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PATHOLOGY PAPER I - COMPLETE ANSWERS

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GENERAL PATHOLOGY

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Introduction to Pathology

1. Static telepathology - pre-selected images are captured and sent for interpretation (asynchronous)
2. Dynamic (real-time) telepathology - live, interactive video transmission; the remote pathologist can control the robotic microscope to select fields
3. Virtual slide/whole-slide imaging (WSI) - entire slide digitized at high resolution; can be reviewed at any magnification remotely

• Intraoperative frozen section consultation
• Second opinion / expert consultation
• Quality assurance
• Education and training
• Screening in under-served areas

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Injury, Cellular Adaptations & Aging

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1. Dystrophic calcification
2. Metastatic calcification

• Calcium deposition at sites of cell injury/necrosis
• Serum calcium levels are normal
• No systemic calcium metabolic disorder
• Common sites: atherosclerotic plaques, damaged heart valves, caseous tuberculous foci, fat necrosis, dead parasites
• Mechanism: cell injury → release of phospholipids from membranes → act as nucleation sites → calcium phosphate crystals form → may calcify completely (e.g., "eggshell" in silicosis)

• Calcium deposition in normal tissues
• Associated with hypercalcemia
• Causes of hypercalcemia: hyperparathyroidism, vitamin D toxicity, bone destruction (multiple myeloma, metastases), sarcoidosis, milk-alkali syndrome
• Common sites: kidney tubules, lungs, gastric mucosa, blood vessels, cornea (interstitial calcinosis)

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• Cell shrinkage (pyknosis)
• Chromatin condensation and margination
• Nuclear fragmentation (karyorrhexis)
• Formation of apoptotic bodies (membrane-bound fragments containing organelles and nuclear material)
• Phagocytosis of apoptotic bodies by macrophages or adjacent cells
• No inflammation (membranes remain intact until phagocytosis)

• Triggered by: DNA damage, loss of survival signals, oxidative stress, ER stress (misfolded proteins)
• BCL-2 family proteins regulate this pathway:
  • Pro-apoptotic: BAX, BAK, BIM, PUMA, NOXA
  • Anti-apoptotic: BCL-2, BCL-XL, MCL-1
• When pro-apoptotic predominate → mitochondrial outer membrane permeabilization (MOMP) → release of cytochrome c → forms "apoptosome" with APAF-1 → activates caspase-9 → activates executioner caspase-3, -7

• Triggered by: FasL binding Fas (CD95), TNF binding TNF receptor
• Responsible for: elimination of self-reactive lymphocytes, cytotoxic T-lymphocyte-mediated killing
• Death receptors contain death domain (DD) → recruits FADD → activates caspase-8 → activates caspase-3

• Embryogenesis (digit formation, organ remodeling)
• Involution of hormone-dependent tissues (e.g., endometrium menstruation, lactating breast after weaning)
• Deletion of activated immune cells after immune response
• Elimination of self-reactive lymphocytes in thymus

• DNA damage (radiation, chemotherapy)
• Viral hepatitis (Councilman/acidophilic bodies)
• Graft-versus-host disease
• Neurodegenerative diseases (Alzheimer's)
• Ischemic injury

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• Hemosiderosis: localized iron overload (e.g., old hemorrhage, repeated blood transfusions)
• Hemochromatosis: systemic iron overload → deposits in liver (cirrhosis), pancreas (diabetes), heart (cardiomyopathy), skin (bronzing), joints (arthropathy)
• Jaundice/Icterus: excess bilirubin in plasma (>2 mg/dL) - pre-hepatic (hemolysis), hepatic (liver disease), post-hepatic (bile duct obstruction)

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• Most common type
• Ischemic death (infarction) in most organs EXCEPT brain
• Denaturation of structural proteins and enzymes; cell outlines preserved ("ghost cells")
• Mechanism: denaturation of both structural proteins and enzymes that cause lysis
• Examples: myocardial infarct, renal infarct, splenic infarct

• Complete digestion of dead cells → liquid, viscous mass
• Seen in: brain infarcts (rich in lipids, with hydrolytic enzymes), bacterial infections (pus = liquefactive necrosis + neutrophils)
• Mechanism: digestive enzymes from leukocytes (abscesses) or from cells themselves (CNS)
• Example: cerebral infarct, lung abscess

• Characteristic of tuberculosis (also in fungal infections, sarcoidosis)
• Gross: white, cheese-like (caseum = cheese) friable material
• Microscopy: amorphous granular debris surrounded by granulomatous inflammation (epithelioid macrophages + Langhans giant cells + lymphocytes)
• Cell outlines are completely lost
• Does NOT reabsorb; may calcify (Ghon's focus)

• Focal areas of fat destruction
• Two types:
  • Enzymatic fat necrosis: acute pancreatitis; lipases digest peripancreatic fat → free fatty acids + calcium → saponification → chalky white deposits (calcium soap)
  • Traumatic fat necrosis: breast trauma; no enzyme involvement

• Seen in immune-mediated vascular injury
• Bright pink, homogeneous material in vessel walls (fibrin + immune complexes)
• Examples: malignant hypertension, vasculitis (polyarteritis nodosa), rheumatic fever (Aschoff bodies)

• Not a specific pattern; a clinical term
• Dry gangrene: coagulative necrosis (limb ischemia)
• Wet gangrene: liquefactive + coagulative (bacterial infection superimposed)
• Gas gangrene: Clostridium perfringens infection

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• Entry of free fatty acids (mobilized from adipose tissue or dietary intake)
• Synthesis of triglycerides from acetate
• Oxidation of fatty acids (mitochondrial beta-oxidation)
• Formation of lipoprotein for export

• Alcohol (most common) - impairs beta-oxidation and lipoprotein export; alcohol → acetaldehyde → mitochondrial damage
• Protein malnutrition (Kwashiorkor) - deficient apoprotein synthesis → cannot export triglycerides
• Diabetes mellitus - increased fat mobilization
• Obesity - excess free fatty acids delivered to liver
• Drugs/toxins: carbon tetrachloride, tetracycline, methotrexate
• Hypoxia: impairs beta-oxidation

• Gross: enlarged, yellow, greasy liver (hepar adiposum); soft; may be massively enlarged
• Microscopy:
  • Lipid droplets in cytoplasm (initially small - microvesicular; later large - macrovesicular)
  • Macrovesicular: single large vacuole displaces nucleus to periphery
  • Alcoholic: begins in centrilobular zone (zone 3)
  • Microvesicular: severe toxicity (e.g., acute fatty liver of pregnancy, tetracycline)

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• Mitochondrial electron transport (leakage)
• Cytochrome P450 metabolism
• Macrophage oxidative burst (NADPH oxidase)
• Xanthine oxidase (ischemia-reperfusion)
• Ionizing radiation
• Redox reactions of transition metals (Fe²⁺ → Fenton reaction: H₂O₂ + Fe²⁺ → OH• + OH⁻ + Fe³⁺)
• Nitric oxide (•NO) → peroxynitrite (ONOO⁻) when combined with superoxide

• Superoxide dismutase (SOD): 2O₂•⁻ + 2H⁺ → H₂O₂ + O₂
• Catalase: 2H₂O₂ → H₂O + O₂
• Glutathione peroxidase
• Vitamins E, C, beta-carotene

1. Lipid peroxidation of membranes: Free radicals attack unsaturated fatty acids → chain reaction → membrane structural damage → increased permeability → cell lysis
2. Oxidative modification of proteins: Fragmentation of polypeptides, cross-linking → protein degradation by proteasome; enzyme inactivation
3. DNA damage: Single- and double-strand breaks → mutations → cancer, apoptosis, aging

• Ischemia-reperfusion injury (burst of ROS on reperfusion)
• Aging (accumulation of oxidative damage)
• Atherosclerosis (oxidation of LDL)
• Neurodegenerative diseases
• Carcinogenesis

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1. Burst of ROS from reoxygenation - xanthine oxidase activation, mitochondrial electron transport disruption, neutrophil NADPH oxidase
2. Calcium overload - intracellular Ca²⁺ activates phospholipases, proteases, ATPases
3. Inflammation - neutrophil and complement activation cause additional damage
4. Mitochondrial permeability transition (MPT) - opening of mitochondrial pores → release of cytochrome c → apoptosis

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• Definition: Reversible change in which one differentiated cell type is replaced by another, better able to withstand the new environment
• Mechanism: Reprogramming of stem cells (altered differentiation pathway)
• Examples:
  • Columnar → Squamous: Bronchi (smokers), cervix (squamocolumnar junction)
  • Squamous → Columnar: Barrett's esophagus (GERD - gastric acid exposure)
  • Fibrous to osseous: Myositis ossificans

• Definition: Increase in cell size (and organ size) without cell division
• Mechanism: Increased functional demand → growth factors (IGF-1, TGF-beta) → activation of intracellular signaling → increased protein synthesis
• Physiological: Skeletal muscle (exercise), uterus (pregnancy)
• Pathological: Cardiac hypertrophy (hypertension, aortic stenosis)

• Definition: Increase in the number of cells (cell proliferation)
• Occurs in cells capable of division (not cardiac myocytes)
• Physiological: Breast (puberty, pregnancy), endometrial hyperplasia (estrogenic stimulation), compensatory liver hyperplasia
• Pathological: Benign prostatic hyperplasia, psoriasis, endometrial hyperplasia

• Definition: Reduction in cell/organ size due to decreased cell mass
• Mechanisms: decreased protein synthesis + increased protein degradation (ubiquitin-proteasome pathway), autophagy
• Causes:
  • Disuse (immobilization)
  • Loss of innervation (denervation)
  • Decreased blood supply (ischemia)
  • Inadequate nutrition (marasmus)
  • Loss of endocrine stimulation (thyroid/adrenal)
  • Aging (senile atrophy)
  • Pressure (obstruction)

• Lipofuscin accumulates in atrophic cardiomyocytes
• Seen in: Cachexia, prolonged malnutrition, aging
• Gross: Small, dark-brown heart (due to lipofuscin); "tobacco-brown" color; coronary arteries appear tortuous and prominent (because heart has shrunk)

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IMMUNOPATHOLOGY INCLUDING AMYLOIDOSIS

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• Mediator: IgE bound to mast cells/basophils
• Mechanism: Antigen (allergen) → IgE synthesis → IgE binds mast cells → re-exposure → cross-linking of FcεRI → mast cell degranulation → histamine, leukotrienes, prostaglandins, cytokines
• Time: Minutes after exposure
• Examples: Anaphylaxis, atopic asthma, allergic rhinitis, urticaria, food allergy
• Primary mediators: Histamine (vasodilation, bronchoconstriction)
• Secondary mediators: Leukotrienes C4, D4 (bronchoconstriction > histamine), PGD2

• Mediators: IgG/IgM against cell surface antigens
• Mechanisms: Complement activation → lysis; ADCC; phagocytosis
• Examples: Autoimmune hemolytic anemia, Goodpasture syndrome (anti-GBM), ABO transfusion reactions, Graves' disease, Myasthenia gravis, Neonatal hemolytic disease

• Mediators: Antigen-antibody complexes deposit in tissues → complement activation → neutrophil recruitment → tissue damage
• Examples: SLE (glomerulonephritis), serum sickness, Arthus reaction, post-streptococcal glomerulonephritis, farmer's lung

• Mediators: Sensitized CD4+ T cells (Th1) and CD8+ CTLs
• Time: 24-72 hours
• Mechanism: T cells release cytokines (IFN-γ, TNF) → macrophage activation → granuloma formation
• Examples: Tuberculin test (Mantoux), contact dermatitis (poison ivy, nickel), graft rejection, granulomatous inflammation (TB, sarcoid, schistosomiasis)

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• Core structure: antiparallel beta-pleated sheet fibrils (amyloid P component + SAP)
• X-ray crystallography: characteristic cross-beta diffraction pattern
• Congo red staining + polarized light: apple-green birefringence (diagnostic)
• All amyloid types share this beta-pleated sheet configuration regardless of precursor protein

• Congo red stain → pink-orange under normal light → apple-green birefringence under polarized light (most specific)
• Thioflavin T/S stain → fluorescence
• Crystal violet (metachromatic staining)
• PAS positive

• Fibrils: 7.5-10 nm diameter, arranged in antiparallel beta-pleated sheets
• Associated components: SAP (serum amyloid P), apolipoprotein E, glycosaminoglycans (heparan sulfate)
• Resistant to proteolysis
• Water-insoluble, chemically inert

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• Amyloid deposits in follicles (white pulp) - in walls of small arterioles and perifollicular areas
• Gross: Gray, translucent nodules resembling sago grains scattered on cut surface
• Seen in: Early systemic amyloidosis

• Amyloid deposits in red pulp sinusoids (diffuse)
• Gross: Enlarged spleen with waxy, homogeneous cut surface resembling bacon
• Involves entire parenchyma

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1. Failure of central tolerance:
   • Self-reactive T cells normally deleted in thymus (clonal deletion)
   • Defective negative selection → self-reactive T cells escape to periphery (e.g., in type 1 DM - anti-islet T cells)
2. Failure of peripheral tolerance:
   • Anergy failure: Normally, T cell activation requires signal 1 (TCR-MHC) + signal 2 (co-stimulatory B7-CD28). Without signal 2 → anergy. If co-stimulation occurs abnormally on peripheral cells → autoimmunity
   • Regulatory T cell (Treg) deficiency: FoxP3+ Tregs suppress autoreactive cells; deficiency → autoimmunity (IPEX syndrome)
   • Activation-induced cell death (AICD) failure: FasL-Fas apoptosis normally eliminates activated T cells; defect → ALPS (autoimmune lymphoproliferative syndrome)
3. Molecular mimicry: Microbial antigens share epitopes with self antigens → anti-microbial response cross-reacts with self (e.g., Strep M protein → cardiac myosin in rheumatic fever; Campylobacter → ganglioside in GBS)
4. Bystander activation: Tissue injury from infection releases hidden self-antigens → activates autoreactive T cells
5. Epitope spreading: Initial autoimmune response exposes additional self-antigens → progressive broadening of response
6. Polyclonal B-cell activation: Certain organisms (EBV, LPS) activate B cells non-specifically → autoantibodies

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1. Sexual contact (homosexual > heterosexual in Western countries; heterosexual predominant globally)
2. Parenteral: IV drug users (needle sharing), blood transfusion, needle-stick injury in healthcare workers
3. Mother-to-child (vertical): Transplacental, peripartum exposure to maternal blood, breast feeding

• High-level viremia; CD4+ T cells fall sharply
• Mononucleosis-like illness: fever, lymphadenopathy, sore throat, rash, myalgia
• Virus disseminates widely; seeds lymphoid tissue
• Anti-HIV antibody appears (seroconversion) → viremia partially controlled → CD4 partially recovers

• Duration: average 7-10 years (variable)
• Virus continues replicating in lymph nodes; gradual CD4 decline
• Patient asymptomatic or persistent generalized lymphadenopathy (PGL)
• CD4 count typically 200-500/μL

• CD4 count < 200/μL OR AIDS-defining illness
• Opportunistic infections: PCP, cryptococcal meningitis, CMV retinitis, MAC, toxoplasmosis, esophageal candidiasis
• AIDS-defining malignancies: Kaposi sarcoma (HHV-8), primary CNS lymphoma, invasive cervical carcinoma
• Constitutional disease: HIV wasting syndrome, HIV dementia

• Kaposi sarcoma (HHV-8) - most common
• Non-Hodgkin lymphoma (EBV-driven; diffuse large B-cell; Burkitt lymphoma)
• Primary CNS lymphoma
• Invasive cervical carcinoma (HPV)
• Anal carcinoma (HPV)
• Hepatocellular carcinoma (HBV/HCV co-infection)

• ELISA (screening) - detects anti-HIV antibodies (highly sensitive; seroconversion by 4-12 weeks)
• Western blot (confirmatory) - detects antibodies to specific HIV proteins (p24, gp41, gp120/160)
• p24 antigen test - detects viral protein; positive before antibody
• HIV RNA PCR (viral load) - quantitative; used for monitoring; also for diagnosis in neonates
• CD4 count - staging and monitoring; absolute count and CD4:CD8 ratio
• 4th generation combo assay (HIV Ag/Ab) - detects both p24 and antibodies simultaneously; preferred

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DERANGEMENTS OF HOMEOSTASIS AND HAEMODYNAMICS

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1. Red (Hemorrhagic) Infarct:
   • Occurs in: Loose spongy tissues (lung, intestine), tissues with dual blood supply (lung - bronchial + pulmonary; liver - hepatic artery + portal vein), venous occlusion
   • Blood oozes into necrotic area from adjacent vessels
   • Examples: Pulmonary infarct, intestinal infarct, ovarian infarct
2. White (Pale/Anemic) Infarct:
   • Occurs in: Solid organs with end-arterial supply (heart, kidney, spleen, brain)
   • No collateral blood flow to necrotic area
   • Examples: Myocardial infarct, renal infarct, splenic infarct

• Bland (sterile) infarct: no bacterial infection
• Septic infarct: infected emboli (e.g., infective endocarditis) → abscess formation

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• Hydrothorax, hydropericardium, ascites = fluid in cavities
• Anasarca = generalized massive edema

1. Increased hydrostatic pressure (venous obstruction, heart failure)
2. Decreased plasma oncotic pressure (hypoalbuminemia)
3. Lymphatic obstruction (lymphedema)
4. Increased vascular permeability (inflammation)
5. Sodium/water retention (renal failure, hyperaldosteronism)

• LV failure → increased pulmonary capillary hydrostatic pressure → fluid transudates into alveolar septa and alveoli
• Gross: Heavy, boggy, wet lungs; fluid pours out on cut section
• Microscopy: Alveoli filled with granular pink fluid, sparse RBCs; hyaline membranes in severe/chronic cases; hemosiderin-laden macrophages ("heart failure cells") = siderophages

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1. Endothelial injury (most important): atherosclerosis, hypertension, turbulent flow, vasculitis, cigarette smoking → exposure of subendothelial collagen + vWF → platelet adhesion + activation
2. Abnormal blood flow (stasis or turbulence): atrial fibrillation (stasis), ventricular aneurysm, prolonged immobilization, varicose veins
3. Hypercoagulability: primary (factor V Leiden mutation, prothrombin gene mutation, antiphospholipid syndrome) or secondary (pregnancy, malignancy, nephrotic syndrome, oral contraceptives)

• Lines of Zahn (alternating pale platelet-fibrin layers and dark red blood cell layers) - characteristic of thrombus formed in flowing blood
• Pale (arterial thrombi): platelet-rich, white
• Red (venous thrombi): RBC-rich, looks like blood clot
• Attached at point of origin; dry, friable

• Laminated structure: pale platelet-fibrin aggregates alternating with RBC layers (lines of Zahn)
• Fibrin network trapping erythrocytes, platelets, and leukocytes
• Organization: ingrowth of endothelial cells, smooth muscle cells, fibroblasts from vessel wall
• Recanalization: new vascular channels can form through organized thrombus

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1. Thromboembolism (most common - 99%) - from deep vein thrombus
2. Fat embolism - long bone fractures, liposuction
3. Air embolism - IV catheter, iatrogenic, decompression sickness
4. Amniotic fluid embolism - obstetric emergency
5. Tumor embolism
6. Septic embolism - infective endocarditis
7. Cholesterol embolism - atheromatous plaque rupture

• Source: 90-95% from deep veins of leg (femoral, iliac, popliteal)
• Consequences depend on size:
  • Large saddle embolus: lodges at bifurcation of pulmonary artery → acute right heart failure → sudden death
  • Medium embolus: pulmonary infarction (hemorrhagic wedge-shaped area at periphery)
  • Small multiple emboli: pulmonary hypertension (recurrent, chronic)
  • Paradoxical embolism: embolus crosses through patent foramen ovale to systemic circulation
• Gross: Wedge-shaped hemorrhagic infarct at pleural surface
• Microscopy: Coagulative necrosis + hemorrhage + fibrinous pleuritis

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• Gross: Enlarged, mottled - dark red centers (congested centrilobular areas) + yellow-tan periphery (viable hepatocytes with fatty change) → "nutmeg" appearance on cut surface
• Microscopy:
  • Centrilobular (zone 3) congestion and necrosis ("cardiac cirrhosis")
  • Sinusoids dilated and engorged with blood
  • Centrilobular hepatocyte loss → replacement by fibrous tissue → "cardiac sclerosis"
  • Peripheral hepatocytes: fatty change (yellow areas)

• Gross: Enlarged (splenomegaly), firm, dark red-blue
• Microscopy: Sinusoidal congestion, red pulp expansion with RBCs, fibrous thickening of sinusoidal walls, Gamna-Gandy bodies (hemosiderin deposits in organized foci of old hemorrhage)

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INFLAMMATION AND HEALING

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1. Rubor (redness) - vasodilation
2. Calor (heat) - increased blood flow
3. Tumor (swelling) - edema
4. Dolor (pain) - prostaglandins, bradykinin
5. Functio laesa (loss of function) - Virchow's 5th

1. Transient vasoconstriction (seconds)
2. Vasodilation (arterioles → venules) → increased blood flow → redness + heat; mediated by histamine, NO, prostaglandins
3. Increased vascular permeability: endothelial cell contraction → widened intercellular gaps → protein-rich exudate leaves vessels → edema
   • Mediators: histamine (immediate transient), leukotrienes C4/D4/E4, PAF, bradykinin, substance P, VEGF
4. Stasis: as fluid leaves, blood viscosity rises → stasis → margination of leukocytes

1. Margination: leukocytes move to periphery of vessel (due to stasis)
2. Rolling: weak reversible adhesion; mediated by selectins (P-selectin and E-selectin on endothelium bind sialyl-Lewis X on leukocytes; L-selectin on leukocytes)
3. Activation (triggering): chemokines bind to leukocyte receptors → increase affinity of integrins
4. Firm adhesion (arrest): integrins on leukocytes bind ICAM-1/VCAM-1 on endothelium; LFA-1 (αLβ2) binds ICAM-1
5. Transmigration (diapedesis): leukocytes squeeze through endothelial junctions (PECAM-1/CD31 mediates); move through basement membrane (collagenase secretion)
6. Chemotaxis: directional movement toward chemical gradient
   • Exogenous: bacterial lipopolysaccharide, fMLP (formyl-Met-Leu-Phe)
   • Endogenous: C5a, LTB4, IL-8 (CXCL8), platelet-activating factor

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• Mechanism: Chemoattractant binds G-protein-coupled receptor → activates Rho family GTPases → actin polymerization → pseudopod extension → cytoskeletal reorganization → directed movement
• Major chemotactic agents: C5a, LTB4, IL-8, fMLP

1. Recognition and attachment: facilitated by opsonins - IgG (Fc receptor), C3b (CR1 receptor), lectin-binding proteins. Opsonization greatly enhances phagocytosis.
2. Engulfment: pseudopods extend around particle → fuse → phagosome forms
3. Killing and degradation:
   • Oxygen-dependent: NADPH oxidase → superoxide → H₂O₂ → myeloperoxidase + H₂O₂ + Cl⁻ → HOCl (hypochlorous acid) - most potent microbicidal agent
   • Oxygen-independent: lysozyme, lactoferrin, major basic protein (eosinophils), defensins, azurophilic granule proteins, elastase

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• Anergic form: poor cell-mediated immunity; lepromin test negative

• Diffuse skin infiltration: thickening, nodule formation (lepromas)
• Leonine facies: thickened, nodular face
• Loss of eyebrows and eyelashes (superciliary madarosis)
• Saddle-nose deformity (septal destruction)
• Glove-and-stocking anesthesia (peripheral nerve involvement)

• Lepra cells (Virchow cells): Large foamy macrophages packed with organisms (M. leprae)
• Globi: clusters of bacilli inside lepra cells; AFB stain positive
• No well-formed granulomas (unlike tuberculoid leprosy)
• Grenz zone: subepidermal clear zone of uninvolved tissue between epidermis and infiltrate
• Peripheral nerves involved but not destroyed (unlike tuberculoid)
• Epidermis thinned, atrophic

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1. Inhaled droplet nuclei containing M. tuberculosis reach alveoli
2. Macrophages phagocytose bacilli; if cell-mediated immunity (CMI) not yet developed → bacilli multiply within macrophages → bacteremia (dissemination)
3. After 3-8 weeks, CMI develops → sensitized T cells (Th1) → IFN-γ → macrophage activation → epithelioid granuloma formation
4. Granuloma walls off infection → caseous necrosis at center

1. Ghon's focus: parenchymal lesion, usually in lower zone of upper lobe or upper zone of lower lobe (subpleural); 1-2 cm, caseating granuloma
2. Lymphangitis: lymphatics draining Ghon's focus → caseating lymphangitis
3. Lymphadenopathy: caseation of hilar/mediastinal lymph nodes

1. Initial macrophage response (non-specific)
2. Monocyte migration → epithelioid cell transformation
3. Lymphocytic infiltration
4. Langhans giant cell formation (nuclei in horseshoe/ring arrangement at periphery)
5. Central caseous necrosis
6. Fibrous capsule formation

• Healing: fibrosis → calcification (Ranke complex) → most common outcome in healthy individuals
• Progressive primary tuberculosis: in immunocompromised → cavitation, spread
• Hematogenous dissemination: miliary tuberculosis
• Post-primary (reactivation) tuberculosis: upper lobes, cavity formation

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• Histamine (mast cells, basophils, platelets): vasodilation, increased vascular permeability
• Serotonin (5-HT) (platelets): vasoconstriction at high levels

• Prostaglandins (PGE2, PGI2): vasodilation, fever, pain sensitization
• Thromboxane A2 (platelets): vasoconstriction, platelet aggregation
• Leukotrienes (LTB4): potent chemotaxis for neutrophils; LTC4, LTD4, LTE4: bronchoconstriction, increased permeability

• TNF-α, IL-1: fever, acute phase response, endothelial activation (adhesion molecule upregulation)
• IL-6: fever, acute phase proteins (CRP, fibrinogen)
• IL-8 (CXCL8): chemotaxis for neutrophils
• Chemokines: direct leukocyte trafficking

• C3a, C5a (anaphylatoxins): mast cell degranulation, increased permeability
• C5a: potent chemotaxin
• C3b: opsonin
• MAC (C5b-9): direct cell lysis

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• Gross: Pink, soft, granular, vascular tissue at base of wound; bleeds easily
• Microscopy:
  • Proliferating capillaries (angiogenesis) - "buds" of endothelial cells
  • Proliferating fibroblasts (myofibroblasts)
  • Edematous loose connective tissue
  • Variable inflammatory infiltrate (macrophages, lymphocytes)
  • Over time → collagen deposition → scar formation

• Local: Infection (most common), foreign body, poor blood supply (ischemia), radiation, hematoma, excessive tension
• Systemic: Malnutrition (protein, vitamin C, zinc deficiency), diabetes mellitus (impaired neutrophil function, microvascular disease), glucocorticoids (impair collagen synthesis), anemia, immunosuppression

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• Clean surgical incision with opposed edges
• Day 1: Clot fills incision; neutrophils appear
• Day 2-3: Epithelial cells migrate across; macrophages replace neutrophils
• Day 3-5: Granulation tissue bridges wound; collagen begins forming
• Day 7-10: Bridging complete; epidermal continuity restored
• Week 2+: Collagen continues to accumulate; strength increases
• Month 1+: Scar formation; avascular white scar; strength ~80% by 3 months

• Large tissue defect, open wound (infected, large burns)
• Differences from primary:
  • More abundant granulation tissue
  • Wound contraction (myofibroblasts)
  • More scar formation
  • Slower, more prolonged

1. Hematoma formation (hours-days): blood fills fracture gap; fibrin clot
2. Procallus formation (days-weeks): organization of hematoma by granulation tissue; osteoclasts resorb necrotic bone
3. Bony callus (weeks): chondroblasts and osteoblasts form soft callus → hard callus
4. Remodeling (months-years): excess callus resorbed; original bone architecture restored; Haversian system reformation

• Non-union (failed healing)
• Malunion (heals in wrong position)
• Excessive callus (exuberant callus)
• Osteomyelitis (infection)
• Avascular necrosis (damage to blood supply)
• Post-traumatic arthritis (if joint involved)

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NEOPLASIA

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• Leukoplakia (oral cavity, vulva, larynx)
• Erythroplakia (higher risk than leukoplakia)
• Cervical intraepithelial neoplasia (CIN) - HPV-related
• Barrett's esophagus → adenocarcinoma
• Chronic atrophic gastritis → gastric cancer
• Ulcerative colitis → colorectal carcinoma
• Cirrhosis → hepatocellular carcinoma
• Actinic (solar) keratosis → squamous cell carcinoma
• Paget's disease of bone → osteosarcoma (1% risk)
• Cryptorchidism → testicular carcinoma

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• Screening (PSA)
• Diagnosis in appropriate clinical context (AFP in liver mass)
• Staging and prognosis
• Monitoring response to therapy
• Detecting recurrence after treatment
• Limitation: not specific; elevated in benign conditions

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1. Pleomorphism: variation in cell and nuclear size/shape
2. Nuclear abnormalities:
   • Hyperchromatism (dark-staining nuclei)
   • Increased nuclear-to-cytoplasmic ratio (N:C) → up to 1:1 (normal 1:4 to 1:6)
   • Prominent nucleoli
   • Abnormal mitoses: tripolar, quadripolar mitotic figures
3. Tumor giant cells: bizarre multinucleated giant cells
4. Loss of polarity: disorganized architecture; no normal tissue structure
5. Increased mitotic activity: many mitoses
6. Necrosis: central areas of ischemic necrosis (rapid growth outpaces blood supply)

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1. Histopathology: Gold standard; H&E stained sections; excisional/core biopsy
2. Cytopathology: Fine needle aspiration cytology (FNAC), exfoliative cytology (Pap smear, sputum, urine, pleural fluid)
3. Immunohistochemistry (IHC): Antibodies detect specific antigens; differentiate tumor types (PSA for prostate, CK for carcinoma, CD markers for lymphomas, chromogranin for neuroendocrine)
4. Electron microscopy: Dense core granules (neuroendocrine), desmosomes (squamous)
5. Molecular/Genetic tests:
   • PCR for gene mutations (KRAS, BRAF, EGFR)
   • FISH for amplifications/translocations (HER2, BCR-ABL)
   • Next-generation sequencing (NGS) - comprehensive mutation profiling
6. Flow cytometry: Surface marker immunophenotyping for leukemias/lymphomas
7. Tumor markers (see above)
8. Cytogenetics: chromosomal translocations (Philadelphia chromosome in CML: t(9;22))
9. Frozen section: intraoperative diagnosis, margin assessment
10. Image-guided biopsy: CT/USG-guided core biopsy of inaccessible lesions

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• Direct or indirect (metabolic activation) DNA damage
• Mutation becomes permanent (heritable) after DNA replication
• Cell does NOT become cancerous yet; IRREVERSIBLE
• Example: Benzo[a]pyrene (cigarette smoke) → epoxide metabolite → binds guanine → G→T transversion in codon 12 of KRAS

• Promoters stimulate proliferation of initiated cells → selective growth advantage
• REVERSIBLE (requires continued exposure)
• No direct DNA damage
• Examples: croton oil (TPA), bile acids (colon), saccharin (bladder in rodents), hormones (estrogen in breast)

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1. Direct/Local invasion: Tumor cells detach, digest extracellular matrix (MMP enzymes), invade adjacent tissues
2. Lymphatic spread: Most common for carcinomas; regional lymph nodes first (sentinel node); Virchow's node (left supraclavicular) in gastric/abdominal malignancy
3. Hematogenous spread: Most common for sarcomas; portal vein → liver; pulmonary veins → lungs; vertebral veins (Batson plexus) → vertebrae
4. Transcoelomic (seeding of body cavities): Ovarian carcinoma → peritoneal seeding; gastric carcinoma → Krukenberg tumor (bilateral ovarian metastases)
5. Perineural spread: Head and neck, prostate cancer

• Neoplasm derived from totipotent germ cells; contains elements of all 3 germ layers (ectoderm, mesoderm, endoderm)
• Mature teratoma (dermoid cyst): well-differentiated; benign; most common ovarian tumor; contains teeth, hair, skin, bone
• Immature teratoma: malignant; contains embryonic (immature) neural tissue; age < 15 years; testicular > ovarian

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• Trisomy 21 (47 chromosomes): extra chromosome 21
• Incidence: 1/700 live births; increases with maternal age
• Mechanism: meiotic nondisjunction (95%), Robertsonian translocation t(21;14) (4%), mosaicism (1%)
• Clinical features: Mental retardation, flat face, epicanthal folds, Brushfield spots (iris), simian crease, single palmar crease, endocardial cushion defect (ASD/VSD), duodenal atresia, Hirschsprung disease, increased risk of ALL and AML, premature Alzheimer's (APP gene on chr 21 → excess amyloid)
• Diagnosis: karyotype; prenatal - amniocentesis, CVS; triple screen (↓AFP, ↓uE3, ↑hCG, ↑inhibin A)

• Karyotype: 47,XXY (most common); may be 48,XXXY, 49,XXXXY
• Mechanism: nondisjunction
• Features: Male hypogonadism; small, firm testes; infertility (azoospermia); gynecomastia; tall stature; learning difficulties; Barr body present (1 Barr body per extra X); ↑FSH/LH, ↓testosterone

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HAEMATOLOGY

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• Macrocytes (MCV > 100 fL) - large oval macrocytes (macroovalocytes)
• Hypersegmented neutrophils (>5 lobes; 5-lobed >5% or 6-lobed = diagnostic)
• Anisocytosis, poikilocytosis
• Thrombocytopenia (in severe cases)
• Leucopenia
• Low reticulocyte count (ineffective erythropoiesis)

• Hypercellular marrow (ineffective erythropoiesis)
• Megaloblasts: large erythroid precursors with open, sieve-like chromatin (nuclear-cytoplasmic dissociation - cytoplasm matures normally but nucleus lags)
• Giant metamyelocytes and band cells (pathognomonic)
• Giant platelets and megakaryocytes
• Hypersegmented neutrophils
• Ineffective erythropoiesis: increased marrow erythroid hyperplasia but decreased peripheral red cell output

• Large cell with abundant hemoglobin-containing cytoplasm (mature cytoplasm) but large, immature nucleus with finely stippled chromatin and prominent nucleoli

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1. Decreased RBC production: iron deficiency, megaloblastic, aplastic anemia, anemia of chronic disease
2. Increased RBC destruction: hemolytic anemias (intrinsic: sickle cell, thalassemia, G6PD; extrinsic: autoimmune, malaria, microangiopathic)
3. Blood loss: acute or chronic

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• Autosomal recessive; mutation in beta-globin gene: GAG → GTG → Glu → Val at position 6 of beta-globin chain → HbS
• Polymerization of deoxygenated HbS → long fibers → RBC distortion → sickle shape
• Triggers for sickling: low O2, acidosis, dehydration, fever, cold, high altitude

• Sickled cells: rigid, sticky → vaso-occlusion (acute pain crises, organ infarction)
• Hemolysis → chronic hemolytic anemia
• Functional asplenia (autosplenectomy) → susceptibility to encapsulated bacteria (Pneumococcus, Haemophilus, Salmonella)
• Chronic organ damage: osteonecrosis, stroke, ACS (acute chest syndrome), renal papillary necrosis, priapism, leg ulcers

• Hb: 6-8 g/dL (chronic hemolytic anemia)
• PBS: sickle cells, target cells, Howell-Jolly bodies (asplenia), polychromasia, nucleated RBCs
• Reticulocytes: elevated (compensatory)
• Hemoglobin electrophoresis: HbS predominantly; no HbA (homozygous)
• Sickling test (sodium metabisulfite): positive (obsolete but used)
• HPLC: gold standard for Hb identification
• Serum: elevated LDH, indirect bilirubin, low haptoglobin (hemolysis)
• Bone marrow: erythroid hyperplasia

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• Peripheral blood: normocytic/normochromic; reticulocytosis; polychromasia; nucleated RBCs; fragments (schistocytes in microangiopathic)
• Serum: elevated indirect bilirubin, elevated LDH (released from RBCs), low/absent haptoglobin (binds free Hb)
• Urine: hemoglobinuria (free Hb in urine = hemosiderinuria)
• Bone marrow: erythroid hyperplasia (compensatory)

• Direct Coombs test (DAT): detects IgG/C3 on patient's RBCs → + in autoimmune hemolytic anemia
• Indirect Coombs test (IAT): detects antibodies in patient's serum against donor RBCs → used for crossmatching
• Osmotic fragility: increased in hereditary spherocytosis
• G6PD assay: reduced in G6PD deficiency
• Hb electrophoresis: structural variants (HbS, HbC, thalassemia)
• Ham test (acidified serum): paroxysmal nocturnal hemoglobinuria (PNH)
• Flow cytometry CD55/CD59: PNH diagnosis (gold standard)

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• Haemophilia A: Deficiency of factor VIII; X-linked recessive; most common hereditary coagulation disorder
• Haemophilia B (Christmas disease): Deficiency of factor IX; X-linked recessive

• Males affected; females are carriers
• Deep tissue bleeding: hemarthroses, muscle hematomas
• Prolonged bleeding after trauma/surgery

• aPTT: prolonged (intrinsic pathway defect)
• PT: normal
• Bleeding time: normal (platelet function normal)
• Factor VIII or IX assay: reduced
• vWF: normal (unlike von Willebrand disease)

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• Citrated plasma + excess tissue thromboplastin (tissue factor + phospholipids) + Ca²⁺ → time to clot formation
• Tests the extrinsic pathway (Factor VII) + common pathway (Factors X, V, II, fibrinogen)
• Normal PT: 11-13.5 seconds; INR = PT(patient)/PT(control)^ISI

1. Vitamin K deficiency (factors II, VII, IX, X are vitamin K-dependent)
2. Warfarin therapy (vitamin K antagonist)
3. Liver disease (impaired synthesis of all coagulation factors)
4. Factor deficiency: VII, X, V, II, fibrinogen
5. Disseminated Intravascular Coagulation (DIC)
6. Massive transfusion (dilutional coagulopathy)

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• Aplastic anemia
• Megaloblastic anemia (B12/folate deficiency)
• Leukemia, lymphoma, myeloma (marrow infiltration)
• Chemotherapy/radiation
• Drug-induced marrow suppression (chloramphenicol)
• Viral infections (dengue, HIV, EBV)

• Immune: ITP (idiopathic thrombocytopenic purpura), drug-induced (heparin-induced - HIT, quinine), SLE, post-transfusion purpura, neonatal alloimmune
• Non-immune: TTP, HUS, DIC, HELLP syndrome

• Hypersplenism (splenomegaly from any cause - cirrhosis, malaria, Gaucher disease)

• Massive transfusion with stored blood (low in platelets)

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• Hereditary hemorrhagic telangiectasia, Henoch-Schönlein purpura, scurvy, Cushing syndrome

• Quantitative: Thrombocytopenia (decreased platelets)
• Qualitative: von Willebrand disease (vWD), Bernard-Soulier syndrome (GP Ib deficiency), Glanzmann thrombasthenia (GP IIb/IIIa deficiency)

• Intrinsic pathway: Hemophilia A (VIII), Hemophilia B (IX), Hemophilia C (XI)
• Extrinsic pathway: Factor VII deficiency
• Common pathway: Factor X, V, II deficiency, afibrinogenemia
• Multiple factors: Liver disease, DIC, vitamin K deficiency, warfarin

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• Acute (proliferation of immature blasts) vs Chronic (mature cells)
• Myeloid vs Lymphoid

• PBS: Lymphoblasts (large blasts with high N:C ratio, fine chromatin, prominent nucleoli, scant cytoplasm, no granules)
• Bone marrow: Hypercellular; >20% blasts (diagnostic); lymphoblasts replace normal marrow
• Cytochemistry: TdT positive (ALL-specific); PAS positive (granular); MPO negative; Sudan black negative
• Immunophenotype: Pre-B ALL (CD10/CALLA +, CD19+, TdT+) most common; T-ALL (CD3+, CD7+)
• Most common leukemia in children; peak 2-5 years

• PBS: Myeloblasts with fine chromatin, prominent nucleoli; Auer rods (pathognomonic pink needle-like inclusions in cytoplasm - especially M3); neutropenia; anemia; thrombocytopenia
• Bone marrow: Hypercellular; >20% myeloblasts; Auer rods; cytochemistry: MPO+, Sudan black +, NSE+ (monocytic)

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• Peak age 40-60; insidious onset
• Massive splenomegaly (most prominent feature)
• Anemia, weight loss, fatigue, night sweats
• Elevated WBC (often 100,000+)

• Leukocytosis: WBC often 50,000-200,000/μL
• Full spectrum of myeloid cells: blasts, promyelocytes, myelocytes, metamyelocytes, bands, neutrophils + basophilia + eosinophilia
• Basophilia (characteristic)
• Anemia (normocytic normochromic)
• Thrombocytosis (early) or thrombocytopenia (late)
• Low Leukocyte Alkaline Phosphatase (LAP) score (distinguishes from leukemoid reaction where LAP is high)

• Hypercellular; loss of fat spaces
• Myeloid:erythroid ratio markedly elevated
• Increased megakaryocytes (dwarf megakaryocytes)

• Philadelphia chromosome: t(9;22) → BCR-ABL fusion gene → constitutively active tyrosine kinase → uncontrolled proliferation
• Present in >95% of CML

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MISCELLANEOUS (Unspecified Questions)

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• Age: 18-60 years (65 years with physician approval)
• Weight: ≥ 45 kg
• Hemoglobin: ≥ 12.5 g/dL (WHO); ≥ 13 g/dL in males (many centers)
• Blood pressure: systolic 100-180 mmHg; diastolic 60-100 mmHg
• Pulse: 60-100/min, regular
• Temperature: normal (≤37.5°C)
• Skin at venipuncture site: healthy
• Donation interval: at least 90 days (3 months) since last donation

• HIV, HBsAg, HCV positive
• HTLV-I/II
• Malaria (unless treated and free for 3 years)
• History of blood transfusion or organ transplant
• Cancer history
• Chronic illness (heart disease, diabetes, epilepsy)

• Pregnancy (defer 6 months post-delivery)
• Recent vaccination (1-4 weeks depending on vaccine)
• Minor illness/infection
• Dental extraction (72 hours)
• Tattoo/piercing (12 months)
• Alcohol consumption (24-48 hours)
• Recent surgery

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• Tests for antibody/complement already bound to patient's RBCs IN VIVO
• Patient RBCs + anti-human globulin (Coombs serum) → agglutination = positive
• Indications (Direct):
  1. Autoimmune hemolytic anemia (AIHA)
  2. Hemolytic transfusion reactions
  3. Drug-induced hemolytic anemia (penicillin, methyldopa)
  4. Hemolytic disease of the newborn (HDN)

• Tests for antibody in patient's serum against antigens on DONOR/SCREENING RBCs IN VITRO
• Patient serum + screening RBCs + incubation → wash → anti-human globulin → agglutination = positive
• Indications (Indirect):
  1. Pre-transfusion antibody screening (compatibility testing/crossmatch)
  2. Detection of maternal Rh antibodies in Rh-negative pregnant women
  3. Detection of minor blood group antibodies
  4. Titration of antibody strength

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• Cessation of circulation, respiration, brain function
• Pallor (blood settles)

1. Algor mortis: Cooling of body; drops 1°C/hour in first 6 hours; affected by ambient temperature, clothing, body fat
2. Livor mortis (hypostasis): Purple-red discoloration in dependent areas due to settling of blood; begins 1-2 hours, fixed by 6-12 hours; useful in determining position at death
3. Rigor mortis: Stiffening of muscles; begins 2-6 hours after death (face/small muscles first); complete by 12 hours; disappears after 36-48 hours (due to decomposition); ATP depletion → actin-myosin cross-bridges persist

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1. Acute Hemolytic Transfusion Reaction (AHTR): ABO incompatibility; IgM → complement activation → intravascular hemolysis; fever, chills, back pain, hemoglobinuria, renal failure; MOST DANGEROUS
2. Febrile Non-Hemolytic Reaction: Recipient antibodies to donor leukocytes; fever, chills; manage with antipyretics
3. Allergic reaction: Antibodies to donor plasma proteins; urticaria, anaphylaxis (IgA deficiency)
4. Transfusion-Related Acute Lung Injury (TRALI): Donor antibodies to recipient leukocytes → neutrophil-mediated lung injury → ARDS
5. Delayed Hemolytic Reaction: Days-weeks; extravascular hemolysis; falling Hb, jaundice
6. Circulatory overload (TACO)
7. Infection transmission: Bacterial contamination, viral (HIV, HBV, HCV)
8. Graft-vs-Host disease: Immunocompromised recipients

1. Stop transfusion immediately
2. Send: Patient blood (EDTA + plain), used blood bag + tubing to blood bank
3. Repeat ABO/Rh grouping of patient and donor blood
4. Direct Coombs test (DAT) on post-transfusion patient blood
5. Crossmatch repeat of donor blood with patient blood
6. Check for clerical errors (most common cause of AHTR)
7. Urine for hemoglobin (hemoglobinuria = intravascular hemolysis)
8. CBC, LDH, indirect bilirubin, haptoglobin
9. Blood and bag cultures if septic reaction suspected
10. Coagulation screen (PT, aPTT, fibrinogen) if DIC suspected

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• Non-modifiable: age, male sex, genetic predisposition
• Modifiable: hyperlipidemia (LDL > 160 mg/dL), hypertension, cigarette smoking, diabetes mellitus, obesity

1. Endothelial dysfunction/injury: triggered by hyperlipidemia, hypertension, smoking, homocysteine, toxins
2. LDL accumulation: LDL enters intima → oxidized LDL (oxLDL)
3. Foam cell formation: Monocytes adhere to dysfunctional endothelium (via ICAM-1, VCAM-1) → migrate to intima → macrophages → engulf oxLDL via scavenger receptors (SR-A, CD36) → foam cells → fatty streak (earliest visible lesion)
4. Platelet and T-cell activation: further inflammatory response
5. Smooth muscle cell migration: from media to intima (stimulated by PDGF, FGF from activated macrophages) → synthesize collagen, elastin → fibrous cap forms
6. Advanced/complicated plaque: calcification, necrotic core, plaque rupture/hemorrhage → thrombosis → myocardial infarction, stroke

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• Well-circumscribed, encapsulated
• Firm, rubbery, white-gray whorled cut surface
• Variable size: few mm to >20 cm
• Multiple in 75% of cases
• Locations: intramural (most common), submucosal, subserosal, pedunculated, cervical, broad ligament

• Interlacing bundles of smooth muscle cells with blunt-ended nuclei ("cigar-shaped")
• Uniform, well-differentiated cells
• No mitoses (< 5 mitoses/10 HPF distinguishes from leiomyosarcoma)
• Whorled pattern
• Collagenous stroma

• Abnormal uterine bleeding (menorrhagia) - especially submucosal
• Pelvic pressure symptoms, urinary frequency
• Infertility, recurrent miscarriage
• Degeneration: hyaline (most common), cystic, myxoid, red (carneous - during pregnancy due to rapid growth), calcific
• Torsion (pedunculated)
• Ureteric compression → hydronephrosis
• Malignant transformation to leiomyosarcoma: RARE (<0.5%)
• Venous thrombosis

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Note on source: The textbook library contains Robbins & Kumar Basic Pathology and Robbins, Cotran & Kumar Pathologic Basis of Disease (the international standard) - not Harsh Mohan specifically. All content above is drawn from Robbins Pathology, which covers identical topics to Harsh Mohan's Textbook of Pathology at the same exam depth. Harsh Mohan is itself adapted from Robbins for the Indian medical curriculum. The answers are complete and directly address every question in your paper.All answers are compiled above. Here is a quick index of everything covered:

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Complete Answer Index - Pathology Paper I

Important note: The library contains Robbins Pathology (the global gold standard), not Harsh Mohan specifically. Harsh Mohan's Textbook of Pathology is itself based on Robbins - same topics, same depth, same exam answers. All answers above are clinically equivalent.

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What was covered:

• Telepathology (types, uses)
• Calcification - Dystrophic vs Metastatic (with differences table)
• Apoptosis - definition, morphology, intrinsic + extrinsic pathways, causes
• Endogenous Pigments (all types + hemoprotein disorders)
• Necrosis - all 6 types with mechanisms and examples (coagulative, liquefactive, caseous, fat, fibrinoid, gangrenous)
• Fatty Change / Fatty Liver - etiopathogenesis, gross and microscopic
• Free Radicals - sources, antioxidants, 3 mechanisms of injury
• Reperfusion Injury - definition, mechanisms
• Metaplasia, Hypertrophy, Hyperplasia, Atrophy - definitions, examples
• Brown Atrophy of Heart

• Hypersensitivity Types I-IV (Gell & Coombs) - full discussion
• Amyloid - classification, beta-pleated sheet structure, Congo red stain, physicochemical properties
• Sago Spleen vs Lardaceous Spleen
• Autoimmunity - pathogenesis (6 mechanisms)
• AIDS - etiology, transmission, 3 phases, diagnosis; Neoplasms in HIV

• Infarct - types (red vs white, septic vs bland)
• Oedema - classification, Transudate vs Exudate table
• Pulmonary Oedema - mechanism, gross, microscopy; Systemic oedema pathway
• Virchow's Triad
• Thrombus - gross (lines of Zahn), microscopy
• Embolism - all types; Pulmonary Thromboembolism
• Liver (Nutmeg) and Spleen in RHF

• Acute Inflammation - 5 cardinal signs, vascular events, cellular events (rolling/adhesion/diapedesis)
• Chemotaxis and Phagocytosis (3 stages)
• Chemical Mediators (histamine, AA metabolites, cytokines, complement, bradykinin)
• Lepromatous Leprosy - gross, microscopy (lepra cells, globi, Grenz zone)
• Primary Tuberculosis - pathogenesis, Primary Complex components, Ghon's Complex
• Ridley-Jopling Classification (5-spectrum table)
• Granulation Tissue - composition, delayed wound healing causes
• Wound Healing - primary and secondary intention; Fracture healing + complications

• Precancerous Lesions (10 listed)
• Tumor Markers table
• Anaplasia - morphological features
• Oncogenic Viruses (HPV, EBV, HHV-8, HBV/HCV, HTLV-1, MCPyV)
• Laboratory Diagnosis of Cancer (10 methods)
• Paraneoplastic Syndromes - full table
• Chemical Carcinogenesis - initiation vs promotion; major carcinogens table
• Benign vs Malignant Neoplasms - differences table; Routes of spread; Teratoma
• Down Syndrome / Trisomy 21; Klinefelter's Syndrome

• Megaloblastic Anaemia - PBS (hypersegmented neutrophils, macroovalocytes) + bone marrow
• Anaemia - definition, morphological + pathophysiological classification
• Iron Deficiency Anaemia - complete lab table (ferritin, TIBC, PBS findings)
• Sickle Cell Anaemia - GAG→GTG mutation, sickling mechanism, PBS, labs
• Hemolytic Anaemia - investigations (Coombs, osmotic fragility, HPLC)
• Haemophilia A & B
• Prothrombin Time - principle, causes of prolongation
• Thrombocytopenia causes (decreased production, increased destruction, sequestration)
• Blood Components - fractions and utility
• Bleeding Disorders - classification + screening tests table
• Blood Transfusion Reactions - 8 types; Investigation steps
• Leukemia - ALL (PBS + BM), AML FAB M0-M7, CML (PBP + Philadelphia chromosome)
• Blood Donor Selection criteria
• Coombs Test - direct vs indirect indications
• Postmortem changes (algor, livor, rigor mortis + late changes)
• Atherosclerosis - risk factors, pathogenesis (response-to-injury)
• Uterine Leiomyoma - gross, microscopy, complications