PGIMER Entrance Pathology Flashcards

24 sample cards from the Pathology deck

Sampled from the end of the deck, so these are different cards from the ones shown on the syllabus page.

1. What is the molecular defect in sickle cell anemia and what conditions promote sickling?

   A point mutation in the beta-globin gene (GAG to GTG) substitutes valine for glutamic acid at position 6, producing HbS. Deoxygenation causes HbS polymerization and sickling. Sickling is promoted by hypoxia, acidosis, dehydration, and increased HbS concentration; HbF is protective.

2. Differentiate alpha-thalassemia from beta-thalassemia in terms of the basic defect.

   Alpha-thalassemia is usually due to deletion of one or more of the four alpha-globin genes, reducing alpha-chain synthesis. Beta-thalassemia is usually due to point mutations reducing (beta+) or abolishing (beta0) beta-chain synthesis. Both cause microcytic hypochromic anemia from imbalanced globin chains.

3. What is the inheritance and enzyme defect in hereditary spherocytosis and the diagnostic test?

   Hereditary spherocytosis is usually autosomal dominant, due to defects in red cell membrane skeletal proteins (most often ankyrin, also spectrin, band 3, protein 4.2). It causes spherocytes, extravascular hemolysis, splenomegaly. Diagnosed by increased osmotic fragility and increased MCHC; eosin-5-maleimide (EMA) flow cytometry is now used.

4. What is the trigger and blood-film hallmark of G6PD deficiency?

   G6PD deficiency (X-linked) reduces NADPH, leaving red cells vulnerable to oxidative stress. Triggers include oxidant drugs (primaquine, sulfa, dapsone), fava beans, and infections. The blood film shows bite cells and Heinz bodies (denatured hemoglobin).

5. Differentiate acute lymphoblastic leukemia (ALL) from acute myeloid leukemia (AML) by age, markers, and cytochemistry.

   ALL: most common in children, blasts are TdT-positive, lymphoid markers (CD10, CD19, CD20 for B-ALL; CD2-CD7 for T-ALL); cytochemistry MPO-negative. AML: more common in adults, blasts MPO-positive with Auer rods (especially APML), express CD13/CD33/CD34; TdT-negative.

6. What genetic translocation and morphologic feature characterize acute promyelocytic leukemia (APML, AML-M3) and its specific treatment?

   APML carries the t(15;17) translocation fusing PML-RARA. It shows abnormal promyelocytes with numerous Auer rods (faggot cells) and is associated with DIC. It responds to all-trans retinoic acid (ATRA), which induces differentiation.

7. What is the diagnostic cytogenetic abnormality of chronic myeloid leukemia (CML) and its phases?

   CML has the Philadelphia chromosome t(9;22) producing the BCR-ABL1 fusion gene with constitutive tyrosine kinase activity (treated with imatinib). It progresses through chronic phase, accelerated phase, and blast crisis, with marked leukocytosis, basophilia, and low leukocyte alkaline phosphatase (LAP).

8. What is the hallmark cell of Hodgkin lymphoma and how does Hodgkin differ from non-Hodgkin lymphoma in spread?

   The hallmark of Hodgkin lymphoma is the Reed-Sternberg cell (large binucleate 'owl-eye' cell, CD15+ and CD30+). Hodgkin spreads in a contiguous, orderly fashion from one nodal group to the next, whereas non-Hodgkin lymphoma spreads non-contiguously/unpredictably and more often involves extranodal sites.

9. What are the diagnostic findings of multiple myeloma?

   Multiple myeloma (malignant plasma cell proliferation) shows: monoclonal (M) spike on serum/urine electrophoresis, Bence Jones proteinuria (light chains), bone marrow plasmacytosis (>10 percent), 'punched-out' lytic bone lesions, hypercalcemia, renal failure, anemia with rouleaux formation, and recurrent infections.

10. Differentiate the lab findings of hemophilia A from von Willebrand disease.

    Hemophilia A (factor VIII deficiency, X-linked recessive): prolonged aPTT, normal PT, normal bleeding time/platelet count, deep tissue and joint bleeds. von Willebrand disease (most common inherited bleeding disorder): prolonged bleeding time, often prolonged aPTT (low VIII), abnormal ristocetin aggregation, mucocutaneous bleeding.

11. Compare PT and aPTT, and differentiate the radiographic/histologic features of osteosarcoma, Ewing sarcoma, and giant cell tumor of bone.

    PT assesses extrinsic and common pathways (VII, X, V, II, fibrinogen; monitors warfarin); aPTT assesses intrinsic and common pathways (XII, XI, IX, VIII...; monitors heparin). Osteosarcoma: metaphysis of long bones in adolescents, Codman triangle and sunburst pattern, malignant osteoid. Ewing sarcoma: diaphysis, onion-skin periosteal reaction, small round blue cells with t(11;22). Giant cell tumor: epiphysis, 'soap-bubble' lytic lesion, multinucleated osteoclast-like giant cells.

12. Differentiate ITP, TTP, and DIC by platelet count, coagulation tests, and key feature.

    ITP: isolated low platelets, normal PT/aPTT, antiplatelet antibodies. TTP: thrombocytopenia plus microangiopathic hemolytic anemia (schistocytes), normal PT/aPTT, ADAMTS13 deficiency, with the pentad of fever, renal and neuro signs. DIC: low platelets, PROLONGED PT and aPTT, low fibrinogen, raised D-dimer (consumption).

13. What is the sequence of morphologic changes in a myocardial infarct over time?

    0-4 hr: no change (or wavy fibers). 4-12 hr: early coagulative necrosis, edema. 1-3 days: neutrophil infiltration, loss of nuclei/striations. 3-7 days: macrophages remove dead myocytes (risk of rupture). 1-2 weeks: granulation tissue. >2 months: dense collagenous scar.

14. Differentiate the most common adult and childhood primary CNS tumors and the histologic hallmarks of glioblastoma and meningioma.

    Most common adult primary CNS tumor is glioblastoma (GBM, astrocytoma grade IV): shows necrosis with pseudopalisading and microvascular proliferation, crosses midline ('butterfly glioma'). Meningioma (benign, dural-based, women) shows whorls and psammoma bodies. In children, pilocytic astrocytoma (Rosenthal fibers) and medulloblastoma (cerebellar, small round blue cells, Homer-Wright rosettes) are common.

15. Differentiate the vegetations of rheumatic, infective, and nonbacterial thrombotic (marantic) endocarditis.

    Rheumatic: small, warty, sterile vegetations along valve closure lines (Aschoff bodies, mitral most affected). Infective: large, friable, destructive vegetations containing organisms, can embolize. Nonbacterial thrombotic (marantic): small, sterile, bland fibrin/platelet vegetations on closure lines, associated with malignancy/hypercoagulable states.

16. Differentiate transudative from exudative pleural effusion and name lobar vs bronchopneumonia patterns.

    Transudative effusion (Light criteria negative) is protein/LDH-poor from systemic causes (heart failure). Exudative effusion is protein/LDH-rich from local inflammation/malignancy. Lobar pneumonia consolidates an entire lobe (classically pneumococcus) with stages of congestion, red then gray hepatization, resolution. Bronchopneumonia is patchy, multifocal, centered on bronchi.

17. Differentiate nephritic from nephrotic syndrome.

    Nephritic syndrome: hematuria with dysmorphic RBCs and red cell casts, hypertension, oliguria, mild-moderate proteinuria, azotemia (e.g. post-streptococcal GN). Nephrotic syndrome: massive proteinuria (>3.5 g/day), hypoalbuminemia, generalized edema, hyperlipidemia, lipiduria (e.g. minimal change disease, membranous nephropathy).

18. Differentiate the cirrhosis-associated patterns and the hepatitis serology markers indicating acute infection, immunity, and infectivity.

    Cirrhosis is diffuse fibrosis with regenerative nodules disrupting architecture. Hepatitis B serology: HBsAg = active infection; anti-HBs = immunity (recovery or vaccination); IgM anti-HBc = acute/recent infection (window period); HBeAg = high infectivity/active replication.

19. Differentiate the histology of the major thyroid carcinomas and their key features.

    Papillary carcinoma (most common, best prognosis): Orphan-Annie eye nuclei, nuclear grooves, psammoma bodies; spreads via lymphatics. Follicular: capsular/vascular invasion, hematogenous spread. Medullary: parafollicular C-cells, amyloid stroma, calcitonin, MEN-2 association. Anaplastic: aggressive, undifferentiated, elderly, poor prognosis.

20. What are the key histologic types and prognostic receptors in breast carcinoma?

    Invasive ductal carcinoma (NOS) is the most common type; invasive lobular carcinoma grows in single-file (E-cadherin loss). Prognosis depends on ER/PR status (hormone-responsive, better prognosis) and HER2/neu (targeted by trastuzumab); triple-negative (ER-/PR-/HER2-) carries the worst prognosis.

21. Differentiate the four types of hypersensitivity reactions with a prototype example of each.

    Type I (immediate/anaphylactic): IgE-mediated mast cell degranulation (anaphylaxis, atopy). Type II (cytotoxic): antibody (IgG/IgM) against cell-surface antigens (autoimmune hemolytic anemia, Goodpasture). Type III (immune-complex): antigen-antibody complex deposition with complement (SLE, serum sickness). Type IV (delayed): T-cell mediated (TB skin test, contact dermatitis).

22. What is the difference between primary and secondary amyloidosis, and the special stain and microscopy used for diagnosis?

    Primary amyloidosis is AL type (amyloid light chains) associated with plasma cell dyscrasias/multiple myeloma. Secondary (reactive) amyloidosis is AA type (serum amyloid-associated protein) from chronic inflammation (TB, rheumatoid arthritis). Diagnosis: Congo red stain gives apple-green birefringence under polarized light; EM shows non-branching fibrils.

23. Differentiate hyperacute, acute, and chronic graft (transplant) rejection by timing and mechanism.

    Hyperacute rejection occurs within minutes to hours due to pre-formed recipient antibodies against donor antigens (type II), causing thrombosis and ischemia. Acute rejection occurs days to weeks later and is cellular (T-cell mediated tubulitis/endothelialitis) and/or humoral (antibody-mediated vasculitis). Chronic rejection occurs months to years later with vascular intimal fibrosis, parenchymal atrophy, and graft fibrosis; graft-versus-host disease occurs when grafted immune cells attack the host.

24. Differentiate the major primary immunodeficiencies by the affected arm of immunity and a prototype example.

    B-cell/humoral defects (recurrent pyogenic/encapsulated bacterial infections): X-linked (Bruton) agammaglobulinemia, selective IgA deficiency, CVID. T-cell defects (viral, fungal, intracellular organisms): DiGeorge syndrome (thymic aplasia, 22q11 deletion). Combined B and T defects: SCID (e.g. adenosine deaminase deficiency). Phagocyte defects: chronic granulomatous disease (NADPH oxidase defect, abnormal nitroblue-tetrazolium test). Complement defects: recurrent Neisseria infections with C5-C9 deficiency.

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