2014 Step 1 Review

2014 Step 1 Review

Pathology

Wednesday, February 1st

Seth Wander

sawander@med.miami.edu

Pathology

•
General comments

•
Leukocyte extravasation

•
Granulomatous diseases

•
Neoplastic progression

•
Clinical oncology

•
Sample questions

Leukocyte
Extravasation

PMN

Sialyl
-
Lewis
x

E
-
selectin

1) Rolling

ICAM
-
1

LFA
-
1

(Integrin)

2) Tight binding

3) Diapedesis

4) Migration

*PMN Type IV collagenase digests basement
membrane

*Chemotactic factors via:

-

Complement

-

Bacterial cells

-

Cytokines

Leukocyte Adhesion Deficiency (LAD)
:

•

AR, loss of
β
2 integrin subunit (CD18) =
impaired LFA
-
1 function

•

Delayed umbilical cord separation
(omphalitis)

•

Poor wound healing

•

Recurrent bacterial/fungal infections
(without pus!)

•

↑↑ neutrophils in peripheral blood

Granulomatous

diseases

Granuloma = TH
1
lymphocytes surrounding a
core of activated macrophages (epithelioid
cells).

•

Type IV (delayed) hypersensitivity reaction

•

Macrophages phagocytize + present antigen
to TH
1

•

TH
1
cells release cytokines (IFN
-
γ
) to
activate macrophages

•

Macrophage activity and death results in
eosinophilic multinucleated giant cells

Macrophage


(APC)

CD4+ TH
1

=

MHC II

IL
-
2

IFN
-
γ

IL
-
12

TH
1

memory

Classic
granulomatous

agents:

1)
TB

2)
Fungal infections

3)
Syphilis

4)
Leprosy

5)
Cat scratch fever

6)
Sarcoidosis

7)
Crohn’s

8)
Berylliosis

Neoplastic

progression

Basement Membrane

Normal tissue architecture

(basal


apical differentiation)

Hyperplasia

Dysplasia

A few confusing terms:

•

Metaplasia

–

reversible replacement of 1 adult cell type with another

•

Anaplasia
–

irreversible loss of cellular differentiation, (malignant neoplasms)

•

Desmoplasia

–

excessive fibrous tissue formation in the stroma of a tumor

•

Hamartoma

–

abnormal tissue in its usual location

•

Choristoma

–

benign/normal tissue in an abnormal (ectopic) location

Neoplastic

progression

Basement Membrane

Carcinoma in situ

Invasion

Metastasis

Key factors during metastasis:

•

Lymphatic vs. hematogenous

•

“Seed and soil”

•

Immune evasion

•

Angiogenesis

Neoplasia

associations

•

Barrett’s esophagus


esophageal adenocarcinoma


•

Cirrhosis


hepatocellular carcinoma


•

Ulcerative colitis


colonic adenocarcinoma


•

Hashimoto’s thyroiditis


thymomas (benign + malginant)


•

Actinic keratosis


squamous cell carcinoma

Chronic inflammatory states predispose to tumorigenesis!

Clinical oncology

Tumor Grading


vs.

Tumor Staging


•

Histological assessment


•

Degree of differentiation?


•

Number of mitoses?

•

Clinical assessment


•

T = size of primary tumor


•

N = involvement of regional nodes?


•

M = distant mets?


•

**
Higher prognostic value

Tumor markers?


-

These are NOT primary
diagnostic tools


-

Confirm diagnosis


-

Monitor recurrence


-

Monitor response to therapy

Clinical oncology
–

paraneoplastic syndromes

Small cell lung ca

ACTH/ACTH
-
like peptide

Cushing’s syndrome

ADH

SIADH

Squamous cell lung ca

Renal cell ca

Breast ca

Multiple myeloma

PTH
-
related protein

Hypercalcemia

Renal cell ca

Hemangioblastoma

Erythropoietin

Polycythemia

Abs


presynaptic Ca2+ ch. @ NMJ

Lambert
-
Eaton syndrome

(also thymoma)

Leukemias

Lymphomas

Hyperuricemia

Gout, urate nephropathy

1) Which of the following is characteristic of a
transudate?



A) Protein rich


B) Specific gravity of 1.12


C) Hypocellularity


D) High degree of local inflammation


2) A young child presents with a history of recurrent
bacterial and fungal infections. The mother reports that,
despite a normal pregnancy, the child developed omphalitis
during the neonatal period. Laboratory examination reveals
a large increase in circulating neutrophils. What is the
underlying defect?



A) A failure in leukocyte diapesis at sites of infection


B) Maternally acquired HIV


C) A defect in leukocyte chemotaxis following extravasation


D) A congenital mutation in the CD18 leukocyte adhesion
gene


3) A patient presents with advanced HIV disease and
concomitant immunosuppression. Despite the diagnosis of
secondary infection with histoplasmosis, no granulomas can
be identified following histological examination. What is the
best explanation for this finding?



A) Granulomas never form during fungal infections


B) Due to patient’s HIV status, the CD4+ helper T population is
reduced, impairing the formation of granulomas


C) The patient lacks the necessary macrophage cell
population


D) The CD8+ T population is lost, preventing granuloma
development


4) Following routine tuberculosis testing, a patient
presents with the ppd shown at right. Biopsy of the
lesion demonstrates the histology shown. This
reaction is due to the release of what cytokine by
the resident macrophage population?



A) IL
-
6


B) IFN
-
γ


C) IL
-
12


D) TNF
-
α


5) An alcoholic patient with a long history of cirrhosis
presents with increasing URQ abdominal pain and
jaundice. He reports a dramatic weight loss over the
previous month. If you suspect a malignancy, which
of the following tumor markers will likely assist with
diagnosis and treatment monitoring?



A) PSA


B) CA
-
125


C) CA
-
19
-
9


D)
α
-
fetoprotein


6) Which of the following statements regarding
cancer epidemiology in the United States is
accurate?



A) Breast cancer is responsible for the highest
number of cancer deaths in women


B) Lung cancer is the most common cancer in men


C) Lung cancer is the most common cause of cancer
-
related mortality in both men and women


D) Cancer is the leasing cause of death in the United
States


7) A patient presents with a thyroid mass. The
following histological finding is evident upon biopsy.
What is the most likely diagnosis?



A) Papillary carcinoma


B) Hashimoto’s thyroiditis


C) Follicular carcinoma


D) Medullary carcinoma


8) Which of the following involve inflammation and
necrosis rather than controlled apoptotic cell death?



A) Embryogenesis


B) Menstruation


C) Atrophy


D) Ischemic myocardial infarction


9) Biallelic disruption of the tumor suppressor found
on 17p, which results in multi
-
organ neoplasias
before the age of 45, is known as which of the
following?



A) Multiple endocrine neoplasia Types II and III


B) Li
-
Fraumeni syndrome


C) Neurofibromatosis Type I


D) Tuberous Sclerosis


10) A female patient with a history of recurrent
breast cancer presents following a hip fracture after
a minor fall. Initial PET scan results do not show
hypermetabolic foci in the skeletal system. What is
the most likely underlying cause of her hip fracture?



A) Occult metastatic foci within the skeletal system


B) Congenital malformations in the hip joint


C) Lambert
-
Eaton syndrome


D) Production of PTH
-
rp by her primary breast
cancer


11) Which of the following factors is relevant to
tumor grade rather than stage?



A) The presence or absence of distant metastases


B) The involvement of regional lymph nodes


C) The number of mitotic events per high powered
field


D) The extent of primary tumor invasion below the
basement membrane and into surrounding muscle


12) Following infarction the organs shown below
demonstrate the associated pathology. Which of the
following is the best anatomical explanation for this finding?



A)
Differences in the size of the

occluded vessel


B) Distinctions in the extent of collateral

blood flow in each organ


C) Hemodynamic status of the patient at the

time of infarction


D) Fibroblast content of each organ


13) Which of the following cellular injuries cannot be
reversed following the
readministration

of O
2
?



A)
Nuclear chromatin clumping


B) Fatty change


C) Ribosomal detachment (decreased protein synthesis)


D) Increased
mitochrondrial

permeability


14) During embryogenesis controlled cell death occurs in a
variety of developing organs. Following an intrinsic shift in
the balance between
Bax

and Bcl
-
2, and before the
activation of the
caspase

cascade, which of the following
events must occur?



A)
Fas
-
ligand

binding to its cognate receptor


B) Killer T
-
cell mediated
perforin

activity


C) Mitochondrial release of
cytochrome

C


D) Cellular and tissue inflammation


15) A patient who had been previously diagnosed with
schistosomiasis

several years earlier presents with a
malignancy. Which of the following is the most likely
diagnosis?



A)
Gastric
adenocarcinoma


B)
Squamous

cell carcinoma of the bladder


C) Kaposi’s sarcoma


D)
Burkitt’s

lymphoma


16) Which of the following clinical scenarios might
be expected to decrease the erythrocyte
sedimentation rate (ESR)?



A) Cancer


B) Pregnancy


C) Polycythemia


D) Inflammatory states