DNB CET Pathology Syllabus

Define anaplasia and list its cytologic hallmarks.

Anaplasia is lack of differentiation, the hallmark of malignancy. Features: pleomorphism, hyperchromatic nuclei, high nuclear-to-cytoplasmic ratio, prominent nucleoli, abnormal/atypical mitoses, and loss of polarity.

Name the major routes of metastatic spread and which is typical of carcinomas versus sarcomas.

Lymphatic spread (typical of carcinomas), hematogenous spread (typical of sarcomas), and seeding of body cavities (transcoelomic, e.g., ovarian carcinoma to peritoneum).

List important tumor markers and their associated tumors: AFP, CEA, PSA, CA-125, CA-19-9, beta-hCG.

AFP: hepatocellular carcinoma, yolk sac/germ cell tumors. CEA: colorectal, pancreatic, gastric, lung carcinomas. PSA: prostate carcinoma. CA-125: ovarian (epithelial) carcinoma. CA-19-9: pancreatic carcinoma. beta-hCG: choriocarcinoma, germ cell tumors.

Name two classic tumor suppressor genes and their associated cancers, and the 'two-hit' hypothesis.

RB (retinoblastoma, osteosarcoma) and TP53 (Li-Fraumeni, most human cancers). Knudson's two-hit hypothesis: both alleles of a tumor suppressor gene must be inactivated for tumor development.

What are the four types of hypersensitivity reactions (Gell and Coombs) with one example each?

Type I: immediate/anaphylactic, IgE-mediated (asthma, anaphylaxis). Type II: antibody-mediated cytotoxic (autoimmune hemolytic anemia, Goodpasture). Type III: immune complex (SLE, serum sickness). Type IV: delayed, T-cell mediated (TB skin test, contact dermatitis).

What is amyloid, how is it identified histologically, and what stain is used?

Amyloid is an abnormal extracellular fibrillar protein with beta-pleated sheet structure. It stains pink with H&E (amorphous, eosinophilic) and with Congo red shows apple-green birefringence under polarized light.

Differentiate AL versus AA amyloid (precursor protein and associated condition).

AL amyloid: derived from immunoglobulin light chains, associated with plasma cell dyscrasias/multiple myeloma (primary amyloidosis). AA amyloid: derived from serum amyloid-associated protein (SAA), seen in chronic inflammatory conditions (secondary amyloidosis).

Classify anemias morphologically (by MCV) with one cause for each category.

Microcytic (MCV<80): iron deficiency, thalassemia. Normocytic (MCV 80-100): acute blood loss, anemia of chronic disease, hemolysis. Macrocytic (MCV>100): B12/folate deficiency (megaloblastic), alcohol, hypothyroidism.

What are the peripheral smear and bone marrow features of megaloblastic anemia?

Smear: macro-ovalocytes, hypersegmented neutrophils (>5 lobes), anisopoikilocytosis, pancytopenia. Marrow: hypercellular with megaloblastic erythroid precursors showing nuclear-cytoplasmic asynchrony (nuclear maturation lags cytoplasm).

Compare the iron studies in iron deficiency anemia versus anemia of chronic disease.

Iron deficiency: low serum iron, high TIBC, low ferritin, low transferrin saturation. Anemia of chronic disease: low serum iron, low/normal TIBC, high/normal ferritin (iron trapped in macrophages via hepcidin).

What is the inheritance and basic defect in sickle cell anemia, and the key smear finding?

Autosomal recessive point mutation (glutamate to valine at position 6 of beta-globin) producing HbS. Deoxygenated HbS polymerizes, causing sickle-shaped RBCs (drepanocytes) and Howell-Jolly bodies (from autosplenectomy) on smear.

Name the diagnostic test and inheritance for hereditary spherocytosis.

Autosomal dominant; defect in RBC membrane proteins (spectrin/ankyrin). Diagnostic: increased osmotic fragility and spherocytes on smear; flow cytometry EMA binding test. Negative direct Coombs (distinguishes from autoimmune hemolytic anemia).

Classify leukemias and state the typical age groups (ALL, AML, CLL, CML).

ALL: children (peak 2-5 yrs). AML: adults. CLL: elderly (>60 yrs). CML: middle-aged adults (40-60 yrs). Acute = blasts; chronic = mature cells.

What is the characteristic cytogenetic abnormality of CML and its molecular product?

Philadelphia chromosome t(9;22) producing the BCR-ABL1 fusion gene, which codes a constitutively active tyrosine kinase. Target of imatinib therapy.

What distinguishes a leukemoid reaction from CML (LAP score)?

Leukemoid reaction (reactive, e.g., infection) has a HIGH leukocyte alkaline phosphatase (LAP) score and toxic granulation. CML has a LOW LAP score and the Philadelphia chromosome.

Name the myeloproliferative neoplasms and the common driver mutation in three of them.

CML, Polycythemia vera, Essential thrombocythemia, Primary myelofibrosis. JAK2 V617F mutation is found in nearly all PV and ~50% of ET and PMF. CML is driven by BCR-ABL1.

What cell type is diagnostic of Hodgkin lymphoma and what are its immunomarkers?

Reed-Sternberg cell (binucleate 'owl-eye' giant cell). Classic HL RS cells are CD15+ and CD30+, but CD45 negative and usually CD20 negative.

Compare Hodgkin and non-Hodgkin lymphoma in terms of spread and nodal involvement.

Hodgkin: orderly, contiguous spread to adjacent nodes, localized to single axial group, rarely extranodal, Reed-Sternberg cells. NHL: non-contiguous (multiple peripheral nodes), frequent extranodal involvement, no RS cells.

What is the translocation and morphology of Burkitt lymphoma?

t(8;14) involving the MYC oncogene. Morphology: 'starry sky' appearance (tingible-body macrophages amid a sea of monomorphic intermediate B cells), very high proliferation index (Ki-67 ~100%). Associated with EBV (endemic form).

Name the most common NHL in adults and its associated translocation.

Diffuse large B-cell lymphoma (DLBCL) is the most common NHL. Follicular lymphoma is the most common indolent NHL and carries t(14;18) overexpressing BCL2.

Outline the intrinsic and extrinsic coagulation pathways and the common pathway.

Extrinsic: tissue factor (TF/factor III) activates factor VII (measured by PT). Intrinsic: factors XII, XI, IX, VIII (measured by aPTT). Common pathway: factor X to Xa, prothrombin (II) to thrombin, fibrinogen (I) to fibrin.

What does PT versus aPTT measure and which factor deficiencies prolong each?

PT/INR measures the extrinsic and common pathway (factors VII, X, V, II, fibrinogen). aPTT measures the intrinsic and common pathway (factors XII, XI, IX, VIII, X, V, II, fibrinogen). VII deficiency: isolated PT prolongation; VIII/IX: isolated aPTT prolongation.

Differentiate Hemophilia A from Hemophilia B and von Willebrand disease.

Hemophilia A: X-linked, factor VIII deficiency, prolonged aPTT. Hemophilia B (Christmas): X-linked, factor IX deficiency, prolonged aPTT. vWD: autosomal dominant, deficient vWF, prolonged bleeding time + aPTT, abnormal ristocetin test.

What are the laboratory findings in disseminated intravascular coagulation (DIC)?

Prolonged PT and aPTT, low fibrinogen, low platelets, elevated D-dimer/FDPs, schistocytes (fragmented RBCs) on smear due to microangiopathic hemolysis.

Describe the stages of atherosclerosis from earliest to advanced lesion.

Fatty streak (lipid-laden macrophages/foam cells) -> intermediate lesion -> fibrous (atheromatous) plaque (lipid core with fibrous cap) -> complicated plaque (calcification, ulceration, hemorrhage, thrombosis, aneurysm).

What is the timeline of gross and microscopic changes in myocardial infarction (0-4 hrs to weeks)?

0-4h: no change. 4-12h: early coagulation necrosis, wavy fibers. 12-24h: contraction bands, neutrophils begin. 1-3d: coagulative necrosis, heavy neutrophils. 3-7d: macrophages, disintegration. 1-2wk: granulation tissue. >2-8wk: collagen scar.

Which cardiac biomarker rises earliest, which is most specific, and their time courses in MI?

Myoglobin rises earliest (1-2h) but nonspecific. Troponin I/T is most specific/sensitive, rises 3-12h, peaks 24-48h, stays elevated 7-10 days. CK-MB rises 3-12h, peaks ~24h, normalizes 2-3 days (useful for reinfarction).

Classify the cardiomyopathies and their key functional defect.

Dilated (systolic dysfunction, all 4 chambers dilated, poor contractility). Hypertrophic (diastolic dysfunction, asymmetric septal hypertrophy, often genetic sarcomere mutation). Restrictive (impaired filling due to stiff walls, e.g., amyloidosis).

Differentiate emphysema from chronic bronchitis (definition and site).

Emphysema: permanent enlargement of airspaces distal to terminal bronchiole with alveolar wall destruction (anatomic definition); centriacinar (smoking) or panacinar (alpha-1-antitrypsin deficiency). Chronic bronchitis: clinical—productive cough >3 months in 2 consecutive years; bronchial mucous gland hyperplasia (Reid index).

Compare the four stages/phases of lobar pneumonia.

Congestion (vascular engorgement, bacteria), Red hepatization (RBCs, neutrophils, fibrin fill alveoli; red, firm liver-like), Gray hepatization (RBCs disintegrate, fibrinosuppurative exudate; gray-brown), Resolution (enzymatic digestion, restoration).

What are the main histologic types of lung cancer and which is most associated with smoking versus nonsmokers?

Adenocarcinoma (most common overall, most common in nonsmokers/women, peripheral), Squamous cell carcinoma (central, strong smoking link, hypercalcemia via PTHrP), Small cell carcinoma (central, smoking, paraneoplastic SIADH/Cushing), Large cell carcinoma.

What are the histologic features and complications of cirrhosis?

Cirrhosis = diffuse bridging fibrosis plus regenerative parenchymal nodules disrupting architecture. Complications: portal hypertension (varices, ascites, splenomegaly), hepatic encephalopathy, hepatorenal syndrome, and hepatocellular carcinoma.

Differentiate Crohn disease from ulcerative colitis (distribution, depth, key features).

Crohn: any GI site (mouth to anus), skip lesions, transmural inflammation, non-caseating granulomas, cobblestoning, fistulae, fat-wrapping. UC: colon only, continuous from rectum, mucosal/submucosal inflammation, crypt abscesses, pseudopolyps, no granulomas.

What are the gross and microscopic features distinguishing acute tubular necrosis from acute glomerulonephritis on urinalysis?

ATN: muddy-brown granular casts and renal tubular epithelial cell casts. Acute glomerulonephritis: dysmorphic RBCs and RBC casts with proteinuria. ATN is the most common cause of intrinsic (renal) acute kidney injury.

What is the most common renal malignancy in adults and its classic histology and triad?

Clear cell renal cell carcinoma (originates from proximal tubule epithelium). Clear cytoplasm (glycogen/lipid), associated with VHL gene. Classic triad: flank pain, hematuria, palpable mass (now uncommon).

Differentiate the urinary findings of nephrotic versus nephritic syndrome.

Nephrotic: massive proteinuria (>3.5 g/day), hypoalbuminemia, edema, hyperlipidemia, lipiduria (oval fat bodies, fatty casts). Nephritic: hematuria (RBC casts), mild-moderate proteinuria, hypertension, oliguria, azotemia.

What are the histologic hallmarks of Alzheimer disease?

Neuritic (senile) plaques containing extracellular beta-amyloid (A-beta), neurofibrillary tangles of hyperphosphorylated tau protein, cerebral amyloid angiopathy, and cortical atrophy with hydrocephalus ex vacuo.

Differentiate ductal carcinoma in situ from invasive ductal carcinoma of the breast.

DCIS: malignant epithelial cells confined within the basement membrane of ducts (no invasion), e.g., comedo type with central necrosis. Invasive ductal carcinoma: malignant cells breach the basement membrane into stroma; most common invasive breast cancer, desmoplastic stroma.

What are the receptor categories used in breast cancer prognostication and the worst-prognosis subtype?

ER (estrogen receptor), PR (progesterone receptor), and HER2/neu. Triple-negative (ER-, PR-, HER2-) breast cancer carries the worst prognosis and does not respond to hormonal or HER2-targeted therapy.

What virus causes cervical cancer, the high-risk subtypes, and the precursor lesion?

Human papillomavirus (HPV), high-risk types 16 and 18 (E6 inactivates p53, E7 inactivates RB). Precursor: cervical intraepithelial neoplasia (CIN)/squamous intraepithelial lesion; most cervical cancers are squamous cell carcinoma.

Identify these peripheral smear inclusions: Howell-Jolly bodies, Heinz bodies, basophilic stippling, Pappenheimer bodies.

Howell-Jolly bodies: nuclear (DNA) remnants—post-splenectomy/hyposplenism. Heinz bodies: denatured hemoglobin (G6PD deficiency, seen with supravital stain). Basophilic stippling: aggregated ribosomes—lead poisoning, thalassemia. Pappenheimer bodies: iron granules—sideroblastic anemia.

What is a dry tap on bone marrow aspiration and which conditions cause it?

A dry tap is failure to aspirate marrow. Causes: myelofibrosis, hairy cell leukemia, metastatic infiltration ('packed marrow'), and faulty technique. Trephine biopsy is needed for diagnosis.

What are the normal myeloid:erythroid (M:E) ratio in marrow and its interpretation?

Normal M:E ratio is about 2:1 to 4:1. Increased ratio: myeloid hyperplasia (infection, CML) or erythroid hypoplasia. Decreased ratio: erythroid hyperplasia (hemolysis, blood loss) or myeloid hypoplasia.

How is leukemia blast percentage used to diagnose acute leukemia per WHO?

WHO criterion: >=20% blasts in bone marrow or peripheral blood defines acute leukemia (lowered from the older FAB cutoff of 30%). Certain recurrent cytogenetic abnormalities (e.g., t(15;17)) are diagnostic of AML regardless of blast count.

Interpret these urine casts: hyaline, RBC, WBC, granular, waxy, fatty.

Hyaline: normal/dehydration. RBC: glomerulonephritis. WBC: pyelonephritis/interstitial nephritis. Granular ('muddy brown'): ATN. Waxy/broad: chronic renal failure. Fatty: nephrotic syndrome.

What does a positive urine dipstick for nitrites and leukocyte esterase indicate, and what is the significance of glucosuria without hyperglycemia?

Nitrites + leukocyte esterase indicate urinary tract infection (nitrite implies nitrate-reducing bacteria like E. coli). Glucosuria with normal blood glucose indicates a proximal tubular defect (e.g., Fanconi syndrome) since the renal threshold (~180 mg/dL) is not exceeded.

How do CSF findings differentiate bacterial, viral and tubercular meningitis (cells, glucose, protein)?

Bacterial: neutrophils high, glucose low, protein high, turbid. Viral: lymphocytes, normal glucose, mildly high protein, clear. Tubercular: lymphocytes, low glucose, high protein, cobweb clot formation.

Name immunohistochemical markers used to identify: carcinoma (epithelial), sarcoma (mesenchymal), lymphoma, melanoma.

Epithelial/carcinoma: cytokeratin (CK), EMA. Mesenchymal/sarcoma: vimentin. Lymphoma: CD45 (LCA, leukocyte common antigen); B cells CD20, T cells CD3. Melanoma: S-100, HMB-45, Melan-A.

Match these special stains to their target: PAS, Congo red, Prussian blue, Ziehl-Neelsen, Masson trichrome, reticulin.

PAS: glycogen/basement membrane/fungi. Congo red: amyloid (apple-green birefringence). Prussian blue (Perls): iron/hemosiderin. Ziehl-Neelsen: acid-fast bacilli (TB). Masson trichrome: collagen/fibrosis. Reticulin (silver): reticulin fibers.

Which IHC markers are used for prostate (PSA/PSAP), neuroendocrine tumors, and GIST?

Prostate: PSA and PSAP (prostatic specific acid phosphatase). Neuroendocrine tumors: chromogranin, synaptophysin, CD56, NSE. GIST (gastrointestinal stromal tumor): CD117 (c-KIT) and DOG1.

What IHC stain confirms HER2 status and what does a score of 3+ versus 2+ mean in breast cancer?

HER2/neu IHC: 3+ = positive (strong complete membrane staining in >10% of cells); 0/1+ = negative; 2+ = equivocal, requiring FISH/ISH for HER2 gene amplification confirmation.

List the morphologic hallmark of caseous necrosis grossly and microscopically and its key special stain.

Grossly: friable, cheese-like, yellow-white material. Microscopically: amorphous granular eosinophilic debris within a granuloma surrounded by epithelioid macrophages and Langhans giant cells. Ziehl-Neelsen stain demonstrates acid-fast bacilli.