2014 Step 1 Review Pathology

1. 2014 Step 1 Review Pathology Wednesday, February 1st Seth Wander sawander@med.miami.edu

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

3. Leukocyte Extravasation • 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 PMN Sialyl-Lewisx 1) Rolling 2) Tight binding LFA-1 (Integrin) ICAM-1 E-selectin • *PMN Type IV collagenase digests basement membrane • *Chemotactic factors via: • Complement • Bacterial cells • Cytokines 3) Diapedesis 4) Migration

4. Granulomatous diseases • Classic granulomatous agents: • TB • Fungal infections • Syphilis • Leprosy • Cat scratch fever • Sarcoidosis • Crohn’s • Berylliosis • 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) = MHC II IL-2 IFN-γ IL-12 TH1 memory CD4+ TH1

5. Neoplastic progression Hyperplasia Dysplasia Normal tissue architecture (basal  apical differentiation) Basement Membrane • 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

6. Neoplastic progression Carcinoma in situ Basement Membrane Invasion • Key factors during metastasis: • Lymphatic vs. hematogenous • “Seed and soil” • Immune evasion • Angiogenesis Metastasis

7. 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!

8. 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

9. Clinical oncology – paraneoplastic syndromes Small cell lung ca ACTH/ACTH-like peptide Cushing’s syndrome SIADH ADH Abs  presynaptic Ca2+ ch. @ NMJ Lambert-Eaton syndrome (also thymoma) Squamous cell lung ca Renal cell ca Breast ca Multiple myeloma Hypercalcemia PTH-related protein Renal cell ca Hemangioblastoma Erythropoietin Polycythemia Leukemias Lymphomas Gout, urate nephropathy Hyperuricemia

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

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

22. 13) Which of the following cellular injuries cannot be reversed following the readministration of O2? • Nuclear chromatin clumping • B) Fatty change • C) Ribosomal detachment (decreased protein synthesis) • D) Increased mitochrondrial permeability

23. 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? • 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

24. 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? • Gastric adenocarcinoma • B) Squamous cell carcinoma of the bladder • C) Kaposi’s sarcoma • D) Burkitt’s lymphoma

25. 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