CHAPTER 6

Pathology

111
HIGH-YIELD PRINCIPLES
112 Section I: General Principles • Questions

Q U E ST I O N S

1. A 57-year-old man is brought to the emergency
department because of blurry vision, difficulty
standing, and mental confusion. On physical
examination the patient appears malnourished,
he had diffuse crackles bilaterally, and on
standing his gait is wide-based and unsteady.
The patient’s friend, who accompanies him,
says the patient “hasn’t been himself lately,”
and is having difficulty remembering to do ev-
eryday tasks. Which neuropathologic findings
are most consistent with this patient’s symp-
toms?
Pathology
(A) Densely packed cells with halos of cyto-
plasm surrounding large round nuclei
(B) Perivascular pseudorosettes with tumor
cells surrounding vessels
(C) Pseudopalisading tumor cells surrounding
necrotic regions
(D) Sharply demarcated areas of tumor cells
located at the grey-white matter junction
(E) Whorled pattern of concentrically ar-
ranged spindle cells with psammoma bod-
ies

3. After a 63-year-old man with a progressive,

(A) Atrophy of the caudate nucleus
chronic movement disorder dies, the family re-
(B) Depigmentation within the substantia ni-
quests an autopsy. On gross inspection of the
gra pars compacta
patient’s brain, the pathologist notes the pres-
(C) Neurofibrillary tangles and widening of
ence of a deep brain stimulator electrode. The
ventricles
pathologist then obtains a tissue specimen of
(D) No neuropathologic findings
the basal ganglia for histologic analysis (see im-
(E) Symmetric lesions in the paraventricular
age) that stains positive for α-synuclein. From
regions of the thalamus and hypothalamus,
which disease did the decedent most likely suf-
mammillary bodies, and periaqueductal
fer?
region of the midbrain

2. A 41-year-old man visits his physician because

of increasingly painful headaches. CT of the
head is shown in the image. If a biopsy of this
tumor were obtained, what would the patholo-
gist likely see under the microscope?

Reproduced, with permission, from PEIR Digital Library

(http://peir.net).

(A) Guillain-Barré syndrome

(B) Huntington’s disease
Reproduced, with permission, from Kantarjian HM, Wolff (C) Parkinson’s disease
RA, Koller CA. The MD Anderson Manual of Medical Oncol- (D) Pick’s disease
ogy. New York: McGraw-Hill, 2006: Figure 30-4. (E) Werdnig-Hoffmann disease
 HIGH-YIELD PRINCIPLES
Chapter 6: Pathology • Questions 113

4. A newborn girl is diagnosed as dysmorphic by (A) History of aniline dye exposure

a pediatrician in the newborn nursery. On
physical examination the girl has a broad neck,
wide-spaced nipples, and a systolic ejection
murmur. An echocardiogram is performed and
demonstrates coarctation of the aorta. The
echocardiography technologist also runs his
transducer across the patient’s abdomen and
notices a renal abnormality associated with this
patient’s syndrome. The most likely observed
renal abnormality increases this patient’s risk
for developing which disease?
(A) Neuroblastoma
(B) Ovarian cancer
(B) History of cyclophosphamide treatment
(C) History of heavy cigarette smoking
(D) History of pelvic irradiation
(E) History of schistosomiasis infection
6. A 2-year-old girl is brought to the ED because
of fevers that have been occurring daily for 3
weeks. Physical examination reveals a 1.2-kg
(2.6-lb) weight loss since her last doctor’s visit 1
month earlier. She also has pallor, hepatomeg-
aly, and splenomegaly. She is admitted to the
hospital and undergoes bone marrow aspira-
tion; results are shown in the image. Which of
the following is the most likely diagnosis?

Pathology
(C) Transitional cell carcinoma
(D) Uterine cancer
(E) Wilms’ tumor

5. A 65-year-old man presents to the office with

complaints regarding his urine. He states that
he has recently had bloody urine, but does not
have any urinary pain, hesitation, dribbling, or
increased frequency. He also says he has lost
4.5 kg (10 lb) over the past 2 months. A biopsy
of the patient’s bladder wall is shown in the im-
age. Which of the following risk factors has the
strongest association with this patient’s disease?

Image courtesy of Armed Forces Institute of Pathology.

(A) Acute lymphoblastic leukemia

(B) Ewing’s sarcoma
(C) Hemophagocytic lymphohistiocytosis
(D) Neuroblastoma
(E) Wilms’ tumor

Reproduced, with permission, from PEIR Digital Library

(http://peir.net).
HIGH-YIELD PRINCIPLES
114 Section I: General Principles • Questions
7. Following a course of chemotherapy, a 5-year-
old male oncology patient develops altered men-
tal status, tachycardia, decreased blood pressure,
flushing of the extremities, and decreased urine
output. After 48 hours in the pediatric intensive
care unit, the patient dies from complications
secondary to overwhelming gram-negative sepsis.
At autopsy, the pathologist notes the abnormal
appearance of the decedent’s kidneys, as shown
in the image. What process most likely caused
the findings demonstrated in the image?
Pathology
10. A 35-year-old woman presents with dull, persis-
Reproduced, with permission, from PEIR Digital Library
(http://peir.net).
(A) Acute pyelonephritis
(B) Diffuse cortical necrosis
(C) Obstructive uropathy
(D) Papillary necrosis
(E) Renal infarction
8. A 26-year-old woman visits her physician with
complaints of vaginal bleeding after sexual in-
tercourse. She started menses at age 14 years
and has 32-day cycles. She acknowledges hav-
11. A 3-year-old developmentally delayed girl pres-
ing unprotected sex with multiple partners. Cy-
tologic specimens are taken from the cervix
and vagina. On microscopy, cervical cells have
large nuclei with open chromatin; several cells
have mitotic figures. What would most likely
be present in the specimens that account for
these findings?
(A) Double-stranded DNA virus
(B) Gram-negative diplococci
(C) Gram-positive cocci
(D) Single-stranded RNA
(E) Squamous cells covered with bacteria
9. A 36-year-old woman with a family history of
hereditary nonpolyposis colon cancer (HN-
PCC) presents to her gastroenterologist for her
annual examination. Because of a strong family
history of colon cancer, she undergoes yearly
colonoscopy. However, she has shown no signs
and symptoms of HNPCC and has no signifi-
cant past medical history. Other than colorec-
tal carcinoma, what is another condition for
which she is at increased risk given a family
history of HNPCC?
(A) Carcinoma of the endometrium
(B) Cholelithiasis causing cholecystitis
(C) Melanin spots of the buccal mucosa
(D) Pseudopolyps of the small or large bowel
(E) Vitamin B12 deficiency due to malabsorption
tent flank and abdominal pain, polyuria, noc-
turia, and frequent urinary tract infections.
Physical examination is notable for blood pres-
sure of 150/90 mm Hg and multiple bilateral
abdominal masses. Urinalysis is notable for mi-
croscopic hematuria and 1+ protein. CT of the
abdomen reveals multiple cysts in the kidneys.
The patient notes that she was adopted and
knows nothing about her family medical his-
tory. What is the most likely etiology of this pa-
tient’s illness?
(A) A mutation on chromosome 3
(B) A mutation on chromosome 6
(C) A mutation on chromosome 9
(D) A mutation on chromosome 16
ents to the pediatric neurologist for evaluation
of new onset seizures. The parents are also
concerned because the child frequently exhib-
its inappropriate outbursts of laughter. Physical
examination is significant for abnormal facies
marked by microcephaly, deep-set eyes, and a
large mouth with a protruding tongue. The
child’s gait is unstable. The most likely diagno-
sis is an example of which of the following ge-
netic phenomena?
 HIGH-YIELD PRINCIPLES
Chapter 6: Pathology • Questions 115

(A) Anticipation 14. A 65-year-old male immigrant from Africa pres-

(B) Heteroplasmy
(C) Imprinting
(D) Locus heterozygosity
(E) Mosaicism
12. A mother brings her 5-year-old son to his pedi-
atrician’s office. The boy has been experienc-
ing frequent falls as well as progressive diffi-
culty with walking, jumping, and hopping.
Laboratory testing reveals a creatine kinase
level of 2840 U/L. Muscle biopsy reveals varia-
tion in fiber diameter, an increased number of
internalized nuclei, and muscle fiber degenera-
tion and regeneration. Western blot analysis
ents to the emergency department after an epi-
sode of gross hematuria. He states that he has
seen small amounts of blood in his urine from
time to time over the past several months. His
physical examination is remarkable only for
mild hepatosplenomegaly. A urology consult is
called, and the urologist performs a bedside
cystoscopy. A large fungating mass is seen ad-
herent to the superior part of the bladder. Re-
sults of a biopsy are shown in the image. What
is the most likely environmental exposure asso-
ciated with this disease in the patient?

Pathology
will most likely reveal the complete absence of
which of the following?
(A) Cystic fibrosis transmembrane conduc-
tance regulator
(B) Dystrophin
(C) Phenylalanine hydroxylase
(D) Spectrin
(E) Type II collagen

13. A 55-year-old recent immigrant from Taiwan

presents to the clinic with a 3-month history of
worsening nasal congestion, epistaxis, and re- Image courtesy of Armed Forces Institute of Pathology.
current ear infections. Physical examination
reveals painless firm lymph node enlargement
in the neck. CT of the head reveal a large mass (A) Cigarette smoking
situated in the upper nasopharynx. Biopsy of (B) Exposure to aniline dyes
the lesion shows large epithelioid cells inter- (C) Helminth infection
mixed with numerous infiltrating lymphocytes. (D) Infection with a papovavirus
The infectious agent directly associated with (E) Long-term indwelling catheter
this patient’s pathology is best described by
which category?
(A) DNA virus
(B) Eubacterium
(C) Fungus
(D) Mycobacterium
(E) RNA virus
HIGH-YIELD PRINCIPLES
116 Section I: General Principles • Questions
15. A patient with AIDS and a CD4+ cell count
<50/mm3 is suffering from an infection that af-
fects his lungs, eyes, gastrointestinal tract, and
central nervous system. Results of a biopsy are
shown in the image. With what is the patient
most likely infected?
Pathology
Image courtesy of the Centers for Disease Control and Pre-
vention’s Public Health Image Library; content provider Dr.
Edwin P. Ewing, Jr.
(A) Candida albicans
(B) Cryptococcus neoformans
(C) Cytomegalovirus
(D) Herpes simplex virus
(E) Mycobacterium avium
(F) Pneumocystis jiroveci
16. A 66-year-old woman has an autosomal reces-
sive disease with multiple sequelae, including
diabetes mellitus and arthritis. Physical exami-
nation reveals hepatomegaly and skin hyper-
pigmentation. A biopsy of her liver is shown in
the image. What is the most likely explanation
for her health problems?
Reproduced, with permission, from PEIR Digital Library
(http://peir.net).
(A) Chronic ingestion of alcohol
(B) Genetic deficiency in the synthesis of
β-globin chains
(C) Inappropriately high iron absorption
(D) Mutation in RBC membrane protein
17. A 37-year-old HIV-positive man presents for
evaluation of anogenital lesions. He states that
the lesions have been present for years, but
have recently grown in size and become pru-
ritic and tender. On examination he is circum-
cised and has multiple hyperkeratotic papules
on his penis shaft, perineum, and anal area. He
also has a palpable rectal mass with guaiac-
positive stool and conjunctival pallor. On fur-
ther questioning, he admits to recent uninten-
tional weight loss, constipation, and bloating.
His CD4+ cell count is 150/mm3 and his he-
matocrit is 26%. CT scan of the abdomen
shows a 3 × 4-cm rectal mass with multiple
metastatic lesions in his liver. What tumor-sup-
pressor protein is targeted by the virus causing
this patient’s rectal cancer?
(A) APC
(B) BRCA1
(C) MSH2
(D) NF1
(E) p53

18. A 5-year-old boy presents with an unsteady gait
and severe vertigo and nausea. A brain lesion is
seen on CT scan; a biopsy of the lesion is
shown in the image. Where in the brain is the
patient's lesion?
Reproduced, with permission, from PEIR Digital Library
(http://peir.net).
Reproduced, with permission, from PEIR Digital Library
(http://peir.net).
20. A 59-year-old man is hospitalized after suffer-
(A) Cerebellar vermis
(B) Intermediate section of the cerebellar
hemisphere
(C) Lateral section of the cerebellar hemi-
sphere
(D) Occipital cortex
(E) Postcentral gyrus of the parietal lobe
19. A 64-year-old retired shipyard worker has been
experiencing shortness of breath, a cough, and
chest pain for 5 months. In that time he has
lost 14.5 kg (32 lb). He develops progressive as-
cites, and ultimately dies due to a pulmonary
embolus. Autopsy results are shown in the im-
age. Exposure to which substance is a risk fac-
tor for this patient’s disorder?
HIGH-YIELD PRINCIPLES
Chapter 6: Pathology • Questions 117
Pathology
(A) Aflatoxin B
(B) Asbestos
(C) Benzene
(D) Cadmium
(E) Silica
ing a severe myocardial infarction. He is ini-
tially treated with nitrates, β-blockers, and aspi-
rin, and subsequently undergoes cardiac
catheterization with placement of two stents.
Following the procedure he is hemodynami-
cally stable without recurrence of chest pain.
However, 5 days after admission his heart rate
is 134/min, blood pressure is 72/35 mm Hg,
and respiratory rate is 29/min. Physical exami-
nation reveals distant heart sounds and an ele-
vated jugular venous pressure. Which of the
following complications is most likely causing
this patient’s symptoms?
(A) Aneurysm formation
(B) Cardiac arrhythmia
(C) Fibrinous pericarditis
(D) Rupture of the papillary muscle
(E) Rupture of the ventricular free wall
HIGH-YIELD PRINCIPLES
118 Section I: General Principles • Answers
AN S W E R S
1. The correct answer is E. This patient presents
with signs and symptoms of Wernicke’s en-
cephalopathy (confusion, ophthalmoplegia,
and ataxia) and Korsakoff’s psychosis (personal-
ity change, confabulation, and memory loss).
This syndrome is secondary to thiamine defi-
ciency and commonly seen in malnourished
alcoholics. On postmortem examination, pa-
tients suffering from Wernicke-Korsakoff syn-
drome commonly present with symmetric le-
sions in the paraventricular regions of the
thalamus and hypothalamus, mammillary bod-
Pathology
ies, and periaqueductal region of the midbrain.
Answer A is incorrect. Atrophy of the caudate
nucleus is found in Huntington’s disease, a dis-
ease of autosomal dominance associated with
chorea and dementia.
Answer B is incorrect. Depigmentation within
the substantia nigra pars compacta is com-
monly seen in Parkinson’s disease, not thia-
mine deficiency.
Answer C is incorrect. Neurofibrillary tangles,
composed of abnormally phosphorylated tau
protein, are commonly found in the frontal
and temporal lobes of patients with Alzheim-
er’s disease.
Answer D is incorrect. Thiamine deficiency is
associated with neuropathologic changes ob-
served on postmortem examination.
2. The correct answer is C. This patient has a le-
sion consistent with glioblastoma multiforme
(GBM), which is the most common primary
brain tumor and is characterized on CT by a
serpentine border and central areas of necrosis.
The diagnosis should be confirmed by MRI
with and without contrast. The lesion consists
of highly malignant astrocyte tumor cells that
surround areas of necrosis; this is known as
pseudopalisading. GBM has been associated
with genetic alterations, including loss of p53
function, increased activity of the epidermal
growth factor receptor gene (EGFR), and loss
of heterozygosity on chromosome arm 10q.
GBM has a poor prognosis, with a mean sur-
vival of 8–10 months after diagnosis; most pa-
tients die within 2 years.
Answer A is incorrect. Densely packed cells
with halos of cytoplasm surrounding large
round nuclei are characteristic of oligodendro-
gliomas, which are slow-growing tumors origi-
nating in the cerebral hemispheres. These le-
sions have a better prognosis than astrocytomas,
with a mean patient survival of 5–10 years.
Answer B is incorrect. Perivascular pseudoro-
settes with tumor cells surrounding vessels are
characteristic of ependymomas, which are tu-
mors located in the periventricular space or in
the spinal cord that may obstruct the flow of
cerebrospinal fluid.
Answer D is incorrect. Sharply demarcated ar-
eas of tumor cells located at the grey-white
matter junction are characteristic of secondary
metastatic lesions from a primary tumor else-
where in the body, most commonly the breast,
lung, thyroid, skin, kidney, and gastrointestinal
tract.
Answer E is incorrect. A whorled pattern of
concentrically arranged spindle cells with cal-
cified psammoma bodies is characteristic of
meningiomas, which are the second most com-
mon primary intracranial neoplasm. Menin-
giomas are benign, slow-growing tumors of the
meninges.
3. The correct answer is C. The tissue section
shown demonstrates the presence of a Lewy
body, which is a cytoplasmic inclusion consist-
ing of aggregated α-synuclein, ubiquitin, tubu-
lin, and neurofilament proteins. The Lewy
body is believed to result from disrupted pro-
teasomal activity, leading to the accumulation
of cellular proteins, which results in the disrup-
tion of normal cellular processes. Lewy bodies
present in the substantia nigra, in the context
of a movement disorder (evidenced by this pa-
tient’s history and the presence of a deep brain
stimulator), are highly suggestive of Parkinson’s
disease.

Answer A is incorrect. Guillain-Barré syn-
drome is a demyelinating disease of the periph-
eral nervous system. Lewy bodies are not pres-
ent.
Answer B is incorrect. Huntington’s disease is
an autosomal dominant disease involving atro-
phy of the caudate nucleus. It is a progressive,
terminal neurodegenerative disorder character-
ized by chorea and dementia. Lewy bodies are
not present.
Answer D is incorrect. Pick’s disease is a neu-
rodegenerative disease characterized by pro-
gressive dementia, aphasia, and parkinsonism.
Pick bodies (intracellular inclusions of aggre-
5. The correct answer is C. This patient has tran-
gated tau protein), not Lewy bodies, are pres-
ent in affected patients.
Answer E is incorrect. Werdnig-Hoffmann dis-
ease (also known as spinal muscular atrophy) is
an autosomal recessive disease involving pro-
gressive degeneration of the anterior spinal
horns. Lewy bodies are not present.
4. The correct answer is E. This patient has clas-
sic findings associated with Turner’s syndrome,
a genetic disorder resulting from a 45,XO com-
plement of chromosomes. Approximately
25%–30% of patients will have associated renal
anomalies, including horseshoe kidney, pelvic
kidney, or duplicated collecting systems. Pa-
tients with horseshoe kidneys are approxi-
mately four times more likely to develop
Wilms’ tumor when compared to the general
population.
Answer A is incorrect. Although it has been
suggested that patients with Turner’s syndrome
are at increased risk of developing malignancy,
they do not have a specific increased risk of de-
veloping neuroblastoma.
Answer B is incorrect. Although it has been
suggested that patients with Turner’s syndrome
are at increased risk of developing malignancy,
they do not have a specific increased risk of de-
veloping ovarian cancer. Familial BRCA gene
mutations or no history of childbirth each in-
creases the risk of ovarian cancer.
Answer C is incorrect. Although it has been
suggested that patients with Turner’s syndrome
HIGH-YIELD PRINCIPLES
Chapter 6: Pathology • Answers 119
are at increased risk of developing malignancy,
they do not have a specific increased risk of de-
veloping transitional cell carcinoma. Smoking
greatly increases the risk of transitional cell car-
cinoma.
Answer D is incorrect. Although it has been
suggested that patients with Turner’s syndrome
are at increased risk of developing malignancy,
they do not have a specific increased risk of de-
veloping uterine cancer. Unopposed estrogen
secretion (eg., hormone replacement therapy
without progesterone) increases the risk of uter-
ine cancer.
Pathology
sitional cell carcinoma of the bladder, as evi-
denced by his painless hematuria and absent
signs of prostate cancer. Histology confirms the
diagnosis with the presence of invasive transi-
tional cells and prominent, atypical nuclei and
mitotic spindles. Numerous factors increase
the risk of developing transitional cell carci-
noma, the most significant of which is an ex-
tensive history of cigarette smoking. Cigarette
smoking increases a patient’s risk by three- to
sevenfold. Treatment of transitional cell carci-
noma largely depends on the stage of disease,
although these tumors have a tendency to re-
cur regardless of disease stage. Low-grade le-
sions may be treated with excision, whereas
higher-grade lesions require a combination of
excision and chemotherapy.
Answer A is incorrect. Aniline dye exposure
(eg., in a textile mill worker) is a risk factor for
the development of transitional cell carcinoma;
however, smoking is the most significant risk
factor.
Answer B is incorrect. Cyclophosphamide
therapy (eg., in a patient with a history of
treated Ewing’s sarcoma) is a risk factor for the
development of transitional cell carcinoma;
however, smoking is the most significant risk
factor.
Answer D is incorrect. Pelvic irradiation (eg.,
in a patient treated for prostatic cancer) is a
risk factor for the development of transitional
cell carcinoma; however, smoking is the most
significant risk factor.
HIGH-YIELD PRINCIPLES
120 Section I: General Principles • Answers
Answer E is incorrect. Schistosomiasis infec-
tion (eg, in a patient with travel to an endemic
area, including the Middle East) is a risk factor
for the development of transitional cell carci-
noma; however, smoking is the most significant
risk factor.
6. The correct answer is C. This patient has
symptoms consistent with hemophagocytic lym-
phohistiocytosis (HLH), and bone marrow aspi-
ration (demonstrating macrophages engulfing
RBCs) confirms the diagnosis. Familial-type
HLH is an autosomal recessive defect in several
genes, including perforin-related genes; the sec-
ondary type is frequently due to infection with
Pathology
Epstein-Barr virus. HLH involves the abnormal
activation and proliferation of lymphohistiocytes
leading to hemophagocytosis and the upregula-
tion of proinflammatory cytokines. Treatment
consists of a combination of etoposide, cortico-
steroids, and methotrexate, although stem cell
transplant is often required.
Answer A is incorrect. Acute lymphoblastic
leukemia frequently presents with constitu-
tional symptoms (fever, weight loss, pallor, he-
patosplenomegaly). Bone marrow aspiration
would not demonstrate hemophagocytosis.
Answer B is incorrect. Ewing’s sarcoma fre-
quently presents in the second decade of life
with constitutional symptoms (fever, weight
loss), bone tenderness, and pathologic frac-
tures. Bone marrow aspiration would not dem-
onstrate hemophagocytosis.
Answer D is incorrect. Neuroblastoma fre-
quently presents with constitutional symptoms
(fever, weight loss, pallor, hepatosplenomeg-
aly). It is the most common malignancy of
infancy. A bone marrow aspirate would not
demonstrate hemophagocytosis.
Answer E is incorrect. Wilms’ tumor frequently
presents with an asymptomatic flank mass and/
or gross hematuria. It is the most common pri-
mary renal tumor in children. Bone marrow
aspiration would not demonstrate hemophago-
cytosis.
7. The correct answer is B. This patient died
from complications secondary to septic shock.
The patient had evidence of early end-organ
failure as demonstrated by his decreased urine
output. Patients suffering from septic shock
can develop diffuse cortical necrosis (shown in
the image) of the kidneys, which is believed to
result from a combination of hypoperfusion,
microangiopathic thrombosis, and infarction;
thromboses may be present in the arterioles,
capillaries, and glomeruli. The areas of necro-
sis are generally confined to the cortex and, on
gross examination, are sharply demarcated
from the rest of the kidney. In cases where the
underlying sepsis is quickly treated with fluid
resuscitation and antibiotics, some function of
the kidneys may be preserved; otherwise, over-
whelming cortical necrosis usually culminates
in death.
Answer A is incorrect. Acute pyelonephritis
results from hematogenous or ascending infec-
tion of the kidneys. On gross pathologic exami-
nation the kidney typically demonstrates
patchy areas of abscess formation, but not dif-
fuse, sharply demarcated areas of cortical
necrosis as seen in the image.
Answer C is incorrect. Obstructive uropathy
results from a blockage distal to the collecting
system of the kidneys. On gross pathologic ex-
amination the kidney typically demonstrates
dilation of the renal pelvis and calyces, but not
sharply demarcated areas of cortical necrosis as
seen in the image.
Answer D is incorrect. Papillary necrosis can
result from infection, analgesic overuse, sickle
cell disease, and a number of other conditions.
On gross pathologic examination the kidney
typically demonstrates yellow-white areas of ne-
crosis limited to the papillae, but not sharply
demarcated areas of cortical necrosis as seen in
the image.
Answer E is incorrect. Renal infarction results
from thromboembolic disease involving the re-
nal vasculature. On gross pathologic examina-
tion the kidney typically demonstrates wedge-
shaped areas of yellow-white infarction
extending from the medulla to the cortex, but
not diffuse, sharply demarcated areas of corti-
cal necrosis as seen in the image.

8. The correct answer is A. The findings on mi-
croscopy indicate a malignant transformation
of normal cells. Increased nuclear-to-cytoplasm
ratio, open chromatin, and mitotic figures indi-
cate that cells are actively dividing. Given the
patient’s history of multiple sexual partners and
postcoital bleeding, these cells likely indicate
the presence of cervical cancer. Cervical can-
cer is commonly linked to human papillomavi-
rus infection. The virus can be isolated during
cytology through various methods. It is a dou-
ble-stranded DNA virus.
Answer B is incorrect. Gram-negative diplo-
cocci are not associated with cervical cancer.
However, they can be found in gonorrhea
cervicitis.
Answer C is incorrect. There are no gram-
positive cocci associated with cervical cancer.
Answer D is incorrect. There is no single-
stranded virus associated with cervical cancer.
Answer E is incorrect. Squamous cells covered
with bacteria can be found in bacterial vagino-
sis, which causes foul-smelling discharge. There
is no known association between bacterial vagi-
nosis and cervical cancer.
9. The correct answer is A. HNPCC, also known
as Lynch’s syndrome, is a rare autosomal domi-
nant disorder associated with an increased inci-
dence of colorectal cancer. Generally, the syn-
drome is associated with mismatch repair.
Approximately 70% of people with the syn-
drome will develop colorectal cancer, typically
at 40–45 years of age. Also, there is a high risk
of extracolonic cancer, including endometrial,
ovarian, urinary tract, small intestinal, stom-
ach, and biliary cancer. As a result, high-risk
patients begin annual screening colonoscopies
at age 20–25 years, or 10 years before the age
of the youngest diagnosed family member.
Women >35 years old typically undergo an-
nual endometrial biopsy due to the high risk of
endometrial carcinoma.
Answer B is incorrect. Cholecystitis is second-
ary to gallstones in 90% of cases. Increased
gallstone formation related to HNPCC may
be plausible if the patient had undergone
HIGH-YIELD PRINCIPLES
Chapter 6: Pathology • Answers 121
resection of the ileum for extracolonic cancer of
the small bowel. Gallstones are known to
occur in such patients after ileal resection due
to disturbed bilirubin metabolism. Moreover,
although HNPCC can be associated with biliary
cancer, the patient in this case has yet to show
signs of HNPCC, and biliary cancer does not
cause cholelithiasis. Thus, the patient presum-
ably has no increased risk of gallstones or chole-
cystitis.
Answer C is incorrect. Melanin spots of the
buccal mucosa and lips can be seen in Peutz-
Jeghers syndrome. This syndrome involves
multiple polyps of the small bowel, although
Pathology
the large bowel and rectum can be involved.
The polyps are generally considered to be non-
malignant hamartomas, but cancer can occa-
sionally develop. Peutz-Jeghers syndrome is not
associated with HNPCC.
Answer D is incorrect. Pseudopolyps, also
known as inflammatory polyps, are areas of re-
generating, normal mucosa around which the
mucosa has been lost. This typically occurs in
the setting of inflammatory bowel disease but
may be seen in colitis related to amebic and
schistosomal infection or bowel ischemia. Al-
though these “polyps” are not premalignant,
they resemble adenomatous polyps on gross
examination and should thus be removed and
examined histologically. Pseudopolyps are not
associated with HNPCC and are unlikely in
this patient with no significant past medical
history.
Answer E is incorrect. Although vitamin B12
deficiency is most commonly associated with
pernicious anemia, abdominal surgery second-
ary to cancer might lead to vitamin B12 defi-
ciency. For example, if the patient underwent
gastrectomy for gastric cancer caused by
HNPCC, intrinsic factor would not be pro-
duced. Furthermore, if the patient underwent
bowel resection, including the ileum for small
bowel cancer related to HNPCC, B12 could
not be absorbed because absorption occurs in
the ileum. However, the patient in this case
has yet to show signs of HNPCC and presum-
ably has normal vitamin B12 levels.
HIGH-YIELD PRINCIPLES
122 Section I: General Principles • Answers

10. The correct answer is D. The patient’s symp-
toms are consistent with adult polycystic kid-
ney disease (APKD), a disease most commonly
caused by mutation of the polycystin 1 gene lo-
cated on chromosome 16. APKD can also be
caused by a mutation in polycystin 2 located
on chromosome 4, although this is less com-
mon. APKD is characterized by the growth of
renal cysts, which are believed to lead to renal
failure by compressing adjacent normal paren-
chyma. The disease often presents in the third
or fourth decade of life, and symptoms and
signs include abdominal discomfort, frequent
urinary tract infections, hematuria, polyuria,
Pathology
of paternal or maternal origin. Deletions in
Prader-Willi syndrome, a phenotypically dis-
tinct disorder, occur exclusively on the pater-
nal chromosome 15, whereas deletions at the
same site of chromosome 15 on the maternal
chromosome result in Angelman’s syndrome.
Answer A is incorrect. Anticipation is the phe-
nomenon in which the severity of a disease
worsens in succeeding generations. This oc-
curs, for example, in triplet repeat diseases such
as Huntington’s disease, wherein the triplet
repeat tends to lengthen, age of onset decreases,
and disease severity increases with successive
generations. This does not occur in Angelman’s

and nocturia. Cystic kidneys are often seen on

imaging. Mild proteinuria is common. Hepatic
cysts, as seen in the image, are also common.
The disease is also associated with berry aneu-
rysms and mitral valve prolapse.
Answer A is incorrect. A mutation on chromo-
some 3 is associated with von Hippel-Lindau
disease, which can not only cause renal cysts
but also retinal angiomas and central nervous
system hemangioblastomas.
Answer B is incorrect. A mutation on chromo-
some 6 is associated with recessive polycystic
kidney disease, which is associated with a
much younger age of onset.
Answer C is incorrect. A mutation on chromo-
some 9 is associated with tuberous sclerosis,
which can not only cause renal cysts, but also
presents with adenoma sebaceum and central
nervous system hamartomas.
11. The correct answer is C. This child most
likely has Angelman’s syndrome. Individuals
with this phenotype have a characteristic facies
with microcephaly, maxillary hypoplasia, deep-
set eyes, and a large mouth with tongue protru-
sion. Their gait is jerky and “puppet-like,” and
their behavior is marked by frequent paroxysms
of inappropriate laughter. Severe mental retar-
dation and speech impairment are usually
present, and 80%–90% of patients have epi-
lepsy. Angelman’s syndrome, along with
Prader-Willi syndrome, is a classic example of
imprinting, which occurs when the phenotype
differs depending on whether the mutation is
syndrome.
Answer B is incorrect. Heteroplasmy describes
the presence of both normal and mutated mito-
chondrial DNA. This phenomenon is responsi-
ble for the variable expression of mitochondrial
inherited diseases.
Answer D is incorrect. Locus heterozygosity
describes the phenomenon by which muta-
tions at different loci can result in the same
phenotype. An example of this is albinism,
which can be caused by a number of different
mutations.
Answer E is incorrect. Mosaicism occurs when
cells in the body have different genetic
makeup. This sometimes occurs, for example,
in Turner’s syndrome. This does not occur in
Angelman’s syndrome.
12. The correct answer is B. Duchenne’s muscu-
lar dystrophy (DMD) is the most common
form of muscular dystrophy, affecting 1 in 3500
live male births. Symptoms become evident by
the age of 5 years and include delayed walking,
clumsiness, weakness in the pelvic girdle mus-
cles, and enlargement of the calf muscles
(termed pseudohypertrophy). Laboratory test-
ing reveals an elevated creatine kinase level.
DMD is caused by an abnormality of Xp21,
the region that codes for dystrophin, a myocyte
anchoring protein.
Answer A is incorrect. Cystic fibrosis trans-
membrane conductance regulator (CFTR)
transports chloride ions across epithelial cell

membranes. Mutations of the CFTR gene lead
to cystic fibrosis, which is associated with symp-
toms such as difficulty breathing, frequent
pneumonias, and pancreatic insufficiency.
Answer C is incorrect. Phenylalanine hydroxy-
lase (PAH) is an enzyme that catalyzes the con-
version of phenylalanine to tyrosine. Deficiency
of PAH leads to phenylketonuria, characterized
by problems with brain development, mental
retardation, and seizures.
Answer D is incorrect. Spectrin is a cytoskele-
tal protein important in maintaining RBC
plasma membrane structure. Absence of spec-
trin leads to hereditary spherocytosis, whose
14. The correct answer is C. This patient is suffer-
symptoms include anemia, splenomegaly, and
jaundice.
Answer E is incorrect. Type II collagen is the
building block of articular and hyaline carti-
lages. Deficiency of type II collagen leads to a
severe form of osteogenesis imperfecta that is
usually lethal in the perinatal period.
13. The correct answer is A. This patient has
developed nasopharyngeal carcinoma, a condi-
tion common in certain parts of the world, in-
cluding Asia and Africa. Development of this
tumor is always associated with infection by
Epstein-Barr virus (EBV), a DNA virus in the
herpesvirus family. Development of this tumor
is believed to be related to a synergistic interac-
tion between EBV and a diet high in carcino-
genic nitrosamines (common in foods that has
been smoked or preserved). Common symp-
toms include nasal congestion, epistaxis, ear
infections (due to tumor-induced blockage of
the Eustachian tubes), and headache.
Answer B is incorrect. Many bacteria are
capable of infecting the nasopharynx; however,
none are directly associated with malignancy.
Answer C is incorrect. Nasopharyngeal zygo-
mycosis is a condition that could present with
these symptoms in an immunocompromised
patient. However, biopsy would show filamen-
tous nonseptate hyphae and a granulomatous
response.
Answer D is incorrect. Although a tubercu-
loma in the nasopharynx can be confused with
HIGH-YIELD PRINCIPLES
Chapter 6: Pathology • Answers 123
a nasopharyngeal tumor, biopsy would show
caseating granulomas with multinucleated
giant cells.
Answer E is incorrect. Although a retrovirus
such as HIV can create an immunocompro-
mised state favoring the development of a
malignancy, it is not the direct cause of tumor
formation. Lymphomas can be associated with
the retrovirus human T-cell lymphoma virus;
however, biopsy would show sheets of malig-
nant T lymphocytes typical of this lymphoma.
Other RNA viruses are not associated with ma-
lignancy.
Pathology
ing from squamous cell carcinoma of the blad-
der. Although this condition is rare in the
United States, it is the most common type of
bladder cancer in the world. The most com-
mon cause is chronic irritation by the eggs of
the helminth Schistosoma haematobium, which
lodge in the bladder wall. Squamous cell carci-
noma can be distinguished from transitional cell
carcinoma pathologically by its appearance.
This specimen shows keratin pearl formation, a
common finding in squamous cell cancers.
Answer A is incorrect. Cigarette smoking is
the most common risk factor associated with
transitional cell bladder carcinoma. In this
case, however, the patient’s presentation and
pathology are more suggestive of squamous
cell carcinoma.
Answer B is incorrect. Aniline dyes are associ-
ated with transitional cell carcinoma, the most
common type of bladder cancer in the United
States. They are not associated with squamous
cell carcinoma of the bladder.
Answer D is incorrect. Papovaviridae such as
human papilloma virus are responsible for gen-
ital warts and cervical carcinoma. They are not
associated with bladder cancers.
Answer E is incorrect. Long-term catheteriza-
tion is associated with the development of
squamous cell carcinoma of the bladder. Based
on the patient’s history, however, there is no rea-
son to assume this patient has had an indwell-
ing catheter at any time.
HIGH-YIELD PRINCIPLES
124 Section I: General Principles • Answers
15. The correct answer is C. The image shows the
typical large, round intranuclear inclusion with
perinuclear halo seen in cells affected by cyto-
megalovirus (CMV) infection. This Cowdry
type A bodies are typically referred to as “owl’s
eyes” due to their microscopic appearance. In
immunocompromised patients, CMV infec-
tion can present as retinitis, pneumonitis,
inflammation along the gastrointestinal tract,
polyradiculopathy, transverse myelitis, and fo-
cal encephalitis. In patients with HIV/AIDS,
these sequelae occur most prominently when
the CD4+ cell count is <100/mm3 or when the
HIV viral load is >10,000 copies/mm3. CMV
Pathology
can cause further immunosuppression, leading
to other opportunistic infections such as Pneu-
mocystis and Aspergillus pneumonia.
Answer A is incorrect. Candida is a fungus
that produces a wide spectrum of diseases,
ranging from superficial mucocutaneous dis-
ease in immunocompetent hosts to invasive ill-
nesses in immunocompromised hosts. Histol-
ogy reveals round or ovoid yeast cells, hyphae,
or pseudohyphae.
Answer B is incorrect. Cryptococcus neofor-
mans causes meningitis and meningoencepha-
litis in patients with AIDS. This fungus is diffi-
cult to observe with routine hematoxylin and
eosin stains, so methenamine silver or periodic
acid-Schiff stains are used to identify the char-
acteristic narrow-based buds and round-to-oval
yeast, surrounded by a polysaccharide capsule.
Answer D is incorrect. Herpes simplex virus in
HIV-infected individuals can cause recurrent
orolabial, genital, and perianal lesions. A
Tzanck smear is positive for multinucleated
epithelial giant cells. It does not cause the
large intranuclear inclusion body shown.
Answer E is incorrect. Mycobacterium avium
causes lung disease in immunocompromised
hosts and is subsequently spread via the blood
to the liver, spleen, bone marrow, and other
sites. Histology of mycobacterium is not consis-
tent with this image. Rather, acid-fast staining
would show organisms in foamy macrophages,
granulomas, giant cells, and cells with eosino-
philic necrosis.
Answer F is incorrect. Pneumocystis jiroveci
(formerly carinii) causes pneumonia in immu-
nocompromised individuals.
16. The correct answer is C. Hereditary hemo-
chromatosis is an autosomal recessive adult on-
set disorder characterized by inappropriately
high iron absorption that leads to progressive
iron overload. The organs damaged by iron
deposition include the liver, heart, pancreas,
pituitary, joints, and skin. Cirrhosis results from
progressive iron deposition in the liver paren-
chyma of patients with hemochromatosis. In
the image, hepatocellular iron deposition is
seen as granular brown cytoplasmic pigment.
Microscopic evidence of cirrhosis includes an
increased quantity of connective tissue extend-
ing from the portal areas. Cirrhosis, which sim-
ply means fibrosis, is the result of past or
chronic tissue destruction. Acute destruction
would be evidenced by the presence of inflam-
matory cells in the portal areas, as is seen in
hepatitis.
Answer A is incorrect. Alcoholic liver disease
occurs in patients who are heavy drinkers.
Liver biopsy in these patients may show cirrho-
sis. However, in contrast to patients with hemo-
chromatosis, the hepatic iron levels are rela-
tively normal, and iron stores are usually <4 g.
Answer B is incorrect. β-Thalassemia is caused
by a mutation in the β-globin gene, resulting in
reduced or absent β-globin. In the more severe
form of the disease, patients must receive peri-
odic RBC transfusions throughout their lives.
This, paired with enhanced iron absorption in
reaction to the anemia, results in iron overload.
The resulting clinical picture is similar to that
observed in primary hemochromatosis (eg., en-
docrine dysfunction, liver dysfunction, cardiac
dysfunction).
Answer D is incorrect. Iron overload may be
due to chronic anemia, with increased effec-
tive erythropoiesis and increased iron absorp-
tion. Examples of conditions that can result in
chronic anemia include hereditary spherocyto-
sis and acquired sideroblastic anemia. In pa-
tients with hereditary spherocytosis, RBCs have
a membrane protein defect, resulting in

cytoskeleton instability and increased RBC
turnover.
17. The correct answer is E. This HIV-positive
patient has multiple anogenital warts, or condy-
lomata acuminata, which are commonly caused
by human papilloma virus (HPV) types 6 and
11. A feared complication of condylomata acum-
inata is anorectal cancer, as seen here. Immuno-
deficiency predisposes to the development of
HPV-induced transformation. The mechanism
of HPV-induced transformation involves the pro-
duction of a viral protein, E6, which binds to a
cellular ubiquitin ligase E6AP. On binding to
E6, E6AP polyubiquitinates the tumor suppres-
sor p53, leading to dysregulated cell proliferation
and, eventually, oncogenesis.
Answer A is incorrect. APC is a tumor suppres-
sor gene mutated in certain hereditary forms of
colon cancer. The APC protein normally de-
grades the transcription factor β-catenin, which
is involved in colonic epithelial cell prolifera-
tion. In the absence of APC, increased levels
of β-catenin accumulate, eventually leading to
oncogenesis.
Answer B is incorrect. BRCA1 is a tumor sup-
pressor gene commonly mutated in hereditary
forms of breast and ovarian cancers. The
BRCA1 protein functions in DNA repair pro-
cesses, and inherited mutations in BRCA1
interfere with DNA repair, leading to the accu-
mulation of mutations and, eventually,
oncogenesis.
Answer C is incorrect. The MSH2 gene regu-
lates a mismatch repair enzyme and is mutated
in certain hereditary forms of colon cancer. In
the absence of MSH2, increased levels of DNA
mutations accumulate, leading to eventual cel-
lular transformation.
Answer D is incorrect. NF1 is a tumor sup-
pressor gene mutated in neurofibromatosis
type 1. The NF1 protein functions as a GTPase
activating protein for the small G protein Ras.
Because Ras is only active when it is GTP-
bound, NF1-mediated GTP hydrolysis leads to
inactivation of Ras. In the absence of NF1, Ras
is hyperactive, leading to enhanced growth fac-
HIGH-YIELD PRINCIPLES
Chapter 6: Pathology • Answers 125
tor signal transduction and, eventually, onco-
genesis.
18. The correct answer is A. The boy’s brain bi-
opsy demonstrates medulloblastoma. This is a
poorly differentiated neuroectodermal tumor
that occurs predominantly in children and ex-
clusively in the cerebellum. The cerebellar
vermis is the medial section of the cerebellum
and is responsible for proximal muscle coordi-
nation, balance, and vestibulo-ocular reflexes.
As seen in this patient, lesions of the vermis
lead to vertigo, nausea, and difficulties in coor-
dinating movement of trunk and proximal limb
muscles. The presence of medulloblastoma
Pathology
commonly leads to obstruction of the outflow
of cerebrospinal fluid and the potential for hy-
drocephalus, a life-threatening condition.
Answer B is incorrect. Medulloblastomas arise
in the midline of the cerebellum in children.
The intermediate section of the cerebellar
hemisphere is more lateral than the vermis. Le-
sions in the intermediate section would cause
deficits in coordinating movements of the ipsi-
lateral distal extremities, not the vertigo and
proximal limb problems seen in this patient.
Answer C is incorrect. Medulloblastomas arise
in the midline of the cerebellum in children.
Lesions of the lateral hemisphere would likely
cause deficits in planning movements of the
ipsilateral distal extremities, not the vertigo and
proximal limb problems seen in this patient.
Answer D is incorrect. Medulloblastomas arise
in the midline of the cerebellum in children,
not in the occipital cortex. Occipital cortex
lesions could lead to defects in vision, not the
vertigo and proximal limb problems seen in
this patient.
Answer E is incorrect. Medulloblastomas arise
in the midline of the cerebellum in children,
not in the parietal cortex. The postcentral
gyrus of the parietal lobe is the primary soma-
tosensory cortex. Lesions of this area would
cause sensory deficits, not the vertigo and prox-
imal limb problems seen in this patient.
19. The correct answer is B. This image demon-
strates an advanced case of mesothelioma, in
HIGH-YIELD PRINCIPLES
126 Section I: General Principles • Answers
which the entire left lung is encased with
tumor. The clinical history supports this diag-
nosis. Asbestos is present in certain building
materials and fire-resistant materials, and expo-
sure to asbestos is a risk factor for the develop-
ment of mesothelioma.
Answer A is incorrect. Aflatoxin B is produced
by Aspergillus and is a common contaminant
of cereals, spices, and nuts. It has been associ-
ated with carcinoma of the liver.
Answer C is incorrect. Long-term exposure to
high levels of benzene can lead to leukemia
and Hodgkin’s lymphoma. Benzene is the
main component of light oil, and is found in
Pathology
gasoline and other fuels.
Answer D is incorrect. Cadmium is a carcino-
gen associated with the development of pros-
tate cancer. It can be found in batteries and in
metal coatings.
Answer E is incorrect. Exposure to silica may
occur in the manufacturing of several materials,
such as glass, ceramics, and electronics. Silicosis
is characterized by bilateral, fine nodularity in
the upper lung lobes. It is slowly progressive. Its
role as a carcinogen is controversial.
20. The correct answer is E. This patient is in
shock due to cardiac tamponade secondary to
the rupture of the ventricular free wall, which
usually occurs 4–10 days after the initial myo-
cardial infarction (MI). It usually presents with
sudden shock with signs of cardiac tamponade,
such as the hypotension, distant heart sounds,
and elevated jugular venous pressure observed
in this patient. Survival depends primarily on
the rapid recognition of myocardial rupture
and the provision of immediate therapy, such
as urgent pericardiocentesis or surgery. Unfor-
tunately, this complication of an MI is often a
fatal one.
Answer A is incorrect. Aneurysm formation
may occur post-MI due to a lack of contractility
that results in the infarcted area. Sequelae of
ventricular aneurysm formation include de-
creased cardiac output, increased risk of arrhyth-
mias, and potential mural thrombus formation
with risk of embolization.
Answer B is incorrect. Cardiac arrhythmias
are a common cause of death in the first few
days after an MI. However, this patient’s clini-
cal picture is more consistent with a diagnosis
of cardiac tamponade secondary to ventricular
free wall rupture.
Answer C is incorrect. Fibrinous pericarditis is
a complication that usually occurs 3–5 days
post-MI. This condition usually presents with
chest pain that is relieved when the patient
leans forward; often a pericardial friction rub
can be auscultated on cardiac examination.
However, this patient’s clinical picture is more
consistent with a diagnosis of cardiac tampon-
ade secondary to ventricular free wall rupture.
Answer D is incorrect. Papillary muscle rup-
ture is another complication of MI that usually
occurs 4–10 days post-MI. However, patients
with papillary muscle rupture usually present
with acute mitral regurgitation, causing the
abrupt onset of heart failure in the setting of a
new systolic murmur. Emergent surgical inter-
vention is the treatment of choice for this
condition.