized by complex, branching glands
without cellular atypia.
Proliferative endometrium (choice C) is characterized by smaller, noncoiled, glands lined with
columnar epithelium without apical (secretory) vesicles.
Simple (cystic) hyperplasia (choice E) is characterized by cystically dilated glands without
cellular atypia.
Which of the following conditions is the most frequent cause of spontaneous abortion in the first
trimester of pregnancy?
A. Abruptio placentae
B. Chorioamnionitis
C. Chromosomal abnormalities
D. Placenta previa
E. Trauma
Explanation:
The correct answer is C. At least 10% to 15% of normally fertilized and implanted ova are lost
in the first trimester of pregnancy because of spontaneous abortion. Studies using immunoassay
of human chorionic gonadotropin (hCG) for early diagnosis of pregnancy suggest that the
percentage of fertilized ova lost in the first trimester might be even higher. The great
majority of these cases are attributable to chromosomal abnormalities. Chromosomal studies are
not routinely performed in such cases, but they are recommended when a malformed fetus has been
identified or when habitual or recurrent abortions occur.
Abruptio placentae (choice A), a complication of the third trimester, occurs when the placenta
detaches prematurely from its implantation site. Retroplacental hemorrhage develops within the
space between placenta and uterine wall, leading to interruption or severe reduction in the
blood supply to the fetus.
Chorioamnionitis (choice B), a complication of the second and third trimesters, results from
ascending infections through the vaginal canal. Infection of chorioamnionic membranes may lead
18
to premature rupture of membranes and abortion or premature labor.
Placenta previa (choice D) is a placenta implanted in the lower segment of the uterus. When
dilatation of this segment begins in late pregnancy, a placenta previa may cause severe
bleeding and lead to premature labor.
Surprisingly, trauma (choice E) is a rare cause of spontaneous abortion.
A 65-year-old woman has a long-standing dementing disorder characterized by deterioration in
personality, neglect of personal hygiene, impaired judgment, and disinhibited behavior. MRI
demonstrates severe cortical atrophy limited to the frontal lobes and anterior two thirds of the
temporal lobes, while the remaining cortex is preserved. No evidence of recent or remote
infarcts is found. Which of the following diagnoses is most consistent with these pathologic and
clinical features?
A. Alzheimer disease
B. Creutzfeldt-Jacob disease
C. Dementia with Lewy bodies
D. Frontotemporal dementia
E. Vascular dementia
Explanation:
The correct answer is D. Not all dementing disorders manifest with the same clinical features.
Although there is considerable overlap in clinical symptomatology among different types of
dementias, making clinical diagnosis somewhat problematic, there are classic presentations that
allow identification of a specific form of dementia with a high degree of confidence. In this
case, the patient has symptoms due to frontal lobe damage, eg, disinhibition, impaired
judgment, and personality changes. Furthermore, MRI demonstrates a specific pattern of cortical
atrophy, restricted to the frontal lobes and anterior portion of the temporal lobes. This
combination points toward a group of dementias called frontotemporal dementia, the most
frequent form of which is Pick disease. Other forms of frontotemporal dementia are very
infrequent. Remember: frontal symptoms in conjunction with frontotemporal atrophy =
frontotemporal dementia/Pick disease.
Alzheimer disease (choice A) is the most frequent form of dementia in industrialized countries.
Although symptoms due to frontal damage may be present in Alzheimer disease, they are usually
associated with a more generalized impairment of higher neurologic functions, eg, language,
memory, and learned movements. In addition, cortical atrophy in Alzheimer disease is widespread
and not limited to the frontal and anterior temporal lobes.
Creutzfeldt-Jacob disease (choice B) represents the prototype of prion diseases. Cortical
atrophy is not a prominent feature of Creutzfeldt-Jacob disease, which manifests with
personality changes, memory loss, and seizures, leading to death after a rapid clinical course
(a few months to 1 year).
Dementia with Lewy bodies, also known as diffuse Lewy body disease (choice C), is one of the
most common forms of dementia in Western countries, possibly more common than vascular
dementia. It is characterized by widespread formation of Lewy bodies in the substantia nigra,
limbic cortex, and subcortical nuclei, such as the basal nucleus of Meynert. Extrapyramidal
symptoms similar to Parkinson disease manifest in this form of dementia as a result of
degeneration of dopaminergic pathways.
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Vascular dementia (choice E) is an umbrella term encompassing dementing conditions that arise
from pathology of large or small cerebral vessels. It manifests with memory loss associated
with focal neurologic symptoms depending on the location of damage. MRI would identify old or
recent infarcts, as well as white matter disease. Conditions associated with vascular dementia
include the following: Multi-infarct dementia, which is caused by multiple, scattered brain
infarcts secondary to atherosclerosis of large arteries of the circle of Willis and/or carotid
arteries. Binswanger disease, which involves rarefaction of cerebral white matter and is caused
by hypertension-related arteriolosclerosis. Lacunar infarcts, which consist of small (< 1 cm)
infarcts in the striatum and thalamus; this condition is related to arteriolosclerosis.
Biopsy of a reasonably well-demarcated mass of the nasopharynx demonstrates a plasma cell proliferation.
Serum electrophoresis shows a small monoclonal IgG spike. Bone marrow evaluation fails to
demonstrate plasma cell proliferation and no lesions are seen on extensive skeletal x-rays.
Which of the following is the most likely diagnosis?
A. Heavy chain disease
B. Monoclonal gammopathy of undetermined significance
C. Multiple myeloma
D. Plasmacytoma
E. Waldenström's macroglobulinemia
Explanation:
The correct answer is D. Plasmacytoma (solitary myeloma) involving soft tissue (lungs,
nasopharynx, nasal sinuses) is a plasma cell proliferation resembling multiple myeloma but
without significant metastatic potential. In contrast, some plasmocytomas involving bone
eventually (up to 10 to 20 years) develop into frank multiple myeloma.
Heavy chain diseases (choice A) constitute a group of rare lymphoplasmacytic malignancies in
which excessive amounts of a defective heavy immunoglobulin chain are produced. They may take
the form of gamma heavy-chain disease (from IgG), alpha heavy-chain disease (from IgA) or mu
heavy-chain disease (from IgM); malignant cells are usually present in marrow in all of these
conditions.
Monoclonal gammopathy of undetermined significance (choice B) is a disease of elderly patients
with a monoclonal spike on serum or urine electrophoresis, but no identifiable mass or bone
marrow lesion; 20% of these patients eventually develop one of the other diseases listed in the
answer choices.
Multiple myeloma (choice C) is a malignancy derived from a single plasma cell clone with
significant metastatic potential. Multiple lytic bone lesions are usually seen.
Waldenström's macroglobulinemia (choice E) is a malignancy of lymphoplasmacytic cells that
secrete IgM. In this disorder, the bone marrow is diffusely rather than focally infiltrated by
lymphocytes, plasma cells, and hybrid forms.
A 65-year-old woman presents with a 30-lb weight loss and malaise. Cancer is suspected. Which of the
following is the correct list, starting with the most prevalent, of the three most common
causes of cancer in women?
A. Breast, lung, colon and rectum
20
B. Breast, uterus, lung
C. Colon and rectum, lung, ovary
D. Lung, breast, ovary
E. Ovary, uterus, lung
Explanation:
The correct answer is A. The correct female incidence sequence is breast (32%), lung (13%),
and colon and rectum (13%). The two major causes of cancer death in women are lung (23%) and
breast (18%). In men, the incidence sequence is prostate (32%), lung (16%), and colon and
rectum (12%). The two leading causes of male cancer deaths are lung (33%) and prostate (13%).
The uterus and ovary (choices B, C, D, and E) are not among the three organs most frequently
affected by cancer in women.
A 50-year-old woman presents with a 5-year history of headaches, generalized tonic-clonic seizures, and
bilateral leg weakness. Skull films reveal hyperostosis of the calvarium. Biopsy of the
responsible lesion shows a whorling pattern of the cells. Which of the following is the most
likely diagnosis?
A. Arachnoid cyst
B. Glioblastoma multiforme
C. Meningioma
D. Metastatic breast cancer
E. Oligodendroglioma
Explanation:
The correct answer is C. The most likely diagnosis is an intracranial meningioma. Meningiomas
are slow-growing, benign tumors comprising 15% of intracranial tumors; they are most common in
the elderly. They originate from either dura mater or arachnoid and are sharply demarcated from
brain tissue. Meningiomas often incite an osteoblastic reaction in the overlying cranial bones.
Microscopically, the meningioma cells have a tendency to encircle one another, forming whorls
and psammoma bodies. Clinically, they present as mass lesions; seizures may occur. The superior
parasagittal surface of the frontal lobes is a favorite site of origin. This can often produce
leg weakness, since the leg motor fibers that pass down through the internal capsule originate
in parasagittal cortical regions. Treatment of meningiomas is usually surgical.
Arachnoid cysts (choice A) are formed by splitting of the arachnoid membrane; most arachnoid
cysts arise near the Sylvian fissure. They may present with mass effect, but would be unlikely
to produce seizures, prominent focal signs, or reactive hyperostosis.
Glioblastoma multiforme (choice B) is an aggressive malignant astrocytoma that would likely
have killed the patient long before 5 years had elapsed.
Metastatic breast cancer (choice D) would generally look different microscopically (the
whorling cell pattern is characteristic of meningioma). It would be unlikely for metastatic
cancer to cause a reaction in the overlying bone, or to be present long enough to cause
21
symptoms for 5 years.
Oligodendrogliomas (choice E) are glial tumors that could produce the described clinical
picture, but usually do not cause hyperostosis of the calvarium or exhibit the characteristic
whorling cell pattern microscopically.
When a histologic section is taken of an abscess, many of the observed neutrophils show a degenerative
change in which the nucleus has undergone fragmentation. This process is known as
A. caseous necrosis
B. coagulative necrosis
C. karyolysis
D. karyorrhexis
E. pyknosis
Explanation:
The correct answer is D. Karyorrhexis refers to a pattern of nuclear degradation in which a
pyknotic or partially pyknotic nucleus undergoes fragmentation followed by complete lysis. This
pattern is common in the neutrophils present in acute inflammation.
The type of necrosis seen in an abscess is liquefactive necrosis. Caseous necrosis (choice A)
is seen in tuberculosis and some other granulomatous diseases; coagulative necrosis (choice B)
is seen following infarctions of many organs (other than the brain).
Karyolysis (choice C) is also a degenerative change affecting nuclei. In this case, however, it
is seen as a decrease in nuclear basophilia, which is presumably the result of DNAse activity.
Pyknosis (choice E) is characterized by nuclear shrinking and basophilia, apparently as a
result of DNA condensation.
A 52-year-old woman has recently undergone a breast resection for carcinoma. Based on the statistics for
breast cancer incidence, which of the following types of carcinoma does this patient most
likely have?
A. Colloid (mucinous)
B. Invasive ductal
C. Invasive lobular
D. Medullary
E. Metastatic bronchogenic
Explanation:
The correct answer is B. Invasive ductal carcinoma is the most likely candidate. Of the various
types of breast adenocarcinoma, invasive ductal carcinoma is by far the most common variant,
accounting for approximately 75% to 80% of all invasive breast carcinomas. Invasive ductal
carcinoma develops from epithelial cells of the terminal duct. Histologically, it is composed
of small, glandular, ductlike structures, lined by variably anaplastic cells. The most common
22
mode of presentation is a palpable mass in the breast. Its prognosis depends mostly on staging
(spread of cancer) rather than grading (degree of differentiation).
The colloid (mucinous) variant (choice A) is relatively rare (about 1% to 2%) and occurs more
frequently in older women. Histologically, this carcinoma is characterized by abundant mucin
secretion. It is associated with a better prognosis than the ductal type.
Invasive lobular carcinoma (choice C) is the second most frequent histologic type of breast
adenocarcinoma, accounting for approximately 10% of all cases. Its presumed cell of origin is
the lobular cell. The most typical histologic characteristic is the presence of cancer cells
lined up in orderly rows ("single-file").
Medullary carcinoma (choice D) tends to occur in younger women and is associated with a
slightly better prognosis. Although a malignant tumor, medullary carcinoma is well
circumscribed and surrounded by a florid lymphoplasmacytic reaction. The name is due to its
soft consistency.
Metastatic cancer may involve the breast like any other organ. Bronchogenic carcinoma (choice
E) may also spread to the breast by lymphatic route or by contiguity, but this would be less
likely than primary breast cancer.
A 55-year-old man is brought to his physician's office with a 3-month history of progressive mental
deterioration in the form of memory loss, mood changes, and errors in judgment. His gait is
unsteady, and he requires assistance to prevent falling. He has no history of seizures, head
trauma, or incontinence. Computed tomography (CT) scan and lumbar puncture are unremarkable.
Physical examination reveals hypertonicity of all extremities, bilateral equivocal plantar
response, ataxic gait, and myoclonic jerks in the lower extremities. What is the mechanism by
which this infectious agent causes its pathology?
A. Amyloid deposition
B. Autoimmune destruction
C. Chronic inflammation
D. Embolization and infarction
E. Toxin production
Explanation:
The correct answer is A. This is the classic presentation of Creutzfeldt-Jacob disease (CJD).
Although the pathogenesis is incompletely understood, these patients develop extracellular
deposition of abnormal fibrillar proteins in the brain, ie, amyloid.
Autoimmune destruction (choice B) is not indicated because there is no immunologic response to
the deposition of these extracellular proteins; thus there is no chronic inflammation (choice
C)
Although embolization and infarction (choice D) could complicate the presentation in the age
group typically afflicted with CJD, these processes are not believed to have any direct role in
this pathology.
No toxin is produced (choice E) to account for the presentation in CJD.
A patient consults a dermatologist about a skin lesion on her neck. Examination reveals a 1-cm diameter,
23
red, scaly plaque with a rough texture and irregular margins. Biopsy demonstrates epidermal and
dermal cells with large, pleomorphic, hyperchromatic nuclei. Which of the following conditions
would most likely predispose this patient to the development of this lesion?
A. Actinic keratosis
B. Compound nevus
C. Dermal nevus
D. Junctional nevus
E. Melanoma
Explanation:
The correct answer is A. The lesion is a squamous cell carcinoma of the skin. Actinic
keratosis, which is a hyperplastic lesion of sun-damaged skin, predisposes for squamous cell
carcinoma. Another predisposing condition to remember is xeroderma pigmentosum, which
predisposes for both squamous cell and basal cell carcinomas of skin.
A nevus is a mole, containing characteristic cells called nevocellular cells. If the
nevocellular cells are located at the dermal-epidermal junction (junctional nevus, choice D),
in the dermis (dermal nevus, choice C), or both (compound nevus, choice B), they do not
predispose for squamous cell carcinomas of the skin. Malignant melanoma (choice E), however,
can arise in pre-existing nevi.
A 24-year-old woman gives birth to an apparently normal infant. The neonate begins feeding well by the
second day, then at ten days, suddenly develops gastrointestinal obstruction. Which of the
following is the most likely cause of this presentation?
A. Adhesions
B. Congenital pyloric stenosis
C. Hirschsprung's disease
D. Intussusception
E. Volvulus
Explanation:
The correct answer is D. All of the conditions listed can cause gastrointestinal obstruction,
but the clinical presentation is most suggestive of intussusception. In intussusception, there
is telescoping of one bowel segment into another, more distal segment. The disorder is
relatively common in infants and children due to the poor support offered by their thin
mesentery. Intussusception produces intestinal obstruction, and it may produce bowel ischemia
or infarction by trapping mesenteric vessels along with the affected segment. In some cases,
the intussusception may be reduced by diagnostic barium enema.
Adhesions (choice A) can cause bowel obstruction following surgery or inflammatory bowel
diseases.
Congenital pyloric stenosis (choice B) typically presents as projectile vomiting in a 3-4 week
old baby.
24
Hirschsprung's disease (choice C), caused by absence of ganglion cells in the distal bowel, is
usually diagnosed in the first few days of life when there is a failure to pass meconium.
Volvulus (choice E) is due to rotation of bowel segments. This is usually a disease of the
elderly.
A middle-aged man with a long history of sexual activity slowly develops testicular enlargement. Needle
biopsy demonstrates the presence of obliterative endarteritis with perivascular cuffing of
lymphocytes and plasma cells. A diffuse interstitial inflammation with edema and prominent
plasma cell infiltrate is also present. Which of the following is the most likely diagnosis?
A. Gonorrhea
B. Mumps
C. Nonspecific orchitis
D. Syphilis
E. Tuberculosis
Explanation:
The correct answer is D. This is one presentation of syphilis, which can involve the testis and
epididymis in both the acquired and congenital types of the disease. Characteristically, the
testis is usually involved before the epididymis. Microscopically, the testis may show either
gumma formation or the findings described in the question stem.
Gonorrhea (choice A) usually causes an acute epididymitis and orchitis with prominent
neutrophils.
Mumps orchitis (choice B) would usually be accompanied by parotitis.
Nonspecific orchitis (choice C) is characterized by prominent neutrophils.
Tuberculosis orchitis (choice E) is characterized by granulomas with acid-fast bacteria.
A 70-year-old woman dies in a nursing home after a heart attack. The time of onset of her clinical
symptomatology and the cause of death are uncertain; furthermore, the possibility of neglect is
being considered. Therefore, an autopsy investigation is arranged. The forensic pathologist
discovers acute thrombosis involving the posterior descending branch of the right coronary
artery with resultant myocardial infarction (MI) in the posterior third of the interventricular
septum. Histologically, there is coagulation necrosis with associated abundant neutrophilic
infiltration. Histiocytes and lymphocytes are scanty. Which of the following is the approximate
period between the onset of pain (ie, beginning of ischemic injury) and death?
A. 1 hour
B. 12 hours
C. 2 days
D. 5 days
E. 10 days
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Explanation:
The correct answer is C. Following irreversible ischemic injury, the heart (and any other
organ) displays an orderly sequence of events that progresses from necrosis of parenchymal
cells to inflammatory reaction, granulation tissue, and scar healing.
Although ischemic injury manifests with pain almost immediately following vascular occlusion,
histologic evidence of necrosis lags behind the clinical symptoms. At 1 hour (choice A) after
ischemia, there is no morphologic change indicative of necrosis. The first signs of necrosis
appear 12 hours (choice B) after irreversible ischemia: myocytes appear intensely eosinophilic
and wavy, but there is no inflammatory reaction yet. Acute inflammatory cells (neutrophils)
infiltrate the infarcted area beginning 1 day and peaking at approximately 2-3 days after
injury. This acute inflammatory response partially overlaps with the subsequent influx of
lymphocytes and histiocytes. Reabsorption of necrotic myofibers by histiocytes, as well as
proliferation of small blood vessels, marks early formation of granulation tissue at around 5
days (choice D). Granulation tissue is advanced at 10 days (choice E) and consists of
fibroblasts, small blood vessels, and residual chronic inflammatory cells within a matrix of
young collagen matrix.
A 54-year-old man presents with a chief complaint of "burning" abdominal pain in the epigastric region.
Endoscopy demonstrates a well-defined, regular gastroesophageal junction located 3 cm above the
esophageal hiatus in the diaphragm. Biopsy of the distal side of the junction demonstrates
normal gastric mucosa. This lesion is best classified as which of the following?
A. Achalasia
B. Esophageal ring
C. Esophageal web
D. Paraesophageal hernia
E. Sliding hernia
Explanation:
The correct answer is E. This patient has a sliding hiatal hernia, which is the most common
(90%) form of hiatal hernia. This condition is frequently associated with gastric reflux.
Achalasia (choice A) is actually a physiologic, rather than an anatomic variation. In this
disorder, the lower esophageal sphincter fails to relax adequately, and esophageal peristalsis
is often abnormal.
Esophageal rings (choice B) are mucosal folds in the esophagus. They are called esophageal webs
(choice C) in the upper esophagus. Schatzki rings are mucosal rings in the lower esophagus, at
the gastroesophageal junction.
In a paraesophageal hernia (choice D), an area of gastric cardia rolls along with the esophagus
through an incompetent hiatus into the thorax. In a paraesophageal hernia, the gastroesophageal
junction would not be displaced.
Which of the following pulmonary conditions is associated with widespread formation of hyaline
membranes
in the alveolar cavities?
26
A. Asthma
B. Bacterial pneumonia
C. Desquamative interstitial pneumonitis
D. Diffuse alveolar damage
E. Hemodynamic pulmonary edema
Explanation:
The correct answer is D. Diffuse alveolar damage, clinically referred to as adult respiratory
distress syndrome (ARDS), is characterized by diffuse damage to the alveolar/capillary barrier,
which may result from diverse acute conditions. The four most frequent causes are trauma,
sepsis, shock, and gastric aspiration. The pathogenesis is not entirely clear, but influx of
neutrophils and release of cytokines, eicosanoids, and free radicals seem to be crucial in
promoting alveolar damage. The most characteristic histopathologic hallmark of diffuse alveolar
damage is formation of hyaline membranes within the alveolar cavities. These consist of
proteinaceous material of plasma origin and necrotic debris from desquamated epithelium. The
condition has a 60% mortality and manifests with acute respiratory failure.
The pathologic features of asthma (choice A) are relatively nonspecific and are similar, for
example, to those of chronic bronchitis, including chronic inflammatory infiltration,
hyperplasia of mucous glands, and hypertrophy of smooth muscle. The presence of numerous
eosinophils, however, is more characteristic of asthma.
Bacterial pneumonia (choice B) is characterized by intra-alveolar exudation of neutrophils,
fibrin, and erythrocytes. Bacteria are also present within the alveolar cavities.
Desquamative interstitial pneumonitis (DIP) (choice C) is a form of interstitial disease
referred to as idiopathic pulmonary fibrosis. In contrast to usual interstitial pneumonitis
(another form of idiopathic pulmonary fibrosis), DIP is more responsive to steroid treatment.
Histopathologically, DIP leads to hyperplasia of pneumocytes and accumulation of histiocytes
that fill the alveolar cavities.
Hemodynamic pulmonary edema (choice E) is caused by increased hydrostatic pressure, as occurs
in acute left ventricular failure. It is due to escape of fluid from the intravascular
compartment into the alveoli.
A baby is born with a flat facial profile, prominent epicanthal folds, and simian crease. She vomits
when fed, and upper GI studies demonstrate a "double bubble" in the upper abdomen. Which of the
following cardiovascular abnormalities might this child also have?
A. Atrial septal defect
B. Berry aneurysm
C. Coarctation of the aorta
D. Endocardial cushion defect
E. Tetralogy of Fallot
Explanation:
27
The correct answer is D. The disease is Down syndrome (trisomy 21). In addition to mental
retardation and the characteristic physical findings described in the question stem, duodenal
atresia is fairly common, as evidenced by the "double bubble" sign on x-ray. These children are
also likely to have various cardiac anomalies; endocardial cushion defect is the most common.
Atrial septal defect (choice A) is one of the most common genetic defects in the general
population, but is less common than endocardial cushion defect in patients with Down syndrome.
Berry aneurysms (choice B), also known as saccular aneurysms, are typically located in the
circle of Willis on the ventral surface of the brain. They occur more frequently in patients
with adult polycystic disease. Rupture can produce subarachnoid hemorrhage.
Coarctation of the aorta (choice C) occurs more commonly in females with a 45, XO genotype
(Turner syndrome).
Tetralogy of Fallot (choice E) is the most common cause of early cyanosis, consisting of a
ventricular septal defect, right ventricular outflow tract obstruction, an overriding aorta,
and right ventricular hypertrophy.
