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
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