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🫁 Pathology of Tuberculosis — Robbins (One Page)

Robbins & Kumar Basic Pathology, Chapter 11

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THE BIG PICTURE (One-Line Memory Anchor)

"MTB enters → MAC responds → Granuloma forms → Caseous CENTER → Fate depends on IMMUNITY"

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1. The Bug

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2. The Core Lesion — GRANULOMA

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3. How the Granuloma Forms — Immunopathology

MTB inhaled → macrophage engulfs it (phagocytosis)
      ↓
MTB survives inside phagosome (blocks phagolysosome fusion)
      ↓
Macrophage presents antigen → activates CD4 T cells (Th1)
      ↓
Th1 releases IFN-γ → activates macrophages fully
      ↓
Activated macrophages → become Epithelioid cells + fuse → Langhans giant cells
      ↓
TNF recruits more cells → GRANULOMA WALL forms
      ↓
Center gets necrotic (hypoxia + toxic macrophage products) → CASEOUS NECROSIS

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4. Primary vs Secondary TB

PRIMARY TB (First Infection)

• Inhaled droplet → lower/mid lung (better ventilated zones)
• Ghon focus = small subpleural granuloma (usually right lung, lower lobe)
• Spreads to hilar lymph nodes → lymph node caseates
• Ghon focus + hilar node = Ghon Complex (also called Primary Complex / Ranke Complex)
• In 95% of immunocompetent people: heals with fibrosis + calcification → becomes the Ghon complex scar visible on CXR
• Bacilli may remain dormant for decades → latent TB

SECONDARY TB (Reactivation / Reinfection)

• Occurs years later when immunity drops (HIV, steroids, diabetes, malnutrition, age)
• Always in the apex of the upper lobe (Simon's focus — seeded during primary bacteremia)
• Much more destructive — larger cavities, more caseation

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5. Morphological Spectrum — What Happens to the Granuloma?

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6. Cavitary TB (The Dangerous Phase)

• Caseous center liquefies (lots of bacteria, ideal for MTB growth)
• Erodes into bronchus → cavitation → organisms enter airway → patient becomes infectious
• Cavity walls: inner layer (necrotic debris) + middle (epithelioid granuloma) + outer (fibrosis)
• Rasmussen aneurysm = erosion into pulmonary artery → massive hemoptysis

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7. Miliary TB

• Hematogenous spread → 1–2 mm yellow-white granulomas scattered like millet seeds in:
  • Lungs, liver, spleen, bone marrow, meninges, kidneys, adrenals
• Seen in immunocompromised or untreated primary TB
• On CXR: "snowstorm" pattern

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8. Histology — What You See Under the Microscope

• Caseating granuloma: Pale pink (eosinophilic) structureless center = caseous necrosis
• Surrounded by epithelioid macrophages (elongated, pink, footprint-shaped nuclei)
• Langhans giant cells: multinucleated, nuclei arranged at periphery in horseshoe/crescent pattern
• Outer lymphocytic cuff
• Ziehl-Neelsen stain: bacilli appear as red rods on blue background (acid-fast)

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9. Special Situations

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10. The MASTER MNEMONIC — TB Pathology in One Shot

"A MAC GIRL Lives in a CAVE"

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Quick Summary Table

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🫁 Pathology of Malignant Mesothelioma — Robbins (One Page)

Robbins & Kumar Basic Pathology + Robbins, Cotran & Kumar Pathologic Basis of Disease

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THE ONE-LINE ANCHOR

"Asbestos → 25–40 years → Pleural RIND → Epithelial / Sarcomatoid / Biphasic → Uniformly Fatal"

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1. What Is It?

• Pleura (most common — 90%)
• Peritoneum
• Pericardium
• Tunica vaginalis (rare)

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2. Cause — Asbestos (The Star)

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3. Pathogenesis — How Asbestos Causes It

Asbestos fibers inhaled
      ↓
Fibers accumulate near mesothelial cell layer
      ↓
Generate Reactive Oxygen Species (ROS)
      ↓
DNA damage → driver mutations accumulate over decades
      ↓
Key mutations:
  • CDKN2A deletion (chr 9p) — ~80% of cases → loss of cell cycle control
  • NF2 mutation → disrupts cell signaling
  • BAP1 mutation → disrupts DNA repair (also germline = familial mesothelioma)
      ↓
Malignant transformation of mesothelial cells

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4. Gross Morphology (Macroscopic)

• Begins localized → spreads by contiguous growth OR diffuse pleural seeding
• Affected lung becomes ensheathed by a thick layer of yellow-white, firm, gelatinous tumor = the classic "pleural rind"
• Obliterates the pleural space
• May directly invade thoracic wall or subpleural lung tissue
• Distant metastases are uncommon (this is a local disease)
• Often preceded by pleural fibrosis and plaques (visible on CT)
• Pleural effusion almost always present (often massive, recurrent, hemorrhagic)

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5. Microscopic Types (Histology)

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6. The BIG Diagnostic Challenge — Mesothelioma vs Adenocarcinoma

Rule of thumb: Calretinin = mesothelioma's signature stain (nuclear + cytoplasmic positivity)

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7. Clinical Features

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8. Peritoneal Mesothelioma (Quick Note)

• Related to heavy asbestos exposure in 60% of males
• Causes intestinal involvement → death from obstruction or inanition
• Half of cases remain confined to abdominal cavity

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9. MASTER MNEMONIC — Everything in One

"ASBESTOS KILLS PLEURA — CAP the Diagnosis"

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Quick Comparison Card

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• Year 0 → Asbestos fiber inhalation (occupational exposure)
• Weeks–Months → Fibers deposit near the mesothelial cell layer (never cleared)
• Months–Years → ROS generation → DNA strand breaks
• Years → Driver mutations accumulate: CDKN2A (80%), NF2, BAP1
• 25–45 year silent latency → No symptoms while mutations build up
• Year 25–45 → Malignant Mesothelioma emerges (Epithelioid / Sarcomatoid / Biphasic)
• Outcome → Median survival 12–18 months