A 34 year old woman presents to her general physician with nonspecific fever

of five days' duration. She says that there are swollen "bumps" in her right
axillary region which are painful. She complains of fatigue, low-grade fever,
and some stomach pain. Physical exam reveals tender right axillary
lymphadenopathy. She also has a minor laceration on her right forearm that
her cat gave her a week ago. She admits to a 5 kg weight loss, but says she is
not hungry. What findings are likely to be prominent if a biopsy was performed
of a right axillary lymph node?

A. Prominent germinal centers

B. Effacement of the nodal architecture

C. Proliferation of cytotoxic CD8 T cells

D. Atypical lymphocytes

E. Numerous band cells

e correct answer is E
This patient is most likely suffering from "cat-scratch disease", a bacterial
infection caused by Bartonella henselae. This unilateral lymphadenopathy on
the side of the scratch combined with nonspecific constitutional symptoms is
characteristic of the disease. The patient thus likely has expansion of germinal
centers, which are aggregates of B cells that can occur upon antigen
presentation.

Effacement of nodal architecture is characteristic of lymphoma,

especially Hodgkin lymphoma in a female patient of this age.

Proliferation of cytotoxic CD8 T cells can occur during a delayed

hypersensitivity reaction to antigens such as tuberculosis.

Atypical lymphocytes are characteristic to infection with Ebstein-Barr Virus or

cytomegalovirus.

Numerous band cells are more common in acute septic infections such as
thos

2. A 41-year-old woman with no significant medical history presents

complaining of fatigue and lightheadedness. Physical exam is notable for
conjunctival pallor, bilateral brisk patellar reflexes, slightly ataxic gait, and
impaired position and vibration sense in the feet bilaterally. Her hematocrit is
23%. Serologic studies are positive for anti-parietal cell antibodies. What
would you expect to see on peripheral blood smear?

A. Burr cells

B. Hypersegmented neutrophils

C. Howell-Jolly bodies

D. Schistocytes

E. Spur cells

Good Work
The correct answer is B
This patient has pernicious anemia, autoimmune attack on parietal cells
causing decreased production of intrinsic factor and resultant vitamin B12
deficiency. B12 deficiency causes a megaloblastic anemia (with
hypersegmented neutrophils on blood smear), stomatitis, glossitis, and
subacute combined degeneration of peripheral nerves and spinal cord (which
can cause ataxia, hyperreflexia, and impaired position/vibration sense). Burr
cells (A) and spur cells (E) are types of poikilocytes - burr cells suggest renal
disease and spur cells (acanthocytes) suggest liver disease or lipid
abnormalities. Howell-Jolly bodies (C) are clusters of DNA within RBC
cytoplasm indicative of asplenia or hyposplenia. Schistocytes (D) are
fragmented red blood cells that are seen in microangiopathic diseases such
as disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic
purpura (TTP), and hemolytic uremic syndrome (HUS).

3. A 45 year-old man with a history of alcoholism develops pancreatitis. What

pathologic changes would likely be seen in this patient's pancreas?

A. Eosinophilic deposits in vascular walls

B. Granulomatous inflammation with some preservation of tissue

architecture
C. Liquefied necrotic tissue

D. Necrotic fat cells, calcium soap formation, and lipid-laden macrophages

E. Tissue architecture well-preserved, with nuclear changes

The correct answer is D

Check It!

Enzymatic fat necrosis is seen in pancreatitis, and is characterized

histologically by necrotic fat cells, calcium soap formation, and lipid-laden
macrophages. The two most frequent causes of pancreatitis
are gallstones and alcohol.

Eosinophilic deposits in vascular walls is representative of fibrinoid necrosis.

Granulomatous inflammation with some preservation of tissue architecture is
representative of caseous necrosis. Liquefied necrotic tissue is representative
of liquefactive necrosis. Tissue architecture well-preserved, with nuclear
changes is representative of coagulative necrosis.
4. A 45-year-old man cannot leave home without antacids because he has
had severe heartburn with every meal for 10 years. Which of the following is
likely to be seen on biopsy of his lower esophagus?

A. Columnar metaplasia

B. Hyperplasia

C. Hypertrophy

D. Normal esophageal epithelium

E. Squamous metaplasia

The correct answer is A

Barrett's esophagus is a complication of gastro-esophageal reflux
disease (GERD). The lower 2/3 of the esophagus is composed of stratified
squamous epithelium. With repeated exposure to caustic gastic acid, tissue in
the lower esophagus is replaced with columnar glandular epithelium with
goblet cells resembling glandular cells of the intestines that secrete mucin.
This process is called metaplasia, in this case columnar.

Hyperplasia is an increase in the number of cells in a tissue region, such as

endometrial hyperplasia. Hypertrophy describes enlargement of existing cells,
such as in hypertrophic cardiomyopathy. Squamous metaplasia would not
occur in the esophagus, where epithelium is normally squamous. Squamous
metaplasia can occur in the bladder, cervix, or lungs.

5. A 46 year-old white male with a family history of esophageal

adenocarcinoma presents complaining of heartburn. On endoscopy, a
crescent-shaped area of erythematous mucosa is seen that extends above the
gastroesophageal junction. A biopsy of this area of mucosa is taken. What
histological features will most likely be seen on H&E stain?

A. Columnar epithelium with goblet cells

B. Columnar epithelium with parietal cells

C. Keratinized squamous epithelium

D. Non-keratinized squamous epithelium

E. Transitional epithelium

The correct answer is A This erythematous mucosa is likely Barrett's

esophagus, or metaplasia of the normal squamous epithelium of the distal
esophagus to columnar epithelium. This usually occurs in the setting of
gastroesophageal reflux. Barrett's is considered pre-malignant for esophageal
adenocarcinoma, but not for squamous cell carcinoma. Goblet cells are
mucous-secreting cells that will easily be seen in Barrett's on H&E stain.
Parietal cells are not associated with the development of Barrett's -
furthermore, they would not easily be seen on H&E stain. Transitional
epithelium is seen in the urinary tract.

6, BASIC SCIENCE: HISTOLOGY

A 65 year-old man with no past medical history presents for his annual check-
up. He notes some increased dyspnea on exertion along with an overall
lethargic feeling for the past few months. Physical exam is normal with the
exception of a heme-occult positive stool test, and he is subsequently found to
have elevated liver function tests. Which of the following is true?
A. A peripheral blood smear will show microcytic erythrocytes

B. A CEA level will be at least twice the upper limit of normal

C. A peripheral blood smear would show polymorphonuclear cells with

more than five lobes of the nucleus

 D. A biopsy of the primary lesion will show signet-ring cells

E. A CEA level will be undetectable

BASIC SCIENCE: HISTOLOGY

A 65 year-old man with no past medical history presents for his annual check-
up. He notes some increased dyspnea on exertion along with an overall
lethargic feeling for the past few months. Physical exam is normal with the
exception of a heme-occult positive stool test, and he is subsequently found to
have elevated liver function tests. Which of the following is true?
A. A peripheral blood smear will show microcytic erythrocytes

B. A CEA level will be at least twice the upper limit of normal

C. A peripheral blood smear would show polymorphonuclear cells with

more than five lobes of the nucleus

D. A biopsy of the primary lesion will show signet-ring cells

E. A CEA level will be undetectable

8. A 65-year-old man presents with worsening symptoms of difficulty rising

from a chair, shuffling gait, drooling, tremor at rest, and constipation. Which of
the following is the most likely finding on examination of tissue if a brain biopsy
was performed?

A. Amyloid neuritic plaques in neocortex

B. Atypical lymphocytes

C. Eosinophilic sphere-shaped inclusions in cytoplasm

 D. Neurofibrillary tangles within neurons

E. Protein aggregations and intranuclear inclusions

Check It!

The correct answer is C

- eosinophilic sphere-shaped inclusions in cytoplasm. These are Lewy
bodies and they are the pathological hallmark of Parkinson's disease along
with degeneration of dopaminergic neurons of the substantia nigra. It is
important to first recognize that this patient's symptoms are seen in
Parkinson's disease.

The other histological findings are seen in other neurological diseases.

Amyloid neuritic plaques and neurofibrillary tangles are seen in Alzheimer's
disease. Atypical lymphocytes may be seen in a viral encephalitis secondary
to Epstein Barr Virus infection. Protein aggregations and intranuclear
inclusions are findings in Huntington's Chorea.

10. A five-month old infant is brought to your office with a distressed mother.
She complains that he bruises easily when on his back and arms when he is
laid in his crib every night. She thinks his joints feel "loose" and that when she
picks him up she is afraid that she may dislocate his shoulders. On exam his
arms feature ecchymoses and cigarette-paper-like stretch marks on the skin.
Which of the following is the likely defect causing this infant's presentation?

A. Deficiency of sphingomyelinase

B. Dynein arm defect

C. Faulty collagen synthesis and misfolding

 D. Fibrillin gene mutation

E. Glycogen accumulation in muscle tissue

The correct answer is C

This infant is exhibiting a classical form of Ehlers-Danlos syndrome,
characterized by hyperextensible joints and skin under physiologic loading,
and a tendency to bleed, due to a defect in collagen synthesis and folding.

Sphingomyelinase deficiency is associated with Niemann-Pick disease.

A dynein arm defect resulting in immotile cilia is found in Kartagener's

syndrome.

The autosomal dominant fibrillin gene mutation is found Marfan's disease.

Glycogen accumulation in the muscle tissue of infants and toddlers can be

verified microscopically in McArdle's disease, a disorder of glycogen storage.

11. A pathologist is performing an autopsy on the brain of a 42-year-old

woman who died in the same way her father and grandmother had which
included a prolonged course of dementia, uncontrolled limb movements, and
mood changes. What is the pathologist most likely to find on autopsy?

A. Cortical amyloid plaques

B. Light colored susbtantia nigra

C. Multiple ischemic lesions

D. Shrunken head of the caudate

E. Vacuoles and gliosis

The correct answer is D
The age, genetic pattern and symptoms in the vignette suggest that the
patient described likely suffered from Huntington's disease. The pathological
findings characteristic of Huntington's include a shrunken head of the caudate
(choice D) and dilated ventricles.

Cortical amyloid plaques (Choice A) are typical findings of Alzheimer's

disease, but would be unlikely in a 42 year old and does not follow a clear
genetic pattern.

Light colored susbtantia nigra (choice B) are classic findings in Parkinson's

disease, where a loss of dopaminergic neurons occurs. Parkinson's is unlikely
to cause dementia in such a young patient.

Multiple ischemic lesions (Choice C) are characteristic of multi-infarct

dementia, which would be unusual in a woman of 42.

Vacuoles and gliosis (choice E) are typical findings in Creutzfeldt-Jakob

Disease, which is generally not a genetic disease.

12. A pathologist receives a normal specimen resected from a patient's

gastrointestinal tract. Under the microscope, she sees that the mucosa
contains columnar cells lacking villi. There are many straight and long tubular
glands. This specimen most likely originates from which portion of the GI
tract?

A. Esophagus

B. Large intestine

C. Pharynx
 D. Small Intestine

E. Stomach

he correct answer is B
The large intestine (choice B) contains the cecum and the colon. Its mucosa is
composed of columnar cells lacking villi, and contains openings which give
way to tubular glands known as the crypts of Lieberkuhn.

The mucosa of the esophagus (choice A) is composed of thick, stratified,

squamous, nonkeratinized epithelium.

The pharynx (choice C) contains stratified, squamous epithelium, as well as

ciliated, pseudostratified, columnar epithelium.

Intestinal villi are the hallmark of the small intestine (choice D). They are
composed of outgrowths of the mucous membrane into the lumen. Crypts of
Lieberkuhn are also found in the small intestine.

The stomach (choice E) mucosa contain simple, columnar cells, but lacks the
crypts of Lieberkuhn.

13. A physician-scientist is conducting an experiment in which she tries to

stimulate growth of cartilage in vitro. She wishes to use a substance to
stimulate histogenesis. Which substance would be best suited to her purposes
based on its stimulation of cartilage growth in vivo?

A. Cortisone

B. Estrogen
 C. Thyroxine

D. Vitamin A

E. Vitamin D

The correct answer is C

Cartilage growth is stimulated by thyroxine (Choice C), testosterone and
growth hormone.

It is inhibited by estrogen (Choice B) and cortisone (Choice A).

Vitamin A (Choice D) and Vitamin D (Choice E) are involved in bone

mineralization.

14. An infant is born prematurely at 32 weeks in respiratory distress. A chest

X-ray shows signs of neonatal respiratory distress syndrome (RDS) and the
infant is treated with exogenous surfactant. Which of the following types of
pulmonary cells makes surfactant?

A. Type I alveolar cells

B. Type II alveolar cells

C. Capillary endothelial cells

D. Clara cells

E. Pseudocolumnar ciliated cells

Surfactant is made by type II alveolar cells and stored in lamellar bodies within
these cells. They start developing after 24 weeks gestation, which is one of
the major reasons birth before 24 weeks is not compatible with life. Type I
alveolar cells make up the majority of the alveolar surface. Capillary
endothelial cells secrete angiotensin-converting enzyme (ACE). Clara cells are
mostly found in the primary bronchioles and contain P450 enzymes to detoxify
harmful chemicals in the lungs. Pseudocolumnar ciliated cells line the trachea,
creating a "muco-ciliary escalator" to expel toxins/dust in the upper airways.

1. An otherwise healthy Kenyan man is prescribed trimethoprim-

sulfamethoxazole for a urinary tract infection. He presents to the
emergency department with jaundice, fatigue, and confusion. Which of
the following might you see in the RBCs of a peripheral smear?
2. A. Heinz bodies

B. Howell-Jolly bodies

C. Basophilic stippling

D. Auer rods

E. Reed-sternberg bodies

The correct answer is A

G6PD deficiency is often asymptomatic until faced with an oxidative
challenge, such as the drug TMP-SMX. It usually occurs in people of central
African, Middle-Eastern, or Western Asian origin. The classic finding in RBCs
is Heinz bodies (Answer A), which are collections of denatured hemoglobin.
Howell-Jolly bodies are nuclear remnants in RBCs that remain due to failure of
splenic sequestration in Sickle-cell disease. Basophilic stippling represents
RNA collections that are most classically associated with lead poisoning. Auer
rods are clumps of granular material diagnostic of acute myeloid leukemia
(AML). Reed-sternberg bodies are the "owl-eyes" pathognomonic for
Hodgkin's lymphoma.
16. In young infants as well as geriatrics patients, "bandemia" (increased band
cells) is a sign of acute bacterial infection. When a band cells differentiates,
which of the following types of cells is a possible mature cell type it can
become?

A. Erythrocyte

B. Lymphocyte

C. Neutrophil

D. Monocyte

E. Platelet

he correct answer is C
Myeloblasts differentiate into promyelocytes, myelocytes, metamyelocytes,
then band cells, and finally branch into neutrophils, eosinophils and basophils.
These types of cells are all known as granulocytes. Lymphoblasts differentiate
into B cell and T cell lymphocytes, as well as natural killer
cells. Monoblasts differentiate into monocytes. Megakaryoblasts turn into
megakaryocytes, which produce platelets.

17.