MBBS Pathology Syllabus

Define neoplasia and distinguish the key features of benign vs malignant tumors.

Neoplasia is an abnormal, autonomous, uncoordinated proliferation of cells persisting after the stimulus stops. Benign: well-differentiated, slow growth, encapsulated, non-invasive, no metastasis. Malignant: poorly differentiated (anaplasia), rapid/erratic growth, invasive, and capable of metastasis.

Explain the nomenclature: -oma, carcinoma, sarcoma, and give examples of mixed/misleading names.

-oma generally denotes a benign tumor (e.g., adenoma, lipoma). Carcinoma = malignant epithelial tumor; Sarcoma = malignant mesenchymal tumor. Misleading: lymphoma, melanoma, seminoma, and mesothelioma are malignant despite the -oma suffix. Teratoma arises from germ cells (≥2 germ layers); hamartoma is disorganized native tissue.

List the hallmarks of cancer (Hanahan and Weinberg).

Self-sufficiency in growth signals, insensitivity to growth inhibitors, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, tissue invasion and metastasis — plus enabling/emerging hallmarks: genomic instability, tumor-promoting inflammation, deregulated metabolism (Warburg effect), and evasion of immune destruction.

Differentiate proto-oncogenes from tumor suppressor genes, giving an example of each and the relevant 'hit' requirement.

Proto-oncogenes promote growth; a gain-of-function mutation in one allele (dominant) creates an oncogene (e.g., RAS, MYC, HER2). Tumor suppressor genes restrain growth; both alleles must be inactivated (Knudson two-hit hypothesis, recessive at cell level) to lose function (e.g., RB, TP53, APC).

What is the function of TP53 and why is it called 'guardian of the genome'?

TP53 (on chromosome 17p) is a tumor suppressor that senses DNA damage and arrests the cell cycle at the $G_{1}/S$ checkpoint (via p21) to allow repair, or triggers apoptosis if damage is irreparable. It is the most commonly mutated gene in human cancers; germline loss-of-function causes Li-Fraumeni syndrome.

Define the TNM staging system and contrast staging with grading.

TNM: T = size/extent of primary tumor, N = regional lymph node involvement, M = distant metastasis. Staging measures the anatomic extent of spread and is the strongest prognostic factor. Grading assesses the degree of differentiation/anaplasia (how the tumor looks histologically). Stage generally has greater prognostic value than grade.

Describe the morphologic sequence and complications of atherosclerosis.

Sequence: endothelial injury → fatty streak (lipid-laden foam cells) → fibrofatty atheroma/plaque (lipid core with fibrous cap, smooth muscle, foam cells). Complications: plaque rupture/thrombosis (causing MI/stroke), calcification, aneurysm formation, and critical luminal stenosis. Major risk factors: hyperlipidemia, hypertension, smoking, diabetes.

List the cardiac biomarkers used in acute myocardial infarction and their timing.

Troponin I/T: rises in 3–6 hours, peaks ~24 hours, remains elevated 7–10 days (most sensitive/specific). CK-MB: rises 3–12 hours, peaks ~24 hours, normalizes in 48–72 hours (useful for detecting re-infarction). Myoglobin rises earliest (1–2 hours) but is non-specific.

Describe the evolving histology of a myocardial infarct over time.

0–4 h: no change (or wavy fibers). 4–24 h: coagulative necrosis, contraction bands. 1–3 days: neutrophil infiltration. 3–7 days: macrophages remove dead myocytes (wall weakest — rupture risk). 1–2 weeks: granulation tissue. >2 months: dense collagenous scar.

Compare the major valvular lesions of acute rheumatic fever and the diagnostic histologic finding.

Acute rheumatic fever follows group A streptococcal pharyngitis (molecular mimicry). It causes pancarditis; the most affected valve is the mitral (then aortic). The pathognomonic histologic lesion is the Aschoff body (focus of fibrinoid necrosis with Anitschkov 'caterpillar' macrophages). Chronic RHD causes mitral stenosis ('fish-mouth').

List the major restrictive vs obstructive pulmonary diseases and the key spirometry difference.

Obstructive (asthma, COPD/emphysema, chronic bronchitis, bronchiectasis): airflow limitation, $\frac{FEV_{1}}{FVC} < 0.7$, increased total lung capacity. Restrictive (interstitial fibrosis, sarcoidosis, pneumoconioses): reduced lung volumes with normal or increased $\frac{FEV_{1}}{FVC}$ and decreased FVC/TLC.

Contrast emphysema and chronic bronchitis (the two forms of COPD).

Emphysema: permanent enlargement of airspaces distal to terminal bronchioles with alveolar wall destruction (loss of elastic recoil); centriacinar (smoking) or panacinar ($\alpha_{1}$-antitrypsin deficiency); 'pink puffer.' Chronic bronchitis: productive cough ≥3 months in ≥2 consecutive years, mucous gland hyperplasia (Reid index increased); 'blue bloater.'

Define the histologic features of diffuse alveolar damage (ARDS) and the key clinical finding.

Diffuse alveolar damage shows hyaline membranes (fibrin-rich exudate lining alveoli), interstitial/alveolar edema, and type II pneumocyte hyperplasia. Clinically, ARDS presents as acute-onset refractory hypoxemia with bilateral infiltrates and non-cardiogenic pulmonary edema (normal wedge pressure).

Compare the most common histologic types of lung cancer and their key associations.

Adenocarcinoma (most common overall, peripheral, also in non-smokers/women; EGFR/ALK mutations). Squamous cell carcinoma (central, smoking, may cause hypercalcemia via PTHrP, keratin pearls). Small cell carcinoma (central, smoking, neuroendocrine, paraneoplastic SIADH/Cushing/Lambert-Eaton, treated medically). Large cell (undifferentiated, poor prognosis).

Compare peptic ulcers caused by H. pylori in the duodenum vs stomach and the underlying mechanism.

H. pylori produces urease (raising local pH to survive) and causes ~90% of duodenal and ~70% of gastric ulcers. Duodenal ulcers relate to increased acid/H. pylori antral gastritis (pain relieved by food). Gastric ulcers relate to impaired mucosal defense (pain worse with food) and carry malignancy risk, requiring biopsy.

Contrast Crohn disease and ulcerative colitis (inflammatory bowel disease).

Crohn: any site (mouth to anus), skip lesions, transmural inflammation, non-caseating granulomas, 'cobblestone' mucosa, fistulae/strictures, terminal ileum common. Ulcerative colitis: colon only, continuous from rectum, mucosa/submucosa inflammation, crypt abscesses, pseudopolyps, no granulomas, higher colorectal cancer risk, associated with PSC.

Describe the adenoma–carcinoma sequence in colorectal cancer and the key gene mutations.

Normal epithelium → (APC loss) → adenoma → (KRAS mutation) → adenoma growth → (loss of 18q/SMAD, then TP53 loss) → carcinoma. APC mutation is the early gatekeeper (germline mutation causes FAP). A separate microsatellite instability pathway involves defective mismatch repair (MLH1/MSH2) seen in Lynch syndrome.

Compare nephritic and nephrotic syndromes by their defining features.

Nephritic: hematuria with RBC casts, hypertension, oliguria, azotemia, mild-moderate proteinuria ($< 3.5\,\text{g/day}$) — inflammatory (e.g., post-streptococcal GN). Nephrotic: heavy proteinuria ($> 3.5\,\text{g/day}$), hypoalbuminemia, generalized edema, hyperlipidemia, lipiduria (e.g., minimal change disease, membranous nephropathy).

Match these glomerular diseases to their characteristic findings: post-streptococcal GN, membranous nephropathy, minimal change disease, IgA nephropathy.

Post-streptococcal GN: subepithelial 'humps' on EM, granular IF, low C3. Membranous nephropathy: subepithelial 'spike and dome,' anti-PLA2R antibodies (nephrotic in adults). Minimal change disease: normal LM, foot process effacement on EM (nephrotic in children, steroid-responsive). IgA nephropathy (Berger): mesangial IgA deposits, hematuria after infection.

Differentiate prerenal, intrinsic (renal), and postrenal acute kidney injury, and give the key urinary marker for prerenal vs intrinsic.

Prerenal: reduced perfusion (hypovolemia/heart failure); $FE_{Na} < 1\%$, BUN:Cr $> 20:1$, concentrated urine. Intrinsic: tubular/glomerular damage (ATN most common); $FE_{Na} > 2\%$, muddy brown casts, BUN:Cr $\approx 10–15:1$. Postrenal: obstruction (stones, BPH) — bilateral or single functioning kidney.

Compare the major anemias by red cell size (MCV) with one cause each.

Microcytic (MCV $< 80\,\text{fL}$): iron deficiency, thalassemia, sideroblastic, chronic disease (late). Normocytic (MCV 80–100): acute blood loss, hemolysis, aplastic, chronic disease. Macrocytic (MCV $> 100$): vitamin $B_{12}$/folate deficiency (megaloblastic), liver disease, alcohol, hypothyroidism.

Contrast Hodgkin and non-Hodgkin lymphoma, including the diagnostic cell of Hodgkin.

Hodgkin lymphoma: contiguous nodal spread, localized, Reed-Sternberg cells (CD15+, CD30+, 'owl-eye' binucleate), bimodal age, often curable. Non-Hodgkin lymphoma: multifocal/non-contiguous spread, more often extranodal, no Reed-Sternberg cells, B- or T-cell origin, variable prognosis.

Describe the pathology of chronic myeloid leukemia, including its defining genetic abnormality.

CML is a myeloproliferative neoplasm with the Philadelphia chromosome — t(9;22) translocation creating the BCR-ABL1 fusion gene encoding a constitutively active tyrosine kinase. It presents with marked leukocytosis (all granulocyte stages), splenomegaly, low leukocyte alkaline phosphatase, and can transform to blast crisis. Treated with tyrosine kinase inhibitors (imatinib).

Compare Graves disease and Hashimoto thyroiditis (autoimmune thyroid diseases).

Graves: hyperthyroidism from anti-TSH receptor stimulating antibodies (TSI); diffuse goiter, exophthalmos, pretibial myxedema. Hashimoto: hypothyroidism from autoimmune destruction (anti-TPO, anti-thyroglobulin antibodies); lymphocytic infiltrate with germinal centers and Hürthle cells; increased risk of B-cell (MALT) lymphoma.

Describe the chronic microvascular and macrovascular complications of diabetes mellitus and their pathologic basis.

Chronic hyperglycemia causes non-enzymatic glycosylation (AGEs) and the polyol pathway. Microvascular: retinopathy, nephropathy (Kimmelstiel-Wilson nodules, basement membrane thickening), and neuropathy. Macrovascular: accelerated atherosclerosis → MI, stroke, peripheral vascular disease. Hyaline arteriolosclerosis is characteristic.

Differentiate the histopathology of Alzheimer disease and Parkinson disease.

Alzheimer disease: cortical atrophy with extracellular β-amyloid (senile) plaques and intracellular neurofibrillary tangles (hyperphosphorylated tau). Parkinson disease: loss of dopaminergic neurons in the substantia nigra (depigmentation) with intracytoplasmic Lewy bodies (α-synuclein aggregates).

Describe the pathophysiology of gout and the characteristic crystal findings.

Gout results from hyperuricemia ($> 6.8\,\text{mg/dL}$) causing deposition of monosodium urate crystals in joints (classically first MTP — podagra). Crystals are needle-shaped and negatively birefringent (yellow when parallel to the polarizer). Chronic deposits form tophi. Contrast: pseudogout uses calcium pyrophosphate crystals — rhomboid, positively birefringent.

Compare the histologic hallmarks of tuberculosis vs a pyogenic (bacterial) abscess.

Tuberculosis: caseating (caseous) granulomas — central caseous necrosis surrounded by epithelioid macrophages, Langhans giant cells, and lymphocytes; acid-fast bacilli on Ziehl-Neelsen stain (type IV hypersensitivity). Pyogenic abscess: localized collection of pus (liquefactive necrosis with neutrophils), typically from Staphylococcus/Streptococcus.

Classify the four types of hypersensitivity reactions (Gell and Coombs) with one example each.

Type I (immediate/IgE-mediated, e.g., anaphylaxis, allergic asthma). Type II (antibody-mediated cytotoxic, e.g., autoimmune hemolytic anemia, Goodpasture). Type III (immune complex, e.g., SLE, serum sickness, post-streptococcal GN). Type IV (delayed, T-cell mediated, e.g., contact dermatitis, TB granuloma, transplant rejection).

Define amyloidosis and state the diagnostic staining characteristic.

Amyloidosis is extracellular deposition of misfolded proteins in a β-pleated sheet configuration. It stains with Congo red, showing apple-green birefringence under polarized light. Major types: AL (light chain, plasma cell dyscrasias) and AA (serum amyloid A, chronic inflammation). Deposits cause organ dysfunction (e.g., restrictive cardiomyopathy, nephrotic syndrome).