Granuloma

A granuloma is a structured collection of immune cells formed to wall off substances perceived as foreign but difficult to eradicate. It is typically composed of aggregates of epithelioid histiocytes (activated macrophages), sometimes fused into multinucleated giant cells, usually surrounded by a ring of lymphocytes, and often with a peripheral layer of fibroblasts and connective tissue. Central necrosis may be present in caseating granulomas.

Formation and function: Granulomas arise from a T helper 1 cell–mediated immune response with interferon-gamma–driven macrophage activation. The aim is to contain persistent stimuli that the immune system cannot readily eliminate.

Common types: Caseating (necrotizing) granulomas have a central necrotic area and are typical of tuberculosis and some fungal infections. Noncaseating granulomas lack central necrosis and are seen in conditions such as sarcoidosis, berylliosis, Crohn disease, and reactions to certain foreign materials.

Etiologies: Infectious agents (Mycobacterium tuberculosis complex, Mycobacterium leprae, certain fungi like Histoplasma), autoimmune and autoinflammatory diseases (notably sarcoidosis), hypersensitivity to inhaled inorganic particles, foreign-body reactions (silica, talc), and some drug reactions.

Diagnosis: Histopathology is central to diagnosis. Special stains (Ziehl-Neelsen for acid-fast bacteria; PAS or Grocott for fungi), cultures, and molecular tests aid identification. Clinical context and imaging support the diagnostic process.

Clinical significance: Granulomas indicate chronic granulomatous inflammation and can affect organ function when extensive. Treatment targets the underlying cause; infectious etiologies require antimicrobial therapy, while noninfectious granulomatoses may require immunosuppression or supportive care.