A non-caseating granuloma in sarcoidosis contains epithelioid macrophages and Langhans giant cells. What is the primary cellular mechanism forming multinucleated giant cells?

• A Neutrophil degeneration and fusion of nuclear fragments
• B B-lymphocyte proliferation in response to insoluble antigen
• C Eosinophil activation by IL-5 in response to parasites
• D IFN-gamma–driven macrophage fusion and maturation into epithelioid cells ✓

Explanation

Granulomas form when macrophages cannot eliminate an antigen and accumulate, driven by Th1-derived IFN-gamma, which activates macrophages to become epithelioid cells and fuse into multinucleated giant cells. IL-12 from macrophages drives the Th1 response. Giant cell formation requires macrophage-macrophage fusion, not neutrophil or B-cell involvement. Eosinophil/IL-5 axis is relevant to parasite-associated granulomas but is not the principal mechanism in immune granulomas.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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