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PA3.3 | Chronic & Granulomatous Inflammation — SDL Guide (Part 2)

Non-specific (Diffuse) Chronic Inflammation

A three-panel pathology diagram shows diffuse chronic inflammation with scattered macrophages, lymphocytes, plasma cells, fibrosis, absence of granulomas, and common clinical examples. — **Panel A:** Diffuse lymphoplasmacytic infiltrate, macrophage, lymphocyte, plasma cell, fibrosis, disrupted tissue architecture. **Panel B:** Scattered infiltrate, no granuloma formation, no discrete nodular aggregate, crossed-out organized granuloma. **Panel C:** Chronic active gastritis with H. pylori, chronic pyelonephritis, chronic cholecystitis, rheumatoid arthritis synovitis with pannus, caution that absence of granulomas does not imply mild disease.

In non-specific chronic inflammation (also called diffuse chronic inflammation), the inflammatory infiltrate of macrophages, lymphocytes, and plasma cells is scattered throughout the tissue without forming organised structures.

Features:
• No granuloma formation
• Accompanying fibrosis often marks the chronic phase
• Tissue architecture is disrupted but no discrete nodular aggregates

Examples:
• Chronic active gastritis (H. pylori) — diffuse lamina propria lymphoplasmacytic infiltrate
• Chronic pyelonephritis — diffuse lymphocytic and plasma cell infiltrate in renal cortex/medulla
• Chronic cholecystitis — lymphocytes and fibrosis in gallbladder wall
• Chronic synovitis in rheumatoid arthritis — diffuse lymphoplasmacytic infiltrate with pannus formation

The absence of granulomas does NOT mean mild disease — chronic non-specific inflammation in rheumatoid arthritis destroys joints; in H. pylori gastritis it leads to gastric adenocarcinoma over decades.

The Granuloma — Definition and Structure

A granuloma is a focal area of granulomatous inflammation characterised by an aggregate of activated macrophages (epithelioid histiocytes), often surrounded by lymphocytes, with or without central necrosis.

Core components:

Epithelioid histiocytes — the defining cells. Pale, eosinophilic, abundant cytoplasm; vesicular (open-face) nucleus; reduced phagocytic capacity but enhanced secretory function (TNF-α, IL-12).

2. Multinucleate giant cells — formed by fusion of epithelioid histiocytes. Two patterns:
• Langhans giant cells: Nuclei arranged in a horseshoe or peripheral ring. Classic for TB and fungal infections.
• Foreign-body giant cells: Nuclei randomly scattered ("jumbled") throughout cytoplasm. Seen around non-digestible foreign material (sutures, talc, silica).

Lymphocytic cuff — CD4+ Th1 cells surrounding the epithelioid aggregate, maintaining macrophage activation via IFN-γ.

Central necrosis — present in caseating granulomas (see next section); absent in non-caseating types.

Fibroblasts and collagen — at the periphery in older or resolved granulomas.

A labelled medical diagram shows the structure of a granuloma, including epithelioid histiocytes, Langhans giant cells, lymphocytic cuff, central necrosis, and peripheral fibrosis. — **Panel A:** Well-formed granuloma showing epithelioid histiocytes, Langhans giant cell, peripheral horseshoe nuclei, lymphocytic cuff, central caseous necrosis, and peripheral fibrosis.. **Panel B:** Epithelioid histiocyte morphology with pale eosinophilic cytoplasm, vesicular open-face nucleus, TNF-alpha secretion, IL-12 secretion, and reduced phagocytic capacity.. **Panel C:** Comparison of Langhans giant cell with peripheral horseshoe nuclei versus foreign-body giant cell with randomly scattered nuclei.. **Panel D:** CD4+ Th1 lymphocytes maintaining macrophage activation through IFN-gamma, with fibroblasts and collagen at the granuloma periphery..

Giant Cell Types — Langhans vs Foreign-Body

Recognising the two giant cell types at microscopy is a high-yield, frequently examined skill.

Feature	Langhans Giant Cell	Foreign-Body Giant Cell
Nuclear arrangement	Peripheral horseshoe or ring	Randomly scattered (central and peripheral)
Size	Large (up to 40–50 µm)	Large, often irregular shape
Number of nuclei	15–20+	20–100+
Associated granuloma	Caseating (TB) or non-caseating (fungal, sarcoid)	Non-caseating
Clinical context	Infectious or immune-mediated	Foreign material (suture, silica, talc, prosthesis)

Memory peg: Langhans → Lined-up nuclei (horseshoe). Foreign-body → Free-floating nuclei (random).

Both types form by fusion of epithelioid histiocytes under IL-4, IL-13, and IFN-γ signalling.

Side-by-side histology diagram comparing Langhans giant cells with peripheral horseshoe nuclei and foreign-body giant cells with randomly scattered nuclei. — **Panel A:** Langhans giant cell with abundant eosinophilic cytoplasm, peripheral horseshoe or ring arrangement of 15–20+ nuclei, surrounding epithelioid histiocytes, granuloma context, optional subtle caseous necrosis, clinical labels for TB, fungal infection, sarcoid, and immune-mediated disease.. **Panel B:** Foreign-body giant cell with irregular outline, 20–100+ randomly scattered central and peripheral nuclei, adjacent foreign material fragment, surrounding non-caseating foreign-body granuloma, clinical labels for suture, silica, talc, and prosthesis.. **Panel C:** Memory peg icons showing Langhans as lined-up horseshoe nuclei and foreign-body as free-floating random nuclei, plus epithelioid histiocyte fusion pathway mediated by IL-4, IL-13, and IFN-γ..