Granulomatous Inflammation

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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. Histopathology of Granuloma

⭐ 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.

Necrotizing Granuloma Diagram and Microscopic Views

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.

  • Infectious:
    • Bacterial:
      • Tuberculosis (TB): Caseating necrosis; Langhans giant cells. AFB positive. Langhans giant cell in granulomatous inflammation
      • 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. Asteroid bodies in sarcoidosis histology
      • 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.

Practice Questions: Granulomatous Inflammation

Test your understanding with these related questions

A 45-year old patient presented with fever, night sweats and weight loss. On X-ray, a mass was seen in apical lobe. On histopathology, caseous necrosis was present. What is the name of underlying process?

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Flashcards: Granulomatous Inflammation

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Acute inflammation arises in response to _____ or tissue necrosis

TAP TO REVEAL ANSWER

Acute inflammation arises in response to _____ or tissue necrosis

infection

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