University of Utah
College of Medicine
GENERAL PATHOLOGY REVIEWER
ATHEROSCLEROSIS AND THROMBOSIS SECTION
A 56-year-old reports reduced exercise tolerance over
the past 5 years. In the past year he has noted chest
pain after ascending a flight of stairs. He smokes 2
packs of cigarettes per day. On examination he has a
blood pressure of 155/95 mm Hg. His body mass index
is 30. Laboratory findings include a total serum
cholesterol of 245 mg/dL with an HDL cholesterol of 22
mg/dL. Which of the following vascular abnormalities is
he most likely to have?
A. Hyperplastic arteriosclerosis
Incorrect. Hyperplastic arteriolosclerosis
can accompany hypertensive emergency
when systolic pressure is >=180 and/or
diastolic pressure >=120 mmHg along
with signs of acute or ongoing end-organ
damage, which he does not have.
B. Lymphedema
Incorrect. Lymphedema is not related to
the risk factors that he has, which are
factors affecting muscular arteries.
C. Medial calcific sclerosis
Incorrect. Medical calcific sclerosis is a
benign form of arteriosclerosis that does
not often contribute to significant disease.
It does not involve coronary arteries.
D. Atherosclerosis
CORRECT. He has multiple risk factors
for atherosclerosis, including his weight,
smoking, hypertension, and high total
cholesterol with low 'good' HDL
cholesterol. His findings suggest
coronary artery disease with risk for an
acute coronary syndrome.
E. Deep venous thrombosis
Incorrect. He does have an increased
risk for thrombosis, but atherosclerosis is
the worst risk, and his symptoms suggest
coronary artery disease.
F. Plexiform arteriopathy
Incorrect. Plexiform arteriopathy is seen
in peripheral pulmonary arteries with
pulmonary hypertension.
A 54-year-old previously healthy woman is hospitalized
for pneumonia. On the 10th hospital day she is found
to have swelling and tenderness of her right leg, which
has developed over the past 48 hours. Raising the leg
elicits pain. An ultrasound examination reveals findings
suggestive of femoral vein thrombosis. Which of the
following conditions is most likely to have contributed
the most to the appearance of these findings?
A. Trousseau syndrome
Incorrect. The hypercoagulable state of
Trousseau syndrome with an underlying
malignancy such as an adenocarcinoma
predisposes to venous thrombosis, but
her prior healthy condition makes
malignancy less likely.
B. Protein C deficiency
Incorrect. Protein C deficiency is
associated with venous thrombosis, but
the onset of the disease is typically much
earlier in life.
C. Immobilization
CORRECT. The immobilization while in
hopsital would predispose to thrombosis
of leg veins. This is the most common
cause for deep venous thrombosis.
D. Pregnancy
Incorrect. The enlarged uterus
obstructing venous return would
predispose to thrombosis. However, her
age is not in the childbearing years, and
prior pregnancies do not significantly
increase the risk for thrombosis.
E. Chronic alcohol abuse
Incorrect. The liver disease of chronic
alcoholism predisposes to coagulopathy
with hemorrhage, not thrombosis.
F. Hypertension
Incorrect. Systemic hypertension
increases the risk for atherosclerosis,
which increases the risk for thrombosis in
the arterial system, such as the coronary
arteries or carotid arteries.
A 63-year-old man has had insulin dependent diabetes
mellitus for over two decades. The degree of control of
his disease is indicated by the laboratory finding of
hemoglobin A1C 10.1%. He has noted episodes of
abdominal pain following meals. These episodes have
worsened over the past year. On physical examination,
there are no masses and no organomegaly of the
abdomen, and he has no tenderness to palpation.
Which of the following pathologic findings is most likely
to be present in this man?
A. Ruptured aortic aneurysm
Incorrect. Atherosclerotic aneurysms of
the abdominal aorta can occur with the
advanced atherosclerosis of diabetes
mellitus, but there can be a pulsatile
mass, and rupture is a medical
emergency.
B. Hepatic infarction
Incorrect. The liver has a dual blood
supply (hepatic arterial plus portal
venous circulations) and is difficult to
infarct.
C. Mesenteric artery occlusion
CORRECT. He has 'abdominal angina'
from diminished blood flow to the bowel
as a consequence of severe
atherosclerosis. Persons with diabetes
mellitus may have this finding, because
all branches of major arteries to the
bowel are affected by atherosclerosis.
Page 1 of 72
 Atherosclerosis and Thrombosis | Pathology Reviewer (Utah) | 2 / 72
D. Acute pancreatitis
Incorrect. Pancreatitis is a disease of the
pancreatic acinar parenchyma, not the
islets. Even in persons with pancreatitis,
diabetes mellitus is a rare outcome.
Diabetes is not a risk for pancreatitis.
E. Chronic renal failure
Incorrect. Nephrosclerosis can lead to
renal failure. However, there is typically
no pain associated with this process.
A 62-year-old man has experienced substernal chest
pain upon exertion with increasing frequency over the
past 6 months. An electrocardiogram shows features
consistent with ischemic heart disease. He has a total
serum cholesterol of 262 mg/dL. By angiography, there
is 75% narrowing of coronary arteries. In which of the
following locations is a mural thrombus most likely to
occur in this man?
A. Left atrium
Incorrect. The left atrium is unlikely to
undergo infarction; it is most often
affected by enlargement from valvular
disease.
B. Left ventricle
CORRECT. The left ventricle is the major
user of oxygen and nutrients and
requires a good blood supply. A
complication of ischemic heart disease
with infarction is development of
overlying mural thrombus. Such mural
thrombi are likely to result from damage
to the left ventricle from ischemic heart
disease, either acutely with an underlying
myocardial infarction, or with a left
ventricular aneurysm formed following
resolution of a large myocardial infarction
C. Right atrium
Incorrect. The right atrium is unlikely to
be involved with ischemic heart disease.
D. Right ventricle
Incorrect. The right ventricle is unlikely to
be involved with ischemic heart disease.
E. Aorta
Incorrect. The aorta may undergo
atherosclerotic changes with aneurysm
formation, in which mural thrombus may
form. In this case, the likelihood of an
acute coronary event is more likely.
F. Vena cava
Incorrect. The systemic venous system is
not directly affected by atherosclerosis.
A 66-year-old man with Parkinson disease develops
pleuritic chest pain. On exam, he has guarding over the
right lower lung with dullness to percussion. A chest CT
scan shows a focal, wedge-shaped pleural baesed
area of hemorrhage in the right lower lobe. Which of
the following is the most likely cause for his pulmonary
lesion?
A. Embolism
CORRECT. A pulmonary infarction is
described. A thromboembolus from the
venous circulation, usually arising in
large leg veins, has lodged in a peripheral
pulmonary arterial branch. The bronchial
arterial supply to the lung does not
provide enough oxygenation to prevent
infarction, but does provide blood to
make the infarct hemorrhagic. His
neurodegenerative disorder with reduced
movement is a risk for phlebothrombosis.
B. Atherosclerosis
Incorrect. Pulmonary atherosclerosis
occurs with pulmonary hypertension, but
is typically limited in extent, without
significant arterial narrowing.
C. Vasculitis
Incorrect. Vasculitis involving the lungs is
likely to be diffuse.
D. Arteriosclerosis
Incorrect. Arteriolosclerosis does not
involve pulmonary circulation.
E. Thrombosis
Incorrect. Thrombosis within the lung
likely occurs in areas of inflammation. In
this case the localized lesion is unlikely to
represent in situ vascular thrombosis.
A 44-year-old woman has a family history of heart
disease. Her father and mother both developed
myocardial infarction and congestive heart failure as a
result of occlusive coronary atherosclerosis. A dietary
modification to include consumption of which of the
following is most likely to reduce her risk for ischemic
heart disease?
A. 40% of total caloric intake as fat
Incorrect. This is far too much fat. No
more than 30% of the diet should consist
of fat.
B. Increased saturated fat
Incorrect. Saturated fats are worse than
unsaturated fats or monosaturated fats.
C. Food with cholesterol
Incorrect. Increased dietary cholesterol is
not good.
D. Cold water fish oil
CORRECT. Fish oils diminish
arachidonic acid metabolites and reduce
platelet aggregation.
E. Fat found in beef products
Incorrect. Animal fats tend to be
saturated fats.
F. Hydrogenated oils with trans-fats
Incorrect. Trans-fats are partially
hydrogenated fats made commercially.
Trans-fats tend to increase LDL
cholesterol, decrease HDL cholesterol,
and increase triglycerides - all of which
are bad effects.
A study of atherogenesis is performed. There is a
propensity for atheromas to form at muscular arterial
branch points, such as the carotid and aortic
bifurcations. Which of the following events in the
arteries at these locations is most likely to initiate
atherogenesis?
A. Collagen synthesis
Incorrect. There is collagen deposition as
atheromatous plaques develop, but this
is not the initiating event.
B. Endothelial dysfunction
CORRECT. A variety of stressors may
affect endothelial cells, including the
shear stress from turbulent flow at arterial
branch points. Endothelial dysfunction is
the initiating event that allows insudation
of lipids to promote atherogenesis.
 Atherosclerosis and Thrombosis | Pathology Reviewer (Utah) | 3 / 72
C. Lactic acidosis
Incorrect. Lactic acid may build up in
tissues with oxygen debt, such as muscle.
The metabolic rate of arterial cells is not
high, and direct diffusion provides
oxygen and nutrients to endothelium.
D. Cholesterol breakdown
Incorrect. Once endothelial injury has
occurred, lipids begin to collect, but lipids
are not the inciting factor at arterial
branch points.
E. Hypoxemia
Incorrect. Hypoxemia does not affect
muscular arteries directly, as the arterial
cells do not have a high metabolic rate.
A 66-year-old woman has the sudden loss of
movement on part of the left side of her body. She has
smoked a pack of cigarettes a day for the past 45 years.
She has vital signs including T 37.1°C, P 80/minute,
RR 16/minute, and BP 160/100 mm Hg. A cerebral
angiogram reveals occlusion of a branch of her middle
cerebral artery. Laboratory findings include a
hemoglobin A1C of 9%. Which of the following
components of blood lipids is most important in
contributing to her disease?
A. Chylomicrons
Incorrect. Chylomicrons are formed by
complexing lipids absorbed from the
small intestine to transport apoproteins.
They then travel to the liver. They do not
directly produce atheromatous plaques.
B. Lipoprotein lipase
Incorrect. Endothelial lipoprotein lipase
splits off fatty acids that are then used as
a substrate in other metabolic pathways
and not in atheroma formation.
C. Oxidized LDL
CORRECT. She has had a 'stroke' which
is most often a consequence of cerebral
atherosclerosis or embolic disease from
the heart as a consequence of ischemic
heart disease from atherosclerosis. LDL
brings cholesterol to arterial walls, and
when increased LDL is present or when
there is hypertension, smoking, and
diabetes, there is more degradation of
LDL to oxidized LDL which is taken up
into arterial walls via scavenger receptors
in macrophages to help form atheromas.
D. VLDL
Incorrect. Both adipose tissue and
muscle are areas where VLDL is
transformed to LDL, and this does not
directly promote atherogenesis.
E. HDL cholesterol
Incorrect. HDL cholesterol helps to
transport lipid away from arterial walls to
the liver, thus protecting against
atheroma formation.
An autopsy study reveals that evidence for atheroma
formation can begin even in children. The gross
appearances of the aortas are recorded and compared
with microscopic findings of atheroma formation.
Which of the following is most likely to be the first visible
gross evidence for the formation of an atheroma?
A. Thrombus
Incorrect. Thrombosis is a complication
of an atheroma.
B. Fatty streak
CORRECT. A fatty streak on the arterial
intimal surface is the first grossly visible
sign of atheroma formation. It is benign
and reversible, but it may be the
precursor to more severe plaques.
C. Calcification
Incorrect. Calcification is a complication
of an atheroma.
D. Hemorrhage
Incorrect. Hemorrhage is a complication
of an atheroma.
E. Exudate
Incorrect. Lymphocytes and
macrophages play a role in
atherogenesis, but their numbers are
relatively small.
F. Ulceration
Incorrect. Ulceration of an atheromatous
plaque is an advanced lesion, not an
early lesion. Ulceration or fissuring of the
plaque increases the likelihood for
overlying thrombosis.
A 63-year-old man has had increasing exercise
intolerance for the past 6 years so that he now
becomes short of breath upon climbing a single flight
of stairs. Laboratory studies have shown fasting blood
glucose measurements from 145 to 210 mg/dL for the
past 25 years, but he has not sought medical treatment.
If he dies suddenly, which of the following is most likely
to be the immediate cause of death?
A. Myocardial infarction
CORRECT. This is the most common
cause of death in persons with diabetes
mellitus, because of the high prevalence
of advanced coronary atherosclerosis.
B. Nodular glomerulosclerosis
Incorrect. Although renal failure is a
common complication of diabetes, it is
not the major cause of death.
C. Cerebral hemorrhage
Incorrect. Cerebrovascular disease in
diabetes is common but is not the major
cause of death.
D. Hyperosmolar coma
Incorrect. This complication may be life-
threatening, but it is not frequent.
E. Right lower leg gangrene
Incorrect. This complication is usually
treated before secondary sepsis
becomes life-threatening.
A 45-year-old man dies suddenly and unexpectedly.
The immediate cause of death is found to be a
hemorrhage in the right basal ganglia region. On
microscopic examination his renal artery branches
have concentric endothelial cell proliferation which
markedly narrows the lumen, resulting in focal
ischemia and hemorrhage of the renal parenchyma. An
elevation in which of the following substances in his
blood is most likely to be associated with these findings?
 Atherosclerosis and Thrombosis | Pathology Reviewer (Utah) | 4 / 72
A. Ammonia
Incorrect. An elevated blood ammonia is
indicative of hepatocyte dysfunction and
increasing hepatic failure.
B. Calcium
Incorrect. Hypercalcemia can be
associated with hyperparathyroidism.
C. Cholesterol
Incorrect. Increased cholesterol leads to
atherosclerotic vascular changes.
D. Renin
CORRECT. The findings suggest
hyperplastic arteriolosclerosis, which
accompanies hypertensive emergency
when systolic pressure is >=180 and/or
diastolic pressure >=120 mmHg along
with signs of acute or ongoing end-organ
damage. Reduced renal blood flow
increases renin, driving hypertension.
E. Troponin I
Incorrect. Myocardial injury increases the
troponin I.
F. Triglyceride
Incorrect. An elevated triglyceride
increases the risk for atherosclerosis with
atheroma formation, but not concentric
endothelial proliferation.
G. C-reactive protein
Incorrect. An increased CRP can be a
marker for an increased risk for
atherosclerosis with atheroma formation,
but not concentric endothelial
proliferation.
A 10-year-old previously healthy child has been noted
by her parents to be constantly thirsty. She is
consuming large amounts of soft drinks. She is
urinating often. Her diet and exercise patterns have not
changed, except for an increased appetite, yet she
appears cachectic and has lost 7 kg over the past 4
months. On physical examination there are no
abnormal findings, other than peripheral muscle
wasting and weakness. Which of the following
laboratory findings would you most strongly suspect is
present in this girl?
A. Increased blood insulin
Incorrect. The insulin is probably
decreased.
B. Decreased blood glucagon
Incorrect. The glucagon is probably
increased.
C. Ketonuria
CORRECT. Ketonuria is typical for type I
diabetes mellitus. The findings of
polydipsia, polyuria, and polyphagia are
present in this case. The absolute
decrease in insulin leads to a catabolic
state, with underutilization of
carbohydrates, and lipolysis with
metabolism of fatty acids to produce
ketone bodies.
D. Increased serum osmolality
Incorrect. This finding is more typical of
type II diabetes mellitus.
E. Decreased plasma H+ (alkalosis)
Incorrect. The child probably has
ketoacidosis.
F. Decreased plasma cortisol
Incorrect. She is unlikely to have an acute
Addison disease which would be
characterized by hypotension and
hypoglycemia, and she is unlikely to
present at this age with congenital
adrenal hyperplasia.
A 73-year-old woman who exercises regularly falls
down the stairs and injures her right hip. A radiograph
is taken of the pelvis. There is no fracture but the
radiograph reveals calcification of the small muscular
arteries lateral to her uterus. What is the probable
vascular lesion which accounts for this calcification?
A. Ulcerative atherosclerosis
Incorrect. Although calcification may
complicate atheromas, this is typically
seen in larger vessels.
B. Calcific medial sclerosis
CORRECT. Monckeberg calcific medial
sclerosis is a benign, incidental finding
most often seen in the elderly. Small
arteries in pelvis, breast, neck, and
extremities are typically involved. The
vascular lumen is not compromised.
C. Metastatic calcification
Incorrect. Metastatic calcification from
hypercalcemia would involve other areas
in lung, kidney and GI tract first.
D. Trauma
Incorrect. Dystrophic calcification
following injury from trauma would be
localized and would take weeks to form.
E. Dystrophic calcification
Incorrect. Dystrophic calcification from
tissue damage would probably not be so
localized to arteries.
A 57-year-old woman has had episodes of abdominal
pain following meals for the past year. Her BMI is 31.
She has hypertension. Her total serum cholesterol is
increased. Which of the following types of blood vessel
is the most likely location for the pathologic abnormality
causing her pain?
A. Artery
CORRECT. She has abdominal angina
from vascular insufficiency. She has
multiple risk factors for atherosclerosis.
Atherosclerosis occurs in muscular
arteries, because the level of blood
pressure in arteries predisposes to
endothelial dysfunction.
B. Arteriole
Incorrect. The blood pressure is
considerably lowered at the level of
arterioles. Instead of atherogenesis,
arteriolosclerosis occurs in arterioles.
C. Capillary
Incorrect. Capillaries are not involved
with atherogenesis.
D. Venule
Incorrect. Venules are not involved with
atherogenesis.
E. Vein
Incorrect. Veins are not involved with
atherogenesis.
 Atherosclerosis and Thrombosis | Pathology Reviewer (Utah) | 5 / 72
A 29-year-old woman is involved in a motor vehicle
accident that results in severe lacerations to her lower
extremities, along with blunt abdominal trauma. In the
emergency room she is noted to have cool, pallid skin.
She has vital signs showing T 36.9°C, P 110/minute,
RR 26/minute, and BP 70/30 mm Hg. She has
decreased urine output. Which of the following
laboratory findings on a blood sample from this patient
is most likely to be present?
A. Hematocrit of 54%
Incorrect. She has signs of marked blood
loss, so her hematocrit should be low--
probably in the 20's or lower.
B. Glucose of 181 mg/dL
Incorrect. Hyperglycemia is not a feature
of blood loss with shock.
C. PaO2 of 20 mmHg
Incorrect. She has had blood loss, but the
oxygen carrying capacity of the
remaining RBCs is not affected, and her
ability to oxygenate is not completely lost.
She is compensating via increased
cardiac output.
D. Lactic acid of 4.8 mmol
CORRECT. She has marked blood loss
with shock. There will be vasoconstriction
in skin and soft tissue in response to the
hypovolemia. Decreased renal blood flow
from shock may lead to acute tubular
necrosis. The lack of tissue perfusion
with shock leads to increased anaerobic
glycolysis and lactic acidosis.
E. Troponin I of 4 ng/mL
Incorrect. An elevated troponin I
suggests myocardial ischemia. With
good coronary blood flow in a young
person, the myocardium is not seriously
affected until the patient is near death.
A 61-year-old man has the sudden onset of severe
chest pain. Vital signs include T 37°C, P 102/minute,
RR 20/minute, and BP 80/40 mm Hg. An
electrocardiogram demonstrates changes that are
consistent with myocardial ischemia involving the left
lateral ventricular free wall. He is given thrombolytic
therapy with tissue plasminogen activator (tPA) 3 hours
after the onset of chest pain. However his serum
creatinine kinase is found to be 450 U/L 3 hours after
this therapy. Which of the following cellular events has
most likely occurred?
A. Cellular regeneration
Incorrect. The elevation in creatine
kinase is indicative of myocardial cell
necrosis, not regeneration.
B. Drug-induced necrosis
Incorrect. The tPA does not produce a
chemical injury, but induces thrombolysis
to help restore blood flow.
C. Reperfusion injury
CORRECT. The restoration of blood flow
is helpful if the existing cell damage is not
great, so further damage can be
prevented. However, the reperfusion of
damaged cells results in generation of
oxygen free radicals to produce a
reperfusion injury.
D. Increased synthesis of creatine kinase
Incorrect. Creatine kinase is released,
but synthesis does not (cannot) increase
from the injured cells.
E. Myofiber atrophy
Incorrect. The elevation in creatine
kinase is indicative of myocardial cell
necrosis, not atrophy. Atrophic myofibers
have less cellular contents - and less
enzymes - to release.
A 52-year-old woman has experienced marked
substernal, crushing chest pain for the past 3 hours.
Her vital signs show T 36.9°C, P 90/minute, RR
18/minute, and BP 100/60 mm Hg. Laboratory studies
include a serum creatine kinase MB fraction of 10
microgm/L as well as a serum troponin I of 4.5 ng/mL.
Which of the following findings is the best evidence for
the presence of a coronary arterial thrombus as the
etiology for her chest pain?
A. Total serum cholesterol of 300 mg/dL
Incorrect. Though an increased total
serum cholesterol suggests a risk for
atherosclerosis and its complications, it
does not predict acute events.
B. Large size of the infarction by
scintigraphic scanning
Incorrect. The size of the infarct gives no
clue as to whether a thrombus was
present or not.
C. 80% coronary occlusion by angiography
Incorrect. The severity of the
atherosclerosis does not necessarily
predict whether a thrombus will have
formed. Narrowing may be produced by
the atheroma formation alone.
D. Response to thrombolytic therapy
CORRECT. The purpose of thrombolytic
therapy is to lyse the thrombus and
restore blood flow. Many acute coronary
events are the result of thrombus
formation on pre-existing atheromas.
Low dose aspirin therapy helps prevent
such events.
E. Hemoglobin A1C of 10.1%
Incorrect. Atherosclerosis is accelerated
and complications are more likely with
diabetes mellitus, but this does not
indicate that a thrombus is present.
In an experiment, a glass bead is embolized to a
branch of the renal artery. A day later there is a focal
area in which the renal parenchymal cells in the
distribution of the occluded artery show karyolysis and
karyorrhexis. The outlines of the cells are still visible,
but the nuclei have lost basophilic staining and the
cytoplasm is eosinophilic but pale. Which of the
following types of cellular necrosis is most likely
present?
A. Caseous
Incorrect. Caseous necrosis is a mixture
of liquefactive and coagulative necrosis,
and is typical for granulomatous
inflammation caused by mycobacterial or
fungal infections.
B. Coagulative
CORRECT. A typical ischemic infarction
with coagulative necrosis is described.
Coagulative necrosis is most likely to
 Atherosclerosis and Thrombosis | Pathology Reviewer (Utah) | 6 / 72
occur in solid internal organs with high
metabolic demands.
C. Fatty
Incorrect. Fat necrosis most often occurs
in breast (with trauma) and in pancreas
(with acute pancreatitis).
D. Gangrenous
Incorrect. Gangrene involves a whole
organ or body part. There can be
elements of coagulative necrosis ('dry'
gangrene) and liquefactive necrosis
('wet' gangrene).
E. Liquefactive
Incorrect. Liquefactive necrosis is most
typical for brain infarction and for
abscesses with many neutrophils.
A 53-year-old man has the sudden onset of chest pain.
He is found to have a serum troponin I of 5 ng/mL. A
year later he has reduced exercise tolerance. An
echocardiogram reveals an akinetic segment of left
ventricle, and he has reduced cardiac output, with an
ejection fraction of 25%. He then experiences a
transient ischemic attack (TIA). His serum troponin I is
now <0.5 ng/mL. Thrombus formation involving which
of the following locations is most likely to have put him
at greatest risk for the TIA?
A. Cerebral vein
Incorrect. The cerebral bridging veins
cross the subdural space and rupture of
them can produce a subdural hematoma.
Cerebral venous thrombosis is far less
common than cerebral arterial
thrombosis or embolism.
B. Vertebral artery
Incorrect. Vertebral artery thrombi are
rare and may be the result of local trauma.
C. Superior vena cava
Incorrect. The superior vena cava may
become occluded by thrombus when
involved by obstruction in the chest, such
as mass effect from a neoplasm in the
lung or medastinum. A thromboembolus
from a leg vein may pass through the
inferior vena cava on the way to the
pulmonary arterial tree.
D. Left ventricle
CORRECT. Mural thrombi can form over
the damaged area of ventricular wall
following myocardial infarction. This can
happen acutely overlying the necrotic
myocardium; it can occur remotely in a
ventricular aneurysm. Portions of the
mural thrombus can break off and
embolize via the systemic arterial
circulation to places such as the cerebral
circulation.
E. Coronary artery
Incorrect. His original myocardial
infarction may have been due to coronary
thrombosis, but his last event was not,
since the troponin I was not elevated.
F. Saphenous vein
Incorrect. A thrombus in the saphenous
vein may become a thromboembolus that
travels to the pulmonary arterial tree of
the lungs. The only way such a
thromboembolus may reach the arterial
circulation is through a patent foramen
ovale - a rare event.
A 25-year-old previously healthy primigravida is in the
first trimester of pregnancy. During two successive
prenatal visits, she has fasting serum glucose levels of
127 and 131 mg/dL. Prior to this pregnancy, her fasting
serum glucose was 80 mg/dL. A hemoglobin A1C level
is 8.1% at the last visit, at 18 weeks gestation. She
feels well and has no major health problems. Which of
the following problems is most likely to become
apparent in the latter part of her pregnancy?
A. Intrauterine fetal growth retardation
Incorrect. The babies of diabetic mothers
tend to have macrosomia (increased
size).
B. Ketoacidosis
Incorrect. This patient has gestational
diabetes, not type 1 diabetes mellitus.
C. Hyperosmolar coma
Incorrect. This unlikely, given that
hyperosmolar coma is more typical of
older type 2 diabetics.
D. Congenital anomalies
Incorrect. The rate of fetal malformation
is slightly increased in mothers with
diabetes mellitus type 1 or 2, but not
gestational diabetes.
E. Placental insufficiency
CORRECT. The big problem in
gestational diabetes is eventual placental
malfunction in later pregnancy (third
trimester) with potential fetal demise.
A 54-year-old man with diabetes mellitus has had 3
urinary tract infections during the past year. He now
sees the physician for an ulceration on his right big toe
which has not healed in 2 months. Laboratory studies
on each of his doctor visits over the past year show
blood glucose levels below 110 mg/dL. This situation
could be best explained by which of the following
laboratory findings?
A. Elevated hemoglobin A1C
CORRECT. Out-of-control diabetes over
time can be better detected because the
glycosylated RBCs will persist for months
and the Hgb A1C increased. Single
glucose values reflect the past few hours.
His problems developed over years.
B. Increased urine ketones
Incorrect. The ketones suggest
ketoacidosis, but this could have been a
recent development.
C. Elevated serum osmolarity
Incorrect. Hyperosmolar coma is
possible, but would be relatively recent in
onset.
D. Decreased plasma insulin
Incorrect. This would be a likely finding
with diabetes mellitus, but would tell you
nothing about the course or the degree of
control of hyperglycemia.
E. Elevated titer of anti-insulin antibodies
Incorrect. In type I diabetes mellitus,
elevated anti-insulin antibodies are often
present, but tell you nothing about the
course or the control of the
hyperglycemia.
 Atherosclerosis and Thrombosis | Pathology Reviewer (Utah) | 7 / 72
A 25-year-old man experiences chest pain on exercise
when he attempts to climb three flights of stairs. This
pain is relieved by sublingual nitroglycerin. He is 178
cm tall and weighs 101 kg. His blood pressure is
130/85 mm Hg. Laboratory studies show a total serum
cholesterol of 550 mg/dL with an HDL cholesterol
component of 25 mg/dL. The blood glucose is 120
mg/dL. He is worried about these findings because his
brother died of a myocardial infarction at age 34. Which
of the following conditions is this man most likely to
have?
A. Diabetes mellitus, type II
Incorrect. Type II diabetes mellitus is
most often a disease of middle aged to
older adults, taking years for
complications to develop. His obesity is a
risk for DM type II.
B. Hypertensive emergency
Incorrect. A hypertensive emergency
may, on occasion, complicate
longstanding hypertension that is
associated with development of
atherosclerosis, but this is usually a
complication seen in middle aged to older
adults.
C. Familial hypercholesterolemia
CORRECT. The very high cholesterol
with symptoms of coronary artery
disease at such a young age, coupled
with the family history, are all consistent
with familial hypercholesterolemia. In
most persons with hypercholesterolemia
from multifactorial causes, including diet
and exercise patterns, the cholesterol
rarely exceeds 400 mg/dL.
D. Cushing syndrome
Incorrect. The hypercortisolism of
Cushing syndrome tends to promote
secondary diabetes mellitus, but the
underlying conditions that lead to
Cushing syndrome are unlikely to allow a
long enough survival to develop severe
atherosclerosis.
E. Morbid obesity
Incorrect. Morbid obesity is a risk for type
II diabetes mellitus, and decades are
required to develop complications of
atherosclerosis. It is unlikely that the
cholesterol would be this high.
In a clinical study of patients with diabetes mellitus, a
group of patients is found who have had blood glucose
measurements ranging from 140 to 180 mg/dL for at
least 10 years. Rectal biopsies from these patients now
show that there is a form of osmotic cellular injury
present in arterioles. This form of injury is most likely to
be manifested elsewhere in the body by which of the
following complications?
A. Cerebral infarction
Incorrect. Atherosclerotic
cerebrovascular disease is more
frequent with diabetes mellitus, but is
usually large vessel disease not directly
related to osmotic vascular injury.
B. Gastric adenocarcinoma
Incorrect. The risk for cancer is not
increased with diabetes mellitus.
C. Congestive heart failure
Incorrect. The major damage to the heart
with diabetes mellitus is done via
atherosclerotic coronary artery disease.
Atherosclerosis affects muscular arteries
by formation of intimal atheromatous
plaques which occlude the lumen and
lead to ischemic injury.
D. Impotence
CORRECT. The hyperglycemia leads to
formation of sorbitol in tissues not
requiring insulin for glucose uptake,
resulting in osmotic cellular injury. This
can occur in small vessels, retina, kidney,
and nerves. The failure of erection and
ejaculation results from diabetic
neuropathy.
E. Pyelonephritis
Incorrect. Pyelonephritis with diabetes is
related to diminished neutrophil function
with hyperglycemia and risk for infection.
A 49-year-old woman has experienced marked pain in
her lower extremities on ambulation more than 300
meters for the past 5 months. On physical examination,
her lower extremities are cool and pale, without
swelling or erythema. No dorsalis pedis or posterior
tibial pulses are palpable. Her body mass index is 32.
She is a smoker. Which of the following abnormalities
of the vasculature is most likely to account for these
findings?
A. Lymphatic obstruction
Incorrect. The result of lymphatic
obstruction is lymphedema, with marked
swelling from collection of interstitial fluid.
Lymphatics normally scavenge the fluid
and protein that escapes at the venule
and capillary level and returns it to
circulation.
B. Arteriosclerosis
Incorrect. Arteriolosclerosis is more
typically found in the kidneys and brain,
not the extremities.
C. Atherosclerosis
CORRECT. She has claudication from
severe peripheral arterial atherosclerosis,
most likely from the iliac arteries down.
Her major risk factor is obesity that
promotes insulin resistance and diabetes
mellitus that leads to atherosclerosis.
D. Medial calcific sclerosis
Incorrect. Medial calcific sclerosis of
Monckeberg is not typically a serious
problem, because there is minimal
arterial vascular luminal narrowing.
E. Venous thrombosis
Incorrect. Venous thrombosis should
lead to a warm, tender, swollen extremity,
typical for phlebothrombosis
(thrombophlebitis).
An autopsy study is conducted involving the gross
appearance of the aorta of adults ranging in age from
60 to 90. In some of these patients, the aorta
demonstrates atheromatous plaques covering from 70
to 95% of the intimal surface area, mainly in the
abdominal portion, with ulceration and calcification.
Which of the following contributing causes of death are
these patients most likely to have?
 Atherosclerosis and Thrombosis | Pathology Reviewer (Utah) | 8 / 72
A. Hyperparathyroidism
Incorrect. Hypercalcemia is not a risk
factor for advanced atherosclerosis.
B. Hypertension
CORRECT. Hypertension is a risk factor
that accelerates atheromatous plaque
formation.
C. Marfan syndrome
Incorrect. In Marfan syndrome, there is
cystic medial necrosis of the aorta, but
not atherosclerosis.
D. Thrombophlebitis
Incorrect. Thrombophlebitis involves
veins. Atherosclerosis does not involve
veins.
E. Vasculitis
Incorrect. Various forms of vasculitis may
produce vascular occlusion, but do not
accelerate atherosclerosis.
F. Colonic adenocarcinoma
Incorrect. Cancer is a debilitating
condition likely to result in reversal of
atheroma formation. Hypercoagulable
states from cancers are most likely to
result in venous thrombosis, though
arterial thrombi are possible, but not
dependent upon prior arterial atheroma
formation.
G. Systemic lupus erythematosus
Incorrect. SLE and autoimmune diseases
in general are debilitating conditions in
which existing atheromas may diminish
in size. The antiphospholipid syndrome
that can sometimes occur with SLE can
lead to thrombosis, not atheroma
formation.
A 58-year-old woman has the sudden onset of severe
dyspnea with chest pain and diaphoresis. A chest CT
scan shows areas of decreased attenuation within the
main pulmonary arteries. Her D-dimer assay is
elevated. Her acute event is most likely to be a
consequence of which of the following?
A. Placement of a hip prosthesis
CORRECT. Immobilization is a major risk
for the development of venous
thrombosis and subsequent pulmonary
embolization (the areas of diminished
attenuation). Immobilization occurs
following surgery. The postoperative goal:
get the patient mobile as soon as
possible, and meanwhile employ
methods to reduce the risk for thrombosis.
B. Marked thrombocytopenia
Incorrect. Thrombocytopenia leads to
bleeding, not to thrombosis.
C. Chronic alcoholism
Incorrect. Chronic alcoholics tend to have
a coagulopathy due to their underlying
liver disease which predisposes them to
bleeding, not thrombosis.
D. Infection with the human
immunodeficiency virus
Incorrect. Some AIDS patients get an
acquired protein S deficiency that
predisposes to thrombosis, but this is not
common.
E. Rheumatoid arthritis
Incorrect. Persons with autoimmune
diseases generally do not have major
problems with thrombosis, though some
can develop an antiphospholipid
syndrome with thrombosis.
At autopsy, the kidneys of a 44-year-old woman who
died suddenly are found to be of normal size. Their
surfaces appear finely granular. There are small
hemorrhages noted. The cortices appear pale.
Microscopically, many small renal arteries and
arterioles demonstrate concentric intimal thickening
with marked luminal narrowing. These findings are
most likely to be present as a result of which of the
following underlying diseases?
A. Amyloidosis
Incorrect. Amyloid deposits can be seen
in small arteries and glomeruli in the
kidney, but do not produce a hyperplastic
arteriolosclerosis.
B. Systemic lupus erythematosus
Incorrect. Lupus nephritis may be
accompanied by a vasculitis and by
glomerular basement membrane
thickening, but not hyperplastic
arteriolosclerosis.
C. Scleroderma
CORRECT. Hyperplastic
arteriolosclerosis is typically seen in
association with severe hypertension,
which can complicate prior 'essential'
hypertension or occur with progressive
systemic sclerosis (scleroderma).
D. Rheumatoid arthritis
Incorrect. There are no prominent
vascular changes with rheumatoid
arthritis.
E. Viral hepatitis
Incorrect. Cryoglobulinemic vasculitis
may complicate some cases of hepatitis
B or C infection. In general viral infections
do not involve the vasculature.
F. Diabetes mellitus
Incorrect. Diabetes mellitus leads to
accelerated atherosclerosis of medium to
large arteries. There may also be hyaline
arteriolosclerosis, but not hyperplastic
arteriolosclerosis.
A 34-year-old previously healthy woman notes that she
has bruises form on her arms and legs with just minor
trauma. Physical examination reveals areas of purpura
from 1 to 3 cm in size over her trunk and extremities,
but no swelling, warmth, or erythema. Peripheral
pulses are all palpable and full. Her blood pressure is
110/70 mm Hg. An ultrasound examination of her lower
extremities with Doppler flow measurement reveals no
evidence for thrombosis. Laboratory findings include
serum urea nitrogen of 16 mg/dL, LDH 300 U/L, total
protein 6.9 g/dL, albumin 5.3 g/dL, alkaline
phosphatase 50 U/L, AST 40 U/L, and ALT 20 U/L.
Which of the following additional laboratory findings is
most likely to be present in this patient?
A. Hyperglycemia
Incorrect. Diabetes mellitus is a disease
marked by hyperglycemia that leads to
early and advanced atherosclerosis with
peripheral vascular disease involving
 Atherosclerosis and Thrombosis | Pathology Reviewer (Utah) | 9 / 72
arteries, with reduced blood flow and
reduced pulses.
B. Hypercholesterolemia
Incorrect. Patients with
hypercholesterolemia are at increased
risk for accelerated atherosclerosis and
peripheral vascular disease involving
arteries.
C. Lactic acidosis
Incorrect. Poor tissue perfusion leads to
increased anaerobic glycolysis and lactic
acidosis. However, her pulses are not
reduced.
D. Thrombocytopenia
CORRECT. The platelets are
responsible for dealing with small leaks in
small vessels. Thrombocytopenia is
marked by petechiae and purpura. She
does not have evidence for peripheral
vascular disease, since her circulation is
good. Venous thrombosis should lead to
swelling and tenderness.
E. Hypoprothrombinemia
Incorrect. She has no evidence for liver
disease, which would reduce
prothrombin production. The pattern of
her bleeding fits best with lack of platelets,
not coagulation factors.
F. Anemia
Incorrect. The amount of bleeding into
soft tissues is unlikely to lower the
hematocrit significantly. Bone marrow
injuries that lead to reduced platelet
production, however, may also lead to
anemia. With anemia, tissue appear pale.
A longitudinal study is conducted to detect serum
markers that predict risk for death from acute coronary
syndromes. A marker is identified that is synthesized
and released from the liver in response to formation of
cytokines in atheromatous plaques. This marker
increases endothelial adhesiveness to platelets. What
is this marker most likely to be?
A. Prostacyclin
Incorrect. Prostacyclin is produced in the
arachidonic acid pathway in endothelium
to reduce platelet activation.
B. Immunoglobulin G
Incorrect. Immunoglobulins are not
directly implicated in atherogenesis.
C. C-reactive protein
CORRECT. An increased CRP predicts a
greater likelihood for adverse events
from atherogenesis. One benefit of
'statin' drugs is their CRP lowering effect.
D. Alpha-1-antitrypsin
Incorrect. AAT is the major circulating
anti-protease. It mitigates neutrophil
proteases. However, atherogenesis is
not related to neutrophil actions.
E. Acetoacetate
Incorrect. Free fatty acids, including
acetoacetate, are released with lipolysis,
but do not directly participate in
atherogenesis.
A 53-year-old woman is found on a routine physical
examination to have vital signs with T 37°C, P
78/minute, RR 16/minute, and BP 165/110 mm Hg.
There are no other significant findings. She has an
abdominal ultrasound examination that shows the right
kidney to be atrophic. Angiography reveals markedly
reduced blood flow to the right renal artery from an
occlusion at the orifice in the abdominal aorta. Which
of the following laboratory findings is she most likely to
have?
A. Serum sodium of 161 mmol/L
Incorrect. Marked dehydration or free
water loss could lead to this degree of
hypernatremia. Many persons with
essential hypertension may have
increased retention of sodium, but it is not
marked by significant hypernatremia.
B. Serologic evidence of anti-cardiolipin
antibody
Incorrect. Anti-cardiolipin antibody is
seen with the antiphospholipid syndrome,
which is a cause for thrombosis. It is
unlikely that the selective renal artery
occlusion represents a hypercoagulable
state.
C. Prothrombin time of 25 seconds
Incorrect. An elevated prothrombin time
predisposes to bleeding.
D. Plasma renin activity of 4.8 ng/mL/hr
supine
CORRECT. She has renal artery
stenosis that is reducing renal blood flow
on the right and simulating the JG cells to
secrete renin to try and raise blood
pressure to increase renal blood flow.
E. Serum lactic acid of 5.5 mmol/L
Incorrect. The decreased perfusion of the
right kidney occurs over a long period of
time, without a significant rise in lactate
that would accompany more global
hypoperfusion.
A study of pathologic findings in the islets of
Langerhans is performed. It is observed that insulitis
may occur in the islets. The inflammatory infiltrate is
predominantly composed of T lymphocytes. Which of
the following is most likely to occur as a consequence
of insulitis?
A. Neoplasia
Incorrect. An insulitis is typical for type I
diabetes mellitus; there is no increased
risk for neoplasia.
B. Malabsorption
Incorrect. The insulitis involves just the
endocrine portion of the pancreas, not
the exocrine portion, so there is no loss
of pancreatic enzymes for digestion.
C. Ketoacidosis
CORRECT. An insulitis is seen with type
I diabetes mellitus. Actually, it is rare to
see it because by the time the patients
present with overt diabetes mellitus, the
islets are long gone.
D. Obesity
Incorrect. Obesity is typically associated
with type II diabetes mellitus; with type I
diabetes mellitus, there is a catabolic
state with weight loss.
 Atherosclerosis and Thrombosis | Pathology Reviewer (Utah) | 10 / 72
E. Sepsis
Incorrect. The lymphocytes in the islets
are part of an autoimmune phenomenon,
not an infectious process.
A 57-year-old man has had blood pressure
measurements in the range of 160/95 to 180/110 mm
Hg for many years. He has taken no medications. A
renal scan reveals kidneys of normal size for age.
These findings with benign nephrosclerosis are most
likely to occur with which of the following vascular
changes?
A. Hyaline arteriosclerosis
CORRECT. Hyaline arteriolosclerosis is
a feature of long-standing hypertension
and is part of benign nephrosclerosis
which may go on for many years with no
complications. The small arterioles are
thickened with pink (hyaline)
proteinaceous deposits.
B. Monckeberg’s medial calcific sclerosis
Incorrect. Medial calcific sclerosis is a
form of arteriolosclerosis without
significant complications. The vascular
lumen is not significantly compromised
by the medial calcification.
C. Complex calcified atherosclerosis
Incorrect. Coronary artery disease is
caused by atherosclerosis that can be
accelerated by hypertension.
Atheromatous plaques occur in medium
to large sized arteries and can be
complicated by calcification of the
plaques.
D. Arterial mural thrombosis
Incorrect. Mural thrombosis typically
occurs in the aorta and its branches when
there is severe atherosclerosis.
E. Hyperplastic arteriosclerosis
Incorrect. Hyperplastic arteriolosclerosis
is usually seen in the kidneys when there
is severe hypertension.
A 45-year-old man feels some crushing chest pain
along with numbness in his left arm after shoveling 15
cm of snow off his driveway. Three hours later he
collapses and is taken to the emergency room. Which
of the following laboratory tests run on a blood
specimen is most useful in this situation?
A. Total white blood cell count
Incorrect. An elevation in WBC count is
not a specific indicator for myocardial
infarction.
B. Glucose
Incorrect. Though he may have diabetes
mellitus as an underlying cause for the
atherosclerosis leading to myocardial
infarction, serum glucose will not help to
diagnose the infarction.
C. Platelet count
Incorrect. Platelet counts are of no value
in diagnosing infarctions, even though
platelets play a role in formation of
thrombi that can lead to infarction.
D. Troponin
CORRECT. Elevations in troponins are
going to be seen acutely with myocardial
infarction beginning within 3 hours and
remaining for up to 14 days. Total
creatine kinase (CK) reflects changes in
any striated muscle, and is not specific
for cardiac muscle. The CK-MB fraction
is most specific to myocardium, but
remains elevated for up to 3 days.
E. Lipase
Incorrect. Lipase is increased with
pancreatitis, which is not related to
cardiovascular disease.
A 68-year-old woman has survived multiple episodes
of pulmonary thromboembolism during the past three
months. On physical examination there are no
abnormal findings. Which of the following is the most
likely underlying condition leading to this patient's
recurrent pulmonary thromboembolism?
A. Micronodular cirrhosis of the liver
Incorrect. Liver disease leads to a
coagulopathy marked by a tendency to
bleeding, not thrombosis.
B. Adenocarcinoma of the pancreas
CORRECT. The recurrent episodes
suggest a hypercoagulable state, and
carcinomas can do this (Trousseau
syndrome) by releasing substances that
act as thromboplastins.
C. Thrombocytopenia
Incorrect. A decreased platelet count is a
risk for hemorrhage, not thrombosis.
D. Familial hypercholesterolemia
Incorrect. Hypercholesterolemia could
accelerate atherosclerosis and
thrombosis, but in arteries, not veins.
E. Mitral valve endocarditis
Incorrect. An endocarditis could lead to
embolization, but into the systemic
circulation from the mitral valve.
F. Type II diabetes mellitus
Incorrect. Diabetes mellitus increases the
risk for atherosclerosis, but
atherosclerosis does not involve veins.
A 57-year-old woman has experienced episodes of
altered mental status for the past month. On physical
examination, she has bilateral carotid artery bruits. She
is given folic acid supplementation. Which of the
following laboratory test findings is she most likely to
have?
A. Factor V Leiden mutation
Incorrect. The factor V Leiden mutation is
a risk for a hypercoagulable state with
venous thrombosis, typically manifested
at a young age.
B. Factor VIII deficiency
Incorrect. Factor VIII deficiency is one
cause for hemophilia with risk for
bleeding into soft tissues, manifested
early in life.
C. Increased carcinoembryonic antigen
Incorrect. An increased CEA can be seen
with some malignancies, such as
adenocarcinoma of the colon. In this
case, the mass is an aortic aneurysm
caused by atherosclerosis.
D. Homocysteinemia
CORRECT. An elevated plasma
homocysteine level is a risk for
atherosclerosis as well as thrombosis.
Her findings point to transient ischemic
 Atherosclerosis and Thrombosis | Pathology Reviewer (Utah) | 11 / 72
attacks (TIAs) with risk for stroke. The
carotid bruits represent arterial narrowing
as the result of atherosclerosis.
E. Increased HDL cholesterol
Incorrect. HDL is the 'good' cholesterol
that tends to protect against
atherosclerosis.
A 70-year-old man has noted coldness and numbness
of his lower left leg, increasing over the past 4 months.
He also experiences pain in this extremity when he
tries walking more than the distance of half a city block.
On physical examination, his dorsalis pedis, posterior
tibial, and popliteal artery pulses are not palpable.
Which of the following laboratory test findings is he
most likely to have?
A. Protein S deficiency
Incorrect. Coagulopathies with
thrombosis may be due to a congenital
anticoagulant factor deficiency, but
thrombotic events are usually sudden.
B. Blood culture with Staphylococcus
aureus
Incorrect. Septic thrombosis and mycotic
aneurysms may be the result of
septicemia, but this is an acute illness.
C. Decreased arterial oxygen saturation
Incorrect. Oxygen saturation is typically
dependent more upon pulmonary
function and is not related to focal events,
as in the lower extremities.
D. Hyperglycemia
CORRECT. This is peripheral arterial
vascular disease from severe
atherosclerosis, which is promoted by
diabetes mellitus. The absence of pulses
defines this as an arterial process, as
does the claudication (pain with exercise).
Thrombophlebitis is a venous process
and leads to swelling and pain in the leg,
but not loss of pulses.
E. Hypercalcemia
Incorrect. Calcium levels have little to do
with vascular problems in general
(except for the rare condition in persons
with renal failure called calciphylaxis).
A 72-year-old man suffered a myocardial infarction
involving half the left ventricular free wall 3 months ago.
He now has increasing dyspnea and orthopnea. On
echocardiography his ejection fraction is 29%. On
examination he has poor capillary filling in hands and
feet. A chest x-ray shows pulmonary edema. Which of
the following laboratory test analytes is most likely to
be increased in this man at this point in time?
A. Sodium
Incorrect. The serum sodium may give an
indication of the degree of hydration, not
tissue perfusion.
B. Creatine kinase
Incorrect. Poor perfusion leading to
myocardial infarction would increase the
creatine kinase.
C. Natriuretic peptide
CORRECT. With congestive heart failure,
there is volume overload that triggers an
increase in natriuretic peptide, typically
measured as the b-type (BNP). This
hormone normally leads to natriuresis,
diuresis, and vasodilation, lessening the
strain on the myocardium.
D. Hematocrit
Incorrect. The hematocrit suggests the
ability of the blood to carry oxygen and
prevent ischemia, but does not predict
whether there is poor perfusion with
ischemia.
E. Sedimentation rate
Incorrect. The sed rate gives an
indication of the presence of
inflammation, a consequence of an
ischemic event.
A 44-year-old African-American man has had elevated
blood pressure for years which has not been treated.
He now has severe headaches. On physical
examination his blood pressure is 275/150 mm Hg.
Laboratory studies show Hgb 13.8 g/dL, serum glucose
76 mg/dL, and creatinine 3.5 mg/dL. These findings are
most likely to be associated with which of the following
pathologic lesions involving his kidneys?
A. Hyperplastic arteriosclerosis
CORRECT. Hyperplastic
arteriolosclerosis is seen in the setting of
hypertensive emergency when systolic
pressure is >=180 and/or diastolic
pressure >=120 mmHg along with signs
of acute or ongoing end-organ damage,
and renal failure is common.
B. Hyaline arteriosclerosis
Incorrect. These are complications
typically seen in association with
diabetes mellitus.
C. Monckeberg medial calcific sclerosis
Incorrect. This is a histologic curiosity
with no major clinical importance.
D. Atherosclerosis
Incorrect. Hypertension is a risk for
coronary artery disease, but a
hypertensive emergency is not
specifically linked to coronary thrombosis.
E. Thrombophlebitis
Incorrect. Venous thrombosis is most
often a result of stasis from
immobilization.
A 60-year-old woman has become increasingly
obtunded over the past day. She was found by her
daughter in a stuporous condition and brought to the
emergency department. On physical examination, she
has poor skin turgor. She is afebrile. Her vital signs
reveal a blood pressure of 90/40 mm Hg, respirations
15 and shallow, pulse 95, and temperature 36°C.
Laboratory studies show a hemoglobin A1C of 10%.
Her serum electrolytes show sodium 144 mmol/L,
potassium 5 mmol/L, chloride 95 mmol/L, CO2 22
mmol/L, and glucose 940 mg/dL. Which of the following
is the most likely diagnosis?
A. Insulin overdose
Incorrect. An overdose of insulin would
lead to hypoglycemia.
B. Hyperosmolar coma
CORRECT. This is an extremely
elevated serum glucose that would
increase the serum osmolality markedly.
 Atherosclerosis and Thrombosis | Pathology Reviewer (Utah) | 12 / 72
C. Hyperlipidemia
Incorrect. Hyperlipidemia can be due to
either an increased serum cholesterol or
serum triglyceride.
D. Ketoacidosis
Incorrect. Diabetics with ketoacidosis
may have a serum glucose around 500 to
600 mg/dL, but generally not over 1000
mg/dL.
E. Overeating
Incorrect. You can't get an extremely high
serum glucose just from oral intake alone.
A study is performed involving persons who have a
history of diabetes mellitus type 1 or type 2. These
patients are found to have cellular injury that results
from glycosylation end products and from sorbitol
accumulation within cells. The same patients are also
shown to have ischemic tissue damage from
accelerated and advanced atherosclerosis. Which of
the following complications is most likely to result from
atherosclerosis in these patients?
A. Hepatic failure
Incorrect. The liver is not primarily
affected by atherosclerosis, as it has a
dual blood supply.
B. Impotence
Incorrect. The neuropathy that occurs
with diabetes mellitus can affect penile
erection in men.
C. Stroke
CORRECT. Stroke from cerebral
atherosclerosis or from embolization of
mural thrombi from a heart involved with
ischemic injury as a consequence of
atherosclerosis.
D. Cataracts
Incorrect. Cataracts involving the
crystalline lens of the eye are seen more
frequently in diabetics.
E. Retinopathy
Incorrect. Blindness from diabetic
retinopathy is a frequent long term
complication of diabetes mellitus.
A 30-year-old man goes to his physician for a routine
health checkup. On physical examination there are no
abnormal findings. Laboratory test findings include
serum glucose 80 mg/dL, hemoglobin A1C 4%, total
cholesterol 240 mg/dL, LDL cholesterol 180 mg/dL,
and HDL cholesterol 20 mg/dL. Through which of the
following mechanisms is endothelial vascular injury in
this patient most likely to occur?
A. Accumulation of sorbitol
Incorrect. The accumulation of sorbitol in
tissues not requiring insulin for glucose
uptake is a feature of diabetes mellitus
with hyperglycemia.
B. Insudation of lipid
CORRECT. He has
hypercholesterolemia with more of the
'bad' LDL cholesterol that can become
oxidized and taken up by modified
arterial wall LDL receptors. The lipid
collects in macrophages that transform to
foam cells. These foam cells accumulate
and becomes a lipid lesion--the precursor
to more serious atheromatous plaques.
C. Inflammation with neutrophils
Incorrect. Neutrophilic inflammation can
be the result of infection and is unusual in
arteries. It is not related to
atherosclerosis.
D. Deposition of immunoglobulins
Incorrect. There can be T-cell activation
with atherogenesis, but B-cells do not
play a significant role.
E. Activation of complement
Incorrect. The process of atherogenesis
proceeds slowly, without significant
inflammation and activation of
complement.
A 65-year-old man has had increasing lower leg
swelling along with reduced exercise tolerance for the
past 5 years. He has chest pain on exertion. He has
not experienced dyspnea. He has had 4 transient
ischemic attacks in the past year. He has experienced
abdominal pain in the past 2 months. Vital signs show
T 37°C, P 82/min, RR 16/min, and BP 130/85 mm Hg.
He has pitting edema to the knees bilaterally. The lower
extremities have palpable pulses, no tenderness, and
no erythema. An abdominal CT scan shows dilation of
the abdominal aorta to 5 cm, filled with mural thrombus.
Other family members have had similar problems.
Which of the following underlying conditions is the most
likely risk factor for his findings?
A. Factor V Leiden mutation
Incorrect. This is a cause for
hypercoagulability, usually manifesting at
an early age, with a risk mainly for
venous thrombosis, not atherosclerosis.
B. Adenocarcinoma of the colon
Incorrect. Malignancies can be
associated with a hypercoagulable state
with thrombosis, but not manifestations
of atherosclerosis. In fact, persons with
malignancies typically have a regression
of atherosclerotic lesions.
C. Multiple blunt trauma
Incorrect. Trauma can cause
hemorrhage, not atherosclerosis. The
'trauma' to arterial endothelium that
promotes atherosclerosis is from altered
blood flow at a microscopic level, not
external trauma.
D. Vasculitis
Incorrect. Vasculitis does not typically
lead to findings in a distribution
associated with atherosclerosis. Some
forms of vasculitis favor thrombosis,
others occlusion.
E. Metabolic syndrome
CORRECT. He has findings associated
with atherosclerosis, including coronary
and aortic disease at least, with
congestive heart failure and evidence for
an aortic aneurysm. Metabolic syndrome
predisposes to atherosclerosis. Some
patients may eventually develop overt
diabetes mellitus type 2.
 Atherosclerosis and Thrombosis | Pathology Reviewer (Utah) | 13 / 72
A study of persons with essential hypertension is
performed. They have blood pressures in the range of
140/90 to 160/100 mm Hg. Laboratory studies show
normal serum electrolyte values. Which of the following
physiologic abnormalities is most likely to account for
their hypertension?
A. Hyperreninemia
Incorrect. Increased renin is likely to
occur with renal arterial abnormalities
that reduce renal blood flow.
B. Hyperaldosteronism
Incorrect. Increased aldosterone may be
elaborated by an adrenal adenoma, and
it is increased in response to increased
renin.
C. Decreased natriuretic peptide
Incorrect. Though natriuretic peptide is
likely not to be elevated with
hypertension, this is not the primary
mechanism for the hypertension.
D. Decreased angiotensin converting
enzyme
Incorrect. ACE is needed to convert
angiotensin I to angiotensin II, to
increase blood pressure. ACE inhibitors
are used to treat hypertension.
E. Sodium retention
CORRECT. The causes for essential
hypertension are obscure. The 'set point'
for sodium diuresis is probably increased
at a higher blood pressure in affected
persons. Diuretics that promotes
natriuresis are effective in treating
essential hypertension.
F. Catecholamine excess
Incorrect. Increased catecholamines may
occur with pheochromocytomas.
A 27-year-old woman had a hemoglobin A1C of 7.9%
noted during a prenatal visit. She gives birth to a 4350
gm baby at 37 weeks gestation. Just after the delivery,
the baby becomes irritable and displays seizure activity.
Which of the following laboratory findings is most likely
to be found in the baby:
A. Decreased hemoglobin A1C
Incorrect. The hemoglobin A1C is
typically increased in diabetics with poor
control.
B. Increased serum osmolality
Incorrect. Hyperosmolar coma with a
markedly elevated serum glucose is a
feature of type II diabetes mellitus in
adults.
C. Hyperlipidemia
Incorrect. Hyperlipidemia in neonates is
unlikely to occur.
D. Hypoglycemia
CORRECT. Infants of diabetic mothers
are at risk for hypoglycemia following
delivery, because they have islet
hypertrophy and hyperplasia, and the
increased islet production of insulin
carries into the immediate postpartum
period.
E. Ketoacidosis
Incorrect. Ketoacidosis is typical for type
I diabetes in which there is an absolute
insulin lack.
Following a meal, lipids are digested and absorbed.
Lipids collect within enterocytes. Which of the following
chemical components of the blood is mainly
responsible for transporting exogenous (dietary)
triglyceride from the intestine to the liver?
A. Apoprotein
Incorrect. There are a number of
apoproteins involved in transport of lipids
in the blood, but they are not the primary
means of transport of dietary lipids to the
liver.
B. Chylomicron
CORRECT. Chylomicrons formed in
intestinal epithelial cells contain
apoproteins, triglyceride and cholesterol.
C. Lipoprotein lipase
Incorrect. Lipoprotein lipase in
endothelium hydrolyzes chylomicrons,
liberating fatty acids for use by fat and
muscle. The cholesterol-rich chylomicron
remnants go to the liver.
D. Oxidized low density lipoprotein
Incorrect. Such LDL is injurious to
endothelium and is more avidly taken up
by macrophages and smooth muscle,
thus promoting atherogenesis in vessels.
E. High density lipoprotein
Incorrect. HDL is 'good' because it
transports cholesterol back to the liver.
Some cells demonstrate glucose uptake from the blood
regardless of the plasma insulin level. In persons who
have had persistent hyperglycemia for years, cellular
injury can occur. Which of the following cell types is
most likely to show injury from hyperglycemia?
A. Cardiac myocytes
Incorrect. Cardiac myocytes are striated
muscle cells that require insulin for
glucose uptake.
B. Fibroblasts
Incorrect. Fibroblasts have GLUT4
receptors responsive to insulin for
glucose uptake, but the effect is less
pronounced than for adipocytes.
C. Steatocytes
Incorrect. Fat cells require insulin for
glucose uptake. Steatocytes also are part
of the endogenous pathway of lipoprotein
transport and convert VLDL to LDL.
D. Neurons
CORRECT. Neurons do not require
insulin for glucose uptake. The excess
glucose diffusing into the cells is shunted
into the sorbitol pathway and can lead to
osmotic injury, resulting in neuropathy.
E. Smooth muscle cells
Incorrect. Smooth muscle requires
insulin for glucose uptake.
During hospitalization, a 40-year-old woman develops
thrombophlebitis. She recovers and is discharged. She
returns to her job as an electrician. A couple of months
later, which of the following terms would best describe
the process seen in a femoral vein after recovery from
her thrombophlebitis:
A. Acute inflammation
Incorrect. Some inflammation, possibly
acute, may have been present at the time
 Atherosclerosis and Thrombosis | Pathology Reviewer (Utah) | 14 / 72
of the original episode of
thrombophlebitis.
B. Rupture
Incorrect. Thrombophlebitis is a process
best known for thrombus formation, and
rupture of a vein wall would be an
extreme rarity.
C. Embolization
Incorrect. After she is mobile again and
months pass, any thrombus capable of
embolizing is long gone.
D. Organization
CORRECT. Thrombi may either lyse or
will organize over time, with much of the
clot eventually removed and the vascular
lumen restored.
E. Propagation
Incorrect. Propagation of a thrombus is
most likely to occur at the time it originally
forms, or soon thereafter.
A 52-year-old man has an ulcerated area on the sole
of his foot that has not healed for 2 months. He is 180
cm tall, weighs 126 kg, and has continued to gain
weight gradually. He has not had any major illnesses.
His blood pressure is normal. Which of the following
laboratory tests performed on serum from a blood
sample would be most useful in elucidating the
underlying cause for his problem:
A. Antithrombin III
Incorrect. ATIII may be diminished in
some cases of recurrent thrombosis.
B. Cortisol
Incorrect. Cortisol may be decreased
with adrenal failure. Increased cortisol
with Cushing syndrome may result in
weight gain, but signs of severe
peripheral atherosclerosis are lacking.
C. Creatine kinase
Incorrect. CK is a good indicator for injury
to muscle, and cardiac ischemia or
infarction in particular, which may be a
consequence of his underlying disease.
D. Glucose
CORRECT. The history suggests
diabetes mellitus, most likely type II, and
persistent hyperglycemia would confirm
the diagnosis.
E. Carcinoembryonic antigen
Incorrect. CEA can be a marker for some
malignancies.
A 71-year-old woman experiences a transient ischemic
attack (TiA). She had an acute myocardial infarction 5
years ago. Which of the following physical examination
findings is most likely to be associated with her TIA?
A. Blood pressure 140/90 mmHg
Incorrect. A blood pressure of 140/90 is
mild hypertension, which is a risk factor
for atherosclerosis, but not directly
related to the TIA.
B. Carotid bruit
CORRECT. Atheromatous plaques tend
to form initially where there is vascular
turbulence, and a bruit is indicative of
arterial narrowing at the carotid
bifurcation. The turbulence drives
endothelial injury that contributes to
atheroma formation.
C. Heart rate of 100/minute
Incorrect. Tachycardia may be due to
many causes but by itself does not
indicate atherosclerotic disease.
D. Leg swelling
Incorrect. Leg swelling is most indicative
of deep venous thrombosis, not
atherosclerotic vascular narrowing.
Wrong end of body.
E. Pulsatile abdominal mass
Incorrect. A pulsatile abdominal mass is
most likely to indicate an atherosclerotic
aortic aneurysm, which leads to
complications in the lower half of the
body.
F. Radial pulse 1+
Incorrect. Reduced pulses may be due to
atherosclerosis with vascular narrowing.
The radial pulse is in the arm.
A 70-year-old healthy woman has a check of her health
status. On examination her blood pressure is 125/80
mm Hg and BMI 24 kg/m2. Laboratory studies show her
serum total cholesterol is 180 mg/dL with LDL
cholesterol 90 mg/dL. There is a family history of
cancer. Which of the following is a constitutional risk
factor for atherosclerotic vascular disease in this
woman?
A. Age
CORRECT. Her age is a risk factor for
atherosclerosis. However, a healthy
lifestyle can negate this risk. Many older
persons are not pursuing a healthy
lifestyle.
B. Blood pressure
Incorrect. Her blood pressure is not
elevated. If it were, it could be modified
by lifestyle changes and by
pharmacologic therapy.
C. Family history
Incorrect. She does not have a family
history of atherosclerotic disease.
Cancer does not count.
D. Gender
Incorrect. Her female gender reduces the
risk.
E. Hyperlipidemia
Incorrect. Her cholesterol levels are in
the normal range.
F. Weight
Incorrect. Her BMI is in the normal range.
 CELLULAR INJURY SECTION
A 48-year-old woman has a malignant lymphoma
involving lymph nodes in the para-aortic region. She is
treated with a chemotherapeutic agent which results in
the loss of individual neoplastic cells through
fragmentation of individual cell nuclei and cytoplasm.
Over the next 2 months, the lymphoma decreases in
size, as documented on abdominal CT scans. By which
of the following mechanisms has her neoplasm
primarily responded to therapy?
A. Coagulative necrosis
Incorrect. When parts of an organ
undergo necrosis in a vascular
distribution from loss of blood supply with
resultant ischemia, then an infarct occurs.
B. Mitochondrial poisoning
Incorrect. The loss of mitochondrial
activity, as can occur with calcium influx
with hypoxia, does not signal apoptosis.
C. Phagocytosis
Incorrect. Phagocytosis is the process of
cells or cellular debris being consumed
by macrophages. Apoptotic bodies may
be consumed in this fashion.
D. Acute inflammation
Incorrect. Acute inflammatory cells
(neutrophils) can release enzymes that
destroy other cells and intracellular
matrix, but this is a highly non-selective
process.
E. Apoptosis
CORRECT. The induction of individual
cell death occurs in the process of
apoptosis. The drug effect is targeted
primarily at the neoplastic cells, not
normal cells.
A 53-year-old man has experienced severe chest pain
for the past 6 hours. On physical examination he is
afebrile, but has tachycardia. Laboratory studies show
a serum troponin I of 10 ng/mL. A coronary angiogram
is performed emergently and reveals >90% occlusion
of the anterior interventricular (left anterior descending)
artery. In this setting, an irreversible injury to
myocardial fibers will have occurred when which of the
following cellular changes occurs?
A. Glycogen stores are depleted
Incorrect. Glycogen depletion within the
cell can be reversed.
B. Cytoplasmic sodium increases
Incorrect. An increase in cellular sodium
(and the water that follows) produces
edema with cellular swelling, but this is a
potentially reversible form of injury.
C. Nuclei undergo karyorrhexis
CORRECT. Chromatin clumping is
reversible, but dissolution of the entire
nucleus is not, and when the nucleus is
lost, the cell will die. An acute coronary
syndrome with myocardial infarction is
described here.
D. Intracellular pH diminishes
Incorrect. Acidosis by itself is reversible.
E. Blebs form on cell membranes
Incorrect. Such membrane blebs
constitute a reversible form of cellular
injury.
While in a home improvement center warehouse
buying paint, a 35-year-old man hears 'Look out below!'
and is then struck on the leg by a falling pallet rack,
which strikes him on his left leg in the region of his thigh.
The skin is not broken. Within 2 days there is a 5 x 7
cm purple color to the site of injury. Which of the
following substances has most likely accumulated at
the site of injury to produce a yellow-brown color at the
site of injury 16 days later?
A. Lipofuscin
Incorrect. This 'wear and tear' pigment
builds up in cells of tissues (such as
myocardium and liver) over many years'
time.
B. Bilirubin
Incorrect. A generalized yellow color,
jaundice, can be the result of
hyperbilirubinemia.
C. Melanin
Incorrect. Melanin pigment darkens the
skin as concentrations of it increase from
sunlight exposure (tanning).
D. Hemosiderin
CORRECT. The iron in the heme
pigment from the red blood cells in the
hemorrhage beneath the skin is
incorporated into hemosiderin granules
that impart the yellow to brown color of
the healing contusion (bruise) from blunt
force trauma.
E. Glycogen
Incorrect. Glycogen is stored in striated
muscle and liver and imparts no grossly
visible color change.
A 54-year-old man with a chronic cough has a
squamous cell carcinoma diagnosed in his right lung.
While performing a pneumonectomy, the thoracic
surgeon notes that the hilar lymph nodes are small, 0.5
to 1.0 cm in size, and jet black in colour throughout.
Which of the following is the most likely cause for this
appearance to the hilar nodes?
A. Anthracotic pigment
CORRECT. The black colour comes from
carbon pigments in dust particles inhaled
over the years, engulfed by
macrophages, and sent via lymphatics to
the lymph nodes. It looks bad but does
not compromise lung function. Smokers
will have more anthracosis.
B. Lipochrome deposits
Incorrect. Lipofuscin pigment builds up
slowly within cell cytoplasm as a result of
internal cellular changes. It is not an
exogenous pigment.
C. Melanin accumulation
Incorrect. Melanin is made by cells
(melanocytes) and is not an exogenous
pigment.
Page 15 of 72

D. Hemosiderosis
Incorrect. Hemosiderin is a storage form
of iron and is not an exogenous pigment.
E. Metastatic carcinoma
Incorrect. Metastatic lesions are typically
firm and white.
A 50-year-old woman with a history of unstable angina
suffers an acute myocardial infarction. Thrombolytic
therapy with tissue plasminogen activator (tPA) is
administered to restore coronary blood flow. In spite of
this therapy, the degree of myocardial fiber injury may
increase because of which of the following cellular
abnormalities?
A. Cytoskeletal intermediate filament loss
Incorrect. Cytoskeletal abnormalities
occur with ischemic injury, but do not
worsen with reperfusion.
B. Decreased intracellular pH from
anaerobic glycolysis
Incorrect. Acidosis is part of ischemia,
but does not specifically cause a
reperfusion injury.
C. Increased free radical formation
CORRECT. Such toxic oxygen radicals
are released from neutrophils when
blood flow is restored following ischemia.
This is a reperfusion injury. Overall, there
is likely to be more good than harm to
restoration of blood flow.
D. Mitochondrial swelling
Incorrect. Mitochondria swell with
ischemic injury, but this is reversible.
E. Nuclear chromatin clumping
Incorrect. This is a reversible change that
may occur with ischemia.
F. Reduced protein synthesis
Incorrect. This is a reversible change that
may occur with ischemia.
A 12-year-old boy has had multiple episodes of ear
pain accompanied by fever. On examination his right
tympanic membrane is red and bulging with yellow
exudate. Laboratory studies of the exudate show
culture positive for Hemophilus influenzae. A year later
he has conductive hearing loss on the right, and a head
CT scan shows a mass in the right middle ear. Which
of the following materials is most likely to be seen in
the tissue curetted from his middle ear?
A. Lipofuscin pigment
Incorrect. Accumulation of lipofuscin is
not a function of hemorrhage or
inflammation, but of collection of cellular
breakdown products, often seen with
aging, and most often in hepatocyte or
myocardial fiber cytoplasm.
B. Russell bodies
Incorrect. Russell bodies are intracellular
accumulations of immunoglobulins in
plasma cells.
C. Neutrophil granules
Incorrect. Neutrophils suggest acute
inflammation more typical for acute otitis
media that accompanied each episode of
acute otitis media, not the complication
this boy now has. Neutrophil granules are
released and dissipate readily.
Cellular Injury | Pathology Reviewer (Utah) | 16 / 72
D. Cholesterol crystals
CORRECT. An inflammatory mass
persisted, with cellular necrosis, and the
lipid from the cell membranes is broken
down and cholesterol crystals form. The
boy has the complication of otitis media
known as a cholesteatoma
E. Anthracotic pigment
Incorrect. Anthracosis results from
accumulation within the lung and lymph
nodes of exogenous carbon pigment
from dusts in the air that we all breathe.
A 43-year-old man has complained of mild burning
substernal pain following meals for the past 3 years.
Upper GI endoscopy is performed and biopsies are
taken of an erythematous area of the lower esophageal
mucosa 3 cm above the gastroesophageal junction.
There is no mass lesion, no ulceration, and no
hemorrhage noted. The biopsies show the presence of
columnar epithelium with goblet cells. Which of the
following mucosal alterations is most likely represented
by these findings?
A. Dysplasia
Incorrect. The growth of the epithelial
cells must become disordered in order to
be dysplastic.
B. Hyperplasia
Incorrect. Hyperplasia may occur with
inflammation, as the number of cells
increases, but hyperplasia does not
explain the presence of the columnar
cells.
C. Carcinoma
Incorrect. A carcinoma has the cellular
atypia with hyperchromatism and
pleomorphism. Goblet cells would not be
seen.
D. Ischemia
Incorrect. Ischemia would be unusual at
this site and would be marked by
coagulative necrosis.
E. Metaplasia
CORRECT. Metaplasia is the
substitution of one tissue normally found
at a site for another. The esophageal
stratified squamous epithelium
undergoes metaplasia in response to the
ongoing inflammation from reflux of
gastric contents. This is common in the
lower esophagus with gastroesophageal
reflux disease (GERD).
A 71-year-old woman had the loss of consciousness
that persisted for over an hour. When she becomes
arousable, she cannot speak nor move her right arm.
A cerebral angiogram revealed an occlusion to her left
middle cerebral artery. Months later, a computed
tomographic (CT) scan shows a large 5 cm cystic area
in her left parietal lobe cortex. This CT finding is most
likely the consequence of resolution from which of the
following cellular events?
A. Liquefactive necrosis
CORRECT. She had a 'stroke' with
cerebral infarction and loss of brain
tissue. The brain undergoes liquefactive
necrosis with infarction. As it resolves,
macrophages remove the dead cells and

debris, leaving a cystic area that forms in
the region of infarction.
B. Atrophy
Incorrect. Atrophy would be a more
generalized process, whereas a single
cystic area in brain suggests a remote
infarction.
C. Coagulative necrosis
Incorrect. Coagulative necrosis is more
typical of parenchymal organs such as
kidney or spleen that do not have as high
a lipid content as brain.
D. Caseous necrosis
Incorrect. Caseous necrosis is more
typical of granulomatous inflammation
with M. tuberculosis.
E. Apoptosis
Incorrect. This is single cell necrosis that
does not result in a grossly visible cystic
area.
A 19-year-old woman gives birth to her first child. She
begins breast feeding the infant. She continues breast
feeding for almost a year with no difficulties and no
complications. Which of the following cellular
processes that began in the breast during pregnancy
allowed her to nurse the infant for this period of time?
A. Stromal hypertrophy
Incorrect. The stroma of the breast
consists of connective tissue that
provides structural support, but does not
have cells that produce milk.
B. Epithelial dysplasia
Incorrect. Dysplasia in epithelia is a pre-
malignant change not part of normal
physiologic events. This would be a
precursor to breast cancer. Pregnancy is
a protective factor against breast cancer.
C. Steatocyte atrophy
Incorrect. With poor nutrition and weight
loss, steatocytes can decrease in size.
However, she loves her baby and will
take care of herself.
D. Ductal epithelial metaplasia
Incorrect. Metaplasia is the exchange of
the normal epithelium for another in
response to chronic irritation. Metaplasia
is not a normal physiologic process.
E. Lobular hyperplasia
CORRECT. There is an increase in the
breast lobules under hormonal influence,
primarily progesterone with pregnancy,
to provide for lactation.
An 84-year-old man dies from complications of
Alzheimer disease. At autopsy, his heart is small (250
gm) and dark brown on sectioning. Microscopically,
there is light brown perinuclear pigment with H&E
staining of the cardiac muscle fibers. Which of the
following substances is most likely increased in the
myocardial fibers to produce this appearance of his
heart?
A. Hemosiderin from iron overload
Incorrect. Hemosiderosis is not a
complication of aging.
B. Lipochrome from ‘wear and tear’
CORRECT. Lipochrome (lipofuscin)
deposition in myocardial cell cytoplasm is
a common finding, though ordinarily
Cellular Injury | Pathology Reviewer (Utah) | 17 / 72
there are small amounts of it, and it has
little effect upon cardiac function. The
'brown atrophy' of the heart in this case is
a rare finding.
C. Glycogen from a storage disease
Incorrect. Glycogen storage diseases are
inherited conditions that usually appear
early in life. Glycogen does not appear
pigmented in H&E stained tissue
sections.
D. Cholesterol from atherosclerosis
Incorrect. The cholesterol accumulates in
atheromatous plaques in the arteries, not
in myocardium.
E. Calcium deposition following necrosis
Incorrect. Calcium deposits appear as
irregular dark blue areas and are not
associated with aging of the myocardium.
In an experiment, a series of immunohistochemical
stains are employed to identify different cellular
components. One particular stain identifies the
presence of intermediate filaments within cells. This
cytokeratin stain is most likely to be useful for which of
the following diagnostic purposes?
A. Cytoskeletal alterations indicate
impending cell death
Incorrect. Cytoskeletal alterations occur
with ischemia, but are not a useful marker
for such an event.
B. A neoplasm is determined to be a
carcinoma
CORRECT. Carcinomas are derived
from epithelium and contain cytokeratins,
while sarcomas derived from
mesenchymal cells contain vimentin.
C. Contractile properties of the cell can be
assessed
Incorrect. Many cell types contain
intermediate filaments.
D. A history of chronic alcoholism can be
confirmed
Incorrect. Mallory's alcoholic hyaline can
be observed by H&E staining. However,
it is not entirely specific for alcoholism.
E. The degree of metaplasia or dysplasia
can be assessed
Incorrect. Metaplasia and dysplasia are
assessed by light microscopic
appearances with H&E staining.
A 20-year-old woman had Goodpasture syndrome
which progressed to chronic renal failure. She is 165
cm tall and weighs 55 kg. She now has blood pressure
measurements in the range of 150/90 to 180/110 mm
Hg, but does not regularly take medications.
Laboratory studies show her blood urea nitrogen is
over 100 mg/dL and she requires chronic dialysis. A
chest x-ray shows an enlarged heart. The size of her
heart is most likely to be the result of which of the
following processes involving the myocardial fibers?
A. Hypertrophy
CORRECT. The ongoing pressure load
of the systemic hypertension led to
myocardial fiber hypertrophy and a heart
that increased in size. Renal failure often
leads to hypertension, and vice versa.

B. Fatty infiltration
Incorrect. Fat in the heart does not
increase in response to the increase in
work load from hypertension.
C. Hyperplasia
Incorrect. Myocardial fibers do not
undergo a significant degree of
hyperplasia.
D. Fatty degeneration
Incorrect. Fatty degeneration of
myocardium is typically the result of a
toxic or hypoxic injury.
E. Edema
Incorrect. Myocardial edema is not a
characteristic feature of myocardial injury
or increased work load. However, heart
failure could lead to peripheral edema.
A 29-year-old man goes on a snorkeling trip to Looe
Key Marine Sanctuary and later spends time on the
beach at Bahia Honda State Park. The next day he has
a darker complexion. His skin does not show warmth,
erythema, or tenderness. His skin tone fades to its
original appearance within a month. Which of the
following substances contributes the most to the
biochemical process leading to these skin changes?
A. Iron oxide
Incorrect. Heme containing iron as part of
hemosiderin from breakdown of red
blood cells can impart a brownish colour,
but this is typically local from trauma or
more global as part of an iron storage
disease such as hemochromatosis. Iron
oxide is also used in tattoo pigments.
B. Lipofuscin
Incorrect. Lipochrome (lipofuscin) is a
'wear and tear' pigment imparting a
golden brown appearance to granules in
cells (such as myocytes or hepatocytes),
but this is not a feature of skin.
C. Tyrosine
CORRECT. The tanning process in skin
is stimulated by ultraviolet light exposure.
Melanocytes have the enzyme
tyrosinase to oxidize tyrosine to
dihydroxyphenylalanine in the pathway
for melanin production. Natural skin tone
is related to the level of tyrosinase
enzyme activity.
D. Homogentisic acid
Incorrect. Homogentisic acid can be part
of the process of the rare disease
alkaptonuria, in which a black pigment is
deposited in connective tissues.
E. Glycogen
Incorrect. Glycogen in quantity is starch-
like and imparts a paler colour to organs
in which it is stored in excess. It does not
involve the skin.
A study is performed to identify predisposing risks for
tissue cellular changes. In some persons epithelial
metaplasia occurs. In which of the following situations
is the process of epithelial metaplasia most likely to
take place?
A. Tanning of the skin following sunlight
exposure
Incorrect. This physiologic event results
from accumulation of melanin pigment.
Cellular Injury | Pathology Reviewer (Utah) | 18 / 72
There is no change of one cell type to
another involved.
B. Lactation following pregnancy
Incorrect. This is a form of physiologic
hyperplasia of breast lobules from
hormonal influence.
C. Vitamin A deficiency
CORRECT. Vitamin A is necessary to
maintain epithelia, and squamous
metaplasia of the respiratory tract may
occur if there is vitamin A deficiency. The
stratified squamous epithelium does not
function as well as the normal
pseudostratified columnar respiratory
epithelium, and there is an increased risk
for respiratory infections.
D. Acute myocardial infection
Incorrect. An acute MI will lead to cardiac
muscle fiber necrosis, which will heal with
production of fibrous scar tissue, but this
is not a reversible metaplasia.
E. Urinary obstruction from an enlarged
prostate
Incorrect. The enlarged prostate
represents primarily glandular
hyperplasia.
In an experiment, a disease process is found which
leads to scattered loss of individual cells, with the
microscopic appearance of karyorrhexis and cell
fragmentation. The overall tissue structure remains
intact. This process is most typical for which of the
following diseases?
A. Viral hepatitis
CORRECT. Viral infection leads to
apoptosis with individual hepatocyte
necrosis, either from effects of viral
replication or from the body's cell
mediated immune response with
cytotoxic T lymphocytes.
B. Brown atrophy of the heart
Incorrect. Brown atrophy of the heart
results when there is marked lipofuscin
deposition in the myocardium.
C. Renal transplant rejection
Incorrect. Tissue destruction with
transplant rejection is more widespread.
D. Chronic alcoholic liver disease
Incorrect. Single cell necrosis is not
evident in chronic alcoholic liver disease.
E. Barbiturate overdose
Incorrect. Barbiturates produce
hypertrophy of smooth endoplasmic
reticulum, not individual cell necrosis.
'Barbs' have gone out of style as drugs of
abuse.
A 60-year-old woman has noted a dark red-black
appearance to her great toe and second and third toes
of her left foot for the past month. On physical
examination, the toes are cold and have no sensation
to touch. The dorsalis pedis and posterior tibial pulses
are not palpable on the left. A transmetatarsal
amputation is performed. These findings are most
typical for a patient with which of the following
conditions?
A. Diabetes mellitus
CORRECT. Gangrenous necrosis is
described. Occlusive peripheral

atherosclerotic vascular disease is
typical for diabetes mellitus. Many
arteries are involved, reducing collateral
flow. This is diabetic gangrene.
B. Gout
Incorrect. Gout can involve joints, and
there can be erosion of bone, but less
likely overlying ulceration. Gout does not
affect circulation.
C. Blunt force trauma
Incorrect. Such focal gangrenous
necrosis is not typical for trauma, unless
blood supply is disrupted, but then the
necrosis should proceed quickly.
D. AIDS
Incorrect. The complications of AIDS are
unlikely to lead to gangrenous necrosis.
E. Rheumatoid arthritis
Incorrect. Rheumatoid arthritis can cause
joint destruction, but not overlying skin
ulceration. An abnormal immune reaction,
such as a type III hypersensitivity
reaction with antigen-antibody complex
deposition, could produce focal vasculitis,
but would not typically result in infarction
of a large area or body part.
A study is performed involving the microscopic analysis
of tissues obtained from surgical procedures. Some of
these tissues have the microscopic appearance of an
increased cell size of multiple cells within the tissue,
due to an increase in the amount of cell cytoplasm, with
nuclei remaining uniform in size. Which of the following
conditions is most likely to have resulted in this finding?
A. Uterine myometrium in pregnancy
CORRECT. This cellular hypertrophy
with increase in cell size (not hyperplasia
with increase in cell number) accounts for
most of the marked increase in size of the
uterus during pregnancy. Following
pregnancy and reduction in hormonal
stimulation, the uterus returns back to its
normal size.
B. Female breast at puberty
Incorrect. This is a form of physiologic
hyperplasia with proliferation of ducts
and lobules leading to an increase in
breast size.
C. Liver following partial resection
Incorrect. This is a form of compensatory
hyperplasia.
D. Ovary following menopause
Incorrect. Following menopause, the
ovary undergoes atrophy and decreases
in size.
E. Cervix with chronic inflammation
Incorrect. The inflamed epithelium
undergoes metaplasia.
A 17-year-old adolescent receives whole body
radiation as part of a preparatory regimen for bone
marrow transplantation to treat acute lymphocytic
leukemia. Which of the following cells and tissues in the
body is most likely to remain unaltered by the effects of
this therapeutic radiation?
A. Primary follicles of the ovary
Incorrect. Germ cells are very
radiosensitive.
Cellular Injury | Pathology Reviewer (Utah) | 19 / 72
B. Small intestinal epithelium
Incorrect. The intestinal mucosa is
actively proliferating and sensitive to
radiation.
C. Erythropoietic cells of the bone marrow
Incorrect. RBC's are constantly being
replaced by precursors that are
proliferating, so they are radiosensitive.
D. Spermatogonia of testicular tubules
Incorrect. Germ cells are very
radiosensitive.
E. Neurons of the cerebral cortex
CORRECT. Neurons are terminally
differentiated cells that do not actively
divide or proliferate, so at therapeutic
doses of radiation, they are relatively
radioresistant. However, at higher
radiation doses, cerebral injury does
occur from damage mainly to white
matter and to the vasculature.
A 79-year-old man has a large myocardial infarction
involving much of the left ventricular free wall. He
develops congestive heart failure (CHF) with
decreased cardiac output. Now, a year later, his CHF
is worsening. By echocardiography there is a large,
bulging akinetic area typical for a left ventricular
aneurysm. Which of the following laboratory tests on
serum would best indicate poor peripheral tissue
perfusion in this patient?
A. Elevated troponin I
Incorrect. An elevated troponin suggests
acute to intermediate myocardial
ischemic injury, but he does not have
another myocardial infarction at this time.
B. Increased sodium
Incorrect. Sodium retention occurs with
CHF, but the serum sodium is not
significantly increased.
C. Elevated lactate
CORRECT. Under conditions of poor
tissue perfusion, there will be more
anaerobic glycolysis and more acidosis
in cells throughout the body. The blood
lactate rises in this condition.
D. Increased hematocrit
Incorrect. Hypoxia can lead to an
increased red blood cell mass over a long
period of time, but this is not a typical
adaptation to CHF.
E. Increased sedimentation rate
Incorrect. The sedimentation rate
increases with inflammatory conditions,
not with CHF.
A 22-year-old woman has a congenital anemia. She
has required multiple transfusions of red blood cells for
many years. She now has no significant findings on
physical examination. Which of the following
microscopic findings would most likely present in her
liver?
A. Steatosis in hepatocytes
Incorrect. This would more likely be a
feature seen with ingestion of great
amounts of alcohol.
B. Bilirubin in canaliculi
Incorrect. The accumulation of iron does
not lead to biliary obstruction or
dysfunction.

C. Hemosiderin in hepatocytes
CORRECT. There is 250 mg of iron in
each unit of blood. The body has no
mechanism for getting rid of excess iron.
A small amount of iron is lost with normal
desquamation of epithelia, and
menstruating women will lose a bit more.
The excess iron becomes storage iron, or
hemosiderin. Over time, hemosiderosis
involves more and more tissues of the
body, particularly the liver.
D. Glycogen in hepatocytes
Incorrect. Glycogen accumulation can be
seen in a variety of inherited glycogen
storage diseases in which the lack of an
enzyme leads to accumulation of a
storage product.
E. Amyloid in portal triads
Incorrect. Amyloid deposition occurs
when there is an excessive production of
a protein that is broken down by
proteases to an insoluble end product
known as amyloid that can collect in
various tissues.
A 20-year-old man is involved in a motor vehicle
accident which results in multiple blunt trauma and
lacerations to his lower extremities. The left femoral
artery is lacerated, and he incurs extensive blood loss
and remains hypotensive for hours during transport to
the emergency department. On admission, his
hematocrit is 12%. Which of the following tissues is
most likely to withstand the impact of these events with
the least damage?
A. Skeletal muscle
CORRECT. The skeletal muscle tissue is
the least metabolically active of the ones
listed; and is also able to function with
anaerobic glycolysis.
B. Intestinal epithelium
Incorrect. Shock can often lead to
ischemic enteritis.
C. Retina
Incorrect. The retinal neurons are very
sensitive to hypoxia.
D. Cerebral cortex
Incorrect. The large neurons of the
cerebral cortex are very active
metabolically.
E. Renal tubules
Incorrect. The cells of renal tubules are
very sensitive to hypoxia, and the
proximal tubules in particular.
A 40-year-old woman has the sudden onset of severe
abdominal pain. On physical examination she has
diffuse tenderness in all abdominal quadrants, with
marked guarding and muscular rigidity. She has
laboratory findings that include serum AST of 43 U/L,
ALT of 30 U/L, LDH 630 U/L, and lipase 415 U/L. An
abdominal CT scan reveals peritoneal fluid collections
and decreased attenuation along with enlargement of
the pancreas. Which of the following cellular changes
is most likely to accompany these findings?
A. Coagulative necrosis
Incorrect. Coagulative necrosis is a
characteristic feature of ischemic injury to
many organs such as heart, spleen, and
liver.
Cellular Injury | Pathology Reviewer (Utah) | 20 / 72
B. Dry gangrene
Incorrect. Gangrenous necrosis refers to
destruction of an organ or body part. Dry
gangrene typically describes a process
involving an extremity such as the foot.
C. Fat necrosis
CORRECT. The enzymes released from
the pancreas with acute pancreatitis
damage the surrounding fat and form
soaps -- localized soft tan to yellow areas
of fat necrosis. The damaged pancreatic
exocrine cells release lipase as a marker
for their injury.
D. Apoptosis
Incorrect. Apoptosis describes
destruction of single cells, not whole
tissues.
E. Liquefactive necrosis
Incorrect. Liquefactive necrosis is more
typical for damage to an organ such as
the brain with abundant lipid. Liquefactive
necrosis is seen in abscesses as well.
A 26-year-old man has had a high fever for the past 2
days. On exam he has a heart murmur.
Echocardiography shows destruction of the aortic
valve by large, irregular vegetations. Staphylococcus
aureus is cultured from his blood. He develops left
upper quadrant pain. Abdominal CT shows a wedge-
shaped 1.5 x 3 cm splenic lesion with base on the
capsule. The splenic lesion is most likely to result from
which of the following cellular abnormalities?
A. Coagulative necrosis
CORRECT. The description is that of a
typical infarct with vascular occlusion
following embolization from vegetations
of infective endocarditis.
B. Abscess formation
Incorrect. An abscess is a localized
collection of pus with a soft yellow
purulent center.
C. Metaplasia
Incorrect. Metaplasia, the replacement of
one cell type with another, typically
occurs on epithelial surfaces.
D. Caseous necrosis
Incorrect. Caseous necrosis is typically
cheesy white and localized to the center
of rounded granulomas.
E. Liquefactive necrosis
Incorrect. Liquefaction leads to soft areas
of tissue necrosis that resolve leaving a
space.
A 35-year-old woman has developed increasing icterus
over the last week. On exam her liver span is increased.
Laboratory studies show hyperammonemia.
Abdominal CT scan shows a liver twice normal size
with markedly reduced attenuation. These changes in
her liver most likely resulted from which of the following
conditions?
A. Galactosemia
Incorrect. Although fatty change in liver
can occur with galactosemia, fibrosis is a
prominent component, and such findings
are typical in infants.
B. Hemochromatosis
Incorrect. Hemochromatosis with
extensive iron deposition would give the

liver a dark brown to orange colour. The
attenuation would not be decreased with
CT imaging.
C. Tuberculosis
Incorrect. Tuberculosis leads to
granuloma formation. Granulomas tend
to be focal areas of inflammation.
D. Alcoholism
CORRECT. The marked fatty change
(steatosis) of the liver with hepatomegaly
is a typical sequel of chronic alcohol
abuse. With x-rays, fat density
approaches that of air density (dark).
Grossly, the liver would appear yellowish.
Microscopically, the hepatocyte
cytoplasm would contain a large lipid
droplet.
E. Hypoxemia
Incorrect. The liver is not a major target
of hypoxic injury because of its dual blood
supply. Hypoxia would lead to focal
necrosis with loss of parenchyma, not
enlargement.
A 71-year-old man has difficulty with urination. His
urinary retention leads to numerous trips to the
restroom per day. On digital rectal examination is
prostate is diffusely enlarged. Which of the following
represents a pathologic change leading to this man's
problem?
A. Dysplasia
Incorrect. Dysplasia is disordered growth
of an epithelium and is a step toward
neoplasia. Dysplasia typically does not
increase the size of a tissue.
B. Hypertrophy
Incorrect. Hypertrophy is what many
people call benign prostatic enlargement,
but it is the number of cells that increase
the most, not cell size, contributing to
enlargement.
C. Hyperplasia
CORRECT. Prostatic hyperplasia is an
example of pathologic hyperplasia in
which prostatic cells become more
sensitive to hormonal stimuli for growth.
Both glands and stroma can increase in
amount. Hyperplasia is an increase in the
number of cells.
D. Metaplasia
Incorrect. Metaplasia is trading one kind
of epithelial cell for another, but in
prostatic hyperplasia, the glands are still
lined by columnar epithelium
E. Neoplasia
Incorrect. Neoplasia is loss of cell growth
control. Pathologic hyperplasias are still
responding to stimuli and have not
reached the point of autonomous growth
A 55-year-old man has a 30-year history of poorly
controlled diabetes mellitus. He has had extensive
black discoloration of skin and soft tissue of his right
foot, with areas of yellowish exudate, for the past 2
months. Staphylococcus aureus is cultured from this
exudate. A below-the-knee amputation is performed.
The amputation specimen received in the surgical
Cellular Injury | Pathology Reviewer (Utah) | 21 / 72
pathology laboratory is most likely to demonstrate
which of the following pathologic abnormalities?
A. Neoplasia
Incorrect. A neoplasm is a mass lesion.
B. Gangrene
CORRECT. Gangrenous necrosis is a
typical complication of diabetes mellitus
with marked peripheral vascular disease
from atherosclerosis. Gangrene is a form
of coagulative necrosis that involves a
body part, including several tissues. The
infection adds an element of liquefactive
necrosis, best described as 'wet
gangrene.'
C. Vasculitis
Incorrect. Such a disorder, with either
thrombosis or hemorrhage, would be
more likely manifested throughout the
body. Coagulopathy is not a feature of
diabetes mellitus.
D. Hemosiderosis
Incorrect. Hemosiderin may form locally
from remote hemorrhage. With iron
overload, it collects in tissues of the
mononuclear phagocyte system.
E. Caseation
Incorrect. Caseation is a part of
granulomatous inflammation. Caseating
granulomas are soft, cheesy, and white.
The lifestyle patterns of healthy persons from 20 to 30
years of age are studied. A subset of these persons
have a lifestyle characterized by consumption of a lot
of pizza and very little physical exercise. Which of the
following tissue changes is most likely to develop in this
subset of persons as a consequence of this lifestyle?
A. Fatty metamorphosis of liver
Incorrect. Fatty change in the liver is due
to toxic and metabolic derangements,
such as those that occur with malnutrition
or alcoholism.
B. Pancreatic fat necrosis
Incorrect. Pancreatic fat necrosis may
occur from injury from inflammation or
trauma.
C. Fatty degeneration of myocardium
Incorrect. Fatty change in the heart is a
consequence of toxic or hypoxic events.
D. Hypertrophy of steatocytes
CORRECT. The fat cells (adipocytes)
increase in size (hypertrophy) with
obesity in adults, and this is the
predominant effect of weight gain.
E. Metaplasia of muscle to adipose tissue
Incorrect. Muscle does not typically
undergo metaplasia in response to
weight gain. Adipocytes in fascial planes
and around the muscle can increase in
size. The muscle may atrophy in
response to the sedentary lifestyle.

In an experiment, a tissue preparation is subjected to
oxidant stress. There are increased numbers of free
radicals generated within the cells. Generation of which
of the following enzymes within these cells is the most
likely protective mechanism to reduce the number of
free radicals?
A. Glutathione peroxidase
CORRECT. The glutathione peroxidase
system is designed to help break down
free radicals generated from various
forms of cell injury. This system works in
the background with small numbers of
free radicals. Disease processes
generating greater amounts of free
radicals and cell injury can overwhelm
this system.
B. Catalase
Incorrect. Catalases decompose
hydrogen peroxide, but they are not
specifically designed to scavenge free
radicals.
C. Hydrogen peroxide
Incorrect. Hydrogen peroxide is
generated by some cells, such as
neutrophils, in order to destroy
phagocytized microbes.
D. NADPH oxidase
Incorrect. NADPH oxidase helps to
generate free radicals within
phagolysosomes in cells such as
neutrophils.
E. Myeloperoxidase
Incorrect. Myeloperoxidase within
neutrophil granules helps in destruction
of phagocytized microbes.
A 38-year-old man incurs a traumatic blow to his upper
left arm. He continues to have pain and tenderness
even after 3 months have passed. A plain film
radiograph reveals a 4 cm circumscribed mass in the
soft tissue adjacent to the humerus. The mass contains
peripheral areas of brightness on the x-ray. Over the
next year this mass gradually resolves. Which of the
following terms best describes the changes described?
A. Dysplasia
Incorrect. Dysplasia refers to disordered
epithelial cell growth and does not apply
to soft tissues.
B. Hyperplasia
Incorrect. There are increased numbers
of cells in this exaggerated healing
process, but that does not account for the
bright calcification.
C. Hypertrophy
Incorrect. Though some cells may
increase in size, the process is one of
bone formation.
D. Metaplasia
CORRECT. The brightness on x-ray
suggests calcification from osseous
metaplasia of connective tissues that
developed in the healing process. This
condition is known as myositis ossificans,
because there is bone formation in the
injured muscle.
E. Neoplasia
Incorrect. This process is one of
metaplastic bone formation as part of an
Cellular Injury | Pathology Reviewer (Utah) | 22 / 72
exaggerated healing process, not the
uncontrolled growth of a neoplasm.
A 31-year-old primigravida has a difficult delivery of a
term infant, with loss of 1500 cc of blood. She has
hypotension for 6 hours. Over the next month, her
ACTH level decreases. Within the next 3 months, her
adrenal glands become decreased in size. This
alteration of the adrenals is primarily due to which of
the following cellular processes?
A. Metaplasia
Incorrect. Metaplasia at this site does not
occur.
B. Gene mutation
Incorrect. Gene transcription may be
downregulated, but the genes do not
change over such a short time frame. The
rate of mutation in normally dividing
somatic cells is very low.
C. Apoptosis
Incorrect. Diminished ACTH from the
pituitary does not typically trigger the loss
of adrenal cortical cells.
D. Autophagocytosis
CORRECT. The loss of ACTH leads to
cortical atrophy from cellular downsizing,
with the consequence of decreased
glucocorticoid and mineralocorticoid
production.
E. Coagulative necrosis
Incorrect. Loss of ACTH does not lead to
infarction of the adrenal. With three
arterial blood supplies, the adrenal is
very hard to infarct.
A 48-year-old man has a history of chronic alcohol
abuse. He is still able to perform work at his job. He has
had no major illnesses. On physical examination, there
are no significant findings. Laboratory studies show a
serum albumin of 4.1 g/dL, ALT 30 U/L, AST 33 U/L,
and total bilirubin 1.1 mg/dL. Which of the following
microscopic findings in his liver is most likely to be
present?
A. Cholestasis
Incorrect. Bile stasis may occur in the late
stages of cirrhosis; or may be a function
of biliary tract obstruction or liver cell
injury.
B. Fatty change
CORRECT. The toxic effects of the
alcohol culminate in large lipid droplet
accumulation within hepatocytes. Over
time, more hepatocytes are affected and
the liver is less able to compensate. At
this point, the man retains sufficient
hepatocyte function.
C. Hemochromatosis
Incorrect. Increased iron in the liver may
occur in association with alcoholism; but
is not nearly as common as fatty change.
D. Hypertrophy of smooth endoplasmic
reticulum
Incorrect. This is the result of chronic
barbiturate ingestion.
E. Coagulative necrosis
Incorrect. Liver infarction is rare because
of the dual blood supply of oxygen

through the hepatic artery and portal
venous system.
A 44-year-old woman has had episodes of right upper
quadrant pain during the past 2 weeks. Her stools have
become pale in colour over the past 3 days. Laboratory
studies show a serum total bilirubin of 9.7 mg/dL. A
cholangiogram shows that a gallstone has passed into
the common bile duct, resulting in obstruction of the
biliary tract. Which of the following tissue
accumulations is most likely to be visualized on her
skin surfaces?
A. Hemosiderosis
Incorrect. Excessive iron can be
accumulated through increased
absorbtion, increased intake, or
prolonged transfusion therapy.
B. Calcification
Incorrect. Dystrophic calcification can
occur in areas of tissue damage, as in
granulomatous diseases. The liver is not
a typical spot for metastatic calcification.
C. Lipofuscin deposition
Incorrect. Steatosis occurs with direct
injury to hepatocytes, not biliary tract
obstruction.
D. Icterus
CORRECT. She has a 'jaundiced'
appearance to her sclerae and skin due
to the increased amount of bilirubin. The
bile pigments impart a yellow colour to
the tissues. She has biliary tract
obstruction from cholelithiasis and
choledocholithiasis.
E. Steatosis
Incorrect. Fatty change is a process that
occurs in the liver, and biliary tract
obstruction does not typically cause it.
A 45-year-old man has a traumatic injury to his forearm
and incurs extensive blood loss. On physical
examination in the emergency department his blood
pressure is 70/30 mm Hg. Which of the following
cellular changes is most likely to represent irreversible
cellular injury as a result of this injury?
A. Epithelial dysplasia
Incorrect. Although dysplasia can be a
premalignant condition, it is still
reversible.
B. Cytoplasmic fatty metamorphosis
Incorrect. Fatty change is potentially a
reversible condition.
C. Nuclear pyknosis
CORRECT. The hypotension leads to
diminished tissue perfusion with ischemic
injury. Nuclear chromatin clumping is
reversible, but nuclear pyknosis is not.
D. Atrophy
Incorrect. 'Downsizing' of the cell in
atrophy is reversible.
E. Anaerobic glycolysis
Incorrect. A lack of sufficient oxygen may
lead to anaerobic metabolism, but this
can be temporary until the hypoxia is
relieved.
F. Autophagocytosis
Incorrect. The cell 'downsizes' with
autophagocytosis of cytoplasmic
Cellular Injury | Pathology Reviewer (Utah) | 23 / 72
organelles, via its own lysosomes, but
the cell does not die.
A 73-year-old man suffers a 'stroke.' On physical
examination he cannot move his right arm. A cerebral
angiogram demonstrates occlusion of the left middle
cerebral artery. An echocardiogram reveals a
thrombus within a dilated left atrium. Which of the
following is the most likely pathologic alteration from
this event that has occurred in his brain?
A. Cerebral softening from liquefactive
necrosis
CORRECT. Liquefactive necrosis typifies
brain infarction. The brain tissue contains
abundant lipid. After the initial softening,
tissue macrophages will increase in
number and clear the necrotic debris,
leaving a cystic space. Since neurons
cannot regenerate, the size of the infarct
determines the amount of functional loss.
The brain has some capacity for rewiring,
but this capacity diminishes with age.
B. Pale infarction with coagulative necrosis
Incorrect. Infarction of most organs is
accompanied by coagulative necrosis,
but not the brain.
C. Predominantly the loss of glial cells
Incorrect. Neurons are far more sensitive
to hypoxia than glial cells.
D. Recovery of damaged neurons if the
vascular supply is re-established
Incorrect. It is unlikely that the vascular
supply can be reestablished in a matter
of minutes.
E. Wet gangrene with secondary bacterial
infection
Incorrect. Gangrenous necrosis is more
typical of a body part, such as a toe or a
foot.
A 30-year-old woman is claiming in a civil lawsuit that
her husband has abused her for the past year. A
workup by her physician reveals a 2 cm left breast
mass. There is no lymphadenopathy. No skin lesions
are seen, other than a bruise to her upper arm. A
needle biopsy of the breast mass is performed. On
microscopic examination, the biopsy shows fat
necrosis. This biopsy result is most consistent with
which of the following etiologies?
A. Physiologic atrophy
Incorrect. At age 30 she is
premenopausal.
B. Breast trauma
CORRECT. Fat necrosis is seen with
trauma to the breast, and her lawyer will
make good use of that documentation.
The pattern of multiple injuries of differing
ages at different sites suggests abuse.
C. Lactation
Incorrect. Lactation leads to a physiologic
hyperplasia of the breast with increase in
lobules.
D. Radiation injury
Incorrect. A variety of vascular and
parenchymal changes can occur with
radiation injury.
E. Hypoxic injury
Incorrect. The breast is not a site for
hypoxic injury.

A 46-year-old man has smoked 2 packs of cigarettes
per day for the past 30 years. He has had a chronic
cough for the past 3 years, worsening over the last 2
weeks. A suspicious left pulmonary parenchymal
lesion is seen on a chest x-ray. He has a bronchoscopy
performed. A biopsy of a segmental bronchus shows
squamous metaplasia. Which of the following is the
most appropriate interpretation of this finding?
A. Ischemic tissue damage
Incorrect. Ischemia could lead to loss of
cells, but the lung is hard to damage from
ischemia because of its dual blood
supply.
B. Irritant effect
CORRECT. The irritant effect, such as
the various chemicals in cigarette smoke,
leads to replacement of the normal
epithelium with another (such as
squamous epithelium replacing
respiratory epithelium). This metaplastic
process is the first step that could lead to
dysplasia and then to neoplasia. Note
that histologists call any flattened
epithelium a 'squamous' epithelium, but
pathologists refer to specific cell types,
and consider a true squamous epithelium
to be a stratified squamous epithelium.
C. Early stage of cancer
Incorrect. Although there can be a natural
history of progression from metaplasia to
dysplasia to carcinoma, most
metaplasias do not become cancers, and
metaplasia by itself is not cancer.
D. Viral infection
Incorrect. Chronic viral infection is not
likely to lead to metaplasia.
E. Congenital anomaly
Incorrect. Metaplasias are typically not
congenital; but acquired. Hint: the
pediatric term 'dysplasia' refers to
disordered development of a tissue,
including cell types that ordinarily are not
present. In adults, dysplasia refers to an
abnormal change in an epithelium,
beyond physiologic alteration, that is
starting down the road to cancer.
A 44-year-old woman has had congestive heart failure
for the past 4 years. She develops a fever that persists
for over a week. On physical examination, a heart
murmur is present. Her temperature is 38.4°C.
Laboratory studies show a blood culture positive for
Streptococcus, viridans group. An echocardiogram
reveals a 1 cm vegetation on the superior aspect of her
mitral valve. Which of the following pathologic changes
is most likely present in her mitral valve?
A. Passive congestion
Incorrect. The heart failure would be
mainly left-sided, with pulmonary
congestion as a consequence.
B. Necrosis
CORRECT. Friable mitral valvular
vegetations from infective endocarditis
can damage the valve. The inflammation
is predominantly neutrophilic, and a
collection of neutrophils release a variety
of enzymes that cause tissue damage.
Cellular Injury | Pathology Reviewer (Utah) | 24 / 72
C. Extensive edema
Incorrect. Edema is not likely to occur at
this location. There can be pulmonary
congestion and edema from left-sided
heart failure.
D. Granulomatous inflammation
Incorrect. Granulomatous inflammation is
more typical for infection with
mycobacteria and fungi, not bacteria.
E. Dystrophic calcification
Incorrect. Dystrophic calcification may
occur in areas of chronic tissue injury, but
the time course here is short.
An 18-year old G2 P1 woman has an amniocentesis
performed at 17 weeks of gestation. Fibroblasts
recovered from amniocentesis are grown in culture to
assess the karyotype of fetal cells. These cells are
subcultured for additional experimental work, but the
culture is lost after 50 doublings of the cells has
occurred, and the fibroblasts no longer grow. Which of
the following factors affecting these cells is most likely
demonstrated by this phenomenon?
A. Nutrition
Incorrect. The state of nutrition can play
a role in survival; but does not put an
upper limit on doublings.
B. Mutation
Incorrect. Mutations occur over time, but
overall are uncommon and have more to
do with appearance of neoplasms.
C. Apoptosis
Incorrect. Apoptosis is programmed cell
death that is controlled by a variety of
factors which should not affect cells
growing in culture.
D. Aging
CORRECT. A number of factors play a
role in aging, but the lack of immortality
of individual cells is one feature. The lack
of telomerase activity in most somatic
cells prevents repeated division. Stem
cells have greater replicative capacity.
E. Oxidation
Incorrect. Cellular damage from
oxidation--such as free radical damage--
contributes to aging but does not limit the
number of generations.
A 54-year-old man has sudden onset of severe, sharp
chest pain with diaphoresis and dyspnea. On physical
examination he has tachycardia with an irregular heart
rhythm. Electrocardiographic changes suggest the
possibility of focal myocardial damage involving the left
lateral ventricular wall. Which of the following
laboratory tests on the patient's serum is most useful in
this situation?
A. Total cholesterol
Incorrect. An elevated total serum
cholesterol, particularly if it is over 200
mg/dL, will suggest an increased risk for
a myocardial infarction, but will not help
to diagnose an acute event.
B. Troponin I
CORRECT. The troponin I will be
elevated with myocardial ischemic injury
for up to 2 weeks. Myoglobin and creatine
kinase can become elevated within 3 to 4
hours following injury, similar to troponin

I, and they are sensitive, but not specific,
markers for myocardial injury, because
they could also be released from skeletal
muscle.
C. Triglyceride
Incorrect. Hypertriglyceridemia suggests
an increased risk for coronary
atherosclerosis and its complications, but
a triglyceride level will not predict an
acute event, nor change because of that
event.
D. Lipase
Incorrect. Lipase can be increased with
injury to the pancreas, not cardiac
muscle.
E. Sedimentation rate
Incorrect. The sed rate is a very non-
specific indicator for inflammation and
infection. It essentially measures 'acute
phase proteins' such as fibrinogen that
increase with acute tissue injuries.
A 42-year-old previously healthy woman notes that
over the past week her eyes have developed a
yellowish appearance. She has had mild nausea and
vomiting over the past week. On physical examination
she has scleral icterus. She has no other major
physical examination findings except for mild right
upper quadrant tenderness. Which of the following
underlying conditions is most likely to contribute to
development of her icterus?
A. Hypercholesterolemia
Incorrect. An increased serum
cholesterol leads to complications of
atherosclerosis, with the possibility of
infarctions in various organs, but not
disturbances of bilirubin metabolism.
B. Thrombocytopenia
Incorrect. A low platelet count will lead to
a coagulopathy marked by petechiae and
purpura, but the bilirubin is not recycled
fast enough to produce jaundice.
C. Metastatic carcinoma
Incorrect. Even metastases to the liver
are unlikely to produce obstructive
jaundice, because of the focal nature of
the masses.
D. Viral hepatitis
CORRECT. Hepatitis, most often an
infectious viral hepatitis, leads to liver cell
dysfunction with impaired uptake,
conjugation, and excretion of bilirubin. As
a result bilirubin is not cleared from the
blood and there is an increasing serum
bilirubin that produces the yellowish
appearance of jaundice (icterus).
E. Diabetes mellitus
Incorrect. Diabetes mellitus has a variety
of complications, mainly from
accelerated atherosclerosis, but liver
failure is not common. Liver has a dual
blood supply.
Cellular Injury | Pathology Reviewer (Utah) | 25 / 72
A 56-year-old woman has smoked 2 packs of
cigarettes per day for the past 35 years. She has had
a chronic cough for the past 8 years, but recently has
noted increased sputum production. On physical
examination she has a few crackles auscultated best
over the lung bases. Bronchoscopy with biopsy is
performed. The biopsy reveals bronchial epithelium
with squamous metaplasia. Which of the following
statements represents the best interpretation of these
findings?
A. Physiologic process of aging
Incorrect. Normal aging does not lead to
metaplastic changes in epithelium.
Epithelia may become thinner with aging.
B. Irreversible, even if she stops smoking
Incorrect. Epithelial metaplasia is a
reversible process; but may progress to
dysplasia.
C. Metastases to the lung
Incorrect. A metastasis would be
composed of malignant cells. Metaplasia
is one step on the way to malignancy, but
is, by itself, not malignant.
D. Risk for infection
CORRECT. The loss of normal
functioning respiratory epithelium with
loss of mucociliary protection means that
the normal innate barrier to infection has
been weakened.
E. Thromboembolism with infarction
Incorrect. Pulmonary infarctions are not
accompanied by squamous metaplasia.
At the end of a normal menstrual cycle, the
endometrium sloughs. Examination of the
endometrium microscopically shows cellular
fragmentation. Which of the following is most likely to
trigger apoptosis in these endometrial cells?
A. Acute inflammation
Incorrect. Though inflammatory cells may
respond to the degenerating
endometrium, this is not the triggering
event. Acute endometritis is a pathologic
process, not a physiologic process.
B. Hypoxia
Incorrect. Hypoxia is not the triggering
event, as the uterine arteries and
branches remain intact and functional.
C. p53 protein accumulation
Incorrect. p53 protein accumulates with
DNA damage, as can occur with
chemotherapy or radiation.
D. Decreased estrogen
CORRECT. This is one form of the
intrinsic pathway for induced apoptosis.
Falling hormone levels late in the
endometrial hormonal cycle induce
menstruation.
E. Anaerobic glycolysis
Incorrect. The type of metabolism of the
endometrium does not change with the
hormonal cycle.
An experiment is conducted to determine if cell
membrane injury is lessened by the effects of vitamin
E ingestion. Which of the following cellular components
is primarily involved in generation of lipid peroxides, the
formation of which is inhibited by the vitamin E?

A. Glutathione
Incorrect. Glutathione is part of the
protective antioxidant mechanism.
B. Ionized calcium
Incorrect. Ionized calcium does not
directly participate in lipid damage.
Calcium influx into mitochondria is an
irreversible cellular injury.
C. Lactate
Incorrect. Under conditions of hypoxia,
cellular respiration becomes anaerobic,
with lactic acid production.
D. Ferric ion
CORRECT. Ferric ion is needed for
reduced oxygen species to injure cells.
Hydroxyl radicals initiate lipid
peroxidation.
E. Lipase
Incorrect. Lipase is a digestive enzyme
that is formed in the pancreatic acinar
parenchyma and excreted into the
pancreatic duct system and conveyed to
the small intestine.
A 35-year-old woman has had headaches and
abdominal pain worsening for 3 months. There are no
remarkable physical examination findings. On
radionucleide scanning of the neck, she is found to
have a mass involving one of her parathyroid glands.
An abdominal CT scan suggests extensive
nephrocalcinosis along with urinary tract calculi. Which
of the following laboratory test findings is most likely to
accompany her disease?
A. CO2 of 30 mmol/L
Incorrect. The CO2 is increased with
respiratory acidosis, but this does not
lead to precipitation of calcium.
B. Phosphorus of 2.2 mg/dL
CORRECT. Metastatic calcification
occurs as a result of a high serum
calcium, which in the case of
hyperparathyroidism is accompanied by
a low serum phosphorus. The high
calcium often induces a fatal cardiac
arrhythmia before metastatic calcification
can occur.
C. Uric acid of 15.1 mg/dL
Incorrect. Uric acid may contribute to
formation of uric acid calculi; but does not
play a role in hyperparathyroidism and
hypercalcemia.
D. Sodium of 121 mmol/L
Incorrect. Hyponatremia could result
from excessive antidiuretic hormone; but
is not part of hyperparathyroidism.
E. Calcium of 4.5 mg/dL
Incorrect. A low serum calcium may
occur when the serum phosphorus rises
with renal failure, not with
hyperparathyroidism.
A 21-year-old woman has a routine Pap smear
performed for a health screening examination. The
pathology report indicates that some cells are found
cytologically to have larger, more irregular nuclei. A
follow-up cervical biopsy microscopically demonstrates
disordered maturation of the squamous epithelium,
with hyperchromatic and pleomorphic nuclei extending
nearly the full thickness of the epithelial surface. No
Cellular Injury | Pathology Reviewer (Utah) | 26 / 72
inflammatory cells are present. Which of the following
descriptive terms is best applied to these Pap smear
and biopsy findings?
A. Dysplasia
CORRECT. Disordered growth of an
epithelium is seen in dysplasia, which
can be a precursor to neoplasia. When
the term 'dysplasia' is used in pediatric
conditions, it refers to disordered
development of a tissue, including cell
types that ordinarily are not present. In
adults, dysplasia refers to an abnormal
change in an epithelium, beyond
physiologic alteration, that is starting
down the road to cancer.
B. Metaplasia
Incorrect. Metaplasia refers to exchange
of one type of epithelium to another not
typically found there. The endocervix,
which normally has columnar epithelium,
may undergo squamous metaplasia with
persistent cervicitis.
C. Anaplasia
Incorrect. Anaplasia refers to such an
irregular appearance of cells in a
neoplasm that it cannot be determined
what kind of cell is present.
D. Hyperplasia
Incorrect. Hyperplasia refers to an
increased number of cells.
E. Aplasia
Incorrect. Aplasia refers to absence of
growth--lack of development, which is
typically a congenital problem.
A 38-year-old man has a health screening examination.
He has a routine chest x-ray that shows a 2 cm nodule
in the right lower lobe. The nodule has focal
calcifications. A wedge resection of the nodule is done.
On microscopic examination the nodule shows
caseous necrosis and calcification. Which of the
following processes explains the appearance of the
calcium deposition:
A. Dystrophic calcification
CORRECT. Calcium is deposited in and
around the granuloma as a reaction to
injury with necrosis. Most pulmonary
granulomas are the result of infection,
typically tuberculosis.
B. Apoptosis
Incorrect. Apoptosis refers to single cell
necrosis, not a process that occur with
the focal tissue destruction seen in a
granuloma.
C. Hypercalcemia
Incorrect. High calcium levels, such as
can occur with hyperparathyroidism, may
lead to calcium deposition, even in
normal tissues, and this is called
metastatic calcification.
D. Metastatic calcification
Incorrect. Metastatic calcification can be
seen with hyperparathyroidism and a
high serum calcium. The calcification
occurs in normal tissues.
E. Excessive ingestion of calcium
Incorrect. Calcium homeostasis is
normally regulated by vitamin D and
parathormone and has little to do with the

amount of ingested calcium, unless a
very large amount is ingested, which
happens rarely. Excess calcium is
typically not absorbed or is excreted.
A 3-year-old child has been diagnosed with ornithine
transcarbamylase deficiency and has developed
hepatic failure. The left lobe of an adult donor liver is
used as an orthotopic transplant. A year later, the size
of each liver in donor and recipient is greater than at
the time of transplantation. Which of the following
cellular alterations is most likely to explain this
phenomenon?
A. Metaplasia
Incorrect. Metaplasia refers to the
exchange of one epithelial cell type for
another.
B. Dysplasia
Incorrect. Dysplasia in cellular terms
refers to disordered cell growth in an
epithelium.
C. Hyperplasia
CORRECT. After removal of part of the
liver, remaining liver can undergo
hyperplasia to compensate. Hepatocytes
are stable cells that are able to re-enter
the cell cycle.
D. Anaplasia
Incorrect. Anaplasia refers to cells of a
neoplasm that are so poorly
differentiated that it is impossible to tell
from what cell type they arose.
E. Neoplasia
Incorrect. Neoplasia refers to the process
of new, uncontrolled growth that forms a
tumor mass growing without physiologic
control.
A morbidly obese 51-year-old woman dies from
complications of heart disease. At autopsy, her heart
weighs 600 gm (normal up to 300 gm) with all the
chambers enlarged. Microscopically, there is increased
fibrous connective tissue seen in the interstitium
between myocardial fibers. The fibers are increased in
size. Beneath the epicardium can be seen adipocytes
interdigitating with the myocardial fibers. Which of the
following terms best describes the presence of the
adipocytes in her myocardium?
A. Steatosis
Incorrect. Steatosis refers to the
intracellular accumulation of lipid, either
as small (micro) or large (macro) droplets
(vesicles). This process occurs in
hepatocytes.
B. Lipid degeneration
Incorrect. Fatty, or lipid, degeneration is
a rare phenomenon in which small lipid
droplets may accumulate within
myocardial fibers under conditions of
severe hypoxia.
C. Fatty infiltration
CORRECT. The adipocytes are normal
fat cells. Obese persons just have more
of them, and the individual cells are larger,
making them more obvious and
prominent on examination. Their
presence in the superficial myocardium is
Cellular Injury | Pathology Reviewer (Utah) | 27 / 72
more a marker of obesity than a risk for
myocardial failure.
D. Cholesterolosis
Incorrect. Cholesterolosis refers to lipid
accumulation (including cholesterol
esters) in macrophages in an epithelium.
The term is generally applied to the
gallbladder.
E. Xanthomatosis
Incorrect. Xanthomas are accumulations
of macrophages filled with lipid that form
a mass effect.
A cellular mutation results in transcription with
translation of a protein that does not fold properly. The
misfolded protein remains within the cell and is not
excreted. Activation of which of the following
cytoplasmic enzymes is most likely to occur?
A. Caspase
CORRECT. Misfolded proteins can
trigger apoptosis with release of
caspases that lead to nuclear and
cytoplasmic fragmentation. Huntington
disease is one example of a genetic
disease with neuronal cell loss from
protein misfolding.
B. Glutathione peroxidase
Incorrect. Glutathione protects cells
against free radicals.
C. NADPH oxidase
Incorrect. NADPH oxidase mutations
underlie chronic granulomatous disease,
where phagocytic cell function is
diminished.
D. Ribonuclease
Incorrect. Ribonucleases degrade RNA,
and this is not the triggering event with
protein misfolding.
E. Telomerase
Incorrect. Telomerase is present in stem
cells and preserves the telomeres at the
end of DNA strands, providing for
ongoing cell division.
A 53-year-old man suffers a cardiac arrest and his wife
calls emergency services. The paramedics arrive a few
minutes later and begin life support measures. A
regular heart rate is established after 40 minutes of
resuscitative efforts as he is being transported to the
hospital. A thrombolytic agent (tPA) is administered.
Which of the following cellular processes is most likely
to occur in his myocardium following administration of
the tPA?
A. Apoptosis
Incorrect. Apoptosis is single cell
necrosis that is not the major mechanism
of cell death from ischemic injury.
B. Free radical injury
CORRECT. The ischemia during the
cardiac arrest followed by reperfusion
established following successful
resuscitation will generate activated
oxygen species to produce free radical
injury. This is the so-called 'reperfusion
injury'.

C. Heterophagocytosis
Incorrect. Heterophagocytosis by
macrophages is a way of clearing debris
from dead cells following infarction.
D. Squamous metaplasia
Incorrect. There is no epithelium in the
myocardium to undergo metaplasia, and
such metaplasia is not a consequence of
ischemic injury.
E. Accumulation of cytokeratins
Incorrect. Such cytokeratin accumulation
is a long-term process, as is seen with
neurofibrillary tangles in Alzheimer's
disease. This is not part of an ischemic
injury.
A 38-year-old woman has severe abdominal pain with
hypotension and shock that has developed over the
past 36 hours. On physical examination, her abdominal
muscles are rigid and her abdomen is extremely tender.
An abdominal CT scan reveals fluid density in the
region of the pancreas, which appears to be enlarged.
Which of the following laboratory test findings in her
serum is most likely to be present?
A. Alanine aminotransferase of 1123 U/L
Incorrect. An increased ALT suggests
hepatocyte injury.
B. Total cholesterol of 324 mg/dL
Incorrect. Hypercholesterolemia is not
associated with pancreatitis; but marked
hypertriglyceridemia (>1g/dL) can be
associated with pancreatitis.
C. Creatine kinase of 869 U/L
Incorrect. An elevated CK suggests injury
to striated muscle.
D. Urea nitrogen of 110 mg/dL
Incorrect. An elevated urea nitrogen
suggests renal failure.
E. Lipase of 1134 U/L
CORRECT. There is evidence for acute
pancreatitis with edema and necrosis.
The necrosis is typically fat necrosis with
grossly visible focal chalky-white
deposits representing areas of
saponification as a consequence of
release of pancreatic enzymes (lipase)
with acute inflammation.
A 45-year-old man has noted scleral icterus for the past
4 days. He has been feeling tired and 'run down' for
about a month. On physical examination, other than
mild tachycardia, his vital signs are normal. No other
physical examination findings are of noted other than
scleral icterus. Laboratory studies show a hematocrit of
25%. Which of the following conditions is most likely to
account for these findings?
A. Systemic hypertension
Incorrect. Hypertension leads to vascular
changes in arteries, but not to hemolysis
with icterus.
B. Excessive iron absorption
Incorrect. With hemolysis, the iron is
recycled and neither lost nor gained.
C. Diabetes mellitus, type I
Incorrect. Diabetes mellitus is not
associated with red blood cell destruction.
D. Intravascular hemolysis
CORRECT. The increased turnover of
red blood cells leads to increased
Cellular Injury | Pathology Reviewer (Utah) | 28 / 72
bilirubin production to cause the icterus,
as the amount of bilirubin generated
exceeds the capacity of the liver to
conjugate and excrete it into the bile. This
also explains his anemia.
E. Pulmonary squamous cell carcinoma
Incorrect. Neoplasms such as
carcinomas are unlikely to lead to
hemolysis, though some (leukemias,
lymphomas) are associated with
autoimmune phenomena that include
antibodies directed at red blood cells.
A 49-year-old man with a history of alcohol abuse has
increasing abdominal girth. On examination his liver
edge is firm. A liver biopsy shows cirrhosis, and
individual hepatocytes contain red, globular inclusions
positive for cytokeratin with immunohistochemical
staining. Which of the following structural elements are
these intracellular globules most likely to contain?
A. Actin and myosin
Incorrect. Thin actin filaments and thick
myosin filaments are components of
muscle tissue.
B. Cholesterol esters
Incorrect. Cholesterol esterified to long
chain fatty acids can be a transport form
of cholesterol utilized in building cell
membranes. Cholesterol may also collect
to form deposits that are a component of
atheromas.
C. Fatty acids
Incorrect. Fatty acids can be taken up by
a variety of cells for lipid biosynthetic
pathways; they may be used in energy
pathways. They may be taken up by fat
cells for lipid storage.
D. Fibronectin
Incorrect. Fibronectin is a component of
the extracellular matrix.
E. Intermediate filaments
CORRECT. Intermediate filaments may
collect in the damaged hepatocytes as
the globular hyaline known as Mallory
hyaline. It is characteristic for alcoholic
liver disease, but not pathognomic for it.
F. Microtubules
Incorrect. Microtubules are a structural
component of cells.
A 31-year-old woman has been previously diagnosed
with systemic lupus erythematosus. She has had chest
pain for the past 6 months. A chest radiograph shows
bilateral pleural effusions. Thoracentesis on the right
yields 400 mL of clear yellow serous fluid, and a cell
count shows only a few cells present. What type of cell
is most likely to be most numerous in this fluid?
A. Basophil
Incorrect. Basophils are few in number in
the blood and are not often seen in
effusions
B. Ciliated columnar cell
Incorrect. Ciliated columnar cells form
the lining of the bronchial tree are would
be sloughed off into the sputum, not into
the pleural cavity.
 Cellular Injury | Pathology Reviewer (Utah) | 29 / 72
C. Eosinophil
Incorrect. Eosinophils may participate in
inflammatory reactions that are most
often allergic or parasitic.
D. Fibroblast
Incorrect. Fibroblasts are part of an
inflammatory process with healing and
collagen deposition, typical of a resolving
inflammatory process leading to pleural
adhesions.
E. Langhans giant cell
Incorrect. Langhans giant cells are
aggregated activated macrophages in a
granulomatous response. If the pleura
were involved, the cell count would be
higher.
F. Lymphocyte
CORRECT. Small numbers of
lymphocytes may be present with this
serous effusion, typical for autoimmune
diseases that include serositis.
G. Neutrophil
Incorrect. Neutrophils are characteristic
for exudates containing many cells and
protein, not transudates with few cells
and protein. Neutrophils are more
characteristic of acute inflammatory
processes, such as bacterial infections.

A 65-year-old woman has the sudden inability to move

her right arm and to speak. MR angiography shows
occlusion of a cerebral artery. She is given tissue
plasminogen activator (tPA). Over the next week she
regains some ability to move her arm and to speak.
Which of the following cellular changes most likely
subsided upon tPA therapy?
A. Cell fragmentation
Incorrect. Fragmentation of the cell is a
sign of irreversible injury. It is most
characteristic of apoptosis.
B. Cell swelling
CORRECT. Cell swelling is reversible.
The tPA provided reperfusion so that
areas of brain that were ischemic but not
infarcted could recover. However, waiting
too long to restore circulation could
increase free radical formation and
reperfusion injury.
C. Cytoplasmic eosinophilia
Incorrect. Cytoplasmic eosinophilia is a
feature of irreversible cell damage
because cell organelles have been
significantly altered.
D. Membrane disruption
Incorrect. Cell membrane or organelle
membrane disruption leads to
irreversible cell injury.
E. Nuclear karyorrhexis
Incorrect. Nuclear karyorrhexis is
fragmentation of the nucleus and
represents irreversible injury.
F. Nuclear pyknosis
Incorrect. Nuclear pyknosis is nuclear
shrinkage to the point of irreversible
injury.
 IMMUNOPATHOLOGY SECTION
A 15-year-old healthy girl with no major medical
problems notes blotchy areas of erythema that are
pruritic over the skin of her arms, legs, and trunk within
an hour every time she eats seafood, followed by
diarrhea. These problems abate within 3 hours, and
then physical examination reveals no abnormal
findings. Which of the following immunologic
abnormalities is she most likely to have?
A. Localized anaphylaxis
CORRECT. Food allergies are typically a
form of type I hypersensitivity reaction.
The allergens react with IgE bound to
mast cells, mainly in skin and
gastrointestinal tract. More severe
allergic reactions may be systemic and
life-threatening from airway obstruction
and circulatory collapse.
B. Cell-mediated hypersensitivity
Incorrect. Cell-mediated immune activity
is a feature of Type IV hypersensitivity.
C. Complement activation
Incorrect. Release of complement C3b is
a feature of Type III hypersensitivity.
Lack of C1 inhibitor is a rare cause for
edema, but it is not allergic.
D. Hypergammaglobulinemia
Incorrect. Plasma cells are not involved
in this clinical setting. Increases in
immunoglobulin occur over days to
weeks.
E. Immune complex deposition
Incorrect. Localized immune complexes
occur in an Arthus reaction with Type III
hypersensitivity. Systemic immune
complex deposition can occur in
diseases such as SLE.
A 55-year-old man has developed progressive renal
failure for the past 5 years. Microscopic examination of
a renal biopsy shows extensive glomerular and
vascular deposition of pink amorphous material on
H&E staining. This material demonstrates apple-green
birefringence under polarized light after Congo red
staining. Immunohistochemical staining of these
deposits is positive for lambda light chains. Which of
the following conditions is most likely to be present in
this man?
A. Rheumatoid arthritis
Incorrect. Rheumatoid arthritis is a
chronic inflammatory disease that may
lead to deposition of AA amyloid.
B. Tuberculosis
Incorrect. Tuberculosis is a chronic
infectious disease that may lead to
deposition of AA amyloid.
C. Systemic lupus erythematosus
Incorrect. SLE is a chronic inflammatory
disease that may lead to deposition of AA
amyloid.
D. Multiple myeloma
CORRECT. The light chains are
elaborated by plasma cells. Light chains
from a plasma cell abnormality contribute
to the formation of the amyloid. Not all
patients with AL amyloid, however, have
multiple myeloma, and conversely just a
subset of myeloma patients develop
amyloidosis.
E. Alzheimer’s disease
Incorrect. There is an amyloid angiopathy
with Alzheimer disease, but it is found in
cortical arteries the brain, and is not
limited to light chains.
A 22-year-old woman has experienced episodes of
myalgias, chest pain, and arthralgias for the past 3
years. On examination a friction rub is audible on chest
auscultation and there is dullness to percussion at
posterior lung bases. No joint deformity is noted. She
has continued working at her job. She has a mild
normocytic anemia. A chest x-ray shows bilateral
pleural effusions. Which of the following laboratory
screening tests is most appropriate to begin the workup
for her condition?
A. CD4 lymphocyte count
Incorrect. A decreased CD4 lymphocyte
count is more typical of AIDS (an immune
deficiency) than of an immunologically
mediated disease process such as SLE.
B. Blood culture
Incorrect. The findings given are non-
specific and do not point to a septicemia.
C. Antinuclear antibody test
CORRECT. These non-specific findings
put together suggest possible
autoimmune disease. An ANA is a good
way to begin the workup, then more
specific tests can be ordered. Antigen-
antibody complexes of many
autoimmune diseases can precipitate in
a variety of locations, typically trapped in
basement membranes in sites such as
skin, synovium, pleura, pericardium, and
glomeruli. The complexes elicit an
inflammatory reaction with
exudates/transudates.
D. Sedimentation rate
Incorrect. The sedimentation rate is a
very non-specific test that is elevated in
many inflammatory conditions. The
history here points more to an
immunologic disease.
E. Creatine phosphokinase
Incorrect. CPK is more useful for
diagnosis of an acute disease --
myocardial infarction. CPK can be
increased with myositis, but with the
multiple manifestations in this woman, it
is not the best screening test.
A male infant is born at term. No congenital anomalies
are noted on examination. A year later he now has
failure to thrive and has been getting one bacterial
pneumonia after another with both Hemophilus
influenzae and Streptococcus pneumoniae cultured
from his sputum. Which of the following diseases is he
most likely to have?
A. DiGeorge syndrome
Incorrect. DiGeorge syndrome from 22q-
is predominantly manifested by loss of T-
Page 30 of 72

cell function, leading to viral, fungal, and
protozoal infections. This is most
pronounced with complete DiGeorge
syndrome, with lesser severity in partial
DiGeorge syndrome. There are often
congenital anomalies.
B. Selective IgA deficiency
Incorrect. A selective IgA deficiency is
seen in about 1 in 600 persons and leads
to mild diarrhea and/or occasional
respiratory tract infections; but is not life-
threatening.
C. Epstein-Barr virus (EBV) infection
Incorrect. EBV infection does not lead to
immunodeficiency states.
D. Acute leukemia
Incorrect. Acute leukemias can result in
immune deficiency, but not so selective
and not typically in infancy.
E. X-linked agammaglobulinemia
CORRECT. Recurrent bacterial
infections suggest a lack of B-cell
immune function with lack of gamma
globulin production. Once protective
maternal antibodies are gone, the
disease is manifested more severely.
A study is performed of outcomes involving patients
who received renal allografts. It is noted that patients
receiving allografts with matching to the donor by tissue
typing for HLA-DR (Class II) antigens have a low rate
of complications. Which of the following immunologic
abnormalities is most likely to be diminished by tissue
typing?
A. Amyloidosis
Incorrect. Amyloidosis is a complication
from chronic inflammation over many
years or from multiple myeloma.
B. Cell lysis by CD8 lymphocytes
Incorrect. Cytotoxic CD8 cell activation is
primarily a function of class I antigen
recognition.
C. Graft versus host disease
Incorrect. GVHD is not a consequence of
renal transplantation, and few if any
donor lymphocytes are present in the
allograft.
D. CD4 lymphocyte activation
CORRECT. Class II HLA antigens are
involved in the process of CD4
lymphocyte activation.
E. Serum sickness
Incorrect. Serum sickness results from
antigen-antibody complexes.
A 5-year-old boy and his 4-year-old brother have had
recurrent pneumonia, meningoencephalitis, sinusitis,
otitis, and diarrhea since infancy. Bacterial and viral
agents have been implicated, as well as Pneumocystis,
Giardia, and Cryptosporidium. Laboratory studies
show serum IgG 47 mg/dL, IgA 5 mg/dL, and IgM 671
mg/dL. Normal numbers of B and T cells are present.
These children are most likely to have a mutation
involving a gene encoding for which of the following?
A. NADPH oxidase
Incorrect. Abnormalities of NADPH
oxidase are found with chronic
granulomatous disease.
B. Wiskott-Aldrich syndrome protein
Immunopathology | Pathology Reviewer (Utah) | 31 / 72
Incorrect. Wiskott-Aldrich syndrome has
atopy with eczema, thrombocytopenia,
and immune defects in both cell
mediated and humoral arms. The protein
is involved with bridging cell surface
receptors to actin filaments.
C. Cytokine receptor common gamma chain
Incorrect. The most common form of
severe combined immunodeficiency
(SCID) seen in boys is the X-linked defect
in the common gamma chain of the
cytokine receptor involved in signlaing for
many of the interleukins.
D. CD40L
CORRECT. He has hyper-IgM syndrome,
an X-linked disorder. The CD40-CD40L
interaction is involved with isotype
switching from IgM production, thus
accounting for his lack of IgG and IgA.
This accounts for bacterial infections.
However, some degree of cell mediate
immune defect is present as well.
E. Complement C1 inhibitor
Incorrect. Lack of C1inh leads to
hereditary angioedema.
A 20-year-old woman has had symmetrical, proximal
muscle weakness for 6 months. On exam she has 4/5
motor strength in all extremities. A deltoid biopsy
shows a neutrophilic infiltrate with focal necrosis of the
muscle fibers. Her antinuclear antibody test is negative,
but she has histidyl-tRNA synthetase (Jo-1) antibody in
her serum. Which of the following additional findings
would be most likely be present in this patient?
A. Heart failure
Incorrect. The cardiac muscle is usually
not involved with polymyositis.
B. Malabsorption
Incorrect. Myositis is not typical for
scleroderma.
C. Peripheral neuropathy
Incorrect. Polymyositis is not
accompanied by neuropathy. A
neuropathy by itself would not account
for inflammation in muscle.
D. Skin rash
CORRECT. Polymyositis-
dermatomyositis is present. The
violaceous skin rash is often quite subtle
and limited to the face.
E. Renal failure
Incorrect. Renal failure is more typical of
systemic lupus erythematosus.
A hypersensitivity response of the immune system is
noted to be stimulated by release of IL-4 and IL-5. This
is accompanied by eosinophilia. This response is most
likely be directed against which of the following?
A. Amyloid protein
Incorrect. Amyloid deposition does not
result in an immune response.
B. Spirochetes
Incorrect. Both cell-mediated and
humoral immune mechanisms play a role
in syphilis, but not specifically a type I
hypersensitivity reaction.

C. Neoplasms
Incorrect. Natural immune mechanisms
directed against neoplasia are not
generally effective.
D. Inhaled dusts
Incorrect. Some organic dusts can lead
to a localized type III reaction.
E. Liver flukes
CORRECT. Parasitic infestations with
organisms that invade tissues can be
accompanied by a type I hypersensitivity
reaction.
A 54-year-old woman has noted that during the past
month her fingers become pale and painful upon
exposure to cold. On exam she has mild dyspnea, but
no wheezing. Her blood pressure is 170/110 mm Hg.
Her antinuclear antibody test is positive with a titer of
1:256 and a nucleolar pattern. Her serum urea nitrogen
is 15 mg/dL with creatinine of 1.1 mg/dL. Which of the
following autoimmune diseases is she most likely to
have?
A. Discoid lupus erythematosus
Incorrect. DLE is characterized mainly by
skin findings.
B. Systemic sclerosis
CORRECT. The nucleolar pattern
suggests scleroderma (systemic
sclerosis) more than the other
autoimmune diseases, and likely diffuse
scleroderma. Complications of
scleroderma include hypertension,
though signs of renal failure may not
occur unless the complication of a
hypertensive emergency supervenes.
She also has features of Raynaud
phenomenon and pulmonary fibrosis.
C. Polymyositis-dermyatomyositis
Incorrect. The major autoantibody
associated with PM is Jo-1. Renal
disease is not a feature of this complex.
D. Sjorgen’s syndrome
Incorrect. SS primarily affects salivary
and lacrimal glands.
E. Rheumatoid arthritis
Incorrect. RA mainly affects small joints
and is associated with an increased
rheumatoid factor (RF). Renal disease is
not a major feature of RA.
Twelve hours after going on a hike through dense
foliage, a 40-year-old man notices a slightly raised and
tender irregular reddish rash on one forearm that was
not covered by clothing. This rash gradually increases
in intensity for 2 days and then fades away after two
weeks. Which of the following forms of immunologic
hypersensitivity is most likely demonstrated in this
patient?
A. Type I hypersensitivity
Incorrect. Type I hypersensitivity
reactions typically occur immediately
upon contact with the antigen.
B. Type II hypersensitivity
Incorrect. A rash is not typical for type II
reactions.
C. Type III hypersensitivity
Incorrect. These findings are not typical
for antigen-antibody complex disease.
Immunopathology | Pathology Reviewer (Utah) | 32 / 72
D. Type IV hypersensitivity
CORRECT. This is a contact dermatitis,
typical of exposure to a plant such as
poison ivy.
A 30-year-old woman has experienced myalgias for the
past 3 months. On physical examination she has 5/5
motor strength in all extremities. She has dullness to
percussion at lung bases. A chest x-ray shows bilateral
pleural effusions. Laboratory studies show a positive
antinuclear antibody test at a titer of 1:1024. Her serum
urea nitrogen is 30 mg/dL. A renal biopsy is performed
and microscopic examination shows a granular pattern
of immunofluorescence staining with antibody to
complement component C1q. This pattern is most
typically produced as a consequence of which of the
following immunologic mechanisms?
A. IgE coating mast cells
Incorrect. This is typical for type I
hypersensitivity reactions, such as
allergic reactions.
B. Antiglomerular basement membrane
antibody
Incorrect. Anti-GBM is a feature of
Goodpasture syndrome, which produces
a linear pattern of immunofluorescence.
C. Antigen-antibody complexes
CORRECT. A granular pattern of
glomerular immunofluorescence staining
is typical of immune complex deposition
that occurs with a type III hypersensitivity
reaction. This patient's findings suggest
SLE.
D. Macrophage release of lymphokines
Incorrect. These findings do not suggest
cell mediated immunity with a type IV
hypersensitivity reaction
E. Release of prostaglandins
Incorrect. Prostaglandin release occurs
with acute inflammation and leads to
increased vasodilation.
The second pregnancy for a 23-year-old woman
appears uncomplicated until ultrasound performed at
19 weeks shows hydrops fetalis. The fetal organ
development is consistent for 19 weeks, and no
congenital anomalies are noted. Her first pregnancy
was uncomplicated and resulted in the birth of a normal
girl at term. The current pregnancy ends with birth of a
baby boy at 32 weeks gestation. On examination the
baby has marked icterus. Laboratory studies show a
hemoglobin of 7.5 g/dL, and neonatal exchange
transfusion is performed. Which of the following
immunologic mechanisms best explains this infant's
findings?
A. Anti-receptor antibody
Incorrect. In this form of type II
hypersensitivity, an antibody is directed
against a cellular receptor, such as
against acetylcholine receptor in
myasthenia gravis.
B. Loss of self-tolerance
Incorrect. Loss of self-tolerance is found
in many autoimmune diseases.
C. Immune complex formation
Incorrect. Immune complexes are found
in many autoimmune diseases and can
produce inflammation, but not anemia.

D. Delayed type hypersensitivity
Incorrect. Type IV hypersensitivity is a
feature of inflammation with granuloma
formation or transplant rejection.
E. Complement mediated cell destruction
CORRECT. This is immune hydrops,
probably from Rh incompatibility,
resulting in maternal antibody crossing
the placenta and destroying baby's RBCs
through complement mediated lysis, a
form of type II hypersensitivity reaction.
A previously healthy 12-year-old girl develops a sore
throat over the past 2 days. On physical examination
she has marked pharyngeal erythema with overlying
yellowish exudate. A throat culture grows group A beta-
hemolytic Streptococcus. Her pharyngitis resolves, but
3 weeks later she develops chest pain along with fever
and malaise. The girl describes aching of her knees,
hips, shoulders, and elbows. Multiple subcutaneous
skin nodules are noted on physical examination, and
she exhibits slight shaking movements of her head and
neck. Her antistreptolysin-O and anti-DNAse B titers
are elevated. Her creatine kinase MB fraction is
elevated. Her findings are most likely the result of
which of the following immunologic mechanisms?
A. Bypass of low-zone tolerance through
cross-reactivity
CORRECT. Acute rheumatic fever
follows a group A beta hemolytic
streptococcal infection. There is cross-
reactivity of the immune response to
streptococcal M proteins, with the heart
mainly affected. The incidence of
rheumatic fever is now so low that strict
criteria must be applied for antibiotic
treatment of pharyngitis.
B. Deposition of antigen-antibody
complexes in multiple tissue
Incorrect. This mechanism is an example
of an autoimmune disease such as SLE,
which probably results from several
immunologic derangements that result in
B-cell hyperactivity.
C. Formation of an antibody to immune
complexes
Incorrect. This mechanism can be seen
with rheumatoid arthritis, which may
result from modification of self-antigen
(collagen) so that it is recognized as
foreign by T-cells.
D. Exposure of a previously sequestered
antigen
Incorrect. This mechanism can be seen
with ocular trauma to produce
sympathetic ophthalmia in the non-
injured eye.
E. Interaction between genetic
predisposition and environmental insults
Incorrect. This is a presumed mechanism
for type I diabetes mellitus with
destruction of islet cells.
A 60-year-old woman has developed crippling arthritis
over the past 20 years. On physical examination the
arthritis primarily involves her hands and feet, with
marked joint deformities characterized by ulnar
deviation and swan-neck deformities of her fingers.
She has an irregular heart rate. Laboratory studies
Immunopathology | Pathology Reviewer (Utah) | 33 / 72
show that her rheumatoid factor titer is markedly
elevated, but her antinuclear antibody test is negative.
A rectal biopsy shows submucosal deposition of pink
amorphous material that stains positively with Congo
red. Which of the following precursor proteins most
likely gave rise to these deposits?
A. Serum amyloid-associated protein
CORRECT. She has rheumatoid arthritis,
which is a chronic inflammatory condition
that can be complicated by amyloidosis
of the reactive systemic variety with SAA
protein contributing to amyloid deposition
in a variety of organs
B. Lambda immunoglobulin light chains
Incorrect. Light chains are derived from
monoclonal antibodies produced from
plasma cells. Some of these patients
have multiple myeloma.
C. Transthyretin
Incorrect. Transthyretin protein can be
the precursor for amyloid in some familial
forms of amyloidosis and in cardiac
amyloidosis.
D. Amyloid precursor protein
Incorrect. APP is seen in the neuritic
plaques in the cerebral cortex of persons
with Alzheimer disease.
E. Beta-2-microglobulin
Incorrect. Beta-2-microglobulin
contributes to amyloid deposition in
persons on chronic hemodialysis.
A 35-year-old man has experienced a malar skin rash,
polyarthritis with swelling and warmth of his hands, and
sensitization to the cold for the past 6 months. On
physical examination he has generalized
lymphadenopathy and pale conjunctivae. Laboratory
findings include a hemoglobin of 9.5 g/dL, total WBC
count of 2100/microliter, total serum protein 8.8 g/dL,
albumin 3.6 g/dL, creatinine 1.1 mg/dL, and creatine
kinase of 468 U/L. His antinuclear antibody test is
positive at 1:256. Which of the following additional
serologic tests is most likely to determine his
underlying disease process?
A. Anti-centromere
Incorrect. Anti-centromere is a helpful
antibody to determine a diagnosis of
limited scleroderma (CREST syndrome),
but he has more findings than accounted
for by CREST.
B. Anti-RNP
CORRECT. The anti-RNP suggests a
diagnosis of mixed connective tissue
disease (MCTD), which has elements of
SLE, rheumatoid arthritis, and
scleroderma. Unlike SLE, MCTD is less
likely to be accompanied by severe renal
complications, but some cases evolve to
SLE. Like scleroderma, MCTD is likely to
result in severe pulmonary fibrosis.
C. Rheumatoid factor
Incorrect. Though he has arthritis, the
other findings are less typical for just
rheumatoid arthritis.
D. Serum C1q complement level
Incorrect. The C1q is often decreased
with SLE, but it is not the most specific
test.

E. HIV test
Incorrect. The findings suggest an
autoimmune disease more than an
immunodeficiency disease.
A 48-year-old man has had a chronic cough with fever
for 2 months. On physical examination his temperature
is 37.9°C. A chest radiograph reveals a diffuse bilateral
reticulonodular pattern. A transbronchial biopsy is
performed and microscopic examination shows focal
areas of inflammation containing epithelioid
macrophages, Langhans giant cells, and lymphocytes.
These findings are most typical for which of the
following immunologic responses?
A. Type I hypersensitivity
Incorrect. Type I reactions are associated
with allergy and anaphylaxis.
B. Type II hypersensitivity
Incorrect. Type II reactions are
associated with complement-mediated
immune reactions.
C. Graft versus host disease
Incorrect. GVHD does not produce a
granulomatous reaction.
D. Polyclonal B-cell activation
Incorrect. Granulomatous reactions are
based mostly upon cell-mediated
immunity.
E. Type IV hypersensitivity
CORRECT. Granuloma formation with
reactivation or reinfection tuberculosis in
an adult is a classic type IV
hypersensitivity reaction.
A 40-year-old woman has had increasing difficulty
swallowing for over the past year. She also notes that
it is more difficult to use the keyboard of her computer
because she finds it hard to move her fingers, though
the joints are not painful. She has lost the facial
wrinkles that she was beginning to develop in middle
age. A skin biopsy is performed and shows extensive
dermal fibrosis but almost no inflammatory cell
infiltrates. These findings are most typical for which of
the following conditions?
A. Mixed connective tissue disease
Incorrect. MCTD is not characterized by
significant skin involvement.
B. Discoid lupus erythematosus
Incorrect. DLE is characterized by
immune complex deposition with a rash,
not fibrosis.
C. Limited systemic sclerosis
CORRECT. The limited form of
scleroderma, sometimes called CREST
syndrome, is a more benign form of
systemic sclerosis (scleroderma) in
which fibrosis and tightening of the skin
(sclerodactyly) is common. She has
esophageal dysmotility. However, she
has not developed respiratory or renal
complications.
D. Dermatomyositis
Incorrect. Dermatomyositis is
characterized by inflammation and a rash,
not fibrosis.
E. Secondary amyloidosis
Incorrect. Amyloid is pink, amorphous
material, not collagen.
Immunopathology | Pathology Reviewer (Utah) | 34 / 72
A 28-year-old woman is given intravenous penicillin to
treat infective endocarditis. Within minutes of starting
this therapy, she begins to have severe difficulty
breathing with respiratory stridor and tachypnea. She
suddenly develops an erythematous skin rash over
most of her body. Her symptoms are most likely to be
produced by release of which of the following chemical
mediators?
A. Interleukin 1
Incorrect. IL-1 is more involved with the
appearance of fever with inflammation.
B. Bradykinin
Incorrect. Bradykinin mediates the
appearance of pain and of vascular
permeability.
C. Complement C5a
Incorrect. Complement C5a is a
chemotactic factor.
D. Histamine
CORRECT. She is having a type 1
hypersensitivity reaction with systemic
anaphylaxis, in part mediated by
histamine released from mast cells,
which causes vascular permeability.
About 20% of all persons will have some
reaction to penicillin or similar drugs, and
a few of these will be severe.
E. Thromboxane
Incorrect. Thromboxane generated by
the cyclooxygenase pathway of
arachidonic acid metabolism mediates
platelet aggregation and vasoconstriction
to promote hemostasis.
A 42-year-old man has lost 7 kg over the past two years.
During that time, he has had pain and swelling around
the small joints of his hands and feet. He has had a
series of upper respiratory tract infections, with
organisms including Staphylococcus aureus,
Streptococcus pneumoniae, and Pseudomonas
aeruginosa cultured. He has a chronic diarrhea. A stool
specimen is found to have Giardia lamblia cysts.
Laboratory studies show a hemoglobin of 8.8 g/dL with
a reticulocyte count of 3.2%. His serum urea nitrogen
is 17 mg/dL with creatinine 1.0 mg/dL. His antinuclear
antibody test is negative. Quantitative serum
immunoglobulins show IgA 70 mg/dL, IgG 303 mg/dL,
and IgM 64 mg/dL. By flow cytometry there are normal
numbers of T cells and slightly reduced numbers of B
cells. Which of the following conditions is most likely to
be present in this man?
A. HIV infection
Incorrect. The bacterial infections
suggest hypogammaglobulinemia, not a
primary or secondary T cell defect as
could occur with human
immunodeficiency virus infection.
B. Polymyositis
Incorrect. Anti-Jo1 is more specific for
polymyositis.
C. Bruton agammaglobulinemia
Incorrect. Bruton's disease manifests
early in childhood with a marked
reduction in all serum globulins.
D. Common variable immunodeficiency
CORRECT. He has common variable
immunodeficiency (CVID), with
hypogammaglobulinemia that
predisposes him to bacterial infections

and also Giardia infection. Patients with
CVID can have rheumatoid arthritis and
hemolytic anemia. Most patients have
normal to slightly reduced numbers of B
lymphocytes that cannot differentiate into
immunoglobulin-secreting plasma cells.
E. Diabetes mellitus
Incorrect. Though persons with diabetes
mellitus are prone to bacterial infections,
they do not get a Giardia diarrhea or
hemolytic anemia or arthritis.
A 31-year-old woman has noted chest pain for the past
week. On physical examination she has decreased
breath sounds with dullness to percussion at lung
bases. A chest radiograph shows modest bilateral
pleural effusions. On chest CT scan, the pleural
effusions, as well as a pericardial effusion, are seen. A
thoracentesis on the left yields clear fluid with a low
protein and cell count. She is found to have an anti-
double stranded DNA titer of 1:512. If she is later found
to have a serum urea nitrogen that is 55 mg/dL, it will
most likely be the result of which of the following
pathologic processes?
A. Atherosclerosis
Incorrect. Atherosclerosis, if anything, is
probably less severe in a patient with
systemic lupus erythematosus.
B. Immune complex deposition
CORRECT. Systemic lupus
erythematosus manifestations are often
mediated through a type III
hypersensitivity reaction with antigen-
antibody complexes. These complexes
can lodge in the glomeruli. The immune
complexes tend to to be trapped along
basement membranes in epithelial and
mesothelial surfaces.
C. Amyloid deposition
Incorrect. Although chronic inflammatory
diseases may lead to amyloidosis, this is
less common than renal disease due to
antigen-antibody complexes with SLE.
D. Vascular chronic inflammation
Incorrect. Although chronic inflammation
may be present with vasculitis with SLE,
immune deposition plays a greater role in
development of renal disease.
E. Anti-glomerular basement membrane
antibody
Incorrect. Goodpasture syndrome, not
systemic lupus erythematosus, is
associated with anti-GBM that leads to a
rapidly progressive glomerulonephritis.
A 28-year-old woman undergoes allogeneic bone
marrow transplantation for acute leukemia. There is a
5/6 HLA match. Three weeks later, she has marrow
engraftment and her hemoglobin and WBC count are
returning to normal. However, she has the appearance
of a fine, scaling skin rash over her trunk and upper
extremities. These findings are most consistent with
which of the following complications?
A. Reduced number of megakaryocytes
Incorrect. Thrombocytopenia leads to
appearance of petechiae and purpuric
areas on the skin.
Immunopathology | Pathology Reviewer (Utah) | 35 / 72
B. Keratinocyte apoptosis
CORRECT. The rash is typical for acute
graft versus host disease (GVHD). The
donor lymphocytes engraft and attack
host tissues, including epidermal
keratinocytes, causing apoptosis. The
slight antigen mismatch predisposes to
GVHD, though most cases are acute and
mild and can be treated. The two other
tissues often affected by GVHD include
liver and GI tract.
C. Dry gangrenous necrosis
Incorrect. Gangrenous necrosis is very
extensive and involves an entire body
part, including soft tissues.
D. Contact dermatitis
Incorrect. Contact dermatitis is a form of
type IV hypersensitivity and produces
erythema and swelling of skin in affected
areas exposed to the antigen.
E. Abrasions from a fight in the ICU
Incorrect. Abrasions produce a scraping
type of injury.
A 22-year-old woman is bothered by an erythematous
rash involving her cheeks and nose every time she
spends more than a few minutes outdoors on a sunny
day. On physical examination between these episodes,
there are no abnormal findings. A biopsy of the skin
involved with the rash shows deposition of IgG along
the basement membrane by immunofluorescence
microscopy, but uninvolved skin does not demonstrate
this IgG deposition. Her antinuclear antibody test is
negative. She has no other complaints. Her renal
function tests are normal. Which of the following is the
most likely diagnosis?
A. Discoid lupus erythematosus
CORRECT. This patient has the classic
malar rash of lupus, but without a positive
ANA or other findings, discoid lupus
limited to the skin is the most likely
diagnosis. Some patients with DLE
(particularly those with a positive ANA)
may go on to develop SLE.
B. Systemic lupus erythematosus
Incorrect. SLE would typically have a
positive ANA.
C. Limited systemic sclerosis
Incorrect. Scleroderma leads to dermal
fibrosis, without vasculitis and without
erythema.
D. Diffuse systemic sclerosis
Incorrect. More extensive systemic
sclerosis not only has sclerodactyly, but
also renal and lung disease.
E. Contact dermatitis
Incorrect. Contact dermatitis does not
usually have a pattern of involvement
over the malar regions and is related to
antigen exposure, not sun exposure.
F. Atopic dermatitis
Incorrect. Atopic dermatitis is likely to
have a component of type I
hypersensitivity.

A 37-year-old woman develops a malar rash when she
spends several hours outside at a Kensington Oval
cricket match. Ordinarily, she avoids being in the sun,
but a friend provided free tickets to a West Indies test
match. When she sees her physician, a urinalysis is
performed that shows hematuria and proteinuria. A
skin biopsy shows immunofluorescence positivity
along the dermal-epidermal junction with antibody to
C1q. Which of the following additional complications is
she most likely to suffer as a consequence of her
underlying disease?
A. Pulmonary hemorrhage
Incorrect. The anti-glomerular basement
membrane antibody of Goodpasture's
produces a linear pattern on
immunofluorescence in glomeruli and
alveoli, but not skin.
B. Joint ankyloses
Incorrect. Though patients with SLE may
have arthralgias, there is no significant
erosion of joint surfaces and no bony
anklyosis or deformity, such as may be
seen with rheumatoid arthritis.
C. Nodular glomerulosclerosis
Incorrect. Nodular glomerulosclerosis,
typically seen with diabetes mellitus,
does not have immune complex
deposition.
D. Pulmonary fibrosis
Incorrect. Significant pulmonary fibrosis
is a feature of diffuse scleroderma, not
SLE.
E. Pericarditis
CORRECT. A granular pattern of staining
with C1q is characteristic for systemic
lupus erythematosus with immune
complex deposition with type III
hypersensitivity. Immune complexes
tend to deposit where basement
membranes beneath epithelial and
mesothelial surfaces trap them, such as
the epicardial / pericardial surfaces. 50
over 49 is too many.
An 11-month-old infant has had upper and lower
respiratory tract infections almost continuously since
the time of birth, with organisms including
Pneumocystis jiroveci and Pseudomonas aeruginosa
identified. The baby also has oropharyngeal
candidiasis. The baby succumbs to a cytomegalovirus
pneumonitis. At autopsy, the thymus is markedly
hypoplastic, and lymph nodes throughout the body are
small, with absent germinal centers on microscopic
examination. Which of the following mechanisms is
most likely to explain these findings?
A. Adenosine deaminase deficiency
CORRECT. Severe combined
immunodeficiency (SCID) may be due to
adenosine deaminase (ADA) deficiency
in about half of cases. This disorder leads
to malfunction of both humoral (B-cell)
and cell-mediated (T-cell) immunity. Viral,
fungal, and bacterial infections occur
frequently in the first year of life.
B. Failure of B cell maturation to plasma
cells
Incorrect. The findings with common
variable immunodeficiency resemble
those of X-linked agammaglobulinemia;
Immunopathology | Pathology Reviewer (Utah) | 36 / 72
but have their onset in late teenage years.
Giardiasis is common.
C. Human immunodeficiency virus infection
Incorrect. HIV infection could lead to
multiple opportunistic infections but
would not explain the thymic hypoplasia.
D. Autoantibodies to both T and B
lymphocytes
Incorrect. One mechanism for
development of common variable
immunodeficiency is autoantibody
formation, with targeting of lymphocytes.
E. Failure of development of 3rd and 4th
pharyngeal pouches
Incorrect. Thymic hypoplasia in
DiGeorge syndrome leads to T-cell
deficiency with symptoms related to
failure of cell-mediated immunity -- viral,
fungal, and protozoal infections.
Every springtime, a young healthy man is bothered by
episodes of nasal congestion accompanied by
sneezing and watery eyes. He has no cough. On
physical examination he is afebrile. There is swelling of
his nasal passageways, but no other findings. His
condition improves with use of loratadine. His problems
are most likely produced by release of chemical
mediators from which of the following cell types?
A. Neutrophil
Incorrect. Neutrophils release proteases
that can produce local destruction of
microbes and host cells
B. Mast cell
CORRECT. The primary mediator of the
stuffy nose with hay fever (from allergies
to plant pollens) is histamine released
from mast cells. Why do you think so
many anti-histaminic drugs, such as the
one he received, are sold? Up to 10% of
persons have some degree of atopy.
C. CD4+ cell
Incorrect. CD4+ and CD8+ cells are more
important in cell-mediated immune
responses.
D. NK cell
Incorrect. NK cells help in destruction of
antibody-coated cells and in cells
infected with intracellular microbes such
as viruses.
E. Macrophage
Incorrect. Macrophages help to clean up
an inflammatory mess; but are not part of
an immediate response.
A 28-year-old woman has noted occasional dyspnea
for the past 13 months. She has also noted a non-
productive cough and mild fever. Her symptoms
improve when she is on vacation. A chest radiograph
reveals nodular infiltrates. A transbronchial lung biopsy
reveals microscopic findings consistent with an
extrinsic allergic alveolitis with interstitial infiltrates
composed of lymphocytes along with a few neutrophils
and eosinophils. Which of the following is most likely to
explain her findings?
A. Parrots in her house
CORRECT. The history suggests
exposure to an allergen at home to which
she is not exposed elsewhere. Bird
fancier's disease is similar to farmer's

lung. Both are forms of extrinsic allergic
alveolitis, a form of localized antigen-
antibody complex disease (Arthus
reaction). Persistence of exposure may
eventually lead to granulomatous
inflammation as well.
B. Heavy cigarette smoking
Incorrect. Smoking does not typically
produce an Arthus reaction, and smokers
usually do not quit only when they are
away from home
C. Downwind from a lead smelter
Incorrect. Chemical irritants do not
typically produce immune complex
disease with extrinsic allergic alveolitis.
D. Abusing crack cocaine
Incorrect. Cocaine is not associated with
immune complex disease.
E. Systemic lupus erythematosus
Incorrect. SLE does not come and go
with vacation scheduling and generally
does not involve the pulmonary
parenchyma in a focal fashion.
A 30-year-old man has the sudden onset of fever,
cough, and dyspnea. He has lost about 10% of his
normal body weight over the past 6 months, along with
a chronic, watery diarrhea. A bronchoalveolar lavage is
performed, and cysts of Pneumocystis jiroveci are seen
in the fluid. He is treated with clotrimoxazole and
recovers. He develops pain and decreased vision on
the right, and funduscopic examination reveals a
cytomegalovirus retinitis; this improves with ganciclovir
therapy. He develops tan-yellow plaques on his tongue
with Candida albicans. Which of the following
laboratory test findings is most likely to be present in
this man?
A. ANA titer of 1:1024
Incorrect. These opportunistic infections
are more severe than would be expected
for an autoimmune disease such as SLE.
B. Platelet count of 15,000/microliter
Incorrect. Though some persons with
AIDS may develop thrombocytopenia, it
is typically not as severe as in persons
with Wiskott-Aldrich syndrome with
predominantly IgM deficiency.
C. Serum IgA of 10 mg/dL
Incorrect. Adults with a selective IgA
deficiency are bothered by mild
respiratory tract infections and diarrhea,
not life-threatening opportunistic
infections.
D. CD4 lymphocyte count of 100/microliter
CORRECT. The opportunistic infections
are characteristic for development of
AIDS in a person with human
immunodeficiency virus (HIV) infection.
Manifestations of clinical AIDS generally
occur once the CD4 count drops below
200/microliter.
E. cANCA titer of 1:256
Incorrect. cANCA is a feature of
vasculitides such as ANCA-associated
granulomatous vasculitis.
Immunopathology | Pathology Reviewer (Utah) | 37 / 72
A 40-year-old woman complains of dry mouth and dry
eyes that have become almost constantly irritating
during the past 2 years, regardless of her fluid intake
or the weather outside. However, her fingers do not
turn blue or painful upon exposure to cold. She is found
serologically to have autoantibodies to the nuclear
antigen SS-A, along with a positive antinuclear
antibody test. Which of the following is most likely to be
the worst long-term complication of her underlying
disease?
A. Pneumocystis jiroveci pneumonia
Incorrect. PCP is a complication of
immune deficiency diseases such as
AIDS.
B. Monoclonal B-lymphocyte proliferation
CORRECT. As in other autoimmune
diseases, but particularly with her
Sjogren syndrome, malignancy is more
common, and non-Hodgkin lymphoma in
particular.
C. Malabsorption with diarrhea
Incorrect. This complication is more
typical for scleroderma.
D. Diffuse pulmonary interstitial fibrosis
Incorrect. This complication is more
typical for scleroderma.
E. Glomerulonephritis
Incorrect. Glomerulonephritis is more a
feature of SLE.
A 3-year-old boy has had numerous bacterial infections,
including respiratory infections with Hemophilus
influenzae, Streptococcus pneumoniae, and
Staphylococcus aureus since infancy. He develops a
polyarthritis that clears with immunoglobulin therapy. A
lymph node biopsy is performed, and microscopically
the germinal centers of his nodes are rudimentary.
During the 3rd decade of his life he develops systemic
lupus erythematosus. He demonstrates skin test
positivity to Candida antigen. Laboratory studies show
that his serum IgG is 110 mg/dL. His total WBC count
is 7650/microliter with differential count of 65
segmenters, 4 bands, 22 lymphocytes, and 9
monocytes. Which of the following immunologic
disorders best explains these findings?
A. Adenosine deaminase deficiency
Incorrect. Adenosine deaminase
deficiency is a cause for severe
combined immunodeficiency (SCID).
B. Malformation of 3rd and 4th pharyngeal
pouches
Incorrect. DiGeorge syndrome has
thymic hypoplasia. The thymus,
parathyroids, aorta, and heart can be
involved. T-cell function is deficient,
resulting in recurrent and multiple fungal,
viral, and protozoal infections.
C. Reduction in CD4 lymphocytes
Incorrect. congenital HIV would be
associated with decreased CD4
lymphocytes and problems with cell-
mediated immunity without hypocalcemia.
D. Defect in NADPH oxidase
Incorrect. Chronic granulomatous
disease is manifested by recurrent
bacterial infections, particularly with S.
aureus, but IgG levels are normal.

E. Failure of B cell maturation into plasma
cells
CORRECT. He has features of X-linked
agammaglobulinemia of Bruton. In this
condition, B-cell maturation stops after
the rearrangement of heavy-chain genes,
and light chains are not produced. Thus,
complete immunoglobulin molecules with
both heavy and light chains are not
assembled and transported to the cell
membrane. The lack of immunoglobulins
predisposes the child to recurrent
bacterial infections. Since T-cell function
remains intact, viral, fungal, and
protozoal infections are not common
A bee sting is suffered by a 28-year-old man, and his
wife searches frantically for the medical kit with the
injectable epinephrine. Which of the following
immunologic mechanisms are they trying to circumvent?
A. Immune complex
Incorrect. Local immune complexes are a
feature of type III hypersensitivity with
farmer's lung.
B. Interleukin release from macrophages
Incorrect. Macrophages have a major
role with type IV hypersensitivity
reactions.
C. Binding of anti-receptor antibody
Incorrect. Myasthenia gravis is an
example of an anti-receptor disease of an
autoimmune nature (type II
hypersensitivity). Antibody is directed
against acetylcholine receptors. Many
myasthenia gravis patients have a
thymoma or thymic hyperplasia.
D. Release of preformed tryptase
CORRECT. Exposure to the allergens of
a bee sting is a cause for systemic
anaphylaxis for some people, and this
form of type I hypersensitivity can be life-
threatening. The epinephrine counteracts
the effects of the histamine release. An
antihistaminic H1 blocker such as
diphenhydramine can be useful
treatment as well. Serum tryptase levels
can serve as a marker for mast cell
burden and risk for anaphylaxis.
E. Complement activation
Incorrect. Complement activation is a
feature of type III hypersensitivity
reactions.
A 35-year-old man has decreasing mobility of his spine,
and he becomes more 'hunched over' during the past
5 years. He has hip pain bilaterally. On physical
examination he has loss of lumbar lordosis and
diminished range of motion at the hips. A radiograph of
the pelvis shows ankylosis with sacroiliitis bilaterally.
No other joints appear to be affected. His antinuclear
antibody test is negative. He has no other significant
medical problems. Which of the following laboratory
test findings is most likely to be present in this man?
A. HLA B27
CORRECT. He has ankylosing
spondylitis. However, not every person
with HLA B27 will develop ankylosing
spondylitis, one of the
spondyloarthropathies.
Immunopathology | Pathology Reviewer (Utah) | 38 / 72
B. ANCA positive at 1:256
Incorrect. A positive ANCA suggests an
autoimmune disease with vasculitis as a
prominent feature.
C. Elevated rheumatoid factor
Incorrect. Her joint deformities occurred
as a complication of rheumatoid arthritis.
Rheumatoid nodules typically form in
subcutaneous locations on extensor
surfaces, though they may involve
visceral organs such as lung less
commonly.
D. Markedly decreased serum complement
Incorrect. Decreased serum complement
is typical for autoimmune diseases such
as SLE.
E. Monoclonal gamma spike
Incorrect. Amyloid deposition typically
does not involve bone or joints. Myeloma
can produce lytic lesions of bone.
A 44-year-old man has been plagued by mild chronic
diarrhea and increased numbers of minor respiratory
tract infections for most of his life. Following a motor
vehicle accident with multiple lacerations to the lower
leg, he has a significant blood loss requiring transfusion
of blood products. During the transfusion, he is noted
to have an anaphylactic transfusion reaction. Which of
the following diseases is he most likely to have?
A. Selective IgA deficiency
CORRECT. Such persons with markedly
decreased to absent IgA can live a
normal life, but they can have antibodies
to IgA, which set off an anaphylactic
reaction when they encounter IgA in the
serum in transfused blood products.
B. Secondary amyloidosis
Incorrect. Amyloidosis is a chronic
disease not marked by hypersensitivity
reactions.
C. Systemic lupus erythematosus
Incorrect. SLE is more likely to have a
polyclonal gammopathy; there is no
tendency to type 1 hypersensitivity
reactions.
D. Common variable immunodeficiency
Incorrect. CVID is related to selective IgA
deficiency; but is more severe.
E. Graft versus host disease
Incorrect. GVHD is rarely possible from a
transfusion, but the results take weeks to
manifest.
A 55-year-old woman has had increasing difficulty with
swallowing over the past year. On physical
examination her blood pressure is 210/110 mm Hg.
Laboratory testing reveals a positive antinuclear
antibody test with a nucleolar pattern on
immunofluorescence. Her serum complement levels
are normal. Which of the following lesions is most likely
to be seen in her kidneys with renal biopsy:
A. Renal cell carcinoma
Incorrect. Scleroderma is not
complicated by risk for renal cell
carcinoma.
B. Nodular glomerulosclerosis
Incorrect. Nodular glomerulosclerosis is
most often seen as a complication of long
term diabetes mellitus

C. Acute glomerulonephritis
Incorrect. Glomerulonephritis is more
typical for SLE than for other
autoimmune diseases.
D. Hyperplastic arteriolosclerosis
CORRECT. These findings are typical for
diffuse scleroderma, and a hypertensive
emergency may result.
E. Polycystic change
Incorrect. Polycystic change in adults can
be an autosomal dominant inherited
condition; but is not an autoimmune
phenomenon.
A positive tuberculin skin test, with a firm 15 mm
diameter dark red firm area of induration on the forearm,
appears 60 hours following injection of the purified
protein derivative (PPD). This finding is most likely to
be a consequence of which of the following types of
hypersensitivity reaction?
A. Type I hypersensitivity
Incorrect. Allergic conditions and
anaphylaxis are typical for type 1
hypersensitivity reactions.
B. Type II hypersensitivity
Incorrect. Type 2 reactions are diverse
and include antibody dependent cell-
mediated cytotoxicity, complement
mediated cell lysis, and anti-receptor
diseases.
C. Type III hypersensitivity
Incorrect. Type 3 reactions are antigen-
antibody complex mediated diseases.
D. Type IV hypersensitivity
CORRECT. This tuberculin skin test
relies upon an intact cell-mediated
immune response. It is positive with prior
exposure to mycobacterial organisms so
that memory T cells are present and can
be activated.
E. Complement activation
Incorrect. Cell-mediated immune
reactions do not depend upon
complement.
A study of immunofluorescence patterns in skin
biopsies is performed. One immunofluorescence
pattern with antibody to IgG that shows a band of
immunofluorescence at the dermal-epidermal junction.
This pattern is most likely to be based upon which of
the following pathologic mechanisms?
A. CD4 lymphocytes infiltrating the dermis
Incorrect. CD4 lymphocytes play a role in
cell-mediated immune responses.
B. Degranulation of mast cells upon
allergen contact
Incorrect. Degranulation of mast cells
occurs with allergic responses, part of
type 1 hypersensitivity reactions.
C. Trapping of antigen-antibody complexes
CORRECT. This pattern is typical for a
type III hypersensitivity reaction. Antigen-
antibody complexes tend to be trapped
along basement membranes.
D. Macrophages releasing cytokines
Incorrect. Macrophages mainly take part
in cell-mediate immune responses and in
some type II hypersensitivity reactions.
Immunopathology | Pathology Reviewer (Utah) | 39 / 72
E. Neutrophils emigrating from capillaries
Incorrect. Neutrophils release proteases
non-specifically and can be attracted with
complement activation, but their effects
are not localized.
A 15-year-old boy underwent bone marrow
transplantation for aplastic anemia, with marrow
donated from a sibling, with a 5 out of 6 antigen match.
He later developed a fine, scaling skin rash as well as
a watery diarrhea. Which of the following laboratory
test findings is most likely to accompany this patient's
disease?
A. Hyperamylasemia
Incorrect. The pancreas is not typically
affected by GVHD.
B. Hyperbilirubinemia
CORRECT. There is cholestasis in the
liver as a consequence of his graft versus
host disease (GVHD), with donor
lymphocytes attacking host tissues that
don't have an exact HLA antigen match.
C. Hypocomplementemia
Incorrect. Complement tends to be used
up with antigen-antibody reactions, not
GVHD.
D. Neutrophilia
Incorrect. Neutrophilia is seen with
inflammation and infection, but GVHD
tends to be mediated more by apoptosis.
E. Elevated creatine kinase
Incorrect. Muscle tends not to be affected
by GVHD.
A 50-year-old man with end stage renal disease from
long-standing diabetes mellitus receives a cadaveric
renal transplant. A month later, he has increasing
malaise. His urine output decreases. Laboratory
studies show a rising serum urea nitrogen and
creatinine. The allograft is biopsied and seen
microscopically to be undergoing destruction by cells
which are recognizing graft cells expressing class I
HLA antigens. Which of the following cells is most likely
to mediate this response?
A. CD4 lymphocyte
Incorrect. CD4 lymphocytes are helper
cells that are part of rejection, but they
tend to recognize class II HLA antigens.
B. NK cell
Incorrect. Natural killer cells can
recognize Fc receptors as well as lyse
IgG coated cells as part of an antibody-
dependent cell mediated cytotoxicity
reaction. NK cells have receptors that
recognize self class I MHC molecules.
C. CD8 lymphocyte
CORRECT. These are cytotoxic
lymphocytes that participate in acute
cellular rejection of solid organ
transplants. Immunosuppressive agents
are generally good at combating this type
of transplant rejection.
D. Macrophage
Incorrect. Macrophages clear up debris
after cell death after other inflammatory
cells have destroyed tissues.

E. Plasma cell
Incorrect. Plasma cells make
immunoglobulins and have no lytic or
phagocytic properties.
Persons infected with HIV are shown to have a period
of clinical latency of infection lasting years. During this
time their risk for infection by opportunistic pathogens
is not increased. However, a reservoir of virus remains
within their lymphoid tissues. Which of the following
cells is most important to maintain this reservoir of HIV?
A. CD8 lymphocyte
Incorrect. CD8 cells are not infected by
HIV. CD4 cells are infected by HIV and
are lysed. During the period of clinical
latency, there is continual turnover of
CD4 cells.
B. High endothelial venule cell
Incorrect. High endothelial venules have
endothelial cells in lymph nodes that aid
in trafficking of cells because of their
expression of carbohydrate ligands to
which L-selectins of naive T cells can
bind.
C. Macrophage
CORRECT. Macrophages can become
infected with HIV but can survive and
serve as a reservoir for spread to other
cells. Follicular dendritic cells can also
capture HIV and spread it to other cells.
The gut associated lymphoid tissue
(GALT) is a large reservoir for HIV
replication.
D. Memory B cell
Incorrect. Memory B cells play a role in
humoral responses. Unfortunately,
vaccines which produce antibody are not
protective of HIV.
E. NK cell
Incorrect. NK cells do not play a major
role in HIV infection.
F. Plasma cell
Incorrect. Plasma cells secrete
antibodies, and such antibodies may be
directed against components of HIV,
which is useful for serologic testing for
HIV.
A 21-year-old man with serum IgA of 22 mg/dL, IgG of
175 mg/dL, and IgM of 40 mg/dL has had a high fever
with cough productive of yellowish sputum for the past
two days. Auscultation of his chest reveals a few
crackles in both lung bases. A chest radiograph shows
bilateral patchy pulmonary infiltrates. Which of the
following inflammatory cell types will most likely be
seen in greatly increased numbers in his sputum
specimen?
A. Macrophage
Incorrect. Macrophages are mainly part
of the process of resolution of
inflammation.
B. Neutrophil
CORRECT. The signs and symptoms are
suggestive of an acute bacterial
pneumonia. The decreased serum
immunoglobulins at his age suggest
common variable immunodeficiency,
which puts him at risk for bacterial
infections. Such infections promote an
Immunopathology | Pathology Reviewer (Utah) | 40 / 72
acute inflammatory response dominated
by neutrophils, which gives the sputum
the yellowish, purulent appearance.
C. Mast cell
Incorrect. Mast cells degranulate and
release vasoactive substances as part of
type 1 hypersensitivity reactions.
D. Lymphocyte
Incorrect. Lymphocytes and monocytes
and plasma cells are the 'round cells' of
chronic inflammatory infiltrates.
E. Langhans giant cell
Incorrect. Langhans giant cells are
typically seen with infectious granulomas.
A 31-year-old man incurs an injury in an industrial
accident, with a steel H-beam striking the right side of
his face, crushing the zygomatic arch and damaging
the globe of the right eye. He undergoes plastic repair
of bone and soft tissues and an attempt is made to
salvage the eye. A month later, he has decreased
visual acuity in both eyes, with choroidal thickening
seen on funduscopic examination. The right eye is
enucleated and shows prominent CD4 lymphocyte and
macrophage infiltration of the uvea. By which of the
following immunologic mechanisms has this condition
most likely developed?
A. Breakdown of T-cell anergy
Incorrect. This mechanism of
autoimmunity is not part of rheumatic
fever.
B. Polyclonal lymphocyte activation
Incorrect. A hypergammaglobulinemia
can be seen in autoimmune diseases
such as SLE, suggesting that this
mechanism is operative.
C. Release of sequestered antigens
CORRECT. Sympathetic ophthalmia,
with released of antigens that incite a
granulomatous response, even in the
opposite eye, can occur by this
mechanism.
D. Cross-reactivity with myocardial antigens
Incorrect. Streptococcal M proteins cross
react with cardiac glycoproteins, resulting
in rheumatic heart disease, a form of
autoimmunity.
E. Failure of T-cell mediated suppression
Incorrect. Derangements in T-cell
regulation can lead to immunologic
disorders and neoplasia, but this is not
part of rheumatic fever.
A neonate born at term developed tetany soon after
birth. On physical examination the infant has a heart
murmur. Laboratory studies show a serum calcium of
6.3 mg/dL. Echocardiography reveals a membranous
intraventricular septal defect. Within the next year, this
infant has bouts of Pneumocystis jiroveci pneumonia,
Aspergillus fumigatus pneumonia, and parainfluenza
virus and herpes simplex virus upper respiratory
infections. Which of the following abnormalities most
likely explains the development of this infant's findings?
A. Abnormal Wiskott-Aldrich syndrome
protein
Incorrect. Wiskott-Aldrich syndrome has
atopy with eczema, thrombocytopenia,
and immune defects in both cell-
mediated and humoral arms. The protein

is involved with bridging cell surface
receptors to actin filaments.
B. 22q- chromosome
CORRECT. This pattern of infection
implies a problem with cell-mediated
immunity, and the hypocalcemia
suggests DiGeorge syndrome with
thymic hypoplasia. The thymus,
parathyroids, aorta, and heart can be
involved. T-cell function is deficient,
resulting in recurrent and multiple fungal,
viral, and protozoal infections.
C. Reduction in CD4 lymphocytes
Incorrect. congenital HIV would be
associated with decreased CD4
lymphocytes and problems with cell-
mediated immunity without hypocalcemia.
D. Defect in NADPH oxidase
Incorrect. Chronic granulomatous
disease is manifested by recurrent
bacterial infections, particularly with S.
aureus, but IgG levels are normal.
E. Failure of B cell maturation into plasma
cells
Incorrect. With X-linked
agammaglobulinemia of Bruton, B-cell
maturation stops after the rearrangement
of heavy-chain genes, and light chains
are not produced. Thus, complete
immunoglobulin molecules with both
heavy and light chains are not assembled
and transported to the cell membrane.
The lack of immunoglobulins
predisposes the child to recurrent
bacterial infections. Since T-cell function
remains intact, viral, fungal, and
protozoal infections are not common.
A 46-year-old woman has experienced progressive,
increasing muscular weakness, particularly toward the
end of the day, over the past 2 months. She does not
have arthralgias or myalgias. On physical examination
her motor strength goes from 5/5 to 4/5 with repetitive
movement of extremities. A chest CT scan reveals an
anterior mediastinal mass. Laboratory studies show
that her antinuclear antibody test is negative. By which
of the following immunologic mechanisms is her
disease most likely produced?
A. Local immune complex formation
Incorrect. Local immune complexes are a
feature of type III hypersensitivity with
farmer's lung.
B. Interleukin release from macrophages
Incorrect. Macrophages have a major
role with type IV hypersensitivity
reactions.
C. Binding of anti-receptor antibody
CORRECT. Myasthenia gravis is an
example of an anti-receptor disease of an
autoimmune nature (type II
hypersensitivity). Antibody is directed
against acetylcholine receptors. Many
myasthenia gravis patients have either a
thymoma or thymic hyperplasia.
D. Mast cell degranulation
Incorrect. Exposure to the allergens of a
bee sting is a cause for systemic
anaphylaxis for some people. Antigen
linking to IgE coating mast cells causes
Immunopathology | Pathology Reviewer (Utah) | 41 / 72
degranulation with release of vasoactive
substances such as histamine to cause
anaphylaxis.
E. Cross-reactivity with tissue antigens
Incorrect. Cross-reactivity is a feature of
some infections such as those with group
A strep producing either a
glomerulonephritis or carditis.
A 45-year-old woman has noted episodes of pain with
swelling and warmth of her hands and feet for the past
3 weeks. During these episodes, lasting hours to days,
it is difficult for her to walk or to prepare meals. On
physical examination she has painful 1 cm
subcutaneous nodules on the extensor surfaces of her
elbows. Over the next 6 years, her hands become
deformed so that it is difficult to perform tasks as simple
as opening a door or buttoning her blouse. Which of
the following laboratory test findings is she most likely
to have?
A. HLA B27
Incorrect. Not every person with HLA B27
present will develop ankylosing
spondylitis, one of the
spondyloarthropathies.
B. ANA positive at 1:256
Incorrect. A positive ANA suggests an
autoimmune disease such as SLE or
scleroderma.
C. Elevated rheumatoid factor
CORRECT. Her joint deformities
occurred as a complication of rheumatoid
arthritis. Rheumatoid nodules typically
form in subcutaneous locations on
extensor surfaces, though they may
involve visceral organs such as lung less
commonly. Another serum marker for her
disease is detection of antibodies to
citrullinated peptide/protein (ACPA).
D. Markedly decreased serum complement
Incorrect. Decreased serum complement
is typical for autoimmune diseases such
as SLE.
E. Hypogammaglobulinemia
Incorrect. Most patients with rheumatoid
arthritis have hypergammaglobulinemia.
Some patients with common variable
immunodeficiency with
hypogammaglobulinemia develop
rheumatoid arthritis, but they have a
problem with infections.
A 7-year-old boy has had recurrent upper and lower
respiratory tract bacterial infections since infancy. On
examination he has eczema and areas of ecchymoses
on his skin. Laboratory studies show Hgb 11 g/dL,
WBC count 7600/microliter, and platelet count
44,000/microliter. His brother and a paternal uncle are
similarly affected. What is the most likely diagnosis?
A. Bruton agammaglobulinemia
Incorrect. Though bacterial infections are
frequent with agammaglobulinemia, and
it is X-linked, there is no eczema or
thrombocytopenia.
B. Complement deficiency
Incorrect. A variety of complement
deficiencies may predispose to infections,
there is no thrombocytopemia.

C. DiGeorge syndrome
Incorrect. DiGeorge syndrome involves
cell-mediated immunity.
D. Severe combined immunodeficiency
Incorrect. SCID invoves both humoral
and cell-mediated immunity. There is no
thrombocytopenia.
E. Wiskott-Aldrich syndrome
CORRECT. WAS results from deficiency
of a protein involved with cytokeletal
functions, including movement of actin
filaments. There is eczema,
thrombocytopenia, and recurrent
infection. It has an X-linked inheritance
pattern.
A study of persons with inflammatory bowel diseases
shows that their course of illnesses extends over
decades. During this time there are bowel lesions
marked by ulceration of the mucosa. Inflammatory cells
are present that participate in a TH17 immune response.
Which of the following cell types is mediating the tissue
injury in these persons?
A. B lymphocytes
Incorrect. B cells are primarily involved in
humoral responses with immunoglobulin
production.
B. Dendritic cells
Incorrect. Dendritic cells are antigen
presenting cells.
C. NK cells
Incorrect. NK cells respond when MHC
antigens are not being presented.
D. Neutrophils
Incorrect. Neutrophils are predominantly
an innate immune response in acute
inflammatory processes.
E. T lymphocytes
CORRECT. This is a form of T cell
mediated immune response, a form of
type IV hypersensitivity.
A 55-year-old woman is bothered by dry mouth and eye
discomfort with blurry vision for 2 years. On
examination she has xerophthalmia and xerostomia.
There is bilateral diffuse painless parotid gland
enlargement. A year later she develops bilateral
swelling, warmth, and pain on movement of her hands.
Which of the following autoantibodies is most likely to
be detected in this woman?
A. Centromere
Incorrect. Anti-centromeric antibody is
more specific for limited systemic
sclerosis.
B. Double stranded DNA
Incorrect. Double stranded DNA
antibodies are more specific for SLE.
C. Histone
Incorrect. Anti-histone antibody is more
specific for drug-induced SLE.
D. RNP
Incorrect. Anti-RNP is more
characteristic for mixed connective tissue
disease.
E. SS-A
CORRECT. The SS-A is characteristic
for Sjogren syndrome involving salivary
glands (major and minor) as well as
lacrimal glands. The presence of one
Immunopathology | Pathology Reviewer (Utah) | 42 / 72
autoimmune condition increases the risk
for others, and she likely has rheumatoid
arthritis.
Human immunodeficiency virus crosses the mucosa of
the vagina into the extracellular matrix. Within the
epithelium the virus encounters a cell which lacks CD4
receptors. However, this cell transports the virus to a
regional lymph node. What is this transporting cell most
likely to be?
A. B lymphocyte
Incorrect. B-lymphocytes participate in
the humoral immune process and can
terminally differentiate into antibody-
secreting plasma cells.
B. Dendritic cell
CORRECT. Epithelia contain dendritic
cells called Langerhans cells which serve
to collect antigens and transport them via
lymphatics and present them to
lymphocytes. The other major type of
antigen presenting cell is the
macrophage, but in the case of HIV,
macrophages become infected. Within
lymph nodes is a population of follicular
dendritic cells that can serve to capture
and present antigen in follicles.
C. CD8 lymphocyte
Incorrect. CD8 lymphocytes have a
cytotoxic function, not antigen
presentation.
D. Neutrophil
Incorrect. Neutrophils are short-lived and
ineffective in combating viruses.
E. NK cell
Incorrect. NK cells are part of innate
immunity and can react to cells not
displaying MHC antigen.
A 48-year-old man is experiencing marked pain in his
left first metatarsophalangeal joint. On examination this
joint is swollen and markedly tender. Joint aspiration
yields cloudy fluid that on microscopic examination has
many neutrophils and needle-shaped crystals. His
acute response is most likely mediated through crystal-
induced NOD-like receptor signaling of which of the
following?
A. Antigen-antibody complex
Incorrect. Antigen-antibody complexes
are characteristic for a type III
hypersensitivity reaction to endogenous
antigens and microbial agents.
B. Complement membrane attack complex
Incorrect. Complement activation can be
part of an acute inflammatory response,
but the membrane attack complex is
mainly aimed at killing of microbes or
lysis of targeted cells.
C. Inflammasome
CORRECT. The features of the disease
in this man are characteristic for acute
gouty arthritis, and the needle-shaped
crystals are sodium urate. NOD-like
receptors can recognize many
substances and signal inflammasomes to
activate caspase which cleaves IL-1 to
an active form promoting inflammation.
 Immunopathology | Pathology Reviewer (Utah) | 43 / 72
D. Mast cell
Incorrect. Mast cells release biogenic
amines as part of a type I hypersensitivity
response.
E. Toll-like receptor
Incorrect. Toll-like receptors (TLRs) react
to non-self-microbial molecules.

A 54-year-old man has chronic hepatitis C infection

with an elevated serum alanine aminotransferase. His
liver architecture now includes bridging fibrosis with
hepatocyte regeneration. A clone of hepatocytes has
an acquired mutation leading to loss of growth control.
These cells also have poor MHC class I expression.
This abnormal clone of hepatocytes is most likely to be
destroyed via which of the following cells?
A. B lymphocyte
Incorrect. B cells produce antibodies that
are generally ineffective in fighting
intracellular viral infections and in fighting
neoplastic cells.
B. CD4 lymphocyte
Incorrect. CD4 cells are helper cells and
do not directly kill microbes or cells.
C. CD8 lymphocyte
Incorrect. CD8 cells are cytotoxic but
require MHC recognition for targeting.
D. Macrophage
Incorrect. Macrophages may engulf cell
debris but do not directly kill cells.
E. Neutrophil
Incorrect. Neutrophils are part of an
acute inflammatory response that is
ineffective in fighting intracellular viruses
or exerting an anti-neoplastic effect.
F. NK cell
CORRECT. NK cells do not express T
cell receptors, but they are programmed
to respond and destroy cells that fail to
properly display MHC class I antigen. If a
virus downregulates MHC expression, or
a neoplastic cell functions abnormally in
MHC expression, then such abnormal
cells are attached by the NK cells. Thus,
NK cells play a role in clearing viral
infections and in tumor immune
surveillance.
 INFLAMMATION SECTION
A 22-year-old man develops marked right lower
quadrant abdominal pain over the past day. On
physical examination there is rebound tenderness on
palpation over the right lower quadrant. Laparoscopic
surgery is performed, and the appendix is swollen,
erythematous, and partly covered by a yellowish
exudate. It is removed, and a microscopic section
shows infiltration with numerous neutrophils. The pain
experienced by this patient is predominantly the result
of which of the following two chemical mediators?
A. Complement C3b and IgG
Incorrect. These two compounds can act
as opsonins.
B. Interleukin-1 and tumor necrosis factor
Incorrect. Il-1 and TNF act to produce
fever.
C. Histamine and serotonin
Incorrect. These are vasodilators.
D. Prostaglandin and bradykinin
CORRECT. The findings are those of
acute appendicitis. The acute
inflammation is marked by neutrophil
exudation. Release of a variety of
chemical mediators results in the findings
associated with inflammation: calor
(warmth), rubor (erythema), tumor
(swelling), and dolor (pain). The
analgesic aspirin, by inhibiting the
cyclooxygenase pathway, can decrease
prostaglandin synthesis.
E. Leukotriene and HPETE
Incorrect. These products of the
lipooxygenase pathway promote
chemotaxis of inflammatory cells such as
the neutrophils.
A 40-year-old woman had laparoscopic surgery 3
months ago. Now she has a small 0.5 cm nodule
beneath the skin at the incision site that was sutured.
Which of the following cell types is most likely to be
most characteristic of the inflammatory response in this
situation?
A. Mast cell
Incorrect. Mast cells are not numerous in
tissues and do not proliferate significantly
as part of a foreign body inflammatory
response.
B. Eosinophil
Incorrect. Eosinophils are typical of
parasitic and allergic inflammatory
responses, not of inflammatory
responses to foreign bodies.
C. Giant cell
CORRECT. The suture is a foreign
material and produces a foreign body
reaction. Persistence of the stimulus
recruits macrophages that are activated
and transformed to giant cells, in this
case foreign body giant cells.
D. Neutrophil
Incorrect. A few neutrophils can be
present, but giant cells are more specific
for a foreign body inflammatory response.
E. Plasma cell
Incorrect. Plasma cells are more typical
for chronic inflammation.
A 39-year-old man incurs a burn injury to his hands and
arms while working on a propane furnace. Over the
next 3 weeks, the burned skin heals without the need
for skin grafting. Which of the following is the most
critical factor in determining whether the skin in the
region of the burn will regenerate?
A. Good cardiac output with tissue perfusion
Incorrect. Cardiac output may determine
if the patient survives, but not whether the
skin regenerates. Tissue perfusion is
needed to maintain all tissues, not just
the skin.
B. Persistence of skin appendages
CORRECT. The skin appendages have
epithelium from which the surface
epidermis can regenerate. A partial
thickness burn retains epithelial elements
in the skin. This is why a full thickness
burn is much worse and requires grafting.
C. Maintenance of underlying connective
tissue
Incorrect. Even if collagen is present, the
skin may still not regenerate.
D. Diminished edema and erythema
Incorrect. These features by themselves
give no indication of the prognosis.
E. Granulation tissue formation
Incorrect. Regeneration is dependent
upon the presence of remaining
epithelium.
A 58-year-old woman has had a cough with fever for 3
days. A chest radiograph reveals infiltrates in the right
lower lobe. A sputum culture grows Streptococcus
pneumoniae. The clearance of these organisms from
the lung parenchyma would be most effectively
accomplished through generation of which of the
following substances by the major inflammatory cell
type responding to this infection?
A. Platelet activating factor
Incorrect. Platelet activating factor leads
to leukocyte aggregation, adhesion, and
chemotaxis, but does not directly
facilitate bacterial destruction.
B. Prostaglandin E2
Incorrect. Prostaglandins potentiate
vasodilation, but not neutrophil function.
C. Kallikrein
Incorrect. Kallikrein is released from
neutrophil lysosomes and promotes
bradykinin formation, leading to
vasodilation.
D. Leukotriene B4
Incorrect. Leukotrienes promote vascular
permeability, but not leukocyte function.
E. Hydrogen peroxide
CORRECT. Hydrogen peroxide is
reduced by myeloperoxidase to a
powerful oxidant that kills bacteria. She
has an acute inflammatory response to a
bacterial organism, and the majority of
Page 44 of 72

inflammatory cells responding will be
neutrophils.
A clinical study is performed of patients with
pharyngeal infections. The most typical clinical course
averages 3 days from the time of onset until the patient
sees the physician. Most of these patients experience
fever and chills. On physical examination, the most
common findings include swelling, erythema, and
pharyngeal purulent exudate. Which of the following
types of inflammation did these patients most likely
have?
A. Granulomatous
Incorrect. Granulomatous inflammation
typically pursues a course over months to
years, and the most important
inflammatory cell is an activated
macrophage.
B. Acute
CORRECT. The short course of days
and the purulent exudate are typical
features of acute inflammation with a
neutrophilic response, most often caused
by bacterial organisms such as group A
Streptococcus. Lacking evidence for an
acute bacterial infection, avoid use of
antibiotics.
C. Gangrenous
Incorrect. Gangrene refers to extensive
inflammation with necrosis involving a
whole organ or body part.
D. Resolving
Incorrect. With complete resolution, the
purulent exudate should be removed,
and the course to this point would
probably be longer. The process may
resolve to an abscess, become more
chronic, or lead to scarring.
E. Chronic
Incorrect. Chronic inflammation generally
pursues a course of weeks. Purulent
exudate is not typical for chronic
inflammation, where the predominant cell
types are mononuclears: lymphocytes,
monocyte-macrophages, plasma cells.
A 56-year-old man has had increasing dyspnea for 6
years. He has no cough or fever. He had chronic
exposure to inhalation of silica dust for many years in
his job. A chest x-ray now shows increased interstitial
markings and parenchymal 1 to 3 cm solid nodules. His
pulmonary problems are most likely to be mediated
through which of the following inflammatory processes?
A. Neutrophilic infiltrates producing
leukotrienes
Incorrect. Leukotrienes are more
important mediators in acute
inflammation, leading to chemotaxis and
increased vascular permeability, among
other functions.
B. Foreign body giant cell formation
Incorrect. Foreign body giant cells are not
a significant feature of silicosis. Even
though dust particles are technically
'foreign' material, they do not elicit
granuloma formation in the manner of
infectious agents. However, the cell-
mediated immune response is similar.
Inflammation | Pathology Reviewer (Utah) | 45 / 72
C. Plasma cell synthesis of
immunoglobulins
Incorrect. Plasma cell proliferation is not
a key feature of silicosis or other
pneumoconioses.
D. Mast cell histamine release
Incorrect. Mast cells release histamine as
an acute inflammatory response, not as
a chronic process.
E. Macrophage elaboration of cytokines
CORRECT. Cytokines including growth
factors are released from macrophages
that have ingested silica crystals, and
these factors stimulate collagen
production by fibroblasts, producing
interstitial fibrosis and nodule formation
that reduces and restricts the amount of
normal lung parenchyma and makes
breathing more difficult.
A 22-year-old woman has premature labor with
premature rupture of fetal membranes at 20 weeks
gestation. Prior to that time, the pregnancy had been
proceeding normally. A stillbirth occurs two days later.
Microscopic examination of the normal-sized placenta
reveals numerous neutrophils in the amnion and
chorion, but no villitis. The premature labor was most
likely mediated by the effects from release of which of
the following substances?
A. Immunoglobulin
Incorrect. Increased immunoglobulin
production from plasma cells takes time
and is a feature of chronic inflammatory
processes.
B. Prostaglandin
CORRECT. Prostaglandins are
mediators of acute inflammation that
promote labor through effects on smooth
muscle and blood vessels.
C. Complement
Incorrect. Complement components are
not as important as the prostaglandins in
this setting.
D. Fibrinogen
Incorrect. Fibrinogen is converted to
fibrin during coagulation.
E. Lymphokines
Incorrect. Lymphokines such as TNF and
interleukins have a greater effect in
producing fever.
After two weeks in the hospital following a fall in which
she incurred a fracture of her left femoral trochanter, a
76-year-old woman now has a left leg that is swollen,
particularly her lower leg below the knee. She
experiences pain on movement of this leg, and there is
tenderness to palpation. Which of the following
complications is most likely to occur next after these
events?
A. Gangrenous necrosis of the foot
Incorrect. Obstruction of the arterial
supply of blood to the foot would be
necessary for necrosis to occur, and this
patient has evidence for venous
thrombosis. Necrosis from venous stasis
is rare.
B. Hematoma of the thigh
Incorrect. She has thrombosis, but this
does not typically lead to vascular rupture.

C. Disseminated intravascular coagulation
Incorrect. DIC is unlikely to occur with
large venous vessel thrombosis.
D. Pulmonary thromboembolism
CORRECT. She has deep and
superficial venous thrombosis as a
consequence of venous stasis from
immobilization following the accident.
The large deep venous thrombi can
embolize to the lungs and lead to death.
E. Soft tissue sarcoma
Incorrect. Thrombosis does not
predispose to neoplasia.
A 43-year-old woman has had a chronic cough with
fever and weight loss for the past month. A chest
radiograph reveals multiple nodules from 1 to 4 cm in
size, some of which demonstrate cavitation in the
upper lobes. A sputum sample reveals the presence of
acid fast bacilli. Which of the following cells is the most
important in the development her lung lesions?
A. Macrophage
CORRECT. Epithelioid cells and giant
cells are derived from activated
macrophages. Tissue macrophages are
derived from blood monocytes. These
cells are important in the development of
granulomatous inflammation in the
adaptive immune response to
tuberculosis.
B. Fibroblast
Incorrect. Although collagen is laid down
around a granuloma as part of the
response, it is not the major component
involved in granuloma formation.
C. Neutrophil
Incorrect. Although some neutrophils
may be present in a granuloma, they are
not the major contributors to granuloma
formation.
D. Mast cell
Incorrect. Mast cells are few in number.
They are involved in release of mediators
primarily in acute inflammatory
responses.
E. Platelet
Incorrect. Platelets are mainly involved in
coagulation.
A 20-year-old man has experienced painful urination
for 4 days. A urethritis is suspected, and Neisseria
gonorrheae is cultured. Numerous neutrophils are
present in a smear of the exudate from the penile
urethra. These neutrophils undergo diapedesis to
reach the organisms. Release of which of the following
chemical mediators is most likely to drive neutrophil
exudation?
A. Histamine
Incorrect. Histamine increases vascular
permeability and promotes vasodilation.
B. Prostaglandin
Incorrect. Prostaglandin is more
important as a mediator of inflammation
in producing pain, vascular permeability,
and vasodilation.
C. Hageman factor
Incorrect. Hageman factor is Factor XII of
the coagulation sequence and is
activated by contact with collagen and
Inflammation | Pathology Reviewer (Utah) | 46 / 72
basement membrane in damaged
tissues.
D. Bradykinin
Incorrect. Bradykinin, a product of the
kinin system and derived from high
molecular weight kininogen, causes pain
and promotes vasodilation and vascular
permeability.
E. Complement
CORRECT. The C5a component of
complement, along with TNF,
leukotrienes, and bacterial products, is
chemotactic for neutrophils.
An episode of marked chest pain lasting 4 hours brings
a 51-year-old man to the emergency room. He is found
to have an elevated serum creatine kinase. An
angiogram reveals a complete blockage of the left
circumflex artery 2 cm from its origin. Which of the
following substances would you most expect to be
elaborated around the region of tissue damage in the
next 3 days as an initial response to promote healing?
A. Histamine
Incorrect. Histamine produces
vasodilation as part of an immediate
inflammatory response. It is not part of
the healing process.
B. Immunoglobulin G
Incorrect. Immunoglobulins are secreted
by plasma cells as part of a response to
inflammation, particularly with infectious
agents.
C. Complement component C3b
Incorrect. C3b is an opsonin.
D. Leukotriene B4
Incorrect. Leukotrienes are best known
as acute inflammatory mediators
generated by the cyclo-oxygenase
pathway of arachidonic acid metabolism.
E. Vascular endothelial growth factor
CORRECT. The VEGF stimulates
angiogenesis to aid in establishing
collateral circulation and restoring blood
flow to the myocardium in this patient with
an acute myocardial infarction.
A 94-year-old woman has developed a fever and cough
over the past 2 days. Staphylococcus aureus is
cultured from her sputum. She receives a course of
antibiotic therapy. Two weeks later she no longer has
a productive cough, but she still has a fever. A chest
radiograph reveals a 3 cm rounded density in the right
lower lobe whose liquefied contents form a central air-
fluid level. There are no surrounding infiltrates. Which
of the following is the best description for this outcome
of her pneumonia?
A. Hypertrophic scar
Incorrect. A hypertrophic scar is an
exaggerated healing response with
extensive collagen deposition that is
most likely to occur with injury to the skin.
B. Abscess formation
CORRECT. The formation of a fluid filled
cavity following an infection with S.
aureus suggests that liquefactive
necrosis has occurred. The cavity is filled
with tissue debris and viable and dead
neutrophils (pus). Localized, pus filled

cavities are called abscesses. The
liquified contents seek a level (air-fluid
level).
C. Regeneration
Incorrect. If lung tissue is destroyed, it
does not regenerate. However, there is
considerable pulmonary reserve capacity,
so pulmonary failure is not an outcome of
a resolved pneumonia.
D. Bronchogenic carcinoma
Incorrect. Neoplasia is not a inflammatory
consequence of acute inflammatory
processes.
E. Chronic inflammation
Incorrect. Pneumonias caused by
bacterial organisms tend to resolve
without becoming chronic.
F. Granulomatous cavitation
Incorrect. Granulomas can become large
and cavitate from central caseous
necrosis. However, this process takes
months. In this case, acute inflammation
was complicated by abscess formation
with liquefactive necrosis. The most
common organism causing pulmonary
granulomas is Mycobacterium
tuberculosis.
A 36-year-old woman has been taking acetylsalicylic
acid (aspirin) for arthritis for the past 4 years. Her joint
pain is temporarily reduced via this therapy. However,
she now has occult blood identified in her stool. Which
of the following substances is most likely inhibited by
aspirin to cause this complication?
A. Leukotriene B4
Incorrect. LTB4 is generated through the
lipooxygenase pathway of arachidonic
acid metabolites, which is not affected by
aspirin. Leukotrienes can affect
neutrophil chemotaxis and do not play a
major role in production of pain.
B. Interleukin-1
Incorrect. IL-1 is a cytokine that is not part
of the arachidonic acid metabolic
pathway. It is not generally associated
with pain.
C. Thromboxane
CORRECT. Asprin inhibits thromboxane
A2 production by platelets, which
reduces the ability of platelets to plug
small vascular defects. Thromboxane is
in the cyclooxygenase arm of the
arachidonic acid pathway.
D. Bradykinin
Incorrect. Aspirin has no direct effect
upon bradykinin generation, even though
bradykinin has role to play in appearance
of pain.
E. Hageman factor
Incorrect. Aspirin does not affect
Hageman factor. The anticoagulant
effect of aspirin occurs mainly through its
action on platelets.
Inflammation | Pathology Reviewer (Utah) | 47 / 72
A small sliver of wood becomes embedded in the finger
of a 25-year-old man. He does not remove it, and over
the next 3 days the area around the sliver becomes red,
swollen, and tender. Neutrophils migrate into the
injured tissue. Expression of which of the following
substances on endothelial cells is most instrumental in
promoting this inflammatory reaction?
A. Interferon gamma
Incorrect. Interferons are produced by a
variety of cells and are mainly part of
reactions involving
lymphocytes.
B. Hageman factor
Incorrect. Hageman factor is involved in
coagulation, but not through platelets.
C. Lysozyme
Incorrect. Lysozyme within the
neutrophils aids in bacterial killing.
D. E-selectin
E. CORRECT. Selectins are adhesive
molecules expressed on endothelial cell
surfaces and attract leukocytes, mainly
neutrophils. P-selectin is expressed
rapidly, while E-selectin is expressed
within several hours.
F. Prostacyclin
Incorrect. Prostacyclin is produced by
endothelium to reduce platelet adhesion.
An inflammatory process that has continued for 3
months includes the transformation of tissue
macrophages to epithelioid cells. There are also
lymphocytes present. Over time, fibroblasts lay down
collagen as the focus of inflammation heals. These
events are most likely to occur as an inflammatory
response to which of the following infectious agents?
A. Mycobacterium tuberculosis
CORRECT. Mycobacterial organisms
are difficult to kill, because of their lipid
coat of mycolic acid. Hence a neutrophilic
response has little effect. This persistent
infection requires macrophage activation
that leads to granuloma formation.
B. Pseudomonas aeruginosa
Incorrect. Bacteria tend to elicit an acute
inflammatory response.
C. Cytomegalovirus
Incorrect. Viral infections tend to produce
chronic inflammatory responses.
D. Giardia lamblia
Incorrect. This intestinal parasite
produces little inflammation.
E. Treponema pallidum
Incorrect. Syphilis can produce
gummatous necrosis, which is a form of
granulomatous response, but neutrophils
predominate.

A 37-year-old man has had nausea and vomiting for 5
weeks. He experienced an episode of hematemesis
yesterday. On physical examination he has no
abnormal findings. Upper GI endoscopy is performed,
and there is a 1.5 cm diameter lesion in the gastric
antrum with loss of the epithelial surface. These
findings are most typical for which of the following
pathologic processes?
A. Abscess
Incorrect. An abscess is a localized
collection of pus. Ulceration may occur
secondarily over an abscess.
B. Serositis
Incorrect. Serositis is inflammation of a
mesothelial surface, such as the pleura
or peritoneum
C. Granuloma
Incorrect. A granuloma is a localized area
of inflammation including epithelioid
macrophages.
D. Gangrene
Incorrect. Gangrenous necrosis includes
coagulative and liquefactive necrosis
involving a body part.
E. Ulcer
CORRECT. The loss of an epithelial
surface with inflammation is called an
ulceration. The presence of hydrochloric
acid in the stomach promotes this
process when epithelial injury occurs.
A 17-year-old truck driver is involved in a collision. He
incurs blunt force abdominal trauma. In response to
this injury, cells in tissues of the abdomen are
stimulated to enter the G1 phase of the cell cycle from
the G0 phase. Which of the following cell types is most
likely to remain in G0 following this injury?
A. Smooth muscle
Incorrect. Smooth muscle cells may
proliferate in response to injury.
B. Endothelium
Incorrect. Endothelium proliferates and
helps to revascularize injured areas.
C. Skeletal muscle
CORRECT. Skeletal and cardiac muscle
cells do not typically proliferate in
response to injury, and necrotic cells are
replaced by connective tissue.
Remaining striated muscle cells,
however, can undergo hypertrophy.
D. Fibroblast
Incorrect. Fibroblasts form an important
part of the response to injury.
E. Hepatocyte
Incorrect. Hepatocytes can proliferate in
response to injury.
A 19-year-old woman who works indoors spends a day
outside gardening. She does not wear a hat or
sunscreen. That evening her partner remarks that her
face appears red. Which of the following dermal
changes most likely accounts for her red appearance?
A. Neutrophil aggregation
Incorrect. Leukotriene-induced
neutrophil aggregation is a function of the
lipooxygenase pathway. There will be
inflammation, and a collection of
neutrophils imparts a yellow color as an
exudate.
Inflammation | Pathology Reviewer (Utah) | 48 / 72
B. Hemorrhage
Incorrect. Complement is present in
serum and can be activated in
inflammatory processes, but vascular
leakage with hemorrhage is an
undesirable effect.
C. Edema
Incorrect. Vascular dilation with
endothelial cell retraction allows
intravascular fluid to leak out, causing the
'tumor' of swelling in an inflammatory
reaction.
D. Hemolysis
Incorrect. Hemolysis is a feature of direct
red blood cell damage, not focal
inflammation.
E. Vasodilation
CORRECT. The inflammatory reaction of
sunburn involves vasodilation and
leakage of fluid. Vasodilation imparts a
red color, which can fade quickly.
Prostaglandins are generated through
the cyclooxygenase pathway of
arachidonic acid metabolism and induce
vasodilation. Histamine contributes to
vasodilation. Sunburn is typically
superficial, and keratinocytes of the
epidermis may undergo apoptosis and
slough off.
A 45-year-old woman has had a chronic, non-
productive cough for 3 months, along with intermittent
fever. She has a chest radiograph that reveals multiple
small parenchymal nodules along with hilar and
cervical lymphadenopathy. A cervical lymph node
biopsy is performed. Microscopic examination of the
biopsy shows noncaseating granulomatous
inflammation. Cultures for bacterial, fungal, and
mycobacterial organisms are negative. Which of the
following chemical mediators is most important in the
development of her inflammatory response?
A. Interferon gamma
CORRECT. This non-caseating
granulomatous inflammation is typical for
sarcoidosis, a non-infectious process.
Granulomas are a form of type IV
hypersensitivity reaction. There are
cytokines such as interferon gamma
produced by lymphocytes that recruit
blood monocytes and stimulate
macrophages to develop a
granulomatous response.
B. Bradykinin
Incorrect. Bradykinin is mainly a product
of acute inflammatory responses and
results in pain.
C. Complement C5a
Incorrect. Complement C5a is a
chemotactic factor for neutrophils in
acute inflammatory reactions.
D. Histamine
Incorrect. Histamine release results in
vasodilation leading to edema with acute
inflammation.
E. Prostaglandin E2
Incorrect. Prostaglandins participate in
acute inflammatory reactions.

A 55-year-old man has a history of
hypercholesterolemia with coronary artery disease and
suffered a myocardial infarction 2 years ago. He now
presents with crushing substernal chest pain. Which of
the following laboratory tests is most useful in
diagnosing the cause of his chest pain?
A. Increased white blood cell count
Incorrect. Although the WBC count may
increase with inflammation and infarction,
it is non-specific.
B. Elevated sedimentation rate
Incorrect. The sedimentation rate is
elevated in a variety of inflammatory
conditions.
C. Decreased serum complement
Incorrect. Complement decrease is more
typical for inflammatory conditions with
immunologic mechanisms.
D. Increased serum troponin
CORRECT. Troponins are released from
the damaged striated muscle. Cell
damage leads to leakage of intracellular
contents, such as enzymes or other
proteins. Some of these are more
specific for certain tissues to aid in
diagnosis.
E. Decreased platelet count
Incorrect. Reduction of the platelet count
suggests a coagulopathy or hematologic
disorder.
F. Increased serum cholesterol
Incorrect. We already know that his
cholesterol has been elevated, and this is
a measure of his risk for coronary artery
disease; but does not help diagnose an
acute coronary event.
A 15-year-old girl has had episodes of sneezing with
watery eyes and runny nose for the past 2 weeks. On
physical examination she has red, swollen nasal
mucosal surfaces. She has had similar episodes each
Spring and Summer when the amount of pollen in the
air is high. Her symptoms are most likely to be
mediated by the release of which of the following
chemical mediators?
A. Complement C3b
Incorrect. C3b acts as an opsonin.
B. Platelet activating factor (PAF)
Incorrect. Although one of the actions of
PAF is to increase vascular permeability,
PAF is not as important as histamine in
this setting.
C. Tumor necrosis factor (TNF)
Incorrect. TNF is involved in chemotaxis
and in producing fever.
D. Histamine
CORRECT. Histamine, mainly released
from mast cells in perivascular locations
in the submucosa beneath the nasal
respiratory epithelium, leads to
vasodilation and fluid exudation. That is
why people with allergies take
antihistamines.
E. Immunoglobulin G
Incorrect. IgG is directed against specific
antigens. It is not as important as IgE in
an allergic response.
Inflammation | Pathology Reviewer (Utah) | 49 / 72
A 45-year-old man has been working hard all day long
carrying loads of bricks to build a wall. He takes a non-
steroidal anti-inflammatory drug (ibuprofen). Which of
the following processes is this drug most likely to
diminish in his arms?
A. Thrombosis
Incorrect. However, aspirin is felt to
diminish platelet function and may have
a longer term benefit in prevention of
thrombosis.
B. Pain
CORRECT. Aspirin, indomethacin, and
NSAIDS block the cyclo-oxygenase arm
of the arachidonic acid pathway, which
generates the prostaglandins that play a
role in development of pain as a
consequence of the inflammatory
process. The inflammation here is
minimal but widespread as a
consequence of the overuse of the
connective tissues in the arms.
C. Necrosis
Incorrect. Necrosis results in cell death.
Normal activities generally do not
produce significant tissue damage. It
generally takes a disease process, such
as infection producing inflammation, or
tissue trauma, or ischemia from loss of
blood supply, to produce necrosis.
D. Fibrinolysis
Incorrect. The fibrinolytic mechanisms
are not affected.
E. Scar formation
Incorrect. Collagen deposition is not
affected.
Within minutes following a bee sting, a 37-year-old man
develops marked respiratory stridor with dyspnea and
wheezing. He also develops swelling and erythema
seen in his arms and legs. An injection of epinephrine
helps to reverse these events and he recovers within
minutes. Which of the following chemical mediators is
most important in the pathogenesis of this man's
condition?
A. Bradykinin
Incorrect. Bradykinin can be released
with acute inflammatory reactions, but it
mainly produces pain, and it is not
released by mast cells with allergic
responses.
B. Complement C5a
Incorrect. Complement C5a is a
chemoattractant for neutrophils, but the
response in this case is more immediate.
C. Nitric oxide
Incorrect. Nitric oxide can be released by
macrophages and endothelial cells and is
not a major part of an allergic response.
D. Tumor necrosis factor
Incorrect. TNF can be released by
activated macrophages and is not a
significant part of an allergic response.
E. Histamine
CORRECT. This is systemic anaphylaxis,
a type I hypersensitivity reaction in which
the antigen contacts preformed IgE
antibody attached to mast cells, leading
to mast cell degranulation with release of
bioactive compounds such as histamine

and production of symptoms. The initial
response typically occurs within minutes.
A 72-year-old woman did not get a 'flu' shot in the fall
as recommended for older persons. In the wintertime,
she became ill, as many people in her community did,
with a respiratory illness that lasted for 3 weeks. During
this illness, she had a fever with a non-productive
cough, mild chest pain, myalgias, and headache. What
was her chest radiograph most likely to have shown
during this illness?
A. Hilar mass
Incorrect. Mass lesions are more typical
for neoplasms or granulomatous
diseases.
B. Interstitial infiltrates
CORRECT. Viral illnesses, including
those caused by common viral
respiratory pathogens such as influenza,
often produce chronic inflammation that
is mainly interstitial in the lungs. The lack
of an alveolar filling process results in the
lack of a productive cough.
C. Hilar lymphadenopathy
Incorrect. Lymphadenopathy is more
typical for acute inflammatory processes,
granulomatous diseases, and metastatic
disease.
D. Lobar consolidation
Incorrect. Consolidation is a more typical
feature for acute infectious processes in
the lung caused by bacterial organisms.
E. Pleural effusions
Incorrect. Pleural effusion is most often a
feature of right heart failure, neoplasia, or
empyema.
In an experiment, Enterobacter cloacae organisms are
added to a solution containing leukocytes and blood
plasma. Engulfment and phagocytosis of the microbes
is observed to occur. Next a substance is added which
enhances engulfment, and more bacteria are
destroyed. Which of the following substances in the
plasma is most likely to produce this effect?
A. Complement C3b
CORRECT. The C3b fragment
generated from the complement cascade
serves as an effective opsonin, attaching
to the bacteria so that phagocytes will
find and engulf them more easily.
B. Glutathione peroxidase
Incorrect. Glutathione peroxidase does
not act as an opsonin; but is involved in
scavenging free radicals.
C. Immunoglobulin M
Incorrect. IgM does not act as an opsonin,
though IgG does.
D. P-selectin
Incorrect. Selectins aid in initial binding of
leukocytes to endothelial surfaces so that
the leukocytes slow down and attach in
preparation for their exit into tissues.
E. NADPH oxidase
Incorrect. NADPH oxidase in leukocytes
aids in the respiratory burst that leads to
killing of phagocytized microbes.
Inflammation | Pathology Reviewer (Utah) | 50 / 72
A 43-year-old woman has had nausea with vomiting
persisting for the past 5 weeks. On physical
examination there are no abnormal findings. She
undergoes an upper GI endoscopy and gastric
biopsies are obtained. The microscopic appearance of
these biopsies shows mucosal infiltration by
lymphocytes, macrophages, and plasma cells. Which
of the following most likely caused her findings?
A. Staphylococcus aureus septicemia
Incorrect. Bacterial infections are
typically accompanied by acute
inflammation, including abscesses in the
case of septicemia with dissemination of
infection.
B. Ingestion of chili peppers
Incorrect. Local irritants such as the
capsaicin in the chilis typically produce a
short-lived acute inflammatory response.
C. Diabetes mellitus
Incorrect. Diabetes mellitus is associated
with an increased risk for acute infections,
but the stomach is not often involved.
D. Tuberculosis
Incorrect. Tuberculosis produces a
granulomatous inflammatory response
and rarely involves the stomach.
E. Infection with Helicobacter pylori
CORRECT. This is a chronic
inflammatory process, based upon the
mononuclear inflammatory cell
components present. H. pylori organisms
live in the mucus above the gastric
epithelium and release chemical
substances that alter epithelial function
and defenses, leading to gastritis. This
organism does not directly infect or
damage the epithelium, and its
persistence leads to the chronic
inflammation.
In an experiment, lymphatic channels are observed in
normal soft tissue preparations. Staphylococcus
aureus organisms are innoculated into the tissues and
the immunologic response observed over the next 24
hours. Which of the following functions is most likely to
be served by these lymphatics to produce a specific
immune response to these organisms?
A. Carry lymphocytes to peripheral tissue
sites
Incorrect. There are valves in the
lymphatics (just as in veins) which result
in a one-way flow of lymph from
peripheral tissues to lymph nodes.
B. Remove extravascular tissue fluid
Incorrect. Excess tissue fluid is drained
by lymphatics, but this does not
specifically serve an immune function,
though antigens may be contained within
the lymphatic fluid.
C. Transport antigen presenting cells
CORRECT. Antigen presenting cells
such as dendritic cells and macrophages
which have trapped antigen in peripheral
tissues can be transported to lymph
nodes where they encounter specific
clones of memory cells capable of
responding to those specific antigens,
and this typically happens within a day.

D. Serve as a route for dissemination of
infection
Incorrect. Infectious agents can gain
access to lymphatics and go to lymph
nodes to produce lymphadenitis. This
spread of infection is not advantageous
to the host.
E. Provide an emigration point for
neutrophils
Incorrect. Most neutrophils marginate,
roll, adhere, and diapedese through
venules and capillaries.
In an experiment, surgical wound sites are observed
following suturing. An ingrowth of new capillaries is
observed to occur within the first week. A substance
elaborated by macrophages is found at the wound site
to stimulate this capillary proliferation. Which of the
following substances is most likely to have this function?
A. Platelet-derived growth factor
Incorrect. PDGF is released from
macrophages as well as activated
platelets and can stimulate fibroblast
growth for collagen synthesis.
B. Phospholipase C-gamma
Incorrect. Phospholipases aid in
stimulation of intracellular protein kinases
that promote protein phosphorylation.
C. Fibronectin
Incorrect. Fibronectin is a component of
the extracellular matrix that helps to link
cells together.
D. Fibroblast growth factor
CORRECT. FGF can stimulate all
aspects of angiogenesis.
E. Epidermal growth factor
Incorrect. EGF is a stimulator of cell
growth through activation of tyrosine
kinases in the cells; it can also stimulate
angiogenesis to a degree.
A 55-year-old man with a history of ischemic heart
disease has worsening congestive heart failure. He
has noted increasing dyspnea and orthopnea for the
past 2 months. On physical examination there is
dullness to percussion at lung bases. A chest x-ray
shows bilateral pleural effusions. A left thoracentesis is
performed, and 500 mL of fluid is obtained. Which of
the following characteristics of this fluid would most
likely indicate that it is a transudate?
A. Cloudy appearance
Incorrect. A cloudy appearance suggests
the presence of increased cells,
characteristic of an exudate.
B. High protein content
Incorrect. Increased protein is
characteristic of an exudate.
C. <3 lymphocytes/microliter
CORRECT. A transudate resembles a
filtrate of plasma and has few cells with
very little protein and has a clear
appearance.
D. Presence of fibrin
Incorrect. Fibrin comes from exuded
fibrinogen, a blood protein.
E. Large size of the effusion
Incorrect. The size of an effusion does
not define exudate or transudate.
Inflammation | Pathology Reviewer (Utah) | 51 / 72
In a clinical study, patients undergoing laparoscopic
cholecystectomy are followed to document the post-
surgical wound healing process. The small incisions
are closed with sutures. Over the 4 weeks following
surgery, the wounds are observed to regain tensile
strength and there is re-epithelialization. Of the
following substances, which is most likely found to
function intracellularly in cells involved in this wound
healing process?
A. Fibronectin
Incorrect. Fibronectin acts in the
extracellular matrix to bind
macromolecules (such as proteoglycans)
via integrin receptors to aid attachment
and migration of cells.
B. Laminin
Incorrect. Laminin is an extracellular
matrix component that is abundant in
basement membranes.
C. Tyrosine kinase
CORRECT. Cell surface growth factor
receptors recruit intracellular protein
kinases that begin a sequence of events
leading to cell division and growth.
D. Hyaluronic acid
Incorrect. Hyaluronic acid is one of the
proteoglycans in the extracellular matrix.
E. Collagen
Incorrect. Collagen fibers are part of the
extracellular matrix that gives strength
and stability to connective tissues.
A 31-year-old woman has a laparotomy performed for
removal of an ovarian cyst. She recovers uneventfully,
with no complications. At the time of surgery, a 12 cm
long midline abdominal incision was made. The tensile
strength in the surgical scar will increase so her normal
activities can be resumed. Most of the tensile strength
will likely be achieved in which of the following time
periods?
A. One week
Incorrect. The wound site has granulation
tissue in this first week, but little collagen
to provide tensile strength at this point.
B. One month
Incorrect. Collagen is being laid down
during this month, but a plateau phase
has not been reached, and wound
strength is still increasing.
C. Three months
CORRECT. About 70 to 80% of the
tensile strength in the scar, compared to
non-wounded skin, is reached at 3
months, which is about as much as will
be obtained.
D. Six months
Incorrect. After 3 months, there will be
little additional gain in tensile strength, so
little more tensile strength will be
achieved in another 3 months.
E. One year
Incorrect. After 3 months, there will be
little additional gain in tensile strength, so
little more tensile strength will be
achieved in another 9 months.

A 9-year-old girl sustains a small 0.5 cm long laceration
to her right index finger while playing 'Queen of Swords'
with a letter opener. Which of the following substances,
on contact with injured vascular basement membrane,
activates both the coagulation sequence and the kinin
system as an initial response to this injury?
A. Thromboxane
Incorrect. Thromboxane, a product of the
cyclooxygenase pathway, is produced by
endothelial cells and promotes
vasoconstriction and platelet aggregation.
B. Plasmin
Incorrect. Plasmin, derived from
plasminogen, is one of the
anticoagulants generated to break down
thrombi.
C. Platelet activating factor
Incorrect. PAF promotes platelet
aggregation and release. It is also
chemotactic to neutrophils and causes
them also to aggregate and adhere.
D. Hageman factor
CORRECT. Hageman factor (factor XII
as measured in the intrinsic coagulation
pathway) becomes activated upon
contact with injured, exposed vascular
basement membrane.
E. Histamine
Incorrect. Histamine functions as a
vasodilator of arterioles and increases
vascular permeability in venules.
A 65-year-old woman has had a fever for the past day.
On physical examination her temperature is 39°C and
blood pressure 90/50 mm Hg with heart rate of
106/minute. Laboratory studies show a WBC count of
12,510/microliter and WBC differential count of 78 segs,
8 bands, 11 lymphs, and 3 monos. A blood culture is
positive for Escherichia coli. Her central venous
pressure falls markedly. She goes into hypovolemic
shock as a result of the widespread inappropriate
release of a chemical mediator derived from
macrophages. She develops multiple organ failure.
Which of the following mediators is most likely to
produce these findings?
A. Nitric oxide
CORRECT. Nitric oxide (NO) acts as a
vasodilator. Small amounts released
from endothelial cells causes
vasodilation and prevents thrombosis.
Macrophages release NO to kill bacteria,
but large amounts released body-wide
can cause hypotension and shock.
B. Bradykinin
Incorrect. Bradykinin produces pain. It is
generated via the kinin system from
substances in plasma activated during
acute inflammation.
C. Histamine
Incorrect. Histamine can contribute to
vasodilation, edema, and vascular
collapse, but much of it is preformed and
released from mast cells or basophils.
Widespread histamine release can be
part of anaphylaxis with type I
hypersensitivity, but infections typically
do not produce this effect.
Inflammation | Pathology Reviewer (Utah) | 52 / 72
D. Prostacyclin
Incorrect. Prostacyclin is generated by
the arachidonic acid pathway and it
promotes vasodilation.
E. Complement C3a
Incorrect. C3a can promote vasodilation
and increase vascular permeability to
promote vascular collapse, but
complement is found in plasma, not cells.
A 20-year-old woman sustains an injury to her right calf
in a mountain biking accident. On physical examination
she has a 5 cm long laceration on the right lateral
aspect of her lower leg. This wound is closed with
sutures. Wound healing proceeds over the next week.
Which of the following factors will be most likely to aid
and not inhibit wound healing in this patient?
A. Commensal bacteria
Incorrect. The commensal population of
organisms on the skin ordinarily does not
gain access to underlying tissues to
establish infection. A wound may provide
a route for infection, a serious
postoperative complication.
B. Decreased tissue perfusion
Incorrect. Diabetics and persons with
severe atherosclerosis have notoriously
poor wound healing.
C. Presence of sutures
CORRECT. Although any foreign body
will delay wound healing to some degree,
the net effect of having sutures is to aid
the process of healing more than to
hinder it, since the sutures close the
wound, so there is less space to fill in by
granulation tissue, and less distance for
cells to move.
D. Corticosteroid therapy
Incorrect. Corticosteroids dampen the
inflammatory response that contributes
to the healing process.
E. Hypoalbuminemia
Incorrect. Poor nutrition is a detriment to
wound healing.
A 24-year-old primigravida is late in the second
trimester of pregnancy. She experiences the sudden
onset of some cramping lower abdominal pain. This is
immediately followed by passage of some fluid per
vagina along with a foul-smelling discharge. The fetus
is stillborn two days later. Examination of the placenta
demonstrates extensive neutrophilic infiltrates in the
chorion and amnion. Which of the following organisms
is most likely to be responsible for these findings?
A. Mycobacterium tuberculosis
Incorrect. Tuberculosis produces a
granulomatous pattern of infection that
develops over weeks to months.
B. Herpes simplex virus
Incorrect. Viral infections typically do not
cause acute inflammation with
neutrophils.
C. Escherichia coli
CORRECT. She developed an acute
chorioamnionitis, and bacterial infections
that precede or follow premature rupture
of membranes are most often to blame.
Bacterial infections tend to elicit
neutrophilic inflammatory responses.

D. Treponema pallidum
Incorrect. Syphilis is not known for
producing acute infection with
neutrophilic infiltrates.
E. Toxoplasma gondii
Incorrect. This parasitic organism
produces a congenital infection over
weeks' time.
A 19-year-old man incurs a stab wound to the chest.
The wound is treated in the emergency room. Two
months later there is a firm, 3 x 2 cm nodular mass with
intact overlying epithelium in the region of the wound.
On examination the scar is firm, but not tender, with no
erythema. This mass is excised and microscopically
shows fibroblasts with abundant collagen. Which of the
following mechanisms has most likely produced this
series of events?
A. Keloid formation
CORRECT. Some persons have an
exaggerated, inappropriate wound
healing response with excessive
collagenization.
B. Development of a fibrosarcoma
Incorrect. Trauma does not lead to
neoplasia.
C. Poor wound healing from diabetes
mellitus
Incorrect. Diabetes mellitus leads to
severe peripheral vascular disease that
delays wound healing, but the wound
would not have excessive collagen.
D. Foreign body response from suturing
Incorrect. Sutures can produce small
foreign body granulomas that are
typically not visible.
E. Staphyloccocal wound infection
Incorrect. A wound infection will produce
dehiscence and abscess formation that
delays or disrupts collagenization.
A 45-year-old man has had a fever and dry cough for 3
days, and now has difficulty breathing and a cough
productive of sputum. On physical examination his
temperature is 38.5°C. Diffuse rales are auscultated
over lower lung fields. A chest radiograph shows a
right pleural effusion. A right thoracentesis is performed.
The fluid obtained has a cloudy appearance with a cell
count showing 15,500 leukocytes per microliter, 98%
of which are neutrophils. Which of the following terms
best describes his pleural process?
A. Serous inflammation
Incorrect. A transudate in a serous
effusion has few cells.
B. Purulent inflammation
CORRECT. The neutrophils suggest an
acute inflammatory process; the fluid is
characteristic for an exudate. Such a
large amount of purulent exudate in the
pleural space can be termed an
empyema.
C. Fibrinous inflammation
Incorrect. Fibrin can often accompany
acute inflammatory processes, but a
process with so many neutrophils is best
characterized as a purulent exudate.
Inflammation | Pathology Reviewer (Utah) | 53 / 72
D. Chronic inflammation
Incorrect. Chronic inflammation has a
preponderance of mononuclear cells, not
neutrophils.
E. Granulomatous inflammation
Incorrect. A granulomatous response is
characterized by mononuclear cells.
A 52-year-old woman with no major medical problems
takes a long airplane flight across the Pacific Ocean.
Upon arrival at Sydney's Kingsford Smith airport
following the flight from Los Angeles, she cannot put
her shoes back on. There is no pain or tenderness.
Which of the following is the most likely explanation for
this phenomenon?
A. Activation of Hageman factor has led to
bradykinin production.
Incorrect. There is no tissue damage in
this situation to activate Hageman factor.
B. A lot of drinks were served in the first-
class section.
Incorrect. Normal renal function will
maintain water and electrolyte balance,
along with trips to the rest room.
C. Femoral vein thrombosis developed.
Incorrect. Though swelling could come
from venous obstruction with thrombosis,
there would likely be pain and tenderness
with thrombosis, and swelling in more
than just her feet. However, the
immobilization with venous stasis from
such a long flight is a risk for thrombosis.
D. A cellulitis developed in her legs.
Incorrect. She would be unlikely to
develop a cellulitis over this short a time.
E. Venous hydrostatic pressure became
increased.
CORRECT. The longest non-stop flight in
the world has its drawbacks. Extracellular
fluid builds up when hydrostatic pressure
is increased over a long time. Remaining
upright and stationary in a cramped
airplane predisposes to reduced venous
and lymphatic return.
In an experiment, a lung tissue preparation is exposed
to Mycobacterium tuberculosis organisms. Over the
next week, it is observed that granulomas form in the
lung. Within the granuloma are found inflammatory
cells expressing class II MHC antigens. These cells
elaborate cytokines that promote fibroblastic
production of collagen within the granulomas. From
which of the following peripheral blood leukocytes are
these cells bearing class II antigen most likely to be
derived?
A. Neutrophils
Incorrect. Neutrophils participate in acute
inflammatory processes and release
enzymes to cause non-specific
destruction of anything nearby.
B. B cells
Incorrect. B cells are activated to become
plasma cells that secrete
immunoglobulins.
C. Monocytes
CORRECT. Blood monocytes can
migrate into tissues and become
macrophages. Macrophages play an
 Inflammation | Pathology Reviewer (Utah) | 54 / 72
important role in delayed hypersensitivity
reactions with cell-mediated immunity.
D. NK cells
Incorrect. Natural killer cells selectively
bind to a target site to destroy it.
E. Basophils
Incorrect. Basophils play a role in allergic
responses.

A 56-year-old man has had increasing difficulty

breathing for the past week. On physical examination
he is afebrile. Auscultation of his chest reveals
diminished breath sounds and dullness to percussion
bilaterally. There is 2+ pitting edema present to the
level of his thighs. A chest radiograph reveals bilateral
pleural effusions. Which of the following laboratory test
findings is he most likely to have?
A. Hypoalbuminemia
CORRECT. The decrease in oncotic
pressure from decreased serum albumin,
the blood protein that accounts for most
of the oncotic pressure, can be significant.
This can be a cause for edema and fluid
transudates. Too little circulating protein
doesn't keep in or draw water into the
vasculature.
B. Glucosuria
Incorrect. Glucosuria with diabetes
mellitus can explain loss of free water
with dehydration, not edema.

C. Neutrophilia
Incorrect. Neutrophilia suggests an acute
inflammatory response, which can
produce localized edema in the area of
inflammation.
D. Anemia
Incorrect. Anemia reduces oxygen
carrying capacity; if severe, it could
eventually lead to a high output
congestive heart failure that would
initially involve mainly the left heart, with
consequent pulmonary congestion and
edema.
E. Hypernatremia
Incorrect. An increased serum sodium
suggests loss of free water and
dehydration, not edema.
 NEOPLASIA SECTION
A 44-year-old woman notes a lump in her left breast
while taking a shower. The nurse practitioner palpates
a 3 cm firm, irregular, non-movable mass in the upper
outer quadrant of her left breast on physical
examination. A fine needle aspiration of this mass is
performed, and cytologically, the cells are consistent
with infiltrating ductal carcinoma. The mass is removed
with lumpectomy along with an axillary lymph node
dissection. Which of the following findings will best
predict a better prognosis for this patient?
A. Tumor cells strongly estrogen receptor
positive
Incorrect. Many breast cancers are
estrogen receptor positive, which
suggests that hormonal therapy will be
helpful.
B. No metastases in the sampled lymph
nodes
CORRECT. The lack of metastases
suggests a lower stage and a better
prognosis. In general, stage is a better
indicator of prognosis than grade. In
general, low stage cancers are more
amenable to surgical resection and
chance for cure.
C. Flow cytometric analysis with aneuploidy
and a high S-phase
Incorrect. Both aneuploidy and a high S-
phase are characteristic for malignancies
and suggest a worse prognosis.
D. One relative who had a similar type of
breast cancer
Incorrect. A history of breast cancer
suggests a greater risk for breast cancer;
but does not predict prognosis.
E. High cytologic tumor grade
Incorrect. A higher grade suggests a
worse prognosis.
A change in bowel habits prompts a 53-year-old
woman to see her physician. On physical examination
there are no lesions noted on digital rectal examination,
but her stool is positive for occult blood. A colonoscopy
is performed and reveals a 6 cm friable exophytyic
mass in the cecum. A biopsy of this mass is performed
and microscopic examination shows a moderately
differentiated adenocarcinoma. Which of the following
laboratory findings is most likely to be present in this
patient?
A. K-RAS mutation in the neoplastic cells
CORRECT. Many human carcinomas
are associated with RAS mutations that
contribute to oncogenesis. Many types of
mutations can be present, and in general
multiple mutations are present. Sporadic
cancers in adults can have many of the
same mutations, such as APC and
mismatch repair, that are found in familial
cancers, but they are acquired and not
inherited.
B. Neoplastic cells positive for vimentin
Incorrect. Vimentin is a more typically
marker for soft tissue malignancies
(sarcomas). Carcinomas are positive for
cytokeratin by immunohistochemistry.
C. Stool culture with Shigella flexneri
Incorrect. Bacterial infections do not tend
to increase the risk for adenocarcinoma.
D. Presence of HIV-1 RNA
Incorrect. Adenocarcinomas of the colon
are generally not seen with significantly
increased frequency in persons with
immunodeficiency diseases.
E. DNA topoisomerase I autoantibody
Incorrect. Adenocarcinomas of the colon
are generally not seen with significantly
increased frequency in persons with
collagen vascular diseases.
An experiment is conducted in which proliferating cells
are subjected to ionizing radiation. The ionizing
radiation leads to arrest in a checkpoint that monitors
completion of DNA replication. It is observed that there
are increased numbers of chromosomal abnormalities
in these cells. Which of the following is the checkpoint
affected by the ionizing radiation?
A. G0/G1
Incorrect. This represents entry into the
cell cycle from the resting, non-
proliferating state. Connective tissue
cells and hepatocytes can be stimulated
to enter the cell cycle, but others such as
neurons are terminally differentiated and
cannot.
B. G1/S
Incorrect. This is the cell cycle checkpoint
at which defects in DNA are detected to
prevent replication with mutations or
chromosomal breaks.
C. S/G2
Incorrect. This is the synthesis phase in
which there is no checkpoint.
D. G2/M
CORRECT. This is the second
checkpoint in the cell cycle; ionizing
radiation activates this checkpoint,
resulting in chromosomal abnormalities
in mitosis.
E. M/G0
Incorrect. This is the point at which a cell
goes back to a resting state.
A clinical study is performed to determine the incidence
of cancers in different countries. The data show that
persons born in Japan and continuing to reside there
have an increased risk for cancer. Which of the
following cancers is most likely seen with increased
frequency in this population?
A. Breast
Incorrect. Breast cancer incidence is
highest for women from Europe and
North America.
B. Colon
Incorrect. Colon cancers are most
prevalent in developed nations and when
diets are low in fiber.
C. Lung
Incorrect. Lung cancer is most related to
smoking.
Page 55 of 72

D. Stomach
CORRECT. Gastric cancers are more
prevalent in Japan. Is this genetics or
environment? The risk goes down with
emigration and subsequent generations
living outside of Japan. The prevlance of
H. pylori infection may play a role.
Incidence of gastric cancer has
diminished in the U.S. The health care
system in Japan has effective screening
programs that diagnose many cases at
the curable early gastric cancer stage.
E. Uterine
Incorrect. Uterine cancers include
endometrium and cervix. The latter is
related to HPV infection, and Pap smear
screening has markedly reduced the risk
for development of fatal cervical cancers.
A 48-year-old woman has a routine physical
examination. A 4 cm diameter non-tender mass is
palpated in her right breast. The mass appears fixed to
the chest wall. Another 2 cm non-tender mass is
palpable in the left axilla. A chest radiograph reveals
multiple 0.5 to 2 cm nodules in both lungs. Which of the
following TNM classifications best indicates the stage
of her disease?
A. T1 N1 M0
Incorrect. This classification is for a small
primary cancer with nodal metastases
but no distant metastases.
B. T1 N0 M1
Incorrect. This classification is for a small
primary cancer with no lymph node
metastases but with distant metastases.
C. T2 N1 M0
Incorrect. This classification is for a larger
primary cancer with nodal metastases
but no distant metastases.
D. T3 N0 M0
Incorrect. This classification is for a larger
primary cancer with no metastases to
either lymph nodes or to distant sites.
E. T4 N1 M1
CORRECT. She has a large invasive
(high T) primary tumor mass with axillary
node (N > 0) and lung (distant)
metastases (M1).
A study is performed to analyze characteristics of
malignant neoplasms in biopsy specimens. The
biopsies were performed on patients who had palpable
mass lesions on digital rectal examination. Of the
following microscopic findings, which is most likely to
indicate that the neoplasm is malignant?
A. Pleomorphism
Incorrect. While cellular pleomorphism
(variation in shape and size) is more
prominent in malignant neoplasms, it
may be present in benign neoplasms, too.
B. Atypia
Incorrect. Atypia can be part of benign or
dysplastic processes that are not
malignant. Some mild atypia may
accompany inflammatory processes.
Dysplasias may be present in the
pathway of progression to carcinomas.
Neoplasia | Pathology Reviewer (Utah) | 56 / 72
C. Invasion
CORRECT. Metastasis would be an
even better indicator, but invasion of
adjacent tissues suggests malignancy
more than the other items listed here.
Size increasing beyond 1 cm is also a risk
for malignancy in a colonic polypoid
lesion.
D. Increased nuclear/cytoplasmic ratio
Incorrect. A high N/C ratio is one feature
of malignancy; but is not the best
indicator.
E. Necrosis
Incorrect. Necrosis may occur for many
reasons. Even a benign tumor could
cause pressure necrosis or outgrow its
blood supply.
Review of a series of surgical pathology reports
indicates that a certain type of neoplasm is diagnosed
as grade I on a scale of I to IV. Clinically, some of the
patients with this neoplasm are found to have stage I
disease. Which of the following is the best
interpretation of a neoplasm with these designations?
A. Unlikely to be malignant
Incorrect. Criteria for malignancy must be
satisfied first, then grading and staging
follow. Benign neoplasms are by
definition well-differentiated and localized.
B. Arising from epithelium
Incorrect. Grading and staging are most
useful for epithelial malignancies; but are
not reserved specifically for them.
C. May spread via lymphatics and
bloodstream
Incorrect. A malignant neoplasm may
indeed spread to lymph nodes,
particularly if it is a carcinoma, or
hematogenously to distant sites, but is
less likely to do so if it has a low grade
and it remains small and localized.
D. Has an in situ component
Incorrect. It may have an in situ
component, but the behavior of most
neoplasms is judged by the worst part of
it, and stage I puts it beyond in situ. The
designation Tis may be used for
carcinoma in situ of epithelial neoplasms.
E. Well-differentiated and localized
CORRECT. A well-differentiated (low
grade) and localized (lower stage)
malignant neoplasm often has both a low
grade and low stage. In such cases
surgery to excise the lesion is more likely
to be curative.
A 51-year-old man has worked for 10 years in a factory
producing plastic pipe but not following safety
standards. He has noted weight loss, nausea, and
vomiting worsening over the past 5 months. On
examination he is afebrile. There is generalized muscle
wasting. Laboratory studies show the serum alkaline
phosphatase is 405 U/L with AST 47 U/L, ALT 35 U/L,
and total bilirubin 1.2 mg/dL. An abdominal CT scan
reveals a 12 cm right liver lobe mass. Liver biopsy
reveals a neoplasm composed of spindle cells forming
irregular vascular channels. With
immunohistochemical staining the cells demonstrate
vimentin positivity and cytokeratin negativity. Exposure

to which of the following substances most likely led to
development of this neoplasm?
A. Benzene
Incorrect. Hydrocarbon exposure can
predispose to development of leukemias.
B. Radon
Incorrect. Radon gas exposure can
increase the risk for lung cancer.
C. Cyclophosphamide
Incorrect. Cyclophosphamide is an
alkylating agent used for chemotherapy,
but this drug can promote leukemia,
lymphoma, and carcinoma.
D. Asbestos
Incorrect. Asbestos exposure can
increase the risk for lung cancer
particularly in persons who smoke. It is
also associated with the rare neoplasm
known as mesothelioma.
E. Vinyl chloride
CORRECT. This is a rare cause of
cancer. However, this causal relationship
is easy to demonstrate, because hepatic
angiosarcoma is a rare neoplasm. What
else could happen in the future? At least
a hundred new chemical compounds are
dumped into the environment each year.
The elevated alkaline phosphatase is
characteristic for hepatic metastases as
well as bone metastases.
A child is born with a single functional allele of a tumor
suppressor gene. At the age of five the remaining
normal allele is lost through a point mutation. As a
result, the ability to inhibit cell cycle progression until
the cell is ready to divide is lost. Which of the following
neoplasms is most likely to arise via this mechanism?
A. Breast ductal carcinoma
Incorrect. Most breast carcinomas are
sporadic, though some are related to
BRCA1 and BRCA2 or other gene
mutations which can be inherited, though
the onset of disease occurs in young
adults.
B. Pulmonary small cell anaplastic
carcinoma
Incorrect. Most small cell carcinomas of
the lung are related to smoking.
C. Ocular retinoblastoma
CORRECT. The RB gene is the classic
example of the 'two hit' mechanism for
loss of tumor suppression. About 60% of
these tumors are sporadic, while others
are familial, and there is inheritance of a
mutated copy of the RB gene. Loss of the
second copy in retinoblasts leads to the
occurrence of retinoblastoma in
childhood.
D. Cerebral astrocytoma
Incorrect. Gliomas of the brain are mostly
sporadic.
E. Chronic myeloid leukemia
Incorrect. CML is most often associated
with the 'Philadelphia chromosome' that
is acquired in adulthood.
Neoplasia | Pathology Reviewer (Utah) | 57 / 72
A 22-year-old woman goes to her physician for a
routine examination. A palpable nodule is found in the
right lobe of her thyroid gland. No lymphadenopathy is
noted. A chest x-ray shows no masses. A fine needle
aspirate of the nodule is performed and cytologic
examination reveals cells present consistent with a
papillary carcinoma of the thyroid. There are no other
family members affected by this disorder. She works as
an administrator for an accounting firm part time and is
earning a college degree. Which of the following
findings would you consider most relevant in her past
history to indicate a risk factor for this neoplasm?
A. Chronic alcoholism
Incorrect. Chronic alcoholism can lead to
micronodular cirrhosis, and in this setting
hepatocellular carcinomas can arise.
B. Radiation therapy in childhood
CORRECT. Radiation is oncogenic.
Cancers of thyroid and bone often
develop in children with radiation
exposure. Leukemias can occur as well.
C. Ataxia telangiectasia
Incorrect. This is an inherited disorder of
DNA instability in which leukemias,
lymphomas, and breast cancers may
arise.
D. Blunt trauma from a fall
Incorrect. Trauma is not a risk for
neoplasia.
E. Occupational exposure
Incorrect. Her jobs do not include any
typical exposure to carcinogens. An
example of an environmental exposure
would be arsenic, to which exposure can
increase the risk for skin cancer. For
years, pressure-treated lumber to
prevent wood rot has relied upon use of
arsenical compounds. There is a lot of
that treated wood out in the environment.
A 50-year-old man has felt vague abdominal discomfort
for the past 4 months. On physical examination he has
no lymphadenopathy, and no abdominal masses or
organomegaly can be palpated. Bowel sounds are
present. An abdominal CT scan shows a 20 cm
retroperitoneal soft tissue mass obscuring the left
psoas muscle. A stool specimen tested for occult blood
is negative. Which of the following neoplasms is this
man most likely to have?
A. Melanoma
Incorrect. Melanomas arise on the skin in
most cases, related to ultraviolet light
exposure, and are rarely visceral or in
soft tissue.
B. Hamartoma
Incorrect. A hamartoma is a peculiar
small benign neoplasm composed of
tissues normal to a site, but just in a
jumbled mass. A pulmonary hamartoma
is the most common of these.
C. Adenocarcinoma
Incorrect. Adenocarcinomas do not arise
in soft tissues. Sarcomas arise in soft
tissues.
D. Lymphoma
Incorrect. It is unlikely that matted nodes
with lymphoma would reach this size.

E. Liposarcoma
CORRECT. Sarcomas are big and bad.
They arise in soft tissues derived from
mesenchymal (connective) tissues.
Retroperitoneum is a typical location for
a sarcoma arising in an adult. Sarcomas
are much less common than carcinomas
in adults.
A 52-year-old man has had increasing fatigue for the
past 6 months. On physical examination he has a
palpable spleen tip. Laboratory studies show a WBC
count of 189,000/microliter. The peripheral blood
smear shows many mature and immature myeloid cells
present. Cytogenetic analysis of cells obtained via
bone marrow aspiration reveals a t(9:22) translocation.
This translocation leads to formation of a hybrid gene
that greatly increases tyrosine kinase activity. Which of
the following genes is most likely translocated to cause
these findings
A. p53
Incorrect. p53 is a tumor suppressor
gene, and mutations can be found in a
variety of human carcinomas.
B. RB
Incorrect. RB is a tumor suppressor gene
best known for association with
retinoblastomas of the eye.
C. ABL
CORRECT. This is the 'Philadelphia
chromosome' of chronic myelogenous
leukemia (CML) and an example of an
abnormal fusion gene driving cell
proliferation. Therapy with a biologic
agent such as a tyrosine kinase inhibitor
(TKI), a monoclonal antibody that targets
the abnormal protein produced by the
BCR-ABL fusion gene is often effective.
First generation TKIs include imatinib,
and more effective 2nd generation TKIs
include dasatinib, nilotinib, and bosutinib.
D. NF-1
Incorrect NF-1 is a tumor suppressor
gene associated with neurofibromatosis.
E. RAS
Incorrect. RAS is an oncogene found in
many human carcinomas.
A clinical study is performed of oncogenesis in human
neoplasms. It is observed that some neoplasms appear
to develop from viral oncogenesis, with serologic
confirmation of past viral infection. Which of the
following neoplasms is most likely to arise in this
manner?
A. Retinoblastoma
Incorrect. Retinoblastomas occur with
loss of alleles for a suppressor oncogene
on chromosome 13.
B. Small cell anaplastic carcinoma
Incorrect. Most of these cancers are
related to smoking.
C. T-cell leukemia
CORRECT. Human T-lymphocytotropic
virus (HTLV) infection can lead to T-cell
leukemia. However, few human cancers
arise as a result of viral oncogenesis.
Some viruses, such as hepatitis viruses
B and C, result in cellular proliferation
Neoplasia | Pathology Reviewer (Utah) | 58 / 72
that increases the risk for subsequent
mutations that drive carcinogenesis.
D. Prostatic adenocarcinoma
Incorrect. Adenocarcinomas of the
prostate are common; but are not
associated with preceding viral infection.
E. Hepatic angiosarcoma
Incorrect. Hepatic angiosarcoma is
causally related to vinyl chloride
exposure.
An experiment is designed to study the genetics of
cancer. The study will link the appearance of cancer to
specific gene abnormalities. Which of the following
forms of cell molecular analysis is most useful to
identify gene alterations involved in carcinogenesis?
A. Florescence in situ hybridization
Incorrect. FISH is useful to identify
abnormal expression of known genes,
because a specific marker is needed.
The best example is detection of
HER2/neu amplification in breast
cancers.
B. Flow cytometry
Incorrect. Flow cytometry analyzes DNA
content and can use markers for known
components of cells.
C. Immunohistochemistry
Incorrect. Immunohistochemistry
identifies protein products of gene
expression; and is most useful to
determine the cell of origin of a cancer, or
identify a characteristic of that cancer,
such as estrogen receptor expression.
D. Single nucleotide polymorphisms
CORRECT. SNPs can be analyzed to
find alterations present in cancer cells.
One could analyze multiple histologically
similar cancers to determine what gene(s)
alteration(s) such as deletions and
amplifications may underlie
carcinogenesis. Using millions of SNPs
can produce a virtual karyotype down to
the gene level.
E. Tumor marker expression
Incorrect. Serum tumor markers, such as
prostate specific antigen, utilize known
characteristics of cancer protein
expression. Tumor markers tend to be
insensitive for early detection of cancer.
A 29-year-old woman with a history of multiple sexual
partners over the last 15 years has a routine physical
examination with no abnormal findings. On pelvic
examination, the cervix shows no abnormalities, but a
Pap smear is taken and dysplastic cells are reported to
be present. A cervical biopsy is performed and shows
a low grade squamous intraepithelial lesion (LSIL), also
known as cervical intraepithelial neoplasia 1 (CIN-1).
Which of the following is the most appropriate
therapeutic strategy for this lesion?
A. No further treatment
Incorrect. Dysplasias should not be
ignored, because they can progress to
carcinomas.
B. Antibiotic therapy
Incorrect. Cervical dysplasias are
associated with human papillomavirus
infection, but HPV cannot be treated with

antibiotic therapy. In general, most
women will clear the virus. However, it is
a sexually transmitted disease, and
further infections can occur.
C. Chemotherapy
Incorrect. Dysplasias are confined to the
epithelium, so there is no benefit to
chemotherapy.
D. Colposcopy
CORRECT. Cervical dysplasia is a pre-
neoplastic condition that has the potential
to develop into a carcinoma if not treated.
Epithelia subjected to initiators and
promoters of carcinogenesis tend to
undergo progression from metaplasia to
dysplasia to carcinoma. Even a
carcinoma is essentially 100% curable
when it is limited to the epithelium (in situ).
That is why you try to diagnose the lesion
as early as possible. Some LSILs on Pap
smear have a more advanced lesion
present with colposcopic screening and
warrants resection. Just LSIL may be
followed with Pap smears, as some
women with HPV infection will clear the
virus. High-grade squamous
intraepithelial lesions (HSIL) correlate
with CIN 2 or 3, which are less likely to
regress and are therefore resected.
E. Radiation therapy
Incorrect. Dysplasias are confined to the
epithelium, and there is no benefit to
radiation therapy.
A 64-year-old man has noted a 5 kg weight loss along
with increasing fatigue over the past year. He has
experienced dull abdominal pain for the past week. He
has developed abdominal distention with lack of stools
in the past two days. On physical examination, bowel
sounds are reduced. An abdominal CT scan reveals a
mass involving the descending colon. At laparotomy, a
partial resection of the left colon is performed, with
removal of an encircling mass. Microscopically, the
mass is found to be a moderately differentiated
adenocarcinoma. Which of the following laboratory test
findings is most likely to be present in this man?
A. Microcytic hypochromic anemia
CORRECT. He has an adenocarcinoma
of the colon. Such lesions are often
associated with blood loss from mucosal
erosion and necrosis. Cancer cells are
less differentiated and less functional
than their normal cell of origin and thus
less functional. With poor construction
come many problems.
B. Positive antinuclear antibody test
Incorrect. Colonic adenocarcinoma is not
typically associated with autoimmune
diseases.
C. Hyperglycemia
Incorrect. Hyperglycemia is unlikely,
though inanition with hypoglycemia is
possible.
D. Elevated alpha-fetoprotein
Incorrect. Elevation of the AFP in
association with neoplasia most often
occurs with testicular and liver cancers.
Neoplasia | Pathology Reviewer (Utah) | 59 / 72
E. Decreased lactate dehydrogenase
Incorrect. The LDH is elevated in a
variety of disease conditions and never
decreased. In this case, metastatic
disease and tissue necrosis may have
elevated the LDH.
A 14-year-old healthy girl has a 0.3 cm reddish, slightly
raised nodule on the skin of the upper part of her chest
found on a routine physical examination. She states
that this lesion has been present for years and has not
appreciably changed in size or color. Which of the
following neoplasms is this nodule most likely to be?
A. Hemangioma
CORRECT. Hemangiomas, teratomas,
and fibromatoses are common pediatric
neoplasms that are benign. Benign
neoplasms tend to grow slowly and
remain localized. They do not invade or
metastasize.
B. Melanoma
Incorrect. Malignant melanomas are
unlikely to appear in the first two decades
of life. They are malignancies that are
characterized by change-growth and
differences in coloration.
C. Carcinoma
Incorrect. Carcinomas are generally
uncommon in children. Carcinomas tend
to enlarge and invade over time.
D. Lymphoma
Incorrect. Lymphomas are never benign.
Leukemias and lymphomas are
malignancies that can occur in childhood,
but they rarely involve skin.
E. Glioma
Incorrect. Gliomas are not benign. They
are one of the common childhood
malignancies and occur in the posterior
fossa of the brain most often.
F. Sarcoma
Incorrect. Sarcomas can arise in soft
tissues such as the dermis, but this is not
a common site for such a neoplasm in
children. Sarcomas comprise a larger
percentage of malignancies in children
than in adults, but only because
carcinomas are far less common in
children than adults. Cancers in general
are not common in children, but the ones
that do occur can be aggressive.
A 56-year-old man has had a chronic cough for the past
year. He is a non-smoker. He had an episode of
hemoptysis 3 days ago. No abnormal findings are
noted on physical examination. A chest x-ray
demonstrates a 6 cm perihilar mass. A sputum sample
is collected, and the sputum cytology report reads
'Atypical cells present suggestive of squamous cell
carcinoma.' Which of the following environmental
exposures is most likely to be associated with these
findings?
A. Asbestos
Incorrect. Asbestos exposure is a risk for
bronchogenic carcinoma in persons who
are smokers. It is rare.

B. Radon
CORRECT. Radon gas is considered to
be the second most common cause for
lung cancer following tobacco smoking.
However, most persons with radon
exposure who develop lung cancer are
also smokers. A small amount of radon
gas naturally seeps up from the soil and
may collect in houses. Commercial
buildings tend to be larger and well
ventilated so little radon collects in them.
C. Silica
Incorrect. The risk for lung cancer is only
slightly increased with silica dust
exposure. Silica is more likely to produce
a restrictive lung disease.
D. Benzene
Incorrect. Benzene, as are other
hydrocarbon compounds, is more likely
to affect the bone marrow.
E. Formaldehyde
Incorrect. Formaldehyde is unpleasant
but not a major risk for lung cancer.
A 60-year-old man who has a 90-pack year history of
cigarette smoking has had a chronic cough for the past
10 years. He has begun to lose weight (3 kg) during the
past year. No abnormal findings are noted on physical
examination. He has a chest radiograph that reveals a
right hilar mass. A sputum cytology shows atypical,
hyperchromatic squamous cells. What is the most
common initial pathway for metastases from this lesion?
A. Bloodstream
Incorrect. Epithelial malignancies spread
late via the bloodstream. Sarcomas
spread early via bloodstream.
B. Pleural cavity
Incorrect. Seeding through body cavities,
such as pleural cavities or peritoneal
cavity, is possible for a cancer, but more
of a late finding for a squamous cell
carcinoma.
C. Contiguous spread to chest wall
Incorrect. Direct spread to chest wall is a
late finding with a central squamous cell
carcinoma. Contiguous spread is a form
of invasion, which is technically not a
metastasis, but still bad.
D. Lymphatics
CORRECT. Epithelial malignancies such
as a squamous cell carcinoma of the lung
often have non-contiguous (metastatic)
spread initially to regional lymph nodes.
This is important to determine for staging,
because the treatment and prognosis
depend upon accurate staging. Lymph
node metastases or hematogenous
metastases imply the malignancy is
systemic and local excision of the lung
mass will not be curative.
E. Bronchi
Incorrect. This is a very unlikely mode of
spread for a squamous cell carcinoma;
however, the cells can be shed into the
bronchial tree and that is how they are
picked up in a sputum specimen.
Neoplasia | Pathology Reviewer (Utah) | 60 / 72
A 55-year-old man has had malaise and a 4 kg weight
loss over the past 6 months. On physical examination
his stool is positive for occult blood. An abdominal CT
scan shows his liver contains multiple tumor masses
from 2 to 5 cm in size with central necrosis. The
surrounding hepatic parenchyma appears normal.
Which of the following characteristics of neoplasia is
best illustrated by these findings?
A. Multicentric origin
Incorrect. Necrosis is unlikely to be a
feature of a benign neoplasm. The liver is
not a common site for multiple benign
masses. A primary hepatocellular
carcinoma could be multicentric; but
arises in the context of chronic
hepatitis/cirrhosis, not normal liver.
B. High tumor grade
Incorrect. The grade of a tumor is a
microscopic diagnosis and indicates the
degree of differentiation.
C. Primary neoplasm in the stomach
Incorrect. The primary neoplasm could
be in the stomach, but more likely the
colon, and any number of primary sites
could exist for such an appearance.
D. Exposure to a carcinogen
Incorrect. It is not possible to state this
with certainty from the radiographic
appearance alone.
E. Advanced stage
CORRECT. The most likely possibility is
that these masses represent metastases
from a primary site elsewhere in the body,
likely the colon because of blood in the
stool. Thus, this is a malignant neoplasm
that has an advanced stage (M1). The
central necrosis is the result of tumor
necrosis with collapse of a tumor nodule.
A 59-year-old man has had a worsening cough with
chest pain for the past 6 months. On physical
examination he has no remarkable findings. A chest x-
ray shows a 3 cm left lung mass. A sputum cytology
specimen yields cells diagnosed as a squamous cell
carcinoma. A mediastinoscopy is performed and
reveals metastases in a lymph node. He is given
radiation therapy, and the mass diminishes in size.
Which of the following cellular mechanisms is most
likely to account for this tumor response?
A. Point mutations in DNA
Incorrect. Mutations occurring in some
irradiated cells would have no significant
immediate effect. Exposure to
environmental radiation has this effect,
which increases the risk for cancer.
B. Generation of free radicals
CORRECT. The purpose of therapeutic
radiotherapy is to try and kill more
neoplastic cells than normal cells. This is
mediated mainly through direct damage
to the cells and one mechanism is
generation of oxidant free radicals.
Cancer cells are more vulnerable than
normal cells. Techniques are available to
focus the beam of radiation energy on the
cancer and reduce collateral damage to
normal tissues.

C. Loss of the blood supply
Incorrect. Vascular changes do occur
following radiation; but are not a desired
effect.
D. Secondary inflammation
Incorrect. Necrosis with inflammation will
occur following radiation, but the desired
effect is to kill neoplastic cells directly
Inflammation by itself does not have
diagnostic or prognostic value in
neoplasia. The immune system may play
a role in tumor surveillance to prevent
malignancies from occurring, but once a
malignancy is established, the immune
system is unlikely to eliminate it unaided.
E. Adenosine triphosphate depletion
Incorrect. ATP depletion may occur as
the neoplastic cells die, but this is not the
main effect of radiotherapy.
A 61-year-old woman has a firm mass with irregular
borders felt in her left breast on a routine physical
examination. A fine needle aspiration is performed and
microscopic examination shows malignant cells. A left
mastectomy with axillary lymph node dissection is
performed. A tissue sample of this neoplasm is
submitted for analysis by flow cytometry. Which of the
following does flow cytometric analysis most likely
provide?
A. Analysis of the karyotype
Incorrect. Flow cytometry does not
distinguish individual chromosomes or
count them.
B. Detection of gene mutations
Incorrect. Flow cytometry cannot be used
to analyze individual genes.
C. Determination of aneuploidy
CORRECT. Flow cytometry can detect
the degree of aneuploidy from the DNA
content. Aneuploidy implies that the
neoplasm is worse (more aggressive)
than if it were not aneuploid.
D. Distinguishing carcinoma from sarcoma
Incorrect. Flow cytometry cannot
distinguish the cell of origin of neoplasms.
E. Quantitation of RNA content
Incorrect. Flow cytometry is used to
measure DNA content, not RNA content.
A 35-year-old healthy woman had a firm nodule
palpable on the dome of the uterus six years ago
recorded on routine physical examination. The nodule
has slowly increased in size and now appears to be
about twice the size it was when first discovered. By
ultrasound scan it is solid and circumscribed. She
remains asymptomatic. Which of the following
neoplasms is she most likely to have?
A. Adenocarcinoma
Incorrect. Adenocarcinomas of the uterus
would arise in the endomtrium and are
often accompanied by hemorrhage.
B. Leiomyosarcoma
Incorrect. The slow growth and her
asymptomatic condition suggest a
benign neoplasm. Leiomyosarcomas of
the uterus do occur; but are not common.
Neoplasia | Pathology Reviewer (Utah) | 61 / 72
C. Hemangioma
Incorrect. This is an unusual place for a
hemangioma, formed of small vascular
channels.
D. Leiomyoma
CORRECT. The slow growth of the
nodule, the circumscribed nature of the
nodule, and the continuing lack of
symptoms suggests a benign course.
Leiomyomas of the uterus are quite
common (up to 50% of women have at
least one).
E. Metastasis
Incorrect. Solitary slow-growing
metastases are quite rare.
A 15-year-old boy has felt lumps in his right neck for
the past 5 months. On physical examination there is
painless lymphadenopathy in the right cervical region.
One of the lymph nodes is biopsied and on microscopic
examination shows effacement of the nodal
architecture by many lymphocytes that are large, with
clumped chromatin and occasional mitoses. The
characterization of this population of lymphocytes as a
neoplasm is best accomplished by which of the
following methods?
A. Immunohistochemical stain for leukocyte
common antigen
Incorrect. Staining with LCA will only tell
you that cells are of leukocyte origin, not
whether they are part of a neoplastic
proliferation.
B. Gene rearrangement studies
demonstrating clonality
CORRECT. Clonality is a key
characteristic of neoplastic cellular
proliferations that distinguishes them
from reactive proliferations (such as
inflammation).
C. Flow cytometry indicating high S-phase
Incorrect. Flow cytometry cannot tell you
with certainty that a neoplasm is present.
D. Differential white blood count showing a
lymphocytosis
Incorrect. Inflammation could lead to
lymphocytosis. Lymphomas are unlikely
to have a lymphocytosis.
E. Light microscopy demonstrating nodal
Incorrect. Fibrosis is a feature of
inflammation as well as neoplasia.
A previously healthy 42-year-old man has a skin nodule
on his right hand that has become larger and darker
with more irregular outlines over the past 3 months. On
physical examination this lesion is 1.2 cm diameter,
darkly pigmented, and a slightly raised nodule on the
dorsum of his right hand. No other skin lesions are
noted. Three non-tender enlarged lymph nodes are
palpable in the right axilla. The lesion is excised and
microscopic examination shows a neoplasm
composed of darkly pigmented polygonal and spindle
cells. Which of the following risk factors is most
important for development of this neoplasm?
A. Cigarette smoking
Incorrect. Smoking is associated with
many malignancies, including those of
lung and the urinary tract, but it is not a
risk for skin cancers.

B. Allergy to latex gloves
Incorrect. Allergies do not give rise to
malignancies.
C. Inheritance of a faulty RB gene
Incorrect. The Rb gene is a tumor
suppressor gene that can be involved
with retinoblastomas and osteosarcomas
when a mutation is inherited.
D. Prior job-related handling of asbestos
Incorrect. Asbestos exposure can
increase the risk for bronchogenic
carcinomas, mesothelioma, and
gastrointestinal adenocarcinomas.
E. Chronic exposure to ultraviolet radiation
CORRECT. Worldwide, more and more
skin cancers, including melanoma, are
occurring because of sun exposure. The
UV light damages the skin and damages
cellular DNA, leading to mutations that
escape cellular repair mechanisms.
Depletion of the earth's protective upper
atmospheric ozone layer has not helped,
either. The ABC's of malignant
melanoma: Asymmetrical shape,
irregular Border, abnormal Color.
A 27-year-old woman in excellent health has a routine
health maintenance examination. A 2 cm firm, rounded
mass is palpable beneath the skin of the left forearm.
She has no difficulty using the arm and there is no
associated pain with the mass, either in movement or
on palpation. The overlying skin appears normal. The
mass does not change in size over the next year.
Which of the following neoplasms is she most likely to
have?
A. Metastatic carcinoma
Incorrect. A patient with widely
disseminated cancer would not be in
excellent health, and there would likely
be many other masses.
B. Melanoma C
Incorrect. Melanomas arise in epidermis
and are typically visible on the skin
surface. They may infiltrate downward.
C. Rhabdomyosarcoma
Incorrect. Such a small, unchanging
mass in a young person is unlikely to be
a sarcoma.
D. Lipoma
CORRECT. The small size of the lesion,
the relatively young age of the patient,
and the lack of other findings suggests a
benign process. Lipoma is the most
common soft tissue neoplasm. Most of
them never reach a size sufficient to
produce problems.
E. Leiomyoma
Incorrect. Leiomyomas can theoretically
arise in any location with smooth muscle,
but in a woman they are most likely to be
found in the myometrium.
A 41-year-old woman has noted a foul-smelling vaginal
discharge for 3 weeks. On physical examination there
is an exophytic 3 cm mass involving the ectocervix.
Pap smear testing is performed; she has never had a
previous Pap smear. Cytologic changes are present
consistent with squamous cell carcinoma. She is found
to have a positive serologic test for syphilis. Her serum
Neoplasia | Pathology Reviewer (Utah) | 62 / 72
glucose is 157 mg/dL. She has been a commercial sex
worker in the past. Which of the following is the most
likely risk factor for her cervical carcinoma?
A. Human papillomavirus infection
CORRECT. HPV infection, a sexually
transmitted disease (STD), is highly
associated with cervical dysplasias and
malignancies, particularly high-risk
subtypes 16 and 18 that are now covered
by the HPV vaccine. Syphilis is not a risk
for epithelial dysplasias or carcinomas,
but if one STD is present, others can be
present as well.
B. Diabetes mellitus, type II
Incorrect. Diabetes mellitus increases the
risk for bacterial infections; but does not
increase cancer risk.
C. Heavy cigarette smoking
Incorrect. Cigarette smoking is a risk for
many cancers, particularly of the lung,
but not for cervical carcinoma.
D. Pelvic inflammatory disease
Incorrect. PID is most often the result of
gonorrheal or chlamydial infections and
is not a risk for cancer.
E. Previous cancer chemotherapy
Incorrect. Previous chemotherapy can
increase the risk for malignancies in
general, but not significantly for cervical
carcinoma.
A 62-year-old man with an 80-pack year history of
smoking experiences an episode of hemoptysis. On
physical examination he has puffiness as well as
plethora of the face, pedal edema, bruises of the skin,
and a blood pressure of 165/100 mm Hg. A chest
radiograph reveals a 5 cm right upper lobe lung mass.
A fine needle aspirate of this mass yields cells
consistent with small cell anaplastic lung carcinoma. A
bone scan shows no metastases.
Immunohistochemical staining of the tumor cells is
likely to be positive for which of the following hormones?
A. Parathormone related peptide
Incorrect. Prp can be secreted as part of
a paraneoplastic syndrome and leads to
hypercalcemia. Of lung neoplasms, the
one most likely to do this is a squamous
cell carcinoma.
B. Erythropoietin
Incorrect. Erythropoietin secretion leads
to increased production of red blood cells.
Renal cell carcinomas can do this.
C. ACTH
CORRECT. He has findings of Cushing
syndrome from ectopic ACTH production
by the lung tumor, a form of
paraneoplastic syndrome common to
small cell carcinomas of the lung, which
have neuroendocrine derivation.
D. Insulin
Incorrect. Insulin can be secreted by
neuroendocrine neoplasms, such as
pancreatic neuroendocrine (islet cell) and
gastrointestinal neuroendocrine
(carcinoid) tumors.
E. Gastrin
Incorrect. Gastrin can be secreted by
neuroendocrine neoplasms, such as
pancreatic neuroendocrine (islet cell) and

gastrointestinal neuroendocrine
(carcinoid) tumors.
A 45-year-old woman has noted a lump on her left
shoulder that has enlarged over the past 4 months. On
physical examination there is a palpable non-tender
supraclavicular lymph node. A biopsy of the node is
performed and on microscopic examination there is a
metastatic neoplasm. Which of the following is the most
likely primary for this neoplasm?
A. Cerebral glioma
Incorrect. Gliomas are primary malignant
brain neoplasms that rarely metastasize
outside the cranial cavity.
B. Adenocarcinoma of the stomach
CORRECT. Lymph node metastases are
typical of spread from carcinomas. The
first stop along the way is regional nodes;
but spread to more distant lymphatic
sites is possible. The right
supraclavicular node receives drainage
from mid-section of the chest, esophagus,
and lungs. Described here is classic
'Virchow node' that involves left
supraclavicular nodal metastasis from
drainage via the thoracic duct, the
abdomen, and thorax.
C. Fibroadenoma of the breast
Incorrect. A fibroadenoma is a benign
lesion that does not metastasize.
D. Liposarcoma of the retroperitoneum
Incorrect. Sarcomas typically do not
spread via lymphatics. Sarcomas are far
less common than carcinomas.
E. Laryngeal papilloma
Incorrect. A papilloma is a benign lesion.
Laryngeal papillomas may recur locally,
but do not spread elsewhere.
A 59-year-old man has had fatigue for the past year.
The only abnormal physical examination finding is a
positive stool guaiac test. Laboratory studies show a
CBC with Hgb 10.0 g/dL, Hct 29.8&, MCV 73 fL,
platelet count 300,000/microliter, and WBC count
8700/microliter. He is found on colonoscopy to have a
4 cm mass lesion arising on the mucosal surface of the
transverse colon. An abdominal CT scan shows
hepatic masses. He receives therapy with cetuximab
directed at vascular endothelial growth factor (VEGF).
Which of the following cell signaling pathways is most
affected by this therapy?
A. Hedgehog
Incorrect. The PTCH genes are involved
in encoding cell membrane 'patched'
protein functioning as a receptor for
hedgehog proteins involved in cell
proliferation. Many basal cell carcinomas
of skin have PTCH mutations.
B. Notch
CORRECT. Cancers must elaborate
growth factors in order to produce an
environment for continued growth. VEGF
promotes angiogenesis that will keep the
neoplasm supplied with blood. VEGF
increases the expression of ligands that
active the Notch signaling pathway.
Biotherapies with monoclonal antibodies
can specifically target protein
components of cancers.
Neoplasia | Pathology Reviewer (Utah) | 63 / 72
C. JAK/STAT
Incorrect. The JAK-STAT pathway
promotes neoplastic cell proliferation, but
is not directly targeted by this agent.
D. TGF-beta
Incorrect. TGF-beta signaling represses
several cyclins and CDKs, as well as C-
MYC, to reduce cell proliferation.
E. WNT
Incorrect. The WNT signaling pathway is
involved in cell proliferation and adhesion,
but is not targeted by this agent.
Columnar epithelial cells from the colonic mucosa are
studied to identify abnormalities in cell signaling
pathways. Abnormal epithelial cells from colonic
adenocarcinoma are shown to have a mutation that
blocks hydrolysis of GTP-bound active RAS. Normal
columnar cells have active RAS protein that undergoes
hydrolysis to the inactive GDP-bound form. Which of
the following signaling pathways is most likely
abnormally stimulated in the carcinoma cells?
A. ADP
Incorrect. ADP is released from platelets
to signal activation and aggregation of
surrounding platelets.
B. BCR-ABL
Incorrect. The BCR-ABL fusion gene
product is the 'Philadelphia chromosome'
of chronic myelogenous leukemia that
has tyrosine kinase activity.
C. Cyclic AMP
Incorrect. Cyclic AMP is not generally
considered part of neoplastic processes.
cAMP is a second messenger from
activation of G-protein coupled cell
surface receptors.
D. Cyclin D1
Incorrect. Cyclin D appears in the mid G1
phase of the cell cycle and is part of the
cell cycle machinery that is influenced by
oncogenes.
E. MAP kinase
CORRECT. The mechanism described is
that of RAS oncogene activation in which
the active RAS is permanently turned on
and through the MAP kinase pathway
activates transcription that drives
abnormal, uncontrolled cellular
proliferation that leads to neoplasia.
Many carcinomas, and
adenocardinomas in particular, have
RAS mutations.
F. p53
Incorrect. The p53 gene product is a
tumor suppressor, and loss of both p53
alleles results in loss of control over cell
proliferation when DNA damage occurs.
A 52-year-old woman feels a lump in her right breast.
On physical examination there is a 3 cm right breast
mass fixed to the chest wall. This mass is biopsied and
on microscopic examination shows nests of cells with
marked hyperchromatism and pleomorphism. These
cells are estrogen receptor positive. Flow cytometry is
performed. Compared with surrounding non-neoplastic
stromal cells, the neoplastic cells are more likely to be
in which of the following phases of the cell cycle?

A. G0
Incorrect. G0 cells are quiescent and not
participating in the cell cycle. This
includes most cells in the body.
B. G1
Incorrect. G1 cells have just entered into
the cell cycle.
C. S
CORRECT. A high S-phase, as well as
aneuploidy, are features often seen in
cancers. The hyperchromatism typical for
malignant cells indicates active DNA
synthesis. The estrogen receptor
positivity suggests that this breast cancer
will respond to hormonal therapy with
letrozole or tamoxifen.
D. G2
Incorrect. G2 is the part of the cell cycle
just before division.
E. M
Incorrect. M is the part of the cell cycle in
which cells are dividing. Although more
mitoses can be seen in cancers than in
normal tissues, the number of cells in
mitosis is still not high.
A 73-year-old man has an episode of hematemesis.
Upper GI endoscopy reveals an irregular 4 cm gastric
antral ulceration. Biopsies are performed and
microscopically reveal crowded irregular gland-like
collections of cells with hyperchromatism and
pleomorphism. Molecular analysis shows DNA
hypermethylation of the CDKN2 complex. Through
which of the following mechanisms has this abnormal
gene expression most likely occurred?
A. Amplification
Incorrect. Amplification of gene
expression typically occurs when there is
reduplication of DNA sequences, often
with hundreds of copies, greatly
increasing the amount of protein
produced, which drives cellular
proliferation.
B. Epigenetic alteration
CORRECT. Epigenetic changes are
common in cancers, and gastric
adenocarcinoma is described here.
Though the DNA may not be altered,
methylation can occur to silence DNA
expression. If selective hypermethylation
of a DNA sequence encoding a tumor
suppressor occurred, then the result
would be similar to loss of the tumor
suppressor gene itself. Genomic
imprinting works the same way.
C. Growth factor binding
Incorrect. Binding of growth factors is one
way to control cell signaling, but this does
not affect DNA methylation directly.
D. Point mutation
Incorrect. Point mutations alter the DNA
directly; methylation affects expression of
normal DNA.
E. Reduced miRNA expression
Incorrect. Micro RNAs often act to inhibit
oncogene translation. Hence, reduced
miRNA expression has the same effect
as loss of a tumor suppressor gene.
Neoplasia | Pathology Reviewer (Utah) | 64 / 72
In an experiment, it is observed that chronic, increased
exposure to ionizing radiation results in damage to
cellular DNA. As a consequence, a protein is now
absent that would arrest the cell in the G1 phase of the
cell cycle. Subsequent to this, the cell is transformed to
acquire the property of unregulated growth. The absent
protein is most likely the product of which of the
following genes?
A. RAS
Incorrect. The RAS oncogene 'turns on'
cells to promote carcinogenesis.
B. TP53
CORRECT. Abnormal TP53 protein has
been identified in many carcinomas. This
loss of normal wild type TP53 with tumor
suppression leads to loss of tumor
suppression driving development of
carcinomas.
C. MYC
Incorrect. The MYC oncogene 'turns on'
cells to promote carcinogenesis.
D. ABL
Incorrect. The BCR-ABL fusion gene
results from a 9:22 translocation
(Philadelphia chromosome of chronic
myelogenous leukemia) that promotes
cellular transformation via protein
kinases.
E. BCL-2
Incorrect. The BCL-2 gene acts by
decreasing apoptosis (cell death) to
cause accumulation of cells, as with
follicular lymphomas.
A 50-year-old woman notes a lump in her breast. Her
physician's assistant palpates a 2 cm firm mass in her
left breast. A fine needle aspiration biopsy is performed,
and on microscopic examination a carcinoma is
present. Molecular analysis shows HER2 positivity but
estrogen receptor negativity in these malignant cells.
Through which of the following mechanisms has this
abnormal expression most likely occurred?
A. Amplification
CORRECT. Amplification of gene
expression typically occurs when there is
reduplication of DNA sequences, often
with hundreds of copies, greatly
increasing the amount of protein
produced, which drives cellular
proliferation. The mutation in HER2
results in amplification of the epithelial
growth factor receptor, as identified by
presence of multiple copies by FISH
analysis.
B. Epigenetic alteration
Incorrect. Epigenetic changes are
common in cancers. The DNA is not
altered, but methylation occurs to silence
DNA expression. If selective
hypermethylation of a DNA sequence
encoding a tumor suppressor occurred,
then the result would be similar to loss of
the tumor suppressor gene itself.
Genomic imprinting works the same way.
C. Growth factor binding
Incorrect. Binding of growth factors is one
way to control cell signaling, but this does
not affect DNA methylation directly.

D. Point mutation
Incorrect. Point mutations alter the DNA
directly; methylation affects expression of
normal DNA.
E. Reduced miRNA expression
Incorrect. Micro RNAs often act to inhibit
oncogene translation. Hence, reduced
miRNA expression has the same effect
as loss of a tumor suppressor gene.
An epidemiologic study is performed to find risk factors
for development of malignant neoplasms. A statistical
analysis of pre-existing medical conditions is done.
Some pre-existing chronic medical conditions are
observed to precede development of malignant
neoplasms, while others do not. Which of the following
conditions is most likely to be statistically related to
development of a malignancy?
A. Essential hypertension
Incorrect. Systemic hypertension is a
common condition; but is not
premalignant. Hypertension promotes
atherogenesis.
B. Coronary artery disease
Incorrect. Coronary artery
atherosclerosis leads to ischemic heart
disease, but this is not premalignant.
C. Chronic bronchitis
Incorrect. Chronic bronchitis itself is not
premalignant. However, cases may
occur in conjunction with inhaled
carcinogens such as cigarette smoke.
D. Ulcerative colitis
CORRECT. Adenocarcinoma of the
colon is more frequent in persons with
chronic ulcerative colitis, an inflammatory
bowel disease that leads to proliferative
changes in which mutations may occur
that contribute to colonic carcinogenesis.
E. Uterine leiomyomas
Incorrect. Many women have multiple
uterine leiomyomas. Leiomyosarcomas
of the myometrium are rare and develop
de novo.
A 35-year-old man has noted several 1 to 2 cm reddish
purple, nodular lesions present on the skin of his right
arm which have increased in size and number over the
past 3 months. The lesions do not itch and are not
painful. He has had a watery diarrhea for the past
month. On physical examination he has generalized
lymphadenopathy and oral thrush. Which of the
following infections is most likely to be related to the
appearance of these skin lesions?
A. Candida albicans
Incorrect. Candida infection is not a risk
for malignancy, but persons with
malignancies treated with chemotherapy
are more likely to get candidal infections.
B. Human herpesvirus 8
CORRECT. These plaque-like reddish
lesions are characteristic for Kaposi
sarcoma. HHV8 (KSHV) is the agent that
promotes angiogenesis from which the
KS arises in persons with HIV infection.
This is an example of viral oncogenesis.
C. Mycobacterium tuberculosis
Incorrect. Mycobacterial infections are
not related to malignancies.
Neoplasia | Pathology Reviewer (Utah) | 65 / 72
D. Pseudomonas aeruginosa
Incorrect. Bacterial infections do not
predispose to neoplasia, but persons
with neoplasms may have more
infections.
E. Pneumocystis jiroveci
Incorrect. Pneumocystis jiroveci can be
seen in persons with AIDS, but it is not
related to the AIDS-associated
malignancies.
A 66-year-old woman has noted increasing abdominal
girth for 3 months. On examination there is an
abdominal fluid wave. Paracentesis yields cloudy fluid
that cytologically contains clusters of malignant cells.
An abdominal CT scan shows bilateral cystic and solid
pelvic masses and multiple peritoneal nodules. She is
treated with chemotherapy with an initial response, but
a year later there is still residual tumor. Which of the
following parameters of the neoplastic cells best
predicts her diminished chemotherapy response?
A. Doubling time
Incorrect. The doubling time indicates
how quickly the neoplastic cells are
dividing, and if no other factors affected
growth, then a palpable 1 cm mass of a
billion cells would be present in just 90
days (30 doublings), but in reality, there
are limits to cell growth as well as cell
loss, so this generally takes years. In
general, a rapidly proliferating mass will
have a fast doubling time and be more
responsive to chemotherapy, but this
does not give the best indication of why
chemotherapy effectiveness diminishes.
B. Extent of apoptosis
Incorrect. Apoptosis determines cell loss.
In general, apoptosis is slowed in
cancers. If one could turn on apoptosis in
cancer, then the cancer would self-
destruct. However, this does not predict
diminished response to chemotherapy.
C. Gene amplification
Incorrect. Gene amplification is one way
where cell proliferation is promoted for
carcinogenesis, but this does not predict
diminished response to chemotherapy.
D. Growth fraction
CORRECT. The proportion of cancer
cells that are actively proliferating will
predict response to chemotherapy. Cells
not actively proliferating are generally
unresponsive to chemotherapeutic
agents. As cancers increase in size,
more cancer cells exit the replicative pool.
During the course of chemotherapy, the
cells in replication are selectively killed,
leaving behind the cells out of the pool
that can continue on. If one were to
completely surgically excise the mass,
then that would solve this issue, but even
if the mass cannot be removed, then at
least one can debulk it, or use radiation
therapy to kill more cells. Chemotherapy
protocols can be designed to include
more agents, thereby reducing cancer
cell resistance, or by giving cycles of
chemotherapy that get more cancer cells
into the replicative pool. Ovarian

carcinomas often seed to the peritoneal
cavity.
E. Telomerase expression
Incorrect. Cancer cells tend to express
telomerase that makes them survive
longer, but this does not predict
diminishing response to chemotherapy.
A 49-year-old man complains of pain in his left thigh for
3 months. On physical examination his thigh is
increased in size, compared to the right. A plain film
radiograph reveals the presence of a 15 cm solid mass
that does not appear to arise from bone, but it does
have infiltrative margins. A biopsy of this mass is taken,
and on microscopic examination the mass is composed
of highly pleomorphic spindle cells. Which of the
following immunohistochemical markers is most likely
to be demonstrated in the cells of this mass?
A. Cytokeratin
Incorrect. The history suggests a
sarcoma arising in soft tissue.
Cytokeratin is a marker for epithelial
malignancies (carcinomas).
B. Factor VIII
Incorrect. Factor VIII as a marker is found
in endothelium. It is possible that this
mass is an angiosarcoma, but other
sarcomas at this site are more common.
C. Alpha fetoprotein
Incorrect. Alpha fetoprotein is a marker
that is found in hepatocellular
carcinomas and in some testicular
carcinomas.
D. Lambda light chain
Incorrect. This component of
immunoglobulin would be a marker for
multiple myeloma.
E. Vimentin
CORRECT. The location and size and
histologic characteristics suggest a
sarcoma. Vimentin is an intermediate
filament often found in neoplasms of
mesenchymal (connective tissue) origin.
A clinical study is performed with patients who had a
diagnosis of breast cancer. Characteristics of the grade,
stage, molecular biology, and histologic type are
analyzed. Of the following characteristics, which is
most likely to be associated with the best prognosis for
these patients?
A. Increased laminin receptor expression
Incorrect. The expression of laminin
receptors is a characteristic of neoplasia
that implies the tumor can more readily
attach to basement membranes and
invade.
B. Increased cathepsin expression
Incorrect. Increased cathepsin, an
enzyme that aids in matrix degradation,
implies a worse prognosis because the
neoplasm can more easily spread.
C. Increased aerobic glycolysis
Incorrect. Neoplastic cells can switch
their metabolism to aerobic glycolysis
(the Warburg effect) to give them a
selective advantage when actively
proliferating in the poorly vascularized
environment. Positron emission
tomography (PET) scans make use of
Neoplasia | Pathology Reviewer (Utah) | 66 / 72
increased glucose uptake to identify the
cancer cells.
D. Amplification of HER2
Incorrect. The amplification of epithelial
growth factor receptor HER2 is a
characteristic of breast cancer cells, not
normal cells.
E. Decreased doubling time
Incorrect. Neoplasms that have a shorter
doubling time are growing faster, which
implies a worse prognosis.
F. Decreased cell cycle S phase
CORRECT. An increased S (DNA
synthetic) phase is a feature of
malignancy, indicating loss of growth
control with increased cell proliferation.
A 66-year-old man has noted darker urine for the past
2 weeks. A urinalysis shows hematuria. Cystoscopy is
performed and there is a 3 cm mass in the dome of the
bladder. Biopsies of the mass are taken and on
microscopic examination show a urothelial carcinoma.
Cells of this neoplasm demonstrate a single mutation
causing cellular inability to hydrolyze GTP, thus
resulting in cellular transformation. Which of the
following oncogenes is most likely implicated in this
case?
A. ABL
Incorrect. This is part of the BCR-ABL
fusion gene of the 'Philadelphia
chromosome' in which the oncogene BL
is spliced onto the BCR region of
chromosome 22, resulting in increased
tyrosine kinase activity. It is associated
with chronic myelogenous leukemia.
B. ERBB2
Incorrect. This ERBB2 oncogene (also
known as HER2/neu) is one of many
epidermal growth factor (EGF) receptors
and appears to be activated by
overexpression and is best associated
with breast cancers.
C. SIS
Incorrect. Overexpression appears to be
the mechanism behind the action of this
oncogene, one form of platelet-derived
growth factor (PBDGF) beta chain
receptor, associated with brain and bone
tumors.
D. RAS
CORRECT. Through mutation the RAS
gene can be turned on, typically by a
point mutation, to make it an oncogene.
Such a mutation can occur in a wide
variety of carcinomas.
E. N-MYC
Incorrect. This oncogene appears to be
activated by amplification and it has been
associated with neuroblastomas.
A 44-year-old woman who has had multiple sexual
partners for the past 30 years has an abnormal Pap
smear with cytologic changes suggesting human
papillomavirus (HPV) infection. Without treatment, she
is most likely to develop which of the following lesions?
A. Squamous cell carcinoma
CORRECT. HPV infection leads to
squamous epithelial dysplasias and
carcinomas involving the uterine cervix.

HPV is a sexually transmitted infection.
HPV produces an E7 protein that binds to
the RB gene product that normally
suppresses cell proliferation. It produces
an E6 protein that binds to the p53
protein to degrade it, so that the cell cycle
is not stopped. Neoplasia can arise in the
setting of abnormal cell proliferation.
B. Non-Hodgkin's lymphoma
Incorrect. Lymphomas are malignant
proliferations of lymphoid cells. They are
rare in the female genital tract.
C. Kaposi sarcoma
Incorrect. Kaposi sarcoma is a rare
condition outside of HIV infection. It is
associated with human herpesvirus 8
infection.
D. Adenocarcinoma
Incorrect. Adenocarcinomas may arise in
the endocervix, but they are not
associated with HPV infection.
E. Leiomyoma
Incorrect. Leiomyomas are benign
smooth muscle neoplasms. They are
most frequent in the uterine myometrium.
In an epidemiologic study, 'fallout' from nuclear bomb
testing and from nuclear power plant disasters is
observed to have released radioactive isotopes into the
environment. One of these isotopes is found to be
strontium-90. It is observed that the strontium-90 in
soils goes into the food chain and eventually
contaminates milk products. This contamination is
most likely to increase the risk for which of the following
neoplasms?
A. Kaposi sarcoma of skin
Incorrect. The epidemic form of this
malignancy is nowadays most often seen
in homosexual men with HIV infection
and AIDS.
B. Small cell anaplastic carcinoma of lung
Incorrect. This lung cancer is nearly
always seen in smokers.
C. Osteosarcoma of bone
CORRECT. The fallout includes
strontium-90, an isotope that can be
taken up into bone just like calcium; but
promotes neoplastic transformation.
Science fiction often serves as a vehicle
for social commentary, and the creator of
'Star Trek' had an alien remark, 'They
irradiated their own planet?' in disbelief
humans would be so stupid to pollute
their own planet.
D. Nasopharyngeal carcinoma
Incorrect. Epstein-Barr virus (EBV)
infection is most often linked to
nasopharyngeal carcinoma and to
Burkitt's lymphoma.
E. Endometrial carcinoma
Incorrect. Endometrial adenocarcinoma
is increased with prolonged estrogen
hormonal imbalance.
Neoplasia | Pathology Reviewer (Utah) | 67 / 72
A clinical trial of a new chemotherapy protocol is
performed involving patients with lung carcinoma. It is
observed that a response occurs that leads to
neoplastic cell DNA strand breakage and cell death.
The primary carcinomas are initially observed to
decrease in size following therapy. However, after 3
months, the carcinoma is no longer regressing with this
therapy. Altered expression of which of the following by
the neoplastic cells has most likely resulted in this
reduced response?
A. Vimentin
Incorrect. The presence of the
intermediate filament vimentin in a
neoplasm suggests a mesenchymal
origin -- a sarcoma.
B. Leukocyte common antigen
Incorrect. LCA identified in a neoplasm
suggests a leukocytic differentiation --
such as a lymphoma.
C. Laminin receptor
Incorrect. Laminin receptors allow
neoplastic cells to attach more readily to
basement membranes.
D. Actin
Incorrect. Actin is a 'thin' filament found
not only in muscle, but a wide variety of
other cell types.
E. DNA topoisomerase II
CORRECT. This topo II is a nuclear
enzyme which untangles DNA at the end
of mitosis. The drugs that target
topoisomerase II freeze the enzyme as it
is cutting DNA strands. This leads to DNA
strand breakage and cell death.
Resistant cells in culture show alterations
in the topoisomerase II protein.
In an experiment, biologic characteristics of neoplastic
and non-neoplastic cells are analyzed in culture. It is
observed that cell division in cells derived from
malignant neoplasms, but not in normal cells, is aided
by the presence of an enzyme which repairs
progressive chromosomal shortening. The lack of
chromosomal shortening allows the malignant cells to
undergo many more divisions than the normal cells.
Which of the following enzymes is most likely to have
this effect?
A. Reverse transcriptase
Incorrect. This is the enzyme used by
retroviruses, such as human
immunodeficiency virus, to transcribe
their RNA into proviral DNA that is
incorporated into the host cell.
B. DNA polymerase
Incorrect. DNA polymerase generates
copies of DNA strands, and it is found in
normal cells.
C. Telomerase
CORRECT. The telomerase synthesizes
telomeric chromosomal ends. The so-
called 'immortal' neoplastic cell lines may
result from the presence of this enzyme.
Interfering with it may promise a new
cancer therapy. Of normal human cells,
stem cells have significant telomerase
activity, but differentiated somatic cells
do not.

D. Protein kinase
Incorrect. Protein kinases are often the
'second messengers' in cells that control
cell growth, and their function may be
altered by oncogenic activity.
E. Topoisomerase
Incorrect. DNA topoisomerase is an
enzyme that untangles DNA at the end of
mitosis. Antineoplastic drugs that target
topoisomerase interfere with this enzyme
to produce DNA strand breakage and cell
death.
A 62-year-old man has complained of pain on urination
for the past week. He is afebrile. On cystoscopy, a
slightly erythematous 1 cm diameter area is seen on
the bladder mucosa. This area is biopsied and on
microscopic examination shows cells with marked
hyperchromatism and increased nuclear/cytoplasmic
ratio involving the full thickness of the epithelium.
However, these changes are confined to the epithelium
above the basement membrane. Which of the following
terms best describes these biopsy findings?
A. Metaplasia
Incorrect. A change of one type of
epithelium for another, called metaplasia,
may be the first step in the process
leading to neoplasia, but it is reversible.
B. Minimal dysplasia
Incorrect. Minimal dysplasia involves
only a portion of the epithelium, not the
full thickness.
C. Microinvasion
Incorrect. A microinvasive neoplasm
penetrates only a short distance (a few
millimeters) beneath the basement
membrane.
D. Hyperplasia
Incorrect. Hyperplastic epithelium is
increased in thickness, and atypical
hyperplasia may be a precursor to a
neoplastic process, but it is reversible.
E. Carcinoma in situ
CORRECT. Malignancy confined to the
epithelium is CIS, and such lesions when
excised have essentially a 100% cure
rate. Unfortunately, urothelial carcinomas
have a propensity to be multifocal.
A 32-year-old woman has noted dull pelvic pain for the
last two months. On physical examination there is a
mass palpated in the right lower quadrant. An
abdominal ultrasound reveals an 8 cm mass involving
the right ovary. The mass is surgically excised. On
gross inspection, the surface of the mass is smooth
and is not adherent to surrounding pelvic structure. On
sectioning it is cystic and filled with hair. On
microscopic examination there is squamous epithelium,
tall columnar glandular epithelium, cartilage, and
fibrous connective tissue. Which of the following
neoplasms is she most likely to have?
A. Choristoma
Incorrect. A choristoma is a mass
composed of tissues that appear
histologically normal, but not found at the
site in which it is located, such as a
salivary gland choristoma of the middle
ear.
Neoplasia | Pathology Reviewer (Utah) | 68 / 72
B. Hamartoma
Incorrect. A hamartoma is a mass
composed of tissues that are normally
found at the site in which it is located, but
the tissues do not form normal structure,
such as a pulmonary hamartoma.
C. Myxoma
Incorrect. A myxoma is a mass
composed of stellate cells in a gelatinous
(myxomatous) matrix of connective
tissue, such as a left atrial myxoma.
D. Teratoma
CORRECT. A teratoma is a neoplasm
derived from totipotential germ cells that
differentiate into tissues that represent all
three germ layers: ectoderm, endoderm,
and mesoderm. When the elements are
all well differentiated, the neoplasm is
'mature' (benign).
E. Mesothelioma
Incorrect. A mesothelioma is a neoplasm
that arises from a mesothelial surface,
such as a pleural mesothelioma.
A 54-year-old woman has an episode of coughing with
blood-streaked sputum. On physical examination she
appears cachectic. A chest x-ray shows a mass lesion
with indistinct borders in the right lung. A transbronchial
biopsy is done and on microscopic examination shows
small cell anaplastic lung carcinoma (SCLC). She is
treated with a multidrug chemotherapy regimen and
has a partial response. However, metastatic disease
develops eight months later. A second chemotherapy
protocol is tried, but no response is noted. Which of the
following neoplastic cell characteristics is the most
likely reason for failure of the second protocol to elicit
a response?
A. Abnormal p53 protein
Incorrect. p53 that is mutated may not
function effectively in suppressing the
appearance of neoplasms by inhibiting
the cell cycle. It is the single most
common genetic alteration in cancers.
B. Viral infection
Incorrect. Viral oncogenesis, such as the
relationship of human papillomavirus
infection and squamous cell carcinomas,
does not predict resistance to
chemotherapy.
C. RAS oncogene activation
Incorrect. The RAS oncogene, activated
by a point mutation, is common in
carcinomas, playing a role in
development of neoplasia, but does not
affect resistance to chemotherapy.
D. P-glycoprotein expression
CORRECT. The increase in P-
glycoprotein allows the cells to pump out
any toxin, including any chemotherapy
agent.
E. Second primary lung cancer
Incorrect. Though a second, separate
primary may be possible, it is not the
most likely reason for this phenomenon
occurring in just a few months. Overall,
about 10% of persons surviving one
malignancy will develop another.

A previously healthy 67-year-old man has been feeling
tired for 5 months. He goes to his physician, who
performs a complete physical examination, including
stool guaiac, which is positive. A colonoscopy is
performed, and a large, sessile 4.5 cm mass with
surface ulceration is found in the cecum. A biopsy of
this mass microscopically shows irregular glands with
crowded, tall columnar cells having marked nuclear
hyperchromatism. Which of the following gene
alterations is he most likely to have?
A. Inherited mutant APC gene
Incorrect. Though a sporadic APC
mutation may be present at his age,
persons with an inherited faulty APC
gene present with polyposis (hundreds of
polyps) by the second decade, with high
risk for malignant transformation.
B. Chromosome translocation with BCR
gene
Incorrect. The t(9;22) producing the
BCR-ABL fusion gene is seen with
chronic myelogenous leukemia.
C. Acquired TP53 gene mutation
CORRECT. He has an adenocarcinoma
of the colon. At his age, a sporadic colon
cancer is more likely, and inherited APC
and HNPCC are very unlikely. It takes
many years for multiple sporadic
mutations to have occurred that
contribute to development of most
malignancies. p53 mutations are found in
many carcinomas.
D. Abnormal germline mismatch repair gene
Incorrect. HNPCC is a condition with
many polyps that typically presents in
young to middle age adults. There are
faulty DNA mismatch repair genes.
E. EBV induction of LMP-1 gene
Incorrect. EBV infection can be
associated with a variety of neoplasms
including lymphomas and
nasopharyngeal carcinomas. It is not
typically associated with colon cancers.
An 8-year-old boy has complained of difficulty
swallowing for the past month. On physical
examination he has a palpable, firm mass in the right
neck. A head CT scan reveals a 7 cm solid soft tissue
mass lateral to the esophagus on the right. A biopsy of
this mass demonstrates pleomorphic spindle cells that
are cytokeratin negative, CD45 negative, and vimentin
positive. Which of the following neoplasms is he most
likely to have?
A. Wilms tumor
Incorrect. A Wilms tumor, a common
childhood neoplasm, arises in the kidney
B. Rhabdomyosarcoma
CORRECT. This is one of the more
common childhood tumors of soft tissue.
Sarcomas tend to be vimentin positive,
while carcinomas are cytokeratin positive
and lymphomas CD45 positive. Overall,
childhood malignancies are not frequent,
compared with adults, but sarcomas
make up a significant number of those
that do occur.
Neoplasia | Pathology Reviewer (Utah) | 69 / 72
C. Neuroblastoma
Incorrect. Neuroblastomas are childhood
tumors but typically arise in the
retroperitoneum in adrenal gland.
D. Ewing sarcoma
Incorrect. Ewing sarcomas are childhood
neoplasms arising in bone.
E. Malignant lymphoma
Incorrect. A malignant lymphoma is likely
to arise within a lymph node in children,
rarely reaching this size. There should be
CD45 positivity.
A 53-year-old woman feels a lump in her right breast.
Her nurse practitioner palpates an irregular 3 cm mass
that is not movable because it appears fixed to the
overlying skin, which is retracted. A mastectomy is
performed and the pathologist on sectioning the breast
finds a 3 x 3.5 cm ovoid mass that does not have
discrete borders; but appears to infiltrate into the
surrounding fibrofatty breast stroma. The mass is firm,
white, and has a fibrous consistency. Which of the
following features is most likely demonstrated by the
gross appearance of this mass?
A. Anaplasia
Incorrect. Anaplasia is a characteristic of
malignant neoplasms in which there is no
differentiation to suggest a particular cell
type.
B. Aplasia
Incorrect. Aplasia refers to the absence
of growth or development.
C. Desmoplasia
CORRECT. Neoplasms, and malignant
neoplasms in particular, can form a
fibrous stroma that gives the tumor a
characteristic firm or hard feel on
palpation. This connective tissue can fix
the tumor to surrounding structures. An
infiltrating ductal carcinoma of the breast
will often have this appearance.
D. Dysplasia
Incorrect. Dysplasia refers to disordered
growth of cells in epithelia. It is
considered a premalignant change.
E. Metaplasia
Incorrect. Metaplasia refers to the
exchange of one epithelial cell type for
another, typically in response to some
form of injury. It may be the first step
toward neoplasia.
An 81-year-old man has a routine physical examination
and a stool sample is positive for occult blood. He
undergoes colonoscopy and a 5 cm sessile mass is
present in the sigmoid colon. Biopsy of the mass yields
a diagnosis of adenocarcinoma. A chest x-ray shows
multiple 1 to 3 cm nodules in both lungs. An alteration
in which of the following molecular components in the
neoplastic cells is most likely to explain the formation
of lung nodules?
A. Vimentin
Incorrect. The presence of the
intermediate filament vimentin in a
neoplasm suggests a mesenchymal
origin -- a sarcoma.
B. Leukocyte common antigen
Incorrect. LCA identified in a neoplasm
suggests a leukocytic differentiation --
such as a lymphoma.

C. Beta-catenin
CORRECT. Beta-catenin can locate to
the nucleus to drive cellular proliferation,
Mutations of the beta-catenin gene, or in
genes such as APC that produce
proteins that downregulate beta-catenin,
will favor carcinogenesis. In addition,
there is loss of normal cell surface e-
cadherin expression that maintains
attachment of cells to each other. Loss of
contact inhibition allows neoplastic cells
to invade and metastasize.
D. Telomerase
Incorrect. Telomerase expressed by
neoplastic cells allows them to continue
division and growth.
E. DNA topoisomerase II
Incorrect. This is a nuclear enzyme which
untangles DNA at the end of mitosis. The
drugs that target topoisomerase II freeze
the enzyme as it is cutting DNA strands.
This leads to DNA strand breakage and
cell death. Resistant cells in culture show
alterations in the topoisomerase II protein.
This may explain cancer chemotherapy
resistance.
A healthy 22-year-old woman undergoes a routine
physical examination. A discrete, firm, rubbery,
movable mass is found in the left breast. She has no
axillary lymphadenopathy. The skin overlying the
breast and the nipple appear normal. Which of the
following neoplasms is most likely to be present in this
woman?
A. Lipoma
Incorrect. Lipomas can be found in a
variety of locations, but in the breast,
tumors arising from ductular structures
are more common.
B. Intraductal carcinoma
Incorrect. Ductal carcinomas, either
confined to the duct or invasive, are the
most common primary breast cancer.
They are quite uncommon at age 22.
They are unlikely to be such a discrete a
mass.
C. Malignant lymphoma
Incorrect. Lymphomas are malignant
proliferations of lymphoid cells. They are
quite rare in the breast.
D. Fibroadenoma
CORRECT. The description is that of a
benign neoplasm. Fibroadenoma is the
most common benign neoplasm of the
breast. As the name implies, there are
glandular and stromal elements in this
neoplasm. Benign neoplasms are slow
growing, discrete masses that do not
invade or metastasize.
E. Leiomyoma
Incorrect. Leiomyomas are benign
smooth muscle neoplasms. They are
most frequent in the uterine myometrium.
An epidemiologic study is performed involving patients
of East Asian ancestry with long-standing Epstein-Barr
virus (EBV) infection. It is observed that these patients
have an increased risk for development of malignant
Neoplasia | Pathology Reviewer (Utah) | 70 / 72
neoplasms in adulthood. Which of the following
neoplasms is most likely to be found in these patients?
A. Kaposi sarcoma of skin
Incorrect. The epidemic form of this
malignancy is nowadays most often seen
in homosexual men with HIV infection
and AIDS.
B. Small cell anaplastic carcinoma of lung
Incorrect. This lung cancer is nearly
always seen in smokers.
C. Osteosarcoma of bone
Incorrect. Radioactive fallout includes
Strontium-90, an isotope that can be
taken up into bone just like calcium; but
promotes neoplastic transformation.
D. Nasopharyngeal carcinoma
CORRECT. EBV infection is most often
linked to nasopharyngeal carcinoma in
Asia and to Burkitt lymphoma in Africa.
E. Endometrial carcinoma
Incorrect. Endometrial adenocarcinoma
is increased with prolonged estrogen
hormonal imbalance.
A clinical study is performed involving children who
have developed skin cancers, including squamous cell
carcinomas and basal cell carcinomas. Molecular
analysis of their cancer cells shows defective DNA
repair from loss of nucleotide excision repair gene
expression. Which of the following genes is most likely
mutated in these children?
A. APC
Incorrect. The APC gene is associated
with familial polyposis of the colon that
can lead to colon carcinomas at a young
age, sometimes by the 2nd decade.
B. BRCA2
Incorrect. BRCA1 and BRCA2 mutations
are associated with breast cancers, and
other cancers including those in ovary.
Inherited mutations can lead to breast
cancers in young adulthood.
C. MSH2
Incorrect. MSH2 mutations are
associated with the hereditary
nonpolyposis colon cancer (HNPCC)
syndrome, with the appearance of colon
cancers from abnormal DNA mismatch
repair in young adulthood.
D. NF1
Incorrect. NF1 mutations are associated
with neurofibromatosis type I, with the
appearance of many neural tumors,
particularly neurofibromas.
E. TP53
Incorrect. p53 mutations are best known
as part of carcinogenesis in many adult
sporadic cancers. The rare LiFraumeni
syndrome results from inheritance of a
faulty p53 gene.
F. XPA
CORRECT. There are multiple
xeroderma pigmentosa (XP) genes, from
XPA to XPG and XPV. Sunlight exposure
with ultraviolet radiation induces
pyrimidine dimer formation that is
ordinarily countered through the action of
excision repair gene products. Mutation
greatly increases the risk for skin cancer

formation; and affected persons must
avoid sunlight.
G. WT1
Incorrect. The WT1 gene is associated
with Wilms tumor in children.
A 29-year-old woman feels a nodule in her neck. On
examination there is a firm 2 cm mass in the right lobe
of her thyroid. A fine needle aspiration shows cells
consistent with papillary carcinoma. 2 years ago, she
had a lobular carcinoma excised from her left breast.
Her 31-year-old sister was recently diagnosed with
endometrial carcinoma. A 34-year-old cousin has had
colon cancer. Over 3 generations, 6 of 24 close
relatives have had a malignancy, most diagnosed
before age 35. Which of the following most likely
explains the increased risk for cancer in these people?
A. Autosomal dominant cancer syndrome
Incorrect. The pattern here is not that of
the 50% recurrence risk for autosomal
dominant conditions. Most autosomal
dominant cancer syndromes involve one
or two specific tissue sites.
B. Defective DNA repair syndrome
Incorrect. Defective DNA repair
syndromes may be inherited in an
autosomal dominant fashion. The most
common is the hereditary non-polyposis
colon cancer (HNPCC) syndrome, which
involves colon.
C. Germline mosaicism
Incorrect. Germline mosaicism can
account for a cluster of findings within
siblings of a single generation. Cancer
syndromes are generally not inherited in
this fashion.
D. Multifactorial inheritance
CORRECT. Cancer that runs in families
often does not have a clearly defined
pattern of inheritance and does not have
a specific genetic marker. Familial
cancers should be suspected when
cancers occur at a younger age, multiple
family members are involved, and
multiple sites are involved. The sites of
involvement (breast, colon, thyroid,
kidney, ovary) are similar to those for
sporadic cancers.
E. Teratogen exposure
Incorrect. Teratogens produce congenital
anomalies via their effects upon the
developing embryo. Cancers are unlikely
to occur in this manner.
F. Viral infection
Incorrect. Few viruses are associated
with human malignancies. Some
persistent viruses such as hepatitis B
virus, may lead to precancerous
conditions such as hepatic cirrhosis in
which neoplasia is more likely to occur.
A study of malignant neoplasms reveals that some of
them have a greater potential for invasion and
metastases. Analysis of the cells of cancers that have
metastasized reveals a mutation which results in
decreased cell surface expression of E-cadherin.
Which of the following genes is most likely mutated to
produce these findings?
Neoplasia | Pathology Reviewer (Utah) | 71 / 72
A. Beta-catenin
CORRECT. Beta-catenin binds to the
intracellular portion of cadherins, which
anchor cells together, and the loss of this
function results in less cell adhesiveness
that favors tumor cell infiltration and
metastases. Beta-catenin also binds to a
nuclear transcription factor that increases
cell proliferation, and loss of normal beta-
catenin function leads to cell proliferation.
B. BRCA-2
Incorrect. BRCA-2 and BRCA-1 act as
tumor suppressors.
C. Cyclin D
Incorrect. Cyclin D operates within the
cell cycle machinery.
D. NF-1
Incorrect. NF-1 codes for the protein
neurofibromin, which acts in the RAS
pathway and promotes GTPase
activating factors which facilitate
conversion of RAS from active to inactive.
The loss of normal NF-1 leads to loss of
cell control.
E. RAS
Incorrect. RAS oncogene mutations
result in loss of control of cell proliferation;
there is no direct effect upon cell surface
proteins.
F. RB
Incorrect. RB acts as a tumor suppressor
gene.
G. RET
Incorrect. RET codes for a protein that
acts as a cell surface receptor for growth
factors. Mutations lead to loss of cell
control because the receptor remains
active even without binding of the growth
factor.
A 66-year-old woman has a chronic cough for 3 months.
A chest radiograph shows a left lung 4 cm peripheral
mass. Fine needle aspiration biopsy is performed and
cytologic examination shows non-small cell carcinoma
(NSCLC). Molecular analysis of these cells shows
upregulation of a pathway form suppression of anti-
tumor lymphocytes. Biotherapy with monoclonal
antibody to which of the following is most likely to be
effective in treating this woman's malignancy?
A. BRAF
Incorrect. BRAF is more likely to be a
target in malignant melanoma. BRAF is
a serine/threonine protein kinase and
mutations lead to stimulation of
downstream kinases.
B. MYC
Incorrect. MYC gene product is part of
transcriptional regulation and may target
genes such as D cyclins.
C. PD-1
CORRECT. The programmed cell death-
1 (PD-1) pathway can enable carcinomas
to suppress lymphocyte function;
antibody blockade of PD-1 with its ligand
PD-L1 have shown effectiveness in
treating in NSCLC.
D. RAS
Incorrect. RAS proteins stimulate the
receptor tyrosine kinase signaling
 Neoplasia | Pathology Reviewer (Utah) | 72 / 72
pathway. RAS proteins are members of In an experiment carcinoma cells are observed to
a family of membrane-associated small evade immune destruction by lymphocytes which have
G proteins that normally flip back and been stimulated to proliferate. Which of the following
forth between an excited signal- mechanisms is most likely to provide the tumor cells
transmitting state in which they are with the capacity to evade immune destruction by
bound to GTP and a quiescent state in lymphocytes?
which they are bound to GDP. A. Downregulation of MHC Class I
Stimulation of receptor tyrosine kinases expression
by growth factors leads to exchange of CORRECT. Tumor cells may not express
GDP for GTP. normal levels of MHC class I molecules
E. TP53 to reduce attack by cytotoxic T cells.
Incorrect. TP53 is a cell cycle regulator However, NK cells may attack tumor cells
and functions in the manner of a tumor expressing ligands for NK cell activating
suppressor gene. receptors.
B. Expression of oncofetal antigens
A 59-year-old woman has a screening mammogram Incorrect. Expression of oncofetal
that identifies a suspicious 3 cm mass in her right antigens is a characteristic for cancer
breast. Fine needle aspiration biopsy is performed and cells and may help in recognizing 'tumor
malignant cells are present. Excisional biopsy is markers' for diagnosis.
performed and molecular analysis of the malignant C. Formation of blocking antibodies
cells shows that they are estrogen receptor positive. In Incorrect. Tumor cells do not produce
addition to anti-estrogen therapy, a biotherapy with antibodies (unless they are myeloma
monoclonal antibody targeting the G1 phase of the cell cells, but such antibodies would not block
cycle involves which of the following targets and may immune attack).
be useful in treating this woman? D. Inhibition of regulatory T cells (Tregs)
A. CDK4 Incorrect. Tumor cells may upregulate
CORRECT. Cyclin-dependent kinases Tregs which keep the immune response
(CDKs) promote transition through the in check.
cell cycle; and may neoplastic are E. Upregulation of caspase production
dependent upon the G1 phase of the cell Incorrect. Caspases may be produced in
cycle. Many events impact neoplastic cell apoptosis, and it would be useful to
proliferation via their influence on CDK4 develop a tumor therapy where apoptosis
or CDK6 complexes in the G1 phase of was increased. Tumor cells may survive
the cell cycle. Multiple genes encode for by reducing apoptotic pathways.
the CDKs, part of a family of
serine/threonine protein kinases. ER+
breast cancers respond to estrogen
signaling for proliferation and survival.
ER blockers diminish tumor cell viability
and lead to cell cycle arrest in the G1
phase, but not all breast cancers respond
to anti-hormonal therapy.
B. BCR-ABL
Incorrect. The t9;22 translocation creates
the fusion gene BCR-ABL with tyrosine
kinase activity. This is characteristic for
chronic myelogenous leukemia.
C. HER2
Incorrect. HER2 is an epithelial growth
factor receptor that is amplified in some
breast carcinomas and is targeted by
trastuzumab.
D. TP53
Incorrect. TP53 is a cell cycle regulator
and functions in the manner of a tumor
suppressor gene.
E. WNT
Incorrect. The WNT signaling pathway is
involved in controlling cell fate, adhesion,
and cell polarity during embryonic
development. WNT signals through a
family of cell surface receptors and
stimulates pathways including beta-
catenin and APC.