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🧬 PATHOLOGY IMPORTANT TOPICS - MBBS 2nd Year

Format: Definition → Etiology → Pathogenesis → Gross → Microscopy Written for quick grasp + 10-mark answers

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1. ACUTE AND CHRONIC INFLAMMATION

ACUTE INFLAMMATION

• Infections (bacteria, viruses, fungi, parasites)
• Physical agents (trauma, heat, cold, radiation)
• Chemical agents (acids, alkalis, toxins)
• Tissue necrosis (infarction)
• Immune reactions (hypersensitivity)
• Foreign bodies

1. Recognition of injurious agent
2. Recruitment of leukocytes (neutrophils first)
3. Removal of agent by phagocytosis
4. Resolution or repair
5. Regulation (anti-inflammatory controls)

• Predominant cell = Neutrophils (PMNs)
• Exudate (protein-rich fluid) in tissue
• Vascular congestion
• Edema

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CHRONIC INFLAMMATION

• Persistent infections (TB, fungal, H. pylori)
• Autoimmune diseases (RA, SLE)
• Prolonged exposure to toxic agents (silicosis, atherosclerosis)
• Persistent acute inflammation

• Macrophage activation is central
• T-lymphocytes release cytokines (IFN-γ activates macrophages)
• Ongoing tissue destruction + fibrosis (scar formation)
• Angiogenesis

• Predominant cells = Lymphocytes, Plasma cells, Macrophages
• Fibrosis (collagen deposition)
• Angiogenesis
• Tissue destruction + repair simultaneously

Memory Trick: Acute = Neutrophils; Chronic = Lymphocytes + Macrophages + Plasma cells

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2. NECROSIS vs APOPTOSIS

NECROSIS

• Cell membrane integrity lost → ions/water flood in
• ATP depleted → Na/K pump fails → cell swells
• Lysosomal enzymes released → autodigestion
• Inflammatory response triggered

• Karyolysis - nucleus fades (DNA digested by DNases)
• Pyknosis - nucleus shrinks, darkens
• Karyorrhexis - nucleus fragments
• Ghost outlines of cells in coagulative necrosis

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APOPTOSIS

• Physiological: embryogenesis, hormone withdrawal, immune cell deletion
• Pathological: DNA damage, virus-infected cells, cancer therapy

• DNA damage / oxidative stress → p53 activation → Bax/Bak activation → Cytochrome C release from mitochondria → Caspase-9 → Caspase-3 (executioner) → Cell death

• FasL binds Fas / TNF binds TNFR → FADD → Caspase-8 → Caspase-3 → Cell death

• Cell shrinkage (opposite of necrosis)
• Chromatin condensation
• Membrane blebbing
• Apoptotic bodies (cell fragments engulfed by macrophages)
• No inflammation (key difference from necrosis)

Key Difference Table:

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3. TYPES OF ANEMIA + CLASSIFICATION + LAB DIAGNOSIS

1. Blood loss: Acute / Chronic hemorrhage
2. Decreased production: Nutritional (Iron, B12, Folate), Aplastic anemia, Bone marrow infiltration
3. Increased destruction (Hemolytic): Hereditary (Sickle cell, Thalassemia, G6PD deficiency) / Acquired (Autoimmune, Malaria)

• CBC: Hb, RBC count, MCV, MCH, MCHC, RDW
• Peripheral blood smear: Cell morphology (most important)
  • Hypochromic microcytic cells → Iron deficiency
  • Macrocytes, hypersegmented neutrophils → Megaloblastic
  • Target cells → Thalassemia
  • Sickle cells → Sickle cell anemia
• Reticulocyte count: High = blood loss/hemolysis; Low = bone marrow failure
• Serum iron, TIBC, Ferritin: For iron deficiency
• Serum B12/Folate: For megaloblastic anemia
• Bone marrow biopsy: Aplastic anemia, infiltration
• Coombs test: Autoimmune hemolytic anemia
• Hb electrophoresis: Thalassemia, Sickle cell

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4. HYPEREMIA vs CONGESTION

• Hyperemia: bright red, warm tissue
• Congestion: blue-red, cyanotic, may have edema

• Dilated venules and capillaries packed with RBCs
• Lung: "Heart failure cells" = hemosiderin-laden macrophages (alveolar macrophages), brown induration
• Liver: "Nutmeg liver" pattern - central vein congestion, centrilobular necrosis

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5. IRON METABOLISM + DISORDERS

• Dietary iron absorbed in duodenum as Fe2+ (ferrous form)
• Transported by Transferrin in blood
• Stored as Ferritin (soluble) and Hemosiderin (insoluble)
• Regulated by Hepcidin (liver hormone - master regulator)

• Most common anemia worldwide
• Etiology: Poor diet, malabsorption, chronic blood loss (menorrhagia, GI bleed)
• Lab: Low serum iron, Low ferritin, High TIBC
• Blood smear: Microcytic, hypochromic RBCs, pencil cells, target cells

• Hemosiderosis: Local hemosiderin accumulation, no tissue damage
• Hemochromatosis: Systemic iron overload + organ damage (liver cirrhosis, diabetes, skin bronzing, cardiac failure - "Bronze diabetes")

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6. HYPERSENSITIVITY - TYPES + DIFFERENCES

• Type I: Mast cell degranulation, eosinophils
• Type II: Complement-mediated cell lysis
• Type III: Vasculitis, neutrophil infiltration, fibrinoid necrosis of vessel walls
• Type IV: Lymphocytes and macrophages, granuloma (in chronic DTH)

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7. TUMOR MARKERS + CLINICAL USE

1. Screening (PSA)
2. Monitoring treatment response
3. Detecting recurrence
4. Prognosis

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8. PHASES OF WOUND HEALING

Phase 1: Hemostasis (immediate, minutes)

• Vasoconstriction → Platelet aggregation → Fibrin clot formation
• Platelet plug seals the wound

Phase 2: Inflammation (Day 1-4)

• Neutrophils arrive first (24-48 hrs) - kill bacteria, clean debris
• Macrophages replace them (day 3-4) - phagocytosis + release growth factors (VEGF, TGF-β, PDGF)

Phase 3: Proliferation/Granulation (Day 4 - Week 3)

• Granulation tissue forms - pink, granular, vascular
• Components: New capillaries (angiogenesis) + fibroblasts + loose collagen + inflammatory cells
• Epithelial cells migrate to cover wound
• Fibroplasia: Type III collagen (temporary) deposited by fibroblasts

Phase 4: Remodeling/Maturation (Week 3 - 1 year)

• Type III collagen replaced by stronger Type I collagen
• Wound contraction by myofibroblasts
• Scar matures and strengthens (max 80% of original strength)

• New blood vessels (thin-walled capillaries)
• Fibroblasts producing collagen
• Mixed inflammatory cells
• Edematous stroma

Primary vs Secondary Healing:

• Primary (First intention): Clean wound, edges approximated (surgical incision) - minimal scar
• Secondary (Second intention): Large/infected wound, open healing - more granulation tissue, more scar, wound contraction

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9. LEUKEMOID REACTION vs LEUKEMIA

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10. REVERSIBLE vs IRREVERSIBLE CELL INJURY

• Cellular swelling
• Cytoplasmic vacuolation (ballooning)
• ER swelling
• Myelin figures

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11. NORMAL HEMOSTASIS

• VWF bridges damaged collagen + GpIb receptor on platelet → Platelet adhesion
• ADP, TXA2 released → Platelet activation and aggregation
• GpIIb/IIIa binds fibrinogen → Platelet-platelet bridging = loose plug

• Extrinsic pathway: Tissue factor (III) + Factor VIIa → Xa
• Intrinsic pathway: XII → XI → IX → X (contact activation)
• Common pathway: Xa + Va → Prothrombin → Thrombin → Fibrinogen → Fibrin
• Cross-linked fibrin stabilizes the platelet plug = firm clot

• Plasminogen → Plasmin (via tPA) → breaks down fibrin → FDPs (D-dimer)

• PT (Prothrombin Time): Tests extrinsic + common pathway (Factors II, V, VII, X, fibrinogen). Normal: 11-14 sec. Prolonged in Warfarin use, liver disease
• aPTT (activated Partial Thromboplastin Time): Tests intrinsic + common pathway (VIII, IX, XI, XII). Normal: 25-35 sec. Prolonged in Hemophilia, heparin use
• Bleeding time: Platelet function test. Normal: 2-7 min
• Platelet count: Normal: 1.5-4 lakh/µL
• D-dimer: Elevated in DIC, DVT, PE

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12. TRANSFUSION REACTIONS

• Hb < 7 g/dL (symptomatic patients)
• Hb < 10 g/dL (cardiac disease patients)
• Active bleeding
• Pre-operative preparation

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13. NEOPLASIA

1. Proto-oncogenes → Oncogenes (growth accelerators - act like stuck accelerator): Mutations cause gain of function. E.g., RAS mutations (most common), HER2/neu amplification, MYC amplification
2. Tumor Suppressor Genes (growth brakes - must lose BOTH copies - Knudson's "2-hit hypothesis"): RB gene (retinoblastoma), p53 (most commonly mutated gene in human cancers - "Guardian of the genome"), APC (colon cancer), BRCA1/2 (breast/ovarian)
3. Apoptosis-regulating genes: BCL2 (anti-apoptotic - overexpressed in follicular lymphoma), BAX (pro-apoptotic)
4. DNA repair genes: HNPCC (Lynch syndrome) - mismatch repair genes
5. Telomerase: Activated in most cancers → immortalization

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14. DYSPLASIA + CARCINOMA IN SITU

• Features: Loss of polarity, increased N:C ratio, hyperchromatic nuclei, increased mitoses
• Not all dysplasia becomes cancer (reversible in mild/moderate)

• Cervical CIS (CIN III), Ductal CIS (DCIS) of breast

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15. GRANULOMATOUS INFLAMMATION

• TB (caseating granuloma - classic)
• Sarcoidosis (non-caseating - most common non-infectious)
• Leprosy
• Fungal infections (Histoplasma, Cryptococcus)
• Crohn's disease
• Foreign body reaction
• Syphilis
• Cat scratch disease

• Persistent antigen that resists phagocytosis → macrophage activation by T-cell (IFN-γ) → Macrophages transform into epithelioid cells → Fusion of macrophages → Giant cells → Granuloma formation

• TB: Caseous (cheese-like, yellow-white) necrosis in center
• Sarcoidosis: Small firm nodules, no necrosis

• Center: Caseous necrosis (in TB) or no necrosis (sarcoidosis)
• Surrounding: Epithelioid cells (activated macrophages with pink cytoplasm, elongated nuclei)
• Giant Cells:
  • Langhans type (nuclei at periphery in horseshoe/C-shape) - TB
  • Foreign body type (nuclei scattered centrally) - Foreign bodies
• Outer zone: Lymphocytes + plasma cells + fibroblasts

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16. EDEMA

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17. PLATELET DISORDERS - CLASSIFICATION

• Autoimmune (IgG vs GpIIb/IIIa)
• Acute (children, post-viral) vs Chronic (women 20-40 years)
• Features: Petechiae, purpura, normal PT/aPTT
• Microscopy of spleen: Megakaryocytes increased in bone marrow; spleen shows sinusoidal congestion

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18. SHOCK

1. Compensated - BP maintained by reflex mechanisms (tachycardia, vasoconstriction)
2. Progressive - BP falls, organs begin to fail
3. Irreversible - Multi-organ failure, death

• Lungs: ARDS (Diffuse Alveolar Damage) - hyaline membrane formation
• Kidneys: Acute Tubular Necrosis (ATN)
• Adrenals: Waterhouse-Friderichsen syndrome (hemorrhagic necrosis)
• Brain: Ischemic encephalopathy

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19. CALCIFICATION

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20. GENERALISED LYMPHADENOPATHY

• Infectious: EBV (infectious mononucleosis - commonest cause), HIV, CMV, TB, toxoplasmosis
• Autoimmune: SLE, RA
• Malignant: Lymphoma (Hodgkin's/Non-Hodgkin's), leukemia, metastatic cancer
• Miscellaneous: Sarcoidosis, drug reaction (phenytoin)

• Reactive lymphadenitis: Follicular hyperplasia (germinal center enlargement) - viral/autoimmune
• Sinusoidal pattern: Metastatic carcinoma
• Reed-Sternberg cells: Hodgkin's lymphoma
• Caseating granuloma: TB

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21. MULTIPLE MYELOMA

• Clonal plasma cells → Monoclonal immunoglobulin (M-protein) → Usually IgG > IgA
• Bence-Jones proteins (free light chains - κ or λ) excreted in urine
• RANKL increased → Osteoclast activation → Lytic bone lesions

• C - hyperCalcemia
• R - Renal failure (light chain nephropathy, amyloid)
• A - Anemia (bone marrow infiltration)
• B - Bone pain + lytic lesions ("punched-out" lesions)

• Sheets of plasma cells (eccentric nucleus, clock-face/cartwheel chromatin, perinuclear hof - clear zone near nucleus)
• Flame cells (IgA variant)
• Dutcher bodies (intranuclear Ig inclusions)
• Russell bodies (cytoplasmic Ig inclusions)

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22. ESR vs CRP AS INFLAMMATORY MARKERS

• Acute MI (cardiac CRP): Risk stratification
• Monitoring antibiotic response in infections
• DIC diagnosis

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23. METAPLASIA (+ TEG = Together with related)

• Smokers: Columnar/ciliated respiratory epithelium → Squamous epithelium (Squamous metaplasia)
• GERD: Esophageal squamous epithelium → Columnar (Barrett's esophagus) - risk of adenocarcinoma
• Bladder stones: TCC epithelium → Squamous metaplasia
• Cervix: Squamocolumnar junction → Squamous metaplasia (transformation zone)

Important: Metaplasia itself is not malignant but predisposes to dysplasia/cancer if stimulus persists.

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24. THROMBOCYTOPENIA

1. Decreased production: Aplastic anemia, leukemia, chemotherapy, B12/folate deficiency
2. Increased destruction:
   • Immune: ITP (autoimmune IgG), SLE, drug-induced (heparin-induced = HIT)
   • Non-immune: TTP, HUS, DIC
3. Increased sequestration: Hypersplenism (spleen traps platelets)
4. Dilutional: Massive transfusion (stored blood has no functional platelets)

• Petechiae (pinpoint hemorrhages) < 50,000
• Purpura (larger hemorrhages)
• Spontaneous bleeding < 20,000
• Critical bleeding (intracranial) < 10,000

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25. CHEMICAL MEDIATORS OF INFLAMMATION

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26. FATE OF THROMBUS

1. Lysis/Resolution: Fibrinolysis (most favorable) - plasmin breaks down clot
2. Propagation: Thrombus grows larger → more vessel occlusion
3. Embolization: Part/whole thrombus breaks off → travels → lodges elsewhere → embolism
4. Organization + Recanalization: Fibroblasts + capillaries grow into thrombus → recanalize (channel forms through clot) → partial restoration of flow
5. Calcification: Old thrombus calcifies → "phlebolith" (in veins)

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27. PRIMARY vs SECONDARY AMYLOIDOSIS

• Affected organ: Enlarged, waxy, pale, firm ("lard-like" on cut surface)
• Spleen: Sago spleen (nodular) in AA; Lardaceous spleen (diffuse) in AL

• H&E: Homogeneous, acellular, eosinophilic (pink) deposits
• Congo Red stain: Apple-green birefringence under polarized light (GOLD STANDARD)
• Crystal Violet/Methyl Violet: Metachromasia (purple → pink/red shift)
• Deposits in vessel walls, glomerular mesangium, interstitium

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28. EMBOLISM

1. Thromboembolism (most common): Detached thrombus - DVT → Pulmonary embolism (most common PE source: deep leg veins)
2. Fat embolism: Fracture of long bones → fat globules enter blood → lung, brain, skin (petechiae)
3. Air/Gas embolism: Surgical procedures, IV lines, decompression sickness ("bends")
4. Amniotic fluid embolism: Obstetric complication → DIC, ARDS
5. Tumor embolism: Malignant cells travel via blood
6. Septic embolism: Infected thrombus fragments

• Saddle embolus: Straddles bifurcation of pulmonary artery (most dangerous)
• Hemorrhagic infarction of lung (wedge-shaped, hemorrhagic)

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29. CELLULAR ADAPTATIONS

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30. HAEMOPHILIA + TYPES

• Mild: >5% activity (bleeding with major trauma)
• Moderate: 1-5% (bleeding with minor trauma)
• Severe: <1% (spontaneous bleeding)

• Hemarthrosis (joint bleeding) - most common, causes chronic joint damage
• Deep muscle hematomas
• Prolonged bleeding after surgery/trauma
• Easy bruising

• PT: Normal
• aPTT: Prolonged (intrinsic pathway affected)
• Bleeding time: Normal
• Platelet count: Normal
• Factor VIII/IX assay: Low (confirmatory)

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31. INFARCTION - FACTORS

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32. RED vs WHITE INFARCT

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33. HODGKIN'S vs NON-HODGKIN'S LYMPHOMA

1. Nodular Lymphocyte Predominant (NLPHL) - best prognosis
2. Classical HL:
   • Nodular Sclerosis (most common in young women)
   • Mixed Cellularity
   • Lymphocyte Rich
   • Lymphocyte Depleted (worst prognosis)

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34. LEUKEMIAS - DEFINITION + WHOLE

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35. GANGRENE

• Caused by Clostridium perfringens
• Gas production in tissues (crepitus on palpation)
• Rapidly fatal, systemic toxemia
• Microscopy: Coagulative necrosis, gas bubbles, gram-positive rods, no neutrophils (toxin kills them)

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36. METASTASIS

1. Local invasion (ECM degradation by MMPs - Matrix Metalloproteinases)
2. Intravasation (enter blood/lymphatics)
3. Survival in circulation (evade immune system)
4. Arrest at distant site
5. Extravasation
6. Micrometastasis formation
7. Angiogenesis → Macrometastasis

• Liver: GI tumors (portal vein drainage)
• Lung: Most common site of any hematogenous metastasis
• Bone: Breast, Prostate, Lung, Thyroid, Kidney ("BPLTiK")
• Brain: Lung > Breast > Melanoma (commonest primary to metastasize to brain)
• Adrenal: Lung, breast, GI carcinomas
• Virchow's node (left supraclavicular LN): Stomach cancer metastasis
• Krukenberg tumor: Bilateral ovarian metastasis from stomach (signet ring cells)
• Sister Mary Joseph nodule: Umbilical metastasis from GI/ovarian tumors

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QUICK REVISION TABLE - ALL STAINS

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QUICK REVISION - PATHOGNOMONIC FINDINGS

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HOW TO USE THESE NOTES FOR 10-MARK ANSWERS

1. Definition (2-3 lines) - 1 mark
2. Etiology (bullet points) - 2 marks
3. Pathogenesis (sequential steps/flow) - 3 marks
4. Gross findings (what you see with naked eye) - 2 marks
5. Microscopy (what you see under microscope) - 2 marks

• ✅ Acute & Chronic Inflammation (SAQ & LAQ)
• ✅ Necrosis & Apoptosis
• ✅ All types of Anemia + Classification + Lab diagnosis
• ✅ Hyperemia vs Congestion
• ✅ Iron Metabolism & Disorders
• ✅ Hypersensitivity (all 4 types + differences)
• ✅ Tumor Markers + Clinical use
• ✅ Phases of Wound Healing
• ✅ Leukemoid reaction vs Leukemia
• ✅ Reversible vs Irreversible cell injury
• ✅ Normal Hemostasis + Coagulation tests
• ✅ Transfusion reactions (indications + reactions)
• ✅ Neoplasia + Molecular basis of Carcinogenesis
• ✅ Dysplasia + Carcinoma in situ
• ✅ Granulomatous inflammation + Giant cells
• ✅ Edema (etiopathogenesis)
• ✅ Platelet disorders + Classification
• ✅ Shock
• ✅ Calcification (Dystrophic vs Metastatic)
• ✅ Generalised Lymphadenopathy
• ✅ Multiple Myeloma
• ✅ ESR vs CRP
• ✅ Metaplasia
• ✅ Thrombocytopenia
• ✅ Chemical mediators of inflammation
• ✅ Fate of Thrombus
• ✅ Primary & Secondary Amyloidosis
• ✅ Embolism (SAQ)
• ✅ Cellular Adaptations
• ✅ Haemophilia + Types
• ✅ Infarction - Factors
• ✅ Red vs White Infarct
• ✅ Hodgkin's vs Non-Hodgkin's Lymphoma
• ✅ Leukemias (Define + whole)
• ✅ Gangrene (Dry vs Wet)
• ✅ Metastasis (Routes + Pathogenesis)

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🫀 SYSTEMIC PATHOLOGY - MBBS 2nd Year Important Topics

Format: Definition → Etiology → Pathogenesis → Gross → Microscopy Written for 10-mark answers | Quick grasp format

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1. MYOCARDIAL INFARCTION (MI)

• Atherosclerosis + plaque rupture + thrombosis (90% of cases)
• Coronary artery spasm (Prinzmetal angina)
• Embolism to coronary arteries
• Vasculitis (rare)

• Atherosclerotic plaque rupture/fissure → platelet aggregation + thrombus formation → complete coronary occlusion → cessation of blood flow → ATP depletion within 30 min → irreversible cell injury → coagulative necrosis

• STEMI (transmural): Full thickness - plaque rupture + complete occlusion
• NSTEMI/NQMI (subendocardial): Inner 1/3 only - incomplete occlusion or demand ischemia

• Troponin I/T - most sensitive + specific; rises 3-6 hrs, peaks 24 hrs, stays elevated 7-10 days
• CK-MB - rises 4-6 hrs, peaks 24 hrs, returns to normal in 48-72 hrs
• LDH - rises late (24-48 hrs), stays elevated 10-14 days
• Myoglobin - first to rise (2 hrs) but not specific

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2. BARRETT'S ESOPHAGUS

• Chronic GERD (reflux of acid + bile) - main cause
• Obesity, hiatus hernia
• Smoking, alcohol

• Chronic acid exposure → Repeated injury to squamous cells → Healing by stem cell reprogramming → Columnar intestinal metaplasia better survives acid → Barrett's esophagus → Dysplasia → Adenocarcinoma

• Salmon-pink/red velvety mucosa in distal esophagus (vs normal pale squamous mucosa)
• "Tongue-like" projections of red mucosa extending from Z-line upward
• Located in distal esophagus (>3 cm above GEJ)

• Replacement of squamous epithelium by columnar epithelium with goblet cells (intestinal metaplasia - HALLMARK)
• Goblet cells: Pale blue/lavender vacuolated cells on H&E
• Dysplasia (low or high grade) may be superimposed
• Alcian blue stain highlights goblet cells (acid mucin - blue)

Risk: 30-40x increased risk of esophageal adenocarcinoma (compared to normal population)

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3. PNEUMONIA

• Bacteria multiply → vascular engorgement → protein-rich edema fluid fills alveoli

• Alveoli packed with RBCs, fibrin, neutrophils → lung feels like liver (hepatization), red color

• RBCs lyse → fibrin + neutrophils remain → grey color, firm

• Macrophages clear exudate → normal structure restored (most favorable)

• Lobar: Entire lobe consolidated, airless, firm, liver-like; gray or red depending on stage
• Bronchopneumonia: Multiple patchy consolidations, scattered throughout lung

• Red hepatization: Alveoli filled with RBCs + fibrin + PMNs; alveolar septa intact
• Grey hepatization: Fibrin meshwork + neutrophils + macrophages; RBCs absent
• Resolution: Macrophages phagocytosing fibrin; re-aeration of alveoli
• Bronchopneumonia: Peribronchial exudate, patchy distribution, alveolar PMN infiltrate

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4. OVARIAN TUMORS

• Serous cystadenoma: Smooth-walled unilocular cyst, serous fluid, bilateral in 20-30%
• Serous carcinoma: Irregular, solid + cystic, papillary projections, bilateral, calcified foci
• Mucinous: Multilocular, large cyst filled with thick mucin, usually unilateral

• Serous tumor: Papillary structures lined by tubal-type epithelium (ciliated columnar cells); Psammoma bodies (concentric calcifications) - characteristic
• Mucinous tumor: Tall columnar cells with basal nuclei + apical mucin vacuoles; resembles intestinal epithelium
• Granulosa cell tumor: Call-Exner bodies (rosette arrangements of granulosa cells around PAS+ material) - PATHOGNOMONIC

• CA-125: Serous carcinoma
• AFP, hCG: Germ cell tumors
• Inhibin: Granulosa cell tumor

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5. NEPHROTIC SYNDROME

• Loss of polyanion (heparan sulfate) from GBM → Loss of charge barrier → Proteinuria → Low albumin → Low oncotic pressure → Edema; Liver compensates → Lipoprotein synthesis → Hyperlipidemia → Lipiduria

• LM: Normal (hence the name!)
• EM: Fusion/effacement of podocyte foot processes (HALLMARK)
• IF: Negative
• Responds to steroids (excellent prognosis)

• LM: Thickened GBM ("spike and dome" pattern on silver stain) - subepithelial deposits
• EM: Electron-dense subepithelial deposits
• IF: Granular IgG + C3 along GBM

• LM: Focal (some glomeruli) and segmental (part of glomerulus) sclerosis + hyalinosis
• EM: Foot process effacement
• IF: Focal IgM + C3

• LM: Lobular glomeruli, mesangial proliferation, tram-track/double contour of GBM
• IF: C3 ± IgG in granular pattern

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6. OSTEOSARCOMA

• Most common primary malignant bone tumor in children/adolescents
• Peak age: 10-20 years
• RB gene mutation (hereditary retinoblastoma patients - 500x higher risk)
• p53 mutations
• Paget's disease (older adults - secondary osteosarcoma)
• Previous radiation

• RB/p53 mutations → uncontrolled osteoblast proliferation → production of malignant osteoid + destruction of cortex → periosteal reaction → metastasis (mainly to lungs via hematogenous route)

• Large, destructive metaphyseal mass
• Gray-white, gritty (due to osteoid)
• Cortical destruction
• Soft tissue extension
• Codman's triangle: Periosteal elevation at margins of tumor (reactive periosteum)

• Pleomorphic malignant stromal cells (sarcomatous stroma)
• Osteoid (pink, lace-like material) produced by tumor cells - DIAGNOSTIC
• High mitotic rate, abnormal mitoses
• Hemorrhage and necrosis
• Cartilage may be present (osteochondrosarcoma variant)

• Bone destruction + new bone formation
• Sunburst pattern (perpendicular spicules of new bone)
• Codman's triangle (periosteal elevation)

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7. FATTY LIVER CHANGES (HEPATIC STEATOSIS)

• Alcoholic: Chronic alcohol excess (most common cause in developed countries)
• Non-Alcoholic Fatty Liver Disease (NAFLD): Obesity, diabetes type 2, metabolic syndrome, hyperlipidemia
• Other: Starvation, TPN, drugs (corticosteroids, amiodarone, methotrexate), pregnancy (acute fatty liver of pregnancy)

• Alcohol → Acetaldehyde + NADH (by alcohol dehydrogenase) → High NADH ratio → Blocks beta-oxidation of fatty acids → Fat accumulates in hepatocytes + Increased fatty acid synthesis → Steatosis

• Insulin resistance → Increased FFA mobilization from adipose → Hepatic fat accumulation → Oxidative stress → Inflammation → NASH → Fibrosis/Cirrhosis ("two-hit hypothesis")

• Enlarged liver (hepatomegaly)
• Yellow-orange color (due to fat)
• Greasy/soft texture
• Rounded edges

• Macrovesicular steatosis (most common): Large fat vacuole displaces nucleus to periphery (like signet ring) - alcoholic/NAFLD
• Microvesicular steatosis: Multiple small fat droplets, nucleus remains central - acute fatty liver of pregnancy, Reye's syndrome (more serious)
• Special stain: Oil Red O (on frozen section) - fat stains red
• Alcoholic Hepatitis additional features: Mallory-Denk bodies (eosinophilic cytoplasmic aggregates of intermediate filaments), neutrophil infiltration, ballooning degeneration

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8. BRONCHOGENIC CARCINOMA + PARANEOPLASTIC SYNDROME

• Carcinogens (tobacco smoke, asbestos, radon) → DNA damage → Mutations in KRAS, EGFR, p53, RB → Squamous metaplasia → Dysplasia → CIS → Invasive carcinoma

• Squamous/SCLC: Central, endobronchial, cavitating mass
• Adenocarcinoma: Peripheral nodule, scar carcinoma (from old scars)
• All: Gray-white firm mass, necrosis, hemorrhage

• Squamous: Keratinization (keratin pearls), intercellular bridges, pink squamous cells
• Adenocarcinoma: Glandular acini, mucin production, TTF-1 positive
• SCLC: Small cells ("oat cells"), scant cytoplasm, dark nuclei, salt-and-pepper chromatin, nuclear molding, no nucleoli, necrosis; Azzopardi effect (DNA encrustation on vessel walls)
• Large cell: Sheets of undifferentiated large cells, abundant cytoplasm, no keratinization/glands

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9. TUBERCULOSIS (TB)

• Mycobacterium tuberculosis (acid-fast bacillus, aerobic, slow-growing)
• Spread: Airborne droplets
• Risk factors: HIV/AIDS, malnutrition, diabetes, poverty, overcrowding, immunosuppression

• First exposure → Bacilli inhaled → Phagocytosed by alveolar macrophages → Macrophages cannot kill mycobacteria (waxy mycolic acid capsule) → Bacilli multiply intracellularly → T-cell activation (2-8 weeks) → Granuloma formation

• Latent TB reactivates (immunosuppression) → Usually apices of lung → Progressive caseation → Cavity formation → Spread

• Caseous necrosis: Cheese-like, yellow-white, crumbly material
• Ghon focus: Subpleural consolidation
• Progressive disease: Cavities (air-filled spaces) in upper lobes
• Healed: Calcified Ghon complex (Ranke complex)
• Military TB: Multiple 1-2 mm pale yellow granules throughout lung ("millet seeds")

• Caseating granuloma: Central eosinophilic (pink) amorphous caseous necrosis
• Epithelioid cells (activated macrophages with elongated nuclei, abundant pink cytoplasm)
• Langhans giant cells (nuclei arranged in horseshoe/peripheral pattern at margins)
• Outer zone: Lymphocytes + fibroblasts (fibrous rim)
• ZN (Ziehl-Neelsen) stain: Red/pink acid-fast bacilli on blue background

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10. CARCINOMA CERVIX (CA CERVIX)

• HPV (Human Papillomavirus) - most important cause; HPV types 16, 18 (high-risk)
• HPV 16 → Squamous cell carcinoma (more common)
• HPV 18 → Adenocarcinoma
• Multiple sexual partners, early sexual activity, smoking, immunosuppression, multiparity

• HPV infects transformation zone → HPV E6 protein degrades p53 → HPV E7 protein inactivates RB gene → Loss of tumor suppressors → Uncontrolled cell proliferation → CIN I → CIN II → CIN III → CIS → Invasive carcinoma

• Early: Not visible (detected by Pap smear)
• Late: Ulcerative/fungating/infiltrating mass at cervix
• Barrel-shaped cervix in advanced disease
• Bleeds easily on touch

• Squamous cell carcinoma (80%): Nests of squamous cells with keratin pearls, intercellular bridges, invasive through BM
• Adenocarcinoma (15-20%): Glandular pattern, mucin-secreting cells
• CIN I: Dysplastic cells in lower 1/3 of epithelium; koilocytes (HPV-infected cells - perinuclear halo + hyperchromatic irregular nucleus)
• CIN III/CIS: Full thickness dysplasia, BM intact

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11. ATHEROSCLEROSIS

• Non-modifiable: Age, male sex, family history, genetic factors
• Modifiable: Hypertension, hyperlipidemia (LDL), diabetes, smoking, obesity, sedentary lifestyle

1. Endothelial injury (by LDL, HTN, smoking) → Endothelial dysfunction
2. Monocyte adhesion to endothelium → Migrate to intima → Become Macrophages
3. Macrophages take up oxidized LDL (via scavenger receptors) → become Foam cells
4. Foam cells accumulate → Fatty streak (earliest lesion)
5. Smooth muscle cells migrate from media → Proliferate in intima → Produce collagen (fibrous cap)
6. Fibrous plaque forms (lipid core + fibrous cap)
7. Plaque rupture → thrombosis → MI/stroke

• Fatty streak: Flat, yellow streaks on intimal surface (earliest lesion, reversible)
• Fibrous plaque (atheroma): Raised, white/yellow elevated lesion; may be calcified
• Complicated plaque: Ulceration, calcification, hemorrhage into plaque, overlying thrombus

• Foam cells (lipid-laden macrophages) - early lesion
• Fibrous cap: SMCs + collagen + proteoglycans
• Necrotic lipid core: Cholesterol crystals (needle-shaped clefts), debris, foam cells
• Calcification (basophilic deposits)
• Lymphocytes in adventitia
• Cholesterol crystals (biconvex rhomboid clefts dissolved out during processing - empty spaces)

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12. INFLAMMATORY BOWEL DISEASE (IBD)

CROHN'S DISEASE vs ULCERATIVE COLITIS

• Transmural inflammation
• Non-caseating granulomas (40-60%)
• Fissures extending through wall
• Lymphoid aggregates throughout bowel wall

• Mucosal/submucosal inflammation only
• Crypt abscesses (neutrophils filling crypts) - characteristic
• Goblet cell depletion
• Mucosal ulceration
• Pseudopolyps (regenerating mucosa)
• Dysplasia in longstanding disease

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13. EMPHYSEMA

• Cigarette smoking (most common) - causes centriacinar emphysema
• Alpha-1 antitrypsin deficiency (A1AT) - causes panacinar emphysema
• Age (senile emphysema)

• Smoking → Neutrophil/macrophage influx → Release of elastase (destroys elastin) + MMP (destroys collagen) → Antiproteases overwhelmed (A1AT normally inhibits elastase) → Alveolar wall destruction → Air trapping

• Enlarged, hyperinflated lungs (barrel chest)
• Pale, voluminous
• Lungs don't collapse when chest opened
• Large bullae (>1 cm air spaces) visible on surface (especially in A1AT deficiency)

• Enlarged airspaces with destruction of alveolar walls
• Loss of alveolar septa (septa appear as floating wisps)
• Thin, attenuated walls
• No significant inflammation or fibrosis (unlike UIP)
• Loss of pulmonary capillary bed (contributes to cor pulmonale)

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14. PYELONEPHRITIS

• E. coli (most common - 85%) - due to P-fimbriae adhesin
• Proteus, Klebsiella, Enterococcus, Staphylococcus
• Risk factors: Female sex, urinary obstruction, urinary catheter, pregnancy, diabetes, vesicoureteric reflux

• Ascending route (most common): Bacteria from fecal flora colonize perineum → urethra → bladder → ureter → kidney (facilitated by VUR in children)
• Hematogenous (descending): Bacteremia → kidneys (less common; Staphylococcus)

ACUTE PYELONEPHRITIS:

• Enlarged kidney
• Abscesses: Small, yellow, raised streaks/wedge-shaped foci extending from medulla to cortex
• Purulent exudate in pelvis
• Hyperemic (red) cortex

• Suppurative inflammation - neutrophils in tubular lumina and interstitium
• Tubular necrosis with PMN casts
• Glomeruli and vessels relatively spared (early)
• Focal abscesses

CHRONIC PYELONEPHRITIS:

• Asymmetric, irregular coarse scarring (unlike diffuse fine scarring in glomerulonephritis)
• Broad U-shaped cortical scars overlying dilated, clubbed calyces
• Contracted, shrunken kidney

• Thyroidization (most characteristic): Tubules filled with pink homogeneous casts resembling thyroid colloid
• Interstitial fibrosis
• Glomerulosclerosis
• Lymphocytic interstitial infiltrate
• Periglomerular fibrosis

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15. NEPHRITIC vs NEPHROTIC SYNDROME

• 2-3 weeks after strep throat/skin infection
• Mechanism: Type III hypersensitivity (immune complex deposition)
• Gross: Enlarged, flea-bitten kidney (petechiae on surface)
• Microscopy: Diffuse hypercellular glomeruli (endothelial + mesangial proliferation); sub-epithelial humps (immunoglobulin deposits); neutrophil infiltrate; "humps" on EM
• IF: Granular IgG + C3 ("starry sky" pattern)

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16. INFECTIVE ENDOCARDITIS

• Acute IE: Staphylococcus aureus (most virulent, attacks normal valves)
• Subacute IE (SBE): Streptococcus viridans (less virulent, attacks damaged valves)
• Risk factors: Rheumatic heart disease, congenital heart disease, IV drug users, prosthetic valves, dental procedures

• Endothelial damage (turbulence, rheumatic disease) → Platelet + fibrin thrombus (sterile vegetation) → Bacteremia → Bacteria seed the thrombus → Infected vegetation forms → Valve destruction + emboli

• Acute IE: Large, bulky, destructive vegetations; valve leaflet perforation; abscess formation
• Subacute IE: Smaller vegetations; less destructive
• Vegetations on mitral valve (most common) then aortic valve
• IV drug users: Tricuspid valve (right-sided)

• Vegetations: Fibrin + platelets + bacteria + inflammatory cells
• Underlying valve: Necrosis, ulceration, inflammatory infiltrate
• Acute: Acute suppurative inflammation, abscess
• Subacute: Granulation tissue + chronic inflammation at base of vegetation

• Osler's nodes (painful tender nodules on fingers/toes)
• Janeway lesions (painless hemorrhagic spots on palms/soles)
• Roth's spots (retinal hemorrhages)
• Splinter hemorrhages (nail beds)

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17. PYOGENIC vs TUBERCULAR OSTEOMYELITIS

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18. GLOMERULONEPHRITIS

1. Immune complex deposition (Type III HSR) - most common
2. Anti-GBM antibodies (Type II HSR) - Goodpasture's disease
3. Pauci-immune (ANCA-associated)

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19. PEPTIC ULCER

• H. pylori infection (70-90% of duodenal ulcers; 65-75% of gastric ulcers) - most important
• NSAIDs (inhibit PGs → reduce mucus/bicarbonate → mucosal damage)
• Stress ulcers (Curling's ulcer - burns; Cushing's ulcer - head injury)
• Zollinger-Ellison syndrome (gastrinoma → massive acid secretion)

• H. pylori → Urease → NH3 → Neutralizes acid around bacteria → Survival → Releases toxins (VacA, CagA) → Disrupts mucosal barrier → Gastritis → Ulcer

• Round/oval punched-out ulcer with CLEAN edges
• Perpendicular (vertical) walls
• Smooth, flat base (due to granulation tissue)
• Surrounding mucosa folds radiate toward ulcer (contrast with malignant ulcer: raised everted edges, necrotic base)

1. Necrotic zone (top) - fibrinous exudate + necrotic debris
2. Inflammatory exudate zone - neutrophils
3. Granulation tissue zone - vessels + fibroblasts
4. Fibrous scar zone (base) - dense collagen

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20. GASTRIC vs DUODENAL ULCER (COMPARISON)

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21. PROSTATE CARCINOMA - GRADING + GLEASON GRADING

• Most common cancer in men (>65 years)
• Risk factors: Age, Black race, family history, BRCA2 mutations, high-fat diet, testosterone

• Androgen receptor signaling → Prostate epithelial cell proliferation → PTEN loss, ETS gene fusion (TMPRSS2-ERG) → Carcinoma development

• Firm, gritty, gray-white nodular mass
• Posterior zone of prostate (peripheral zone)
• Early: Not visible grossly; detected by biopsy
• Advanced: Hard, stony prostate on PR exam; spread to seminal vesicles, bladder, rectum

• Small glands, closely packed, back-to-back (no intervening stroma)
• Single cell lining (loss of basal cell layer - important diagnostic feature)
• Prominent nucleoli
• Intraluminal crystalloids (eosinophilic)
• Perineural invasion (diagnostic of malignancy)

• Based on glandular architecture (not cytology)
• Grade 1-5 assigned to the two most common patterns (primary + secondary)
• Gleason Score = Primary grade + Secondary grade (range 2-10)

• Grade 1: Uniform, round, well-separated glands
• Grade 3 (most common): Infiltrating separate glands, variable size
• Grade 4: Fused/ill-defined glands, cribriform pattern
• Grade 5: No gland formation, single cells, solid sheets

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22. WILMS' TUMOR (NEPHROBLASTOMA)

• Peak age: 3-4 years
• WT1 gene mutation (Wilms tumor gene 1 - chromosome 11p13)
• Associated syndromes:
  • WAGR syndrome: Wilms tumor + Aniridia + Genitourinary anomalies + mental Retardation
  • Beckwith-Wiedemann syndrome
  • Denys-Drash syndrome

• WT1 gene (tumor suppressor) mutation → Failure of normal nephroblast differentiation → Persistent embryonal tissue → Nephrogenic rests → Wilms tumor

• Large, solitary, well-encapsulated renal mass
• Soft, gray-white, fish-flesh cut surface
• Hemorrhage, cysts, necrosis
• Replaces most of kidney
• Unilateral in 95%

1. Blastemal component: Small, round, blue cells (primitive, undifferentiated - like small round blue cell tumor)
2. Epithelial component: Tubules and glomeruloid structures (attempted differentiation)
3. Stromal component: Spindle cells (mesenchyme-like)

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23. CELIAC DISEASE (GLUTEN-SENSITIVE ENTEROPATHY)

• Gluten/gliadin exposure
• Genetic: HLA-DQ2 (90%) or HLA-DQ8
• Autoimmune: Anti-tissue transglutaminase (anti-tTG) antibodies

• Gliadin → Deamidated by tissue transglutaminase → Presented by HLA-DQ2/DQ8 on APCs → CD4 T-cell activation → Th1 cytokines (IFN-γ, TNF) → Villous atrophy + Crypt hyperplasia → Malabsorption

• Small intestine: Loss of visible mucosal folds (flattened, smooth mucosa)
• Atrophic appearance

1. Villous atrophy (short, blunted, or absent villi - reduced surface area)
2. Crypt hyperplasia (deep, elongated crypts - compensatory)
3. Intraepithelial lymphocytes (IELs) >30 per 100 epithelial cells - most sensitive finding

• Lamina propria: Plasma cells, lymphocytes, eosinophils

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24. BRONCHIECTASIS

• Post-infectious: TB, whooping cough (most common causes globally), measles
• Cystic fibrosis (most common cause in developed countries)
• Immunodeficiency (recurrent infections)
• Bronchial obstruction (foreign body, tumor)
• Congenital: Kartagener's syndrome (immotile cilia - situs inversus + sinusitis + bronchiectasis)

• Persistent infection → Inflammation → Neutrophil elastase/MMP release → Destruction of bronchial wall elastic tissue and muscle → Bronchial dilation → Pooling of secretions → More infection ("vicious cycle")

• Dilated bronchi extending to pleural surface (normally don't reach pleura)
• Filled with purulent mucus
• Types: Cylindrical, Varicose, Saccular (most severe) dilation
• Lower lobes predominant (gravity-dependent pooling)

• Dilated bronchi with inflammatory exudate in lumen
• Destruction of bronchial wall: Loss of cartilage, smooth muscle, elastic tissue
• Ulceration of bronchial mucosa
• Squamous metaplasia of epithelium
• Peribronchial fibrosis
• Lymphocytic inflammation in wall

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25. ENDOMETRIAL HYPERPLASIA

• Unopposed estrogen (no progesterone counterbalance)
• Anovulatory cycles (PCOS), obesity (peripheral estrogen from fat), exogenous estrogen
• Estrogen-secreting tumors (granulosa cell tumor of ovary)
• Tamoxifen use (partial agonist at uterus)

• Excess estrogen → Continuous proliferative phase → Gland crowding → Hyperplasia → If PTEN mutation → Endometrial intraepithelial neoplasia (EIN) → Endometrioid carcinoma

1. Simple hyperplasia without atypia - cystic glands, low malignant potential (1%)
2. Complex hyperplasia without atypia - crowded glands, low risk (3%)
3. Simple hyperplasia with atypia - cytologic atypia, moderate risk (8%)
4. Complex hyperplasia with atypia - crowded + atypical cells; 29% risk of carcinoma

• Simple: Dilated (cystic) glands lined by columnar epithelium, normal stroma
• Complex: Back-to-back glands ("gland-in-gland"), reduced stroma
• Atypical: Round cells, prominent nucleoli, loss of polarity, increased N:C ratio

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26. EWING'S SARCOMA

• Peak age: 5-20 years (teenage boys most common)
• 2nd most common malignant bone tumor in children (after osteosarcoma)
• t(11;22) translocation → EWSR1-FLI1 fusion gene - PATHOGNOMONIC

• EWSR1-FLI1 fusion → Abnormal transcription factor → Primitive mesenchymal cell transformation → Small round blue cell tumor

• Destructive, gray-white soft mass in diaphysis
• Cortical destruction with periosteal elevation
• Soft tissue extension
• "Onion-skin" periosteal reaction (layers of reactive periosteum) - X-ray finding

• Small, round, blue cells (uniform, dark nuclei, scant cytoplasm)
• Arranged in lobules/sheets
• Homer-Wright pseudorosettes (cells arranged around central neurofibrillary core - in PNET component)
• PAS positive (glycogen in cytoplasm - important diagnostic feature)
• CD99 (MIC2) positive - immunohistochemistry
• No osteoid formation (unlike osteosarcoma)

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27. HEPATITIS B

• Parenteral: Blood transfusion, needle sharing (IV drug use), needlestick injury
• Sexual transmission (unprotected sex)
• Vertical (perinatal): Mother to child (most common mode in endemic areas)
• Hemodialysis patients, healthcare workers

• HBV infects hepatocytes → Cell-mediated immunity (CTLs) attack infected hepatocytes → Liver cell injury (NOT direct cytopathic; immune-mediated)
• Chronic infection → Cirrhosis → Hepatocellular carcinoma (HCC)
• HBsAg → If remains positive >6 months = Chronic carrier

• Acute: Enlarged, yellow-green liver (jaundice); soft
• Chronic/Cirrhosis: Shrunken, nodular, firm liver

• Hepatocyte swelling (ballooning degeneration)
• Acidophil bodies (Councilman bodies) = apoptotic hepatocytes (rounded, eosinophilic)
• Lobular disarray
• Lymphocytic infiltration in portal tracts

• Ground glass hepatocytes (HBsAg accumulation in SER - pale, homogeneous, pink cytoplasm) - PATHOGNOMONIC of HBV
• Portal tract fibrosis
• Interface hepatitis (piecemeal necrosis)
• Cirrhosis (bridging fibrosis → regenerative nodules)

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28. ACUTE APPENDICITIS

• Obstruction by fecalith (hardened feces) - most common in adults
• Lymphoid hyperplasia - most common in children
• Foreign body, worms (Oxyuris/Enterobius)

• Obstruction → Mucus secretion continues → Intraluminal pressure increases → Venous occlusion → Bacterial proliferation (E. coli, Bacteroides, others) → Inflammation → Neutrophil infiltration → Gangrene → Perforation → Peritonitis

• Early: Red, congested, swollen appendix; serosal surface dull
• Acute suppurative: Enlarged, tense, red-purple; fibrinopurulent exudate on serosa
• Gangrenous: Black-green discoloration; about to perforate
• Perforated: Hole visible, fecal peritonitis

• Neutrophil infiltration of the muscularis propria - DIAGNOSTIC (minimal diagnostic criterion)
• Congestion of submucosal vessels
• Ulceration of mucosa
• Edema of wall
• Fibrinopurulent periappendicitis on serosa
• Gangrenous appendicitis: Transmural necrosis, hemorrhage, bacteria in wall

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29. COPD (CHRONIC OBSTRUCTIVE PULMONARY DISEASE)

• Smoking (most important cause - 90% of cases)
• Air pollution, occupational dust, biomass fuel
• Genetic: Alpha-1 antitrypsin deficiency (emphysema component)

• Productive cough for at least 3 months in 2 consecutive years
• Mechanism: Smoking → Mucus hypersecretion → Infection → Chronic inflammation

• Thickened, edematous bronchial walls
• Mucus plugging
• Enlarged airways, purulent secretions

• Reid Index >0.5 (DIAGNOSTIC): Ratio of mucous gland thickness to bronchial wall thickness (normally <0.4; elevated due to mucous gland hypertrophy)
• Goblet cell hyperplasia (in small airways)
• Squamous metaplasia of bronchial epithelium
• Chronic inflammatory infiltrate (lymphocytes, macrophages)
• Smooth muscle hypertrophy

Blue Bloater (Chronic Bronchitis): Obese, cyanotic, edematous, productive cough Pink Puffer (Emphysema): Thin, pursed lips breathing, hyperinflated chest, minimal cyanosis

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30. TYPE I vs TYPE II DIABETES MELLITUS

• Type I: Insulitis (lymphocytic infiltration of islets), loss/absence of beta cells
• Type II: Amyloid deposition in islets (islet amyloid polypeptide = IAPP), reduced beta cell mass

• Microvascular: Diabetic nephropathy, Diabetic retinopathy, Diabetic neuropathy
• Macrovascular: MI, stroke, peripheral vascular disease
• Others: Recurrent infections, cataracts, Charcot's joint

• Kimmelstiel-Wilson lesion (nodular glomerulosclerosis) - PATHOGNOMONIC of DM
• Diffuse glomerulosclerosis (more common but less specific)
• GBM thickening

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31. RHEUMATIC FEVER + RHEUMATIC HEART DISEASE

• Group A beta-hemolytic Streptococcus (Strep. pyogenes) pharyngeal infection
• Autoimmune (molecular mimicry): Streptococcal M-protein antigens mimic cardiac proteins

• Strep pharyngitis → Antibodies form against M-protein → Cross-react with cardiac antigens (sarcolemmal proteins, tropomyosin) → Type II + IV HSR → Carditis, arthritis, chorea

• Major: Carditis, Migratory polyarthritis, Sydenham's chorea, Erythema marginatum, Subcutaneous nodules
• Minor: Fever, elevated ESR/CRP, prolonged PR interval, previous RF

• Focal collection of inflammatory cells around central area of fibrinoid necrosis
• Aschoff cells (Caterpillar/Owl-eye cells): Large macrophage-derived cells with distinctive nuclei
  • "Caterpillar" (Anitschkow cells): Ribbon-like chromatin in owl-eye arrangement
• Surrounded by lymphocytes + plasma cells
• Located in myocardium (interstitial) - myocarditis

• Mitral stenosis (most common valve lesion in RHD)
• "Fish mouth"/"Buttonhole" deformity of mitral valve (stenotic orifice)
• Thickened, fused, calcified valve leaflets
• Fusion of commissures
• Leaflets shortened, rigid; chordae tendineae fused + shortened

• Aschoff bodies in myocardium (acute phase)
• Fibrous thickening of valve leaflets
• Neovascularization of valve (new capillaries)
• Calcification (chronic)
• Vegetations on valve closure line (small, warty, 1-2mm - on ATRIAL surface of mitral valve)

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32. PORTAL HYPERTENSION

• Obstruction → Portal pressure rises → Portosystemic collateral vessels open → Varices → Complications

• Regenerative nodules surrounded by fibrous septa (bridging fibrosis)
• Loss of normal lobular architecture
• Fatty change, hepatocyte necrosis, inflammation
• Reticulin stain highlights fibrosis; Masson's Trichrome stains collagen blue

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33. SALIVARY GLAND TUMORS

• "Pleomorphic" = Two-component tumor:
  • Epithelial component: Duct-like structures (inner luminal cells)
  • Myoepithelial component: Outer myoepithelial cells
• Mesenchymal/stromal component: Chondroid (cartilage-like), myxoid, osteoid areas - MIXED/PLEOMORPHIC
• No atypia in benign form
• Incomplete encapsulation → recurrence if inadequate excision

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34. ASTHMA

• Lungs hyperinflated, don't fully deflate
• Mucus plugs throughout airways
• Thickened bronchial walls

• Curschmann spirals (whorled mucus plugs in airways)
• Charcot-Leyden crystals (crystallized eosinophil proteins - diamond-shaped)
• Eosinophilic infiltration of airway wall - HALLMARK
• Thickened basement membrane (subepithelial fibrosis)
• Smooth muscle hypertrophy
• Mucous gland hyperplasia
• Goblet cell hyperplasia

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35. DIABETIC NEPHROPATHY

• Hyperglycemia → Non-enzymatic glycosylation of GBM proteins → GBM thickening → Loss of anionic charge → Proteinuria
• Hyperfiltration → Glomerular hypertrophy → Eventually scarring
• AGE (Advanced Glycation End-products) → Mesangial expansion

• Early: Enlarged kidneys (hyperfiltration)
• Late: Shrunken, scarred (sclerosis)
• Waxy cortex

• Diffuse glomerulosclerosis: Diffuse increase in mesangial matrix (most common)
• Nodular glomerulosclerosis (Kimmelstiel-Wilson lesion): Ovoid/spherical hyaline nodules in peripheral mesangium - PATHOGNOMONIC
• GBM thickening
• "Capsular drop" lesion (hyaline deposit between Bowman's capsule and parietal epithelium)
• "Fibrin cap" lesion (hyaline on glomerular capillary wall)
• Arteriolosclerosis (hyaline arteriosclerosis) - affects BOTH afferent AND efferent arterioles (unique to DM)

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36. ANEURYSM

• Abdominal Aortic Aneurysm (AAA): Below renal arteries; >3 cm; Atherosclerosis; Risk of rupture (>5 cm)
• Berry (Saccular) Aneurysm: Circle of Willis; Congenital; Rupture → Subarachnoid hemorrhage
• Mycotic Aneurysm: Infected vessel wall (from bacteremia, IE)
• Syphilitic Aneurysm: Ascending aorta; Obliterative endarteritis of vasa vasorum → Media ischemia

• Saccular (berry-shaped, local bulge) or Fusiform (spindle-shaped, diffuse)
• May contain laminated thrombus
• Atherosclerotic plaque in wall

• Thinning + fibrosis of media
• Loss of elastic fibers (elastin breakdown)
• Atherosclerosis of intima
• Cystic medial necrosis (Marfan's): Loss of smooth muscle cells + elastic fibers in media; filled with mucoid material ("cystic" spaces)

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37. FIBROADENOMA (BREAST)

• Young women (15-35 years)
• Estrogen-sensitive (may enlarge in pregnancy)
• Lobular origin

• Well-encapsulated, mobile, rubbery, firm nodule
• "Breast mouse" (moves freely on palpation)
• Gray-white, whorled cut surface
• 1-3 cm usually

• Two patterns (intracanalicular vs pericanalicular):
  • Intracanalicular: Stroma compresses ducts into slit-like spaces ("antler-horn" pattern)
  • Pericanalicular: Stroma surrounds open, round ducts
• Benign epithelial cells lining glands (no atypia)
• Abundant fibrous stroma
• No mitoses

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38. CARCINOMA BREAST

• BRCA1 (chromosome 17q) + BRCA2 (chromosome 13q) mutations - hereditary (5-10%)
• Female sex, age, family history, early menarche, late menopause, nulliparity, obesity
• HER2/neu amplification, hormone receptor status

• Invasive Ductal Carcinoma (IDC) - NOS: Most common (75%) - no special features
• Invasive Lobular Carcinoma (ILC): 10%; Single-file ("Indian file") pattern; bilateral
• Ductal Carcinoma In Situ (DCIS): Pre-invasive; Comedo type has central necrosis
• Lobular CIS (LCIS): Marker of risk; not treated as cancer

• Hard, gritty, gray-white mass
• Irregular, stellate (star-shaped) outline (due to fibrotic reaction)
• Poorly defined borders
• Skin dimpling (ligament of Cooper involvement)
• Nipple retraction

• IDC: Irregular nests/cords/sheets of carcinoma cells in desmoplastic stroma; nuclear pleomorphism + mitoses
• ILC: Single-file arrangement (Indian file), targetoid pattern around ducts; small cells
• DCIS: Ductal structures filled with carcinoma cells, BM intact; Comedo type has central necrosis + calcification

1. Tubule formation
2. Nuclear pleomorphism
3. Mitotic count (Grade 1 = well; Grade 3 = poorly differentiated)

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39. BENIGN PROSTATIC HYPERPLASIA (BPH)

• Age-related (>50 years; present in 90% men >80 years)
• Androgens (DHT - Dihydrotestosterone) - main driver (5-alpha reductase converts testosterone → DHT)
• Estrogen may sensitize tissue to DHT

• Enlarged prostate (normal: 20g; BPH: 60-100g+)
• Multiple firm, rubbery nodules in central zone
• Cut surface: White-yellow nodules + cystic spaces

• Stromal hyperplasia: Increased fibromuscular stroma
• Glandular hyperplasia: Large irregular glands lined by two cell layers (inner columnar + outer basal)
• Papillary infoldings into gland lumina
• Corpora amylacea (concentric, calcified, laminated bodies in gland lumina) - characteristic but not specific

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40. AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD)

• ADPKD1: PKD1 gene (chromosome 16) - encodes Polycystin-1 (85% of cases; more severe)
• ADPKD2: PKD2 gene (chromosome 4) - encodes Polycystin-2 (15% of cases; milder)
• Autosomal dominant inheritance (50% chance per child)

• Mutant polycystin → Abnormal ciliary signaling in renal tubular cells → Tubular cell proliferation + fluid secretion → Cyst formation and growth → Compression of normal parenchyma → Renal failure

• Massively enlarged bilateral kidneys (can weigh >4 kg each!)
• Replaced by innumerable cysts of varying sizes
• Normal kidney architecture destroyed
• Cysts contain clear serous or hemorrhagic fluid

• Large cysts lined by flat to cuboidal epithelium
• Intervening compressed normal renal parenchyma
• Fibrosis in areas of compressed tissue

• Liver cysts (most common extrarenal - 30%)
• Berry aneurysms (intracranial - rupture = subarachnoid hemorrhage)
• Mitral valve prolapse
• Pancreatic cysts

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41. ADULT RESPIRATORY DISTRESS SYNDROME (ARDS)

• Direct (pulmonary) injury: Pneumonia, aspiration, inhalation of toxic gases, drowning
• Indirect (systemic) injury: Sepsis (most common cause overall), major trauma, burns, DIC, pancreatitis, massive transfusion

• Injury to alveolar epithelium (type I pneumocytes) + capillary endothelium → Increased permeability → Protein-rich fluid floods alveoli → Surfactant destroyed → Alveolar collapse → Hypoxemia → Cytokine storm perpetuates damage

1. Exudative phase (Day 1-7): DAD with edema + inflammation
2. Proliferative phase (Day 7-21): Type II pneumocyte proliferation (repair attempt)
3. Fibrotic phase (>21 days): Fibrosis replaces damaged tissue

• Heavy, wet, red-purple lungs ("liver-like")
• No airspace visible
• No foam (non-cardiogenic)

• Hyaline membranes (pink, glassy membranes lining alveolar ducts - PATHOGNOMONIC of ARDS)
• Intra-alveolar edema + fibrin
• Type I pneumocyte necrosis
• Type II pneumocyte hyperplasia (repair phase - cuboidal cells replace normal flat type I)
• Interstitial inflammation

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42. GLIAL TUMORS OF CNS

• Butterfly glioma (crosses corpus callosum)
• Variegated appearance: Gray-white + areas of hemorrhage (red) + yellow necrosis
• Infiltrative, no defined border

• Pseudopalisading necrosis (tumor cells lining up around necrotic areas) - PATHOGNOMONIC
• Glomeruloid microvascular proliferation (new vessel formation)
• High cellularity, pleomorphism, abundant mitoses
• Serpiginous necrosis

• "Fried egg" cells = Round nuclei with clear cytoplasm (artifact of fixation)
• Chicken-wire vasculature (delicate branching capillaries)
• Calcifications (psammoma-like)
• IDH mutation + 1p/19q deletion = better prognosis + chemoradiant sensitive

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43. ASCHOFF BODIES + CARDIAC LESIONS (RHEUMATIC FEVER)

• Central fibrinoid necrosis
• Surrounding Anitschkow cells (caterpillar cells) - pathognomonic
• Lymphocytes + plasma cells
• Aschoff giant cells (multinucleate macrophages)

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44. PYOGENIC vs TUBERCULAR MENINGITIS

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45. DM → COMPLICATIONS

DIABETES → 
├── MICROVASCULAR
│   ├── Nephropathy → Kimmelstiel-Wilson lesions → ESRD
│   ├── Retinopathy → Cotton-wool spots → Neovascularization → Blindness
│   └── Neuropathy → Peripheral + Autonomic neuropathy
├── MACROVASCULAR
│   ├── Atherosclerosis (accelerated) → MI, Stroke
│   └── Peripheral vascular disease → Diabetic foot + Gangrene
└── OTHERS
    ├── Infections (impaired immunity)
    ├── Cataracts + Glaucoma
    ├── Charcot's joint (neuropathic)
    └── Acanthosis nigricans (Type II DM)

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46. HEPATOCELLULAR CARCINOMA (HCC)

• Hepatitis B + C (most common causes worldwide)
• Cirrhosis (from any cause)
• Aflatoxin B1 (from Aspergillus flavus in stored grains - especially in Africa/Asia)
• Alcohol, NAFLD, Hemochromatosis, Wilson's disease
• Tumor marker: AFP (Alpha-fetoprotein) elevated in 75%

• Chronic hepatocyte injury → Regeneration → Accumulation of mutations (TP53, CTNNB1/β-catenin, TERT) → HCC
• HBV: HBx protein disrupts p53; integrates into genome

• Usually on background of cirrhosis
• Solitary or multinodular mass
• Yellow-green (bile-staining), soft, hemorrhagic
• Vascular invasion common (portal vein thrombosis)

• Cells resemble hepatocytes (large polygonal cells, prominent nucleoli, abundant granular cytoplasm)
• Trabecular (plate-like) pattern - most common
• Bile production by tumor cells (diagnostic)
• Mallory-Denk bodies may be present
• Vascular invasion (distinguishes from benign adenoma)
• CD10+, AFP+, HepPar-1+ (hepatocyte paraffin-1) on IHC

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47. GASTRITIS

ACUTE GASTRITIS:

• Etiology: NSAIDs (most common - reduce PGs), alcohol, stress, H. pylori (acute)
• Gross: Congested, edematous mucosa; superficial erosions; hemorrhagic streaks
• Microscopy: Neutrophilic infiltration of lamina propria + superficial epithelium; edema; mucosal erosion

CHRONIC GASTRITIS:

• Autoantibodies against parietal cells and intrinsic factor
• Affects body/fundus → Loss of parietal cells → Achlorhydria → Pernicious anemia (B12 deficiency)
• Gross: Atrophic, thinned gastric body mucosa
• Microscopy: Loss of parietal + chief cells; lymphocytic/plasma cell infiltrate; intestinal metaplasia; enterochromaffin-like cell hyperplasia

• H. pylori infects antrum preferentially
• Gross: Antral mucosa with thickened, nodular folds or erosions
• Microscopy: Neutrophils in crypts (cryptitis - active gastritis), H. pylori organisms visible on surface (curved rods), lymphoid follicles (lymphoid follicles = hallmark of H. pylori chronic gastritis)
• Giemsa/Warthin-Starry stain to identify H. pylori

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48. GIANT CELL TUMOR OF BONE (GCT)

• Young adults (20-40 years; after skeletal maturity)
• Slightly more common in females
• Most common site: Epiphysis of long bones (distal femur, proximal tibia, distal radius)
• "Around the knee" most common

• Neoplastic stromal cells express RANKL → Recruit and activate osteoclast precursors → Osteoclast-like giant cells → Bone destruction
• H3F3A mutations in stromal cells (p.Gly34Trp)

• Epiphyseal + metaphyseal lytic lesion extending to subchondral bone
• "Soap bubble" appearance on X-ray (expansile, multiloculated)
• Red-brown, soft, friable mass
• Hemorrhage and cystic spaces
• No clear margins (locally aggressive)

• Osteoclast-like giant cells (multinucleate, abundant cytoplasm, 50-100 nuclei/cell)
• Mononuclear stromal cells (spindle-shaped; the neoplastic component!)
• Evenly distributed giant cells throughout the stroma (not clustered around necrosis)
• Hemosiderin deposits
• No osteoid formation
• Reactive bone at periphery

Key point: The giant cells are REACTIVE (they're just osteoclasts recruited by the neoplastic stromal cells)

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QUICK STAIN REMINDER FOR SYSTEMIC PATHOLOGY

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HISTOPATH DIAGRAMS TO REMEMBER (As noted in your image - ★ MUST)

1. Coagulative necrosis - ghost cells, anucleate
2. Granuloma with Langhans giant cell - horseshoe nuclei
3. Reed-Sternberg cell - owl-eye nucleolus
4. Auer rods in AML
5. Kimmelstiel-Wilson lesion - nodular mesangial deposits
6. Hyaline membrane in ARDS
7. Pseudopalisading necrosis in GBM
8. Triphasic Wilms' tumor
9. Psammoma bodies in ovarian serous tumor
10. Call-Exner bodies in granulosa cell tumor
11. Indian file arrangement in lobular carcinoma breast
12. Barrett's esophagus with goblet cells
13. Crypt abscess in UC
14. Non-caseating granuloma in Crohn's/Sarcoidosis
15. Ground glass hepatocytes in Hepatitis B
16. Fried egg cells in oligodendroglioma
17. Aschoff body in rheumatic fever
18. Thyroidization of tubules in chronic pyelonephritis

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Exam Tip from your note: 5 marks = 8-9 points | 10 marks = 15 points | Histopath diagrams are a MUST ★