🧠 Granuloma Formation for USMLE Step 1: Immune Mechanism, Histology, and Disease Associations
A granuloma is a collection of activated macrophages (epithelioid cells) surrounded by lymphocytes. It represents the immune system's attempt to contain a persistent antigen that it cannot clear. Step 1 loves to test:
Granuloma types (caseating vs non-caseating)
Mechanism and histology
Diseases that form granulomas
🔬 What Triggers Granuloma Formation?
| Step | Action |
|---|---|
| 1 | Persistent antigen activates macrophages |
| 2 | Macrophages present antigen to CD4⁺ Th1 cells |
| 3 | Th1 cells secrete IFN-γ → activates macrophages |
| 4 | Macrophages become epithelioid and multinucleated giant cells |
| 5 | Lesion surrounded by lymphocytes and fibroblasts |
💡 Mechanism = Type IV (delayed) hypersensitivity
📘 Histology Hallmarks
| Cell Type | Description |
|---|---|
| Epithelioid histiocytes | Activated macrophages with pink cytoplasm |
| Multinucleated giant cells | Fused macrophages; common in TB and fungal infections |
| Langhans giant cells | Peripheral, horseshoe-shaped nuclei |
| Central necrosis | Seen only in caseating granulomas |
🔍 Caseating vs Non-Caseating Granulomas
| Type | Center | Examples |
|---|---|---|
| Caseating | Necrotic, cheese-like | TB, histoplasmosis |
| Non-Caseating | Solid, no necrosis | Sarcoidosis, Crohn's, berylliosis |
🧠 Caseous = cheese-like necrosis
🧠 Non-caseous = clean, tight macrophage ring
🧪 Diseases That Cause Granulomas
| Category | Diseases |
|---|---|
| Infectious | Tuberculosis, leprosy, fungal infections, syphilis |
| Autoimmune | Sarcoidosis, Crohn’s disease, GPA |
| Inorganic | Berylliosis, silicosis |
| Parasitic | Schistosomiasis |
🧠 Mnemonics
“Gran-U-Late = Gather Up Lymphocytes And T-cell Effects”
“CASE for TB” = CAseating, Silicosis, Extracellular antigen (TB)
⚠️ USMLE Clinical Clue
A 33-year-old woman presents with bilateral hilar lymphadenopathy. Biopsy reveals tight, non-necrotizing granulomas. What’s the most likely diagnosis?
✅ Answer: Sarcoidosis
✅ Clue: Non-caseating granulomas + hilar lymph nodes + African-American woman
📚 Final Summary Table
| Feature | Caseating | Non-Caseating |
|---|---|---|
| Necrosis | Yes | No |
| Classic cause | TB | Sarcoidosis |
| Pathogen presence | Usually | Rare |
| Histology | Central acellular debris | Compact epithelioid cell core |
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