Granuloma Histopathology and Clinical Correlates

Histologic Composition

Granulomas are composed of loose clusters of epithelioid cells and multinucleated histiocytes, representing the core cellular elements of these lesions. 1, 2
Lymphocytes typically surround the central macrophage aggregates, with CD4⁺ T‑cells positioned centrally and CD8⁺ T‑cells and B‑cells located at the periphery. 3

Well‑formed granulomas display tightly packed epithelioid cells with distinct borders and are characteristic of sarcoidosis, where they may coalesce along lymphatic pathways. 3, 4
Poorly‑formed granulomas consist of loose aggregates of epithelioid cells and multinucleated histiocytes and are typically observed in hypersensitivity pneumonitis. 1, 2, 5

Non‑necrotizing (non‑caseating) granulomas lack central necrosis and are a hallmark of sarcoidosis, although they appear in a broad differential diagnosis. 3

Granulomas are most often located within the interstitium of the lung but may also be present within airspaces. 1, 2
In pulmonary tissue, granulomas frequently show a peribronchiolar distribution, a pattern especially common in hypersensitivity pneumonitis. 1, 6

Granulomas may contain cholesterol clefts. 1, 5
Schaumann bodies are occasionally identified within granulomas, occurring more often in sarcoidosis. 1, 5
Birefringent oxalate crystals can be present in granulomas, also more frequently associated with sarcoidosis. 1, 5

Mycobacterial infections (including tuberculosis and atypical mycobacteria) characteristically produce robust, frequently necrotizing granulomas. 4, 7

Sarcoidosis is a non‑infectious granulomatous disease that typically yields non‑necrotizing, well‑formed granulomas. 3, 4
Hypersensitivity pneumonitis represents a non‑infectious hypersensitivity reaction that commonly generates poorly‑formed granulomas with a peribronchiolar distribution. 1, 2, 5
Connective‑tissue autoimmune diseases can give rise to granulomatous inflammation. 5
Certain drug toxicities are capable of inducing granuloma formation. 5