Granulomatous Inflammation

Definition & Cells - Granuloma Fortress Intro

• Granuloma: A focal, organized collection of activated macrophages (epithelioid cells), typically surrounded by a lymphocytic rim. Represents a chronic inflammatory response.
• Purpose: To contain or "wall off" persistent, poorly digestible injurious agents (e.g., M. tuberculosis, fungi, foreign material).
• Cellular "Bricks" of the Fortress:
  • Epithelioid Macrophages: Activated, modified macrophages; hallmark. Elongated, pale eosinophilic cytoplasm, indistinct cell borders.
  • Multinucleated Giant Cells (MGCs): Formed by fusion of epithelioid cells.
    • Langhans type: Nuclei arranged peripherally (horseshoe/ring).
    • Foreign body type: Nuclei scattered haphazardly.
  • Lymphocytes: Predominantly T-cells (CD4+ > CD8+), forming a collar.

⭐ The presence of epithelioid cells is the defining histological feature of a granuloma.

Types & Classification - Granuloma Varieties

• Immune Granulomas:
  • T-cell (CD4+ Th1) mediated; Type IV hypersensitivity.
  • Response to persistent, poorly soluble antigens.
  • Subtypes:
    • Caseating Granulomas:
      • Central amorphous, eosinophilic necrosis. 📌 "Caseous = Cheesy necrosis".
      • Examples: Tuberculosis (classic), Fungal (Histoplasma, Coccidioides), Syphilis (gumma).
      • Key: Loss of cellular detail in center.
    • Non-caseating Granulomas:
      • No central necrosis; cells intact.
      • Examples: Sarcoidosis, Crohn's disease, Tuberculoid leprosy, Berylliosis.

      • ⭐ In Sarcoidosis, look for Schaumann bodies (laminated calcium concretions) & Asteroid bodies (stellate inclusions within giant cells).

• Foreign Body Granulomas:
  • Reaction to inert materials (e.g., sutures, talc, silica, splinters).
  • Material often visible (may be birefringent under polarized light).
  • Foreign body giant cells engulf material; less lymphocytic infiltrate.

Pathogenesis - Making a Granuloma

• Initiation: Caused by indigestible antigens (e.g., M. tuberculosis, fungal hyphae, suture material) or T-cell mediated hypersensitivity.
• Mechanism - Immune Granuloma Formation:

• Key Mediators & Cells:
  • Macrophages: Activated by IFN-γ, transform into:
    • Epithelioid cells: Elongated, pink cytoplasm; primary function is secretion.
    • Giant cells: Fusion of epithelioid cells (e.g., Langhans, foreign body type).
  • CD4+ Th1 cells: Orchestrate response via IFN-γ.
  • Cytokines:
    • IFN-γ: Prime macrophage activator.
    • TNF-α: Essential for recruiting macrophages and maintaining granuloma structure.
    • IL-12: Drives Th1 differentiation.

⭐ TNF-α inhibitors, used for autoimmune diseases, can disrupt granulomas and lead to reactivation of latent tuberculosis.

Associated Diseases - Granuloma Rogues' Gallery

• Infectious:
  • Bacterial:
    • Tuberculosis (TB): Caseating necrosis; Langhans giant cells. AFB positive.
    • Leprosy: Tuberculoid (non-caseating), Lepromatous (foamy macrophages).
    • Syphilis (tertiary): Gumma (central coagulative necrosis).
    • Cat-scratch disease (Bartonella henselae): Stellate, necrotizing granulomas.
  • Fungal: (e.g., Histoplasmosis, Coccidioidomycosis, Blastomycosis): Caseating or non-caseating. PAS/GMS+.
  • Parasitic: (e.g., Schistosomiasis): Granulomas around ova; eosinophils.
• Non-Infectious:
  • Immune-Mediated:
    • Sarcoidosis: Non-caseating. Bilateral hilar lymphadenopathy. Schaumann/Asteroid bodies. ↑Serum ACE.
    • Crohn's Disease: Non-caseating granulomas in bowel wall.
    • Granulomatosis with Polyangiitis (Wegener's): Necrotizing; respiratory tract, kidneys; c-ANCA+.
  • Foreign Body: (e.g., Sutures, talc, beryllium-Berylliosis): Around material.
  • Idiopathic: (e.g., Granuloma annulare): Dermal.

⭐ Sarcoidosis is a multisystem disorder characterized by non-caseating epithelioid granulomas, frequently involving bilateral hilar lymphadenopathy and elevated serum Angiotensin-Converting Enzyme (ACE).

High‑Yield Points - ⚡ Biggest Takeaways

• Granulomatous inflammation: Chronic inflammation with aggregates of epithelioid macrophages.
• Features epithelioid histiocytes, Langhans and Foreign body giant cells.
• Caseating granulomas (e.g., Tuberculosis) have central necrosis; Non-caseating (e.g., Sarcoidosis) do not.
• Mediated by Type IV hypersensitivity; IFN-γ from Th1 cells is crucial.
• Key causes: Tuberculosis, Sarcoidosis, fungal infections, Crohn's disease, leprosy.
• Look for Schaumann and Asteroid bodies in Sarcoidosis.