2014 Step 1 Review Pathology

Wednesday, February 1stSeth Wandersawander@med.miami.edu

Pathology

• General comments• Leukocyte extravasation• Granulomatous diseases• Neoplastic progression• Clinical oncology• Sample questions

Leukocyte Extravasation

PMN

Sialyl-Lewisx

E-selectin

1) Rolling

ICAM-1LFA-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 β2 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 = TH1 lymphocytes surrounding a core of activated macrophages (epithelioid cells).• Type IV (delayed) hypersensitivity reaction• Macrophages phagocytize + present

antigen to TH1

• TH1 cells release cytokines (IFN-γ) to activate macrophages

• Macrophage activity and death results in eosinophilic multinucleated giant cells

Macrophage (APC)

CD4+ TH1

=

MHC II IL-2IFN-γ

IL-12

TH1 memory

Classic granulomatous agents:1) TB2) Fungal infections3) Syphilis4) Leprosy5) Cat scratch fever6) Sarcoidosis7) Crohn’s8) 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 caRenal cell caBreast caMultiple myeloma

PTH-related protein Hypercalcemia

Renal cell caHemangioblastoma

Erythropoietin Polycythemia

Abs presynaptic Ca2+ ch. @ NMJ Lambert-Eaton syndrome(also thymoma)

LeukemiasLymphomas

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 collateralblood flow in each organ

C) Hemodynamic status of the patient at thetime of infarction

D) Fibroblast content of each organ

13) Which of the following cellular injuries cannot be reversed following the readministration of O2?

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