Inflammation morphology: acute and chronic patterns, giant cell types

Overview

• Recognising distinct morphological patterns of inflammation is fundamental in anatomical pathology.
• Rather than a single uniform process, inflammation encompasses a spectrum of tissue reactions whose pattern reflects the nature of the injurious agent, the tissue involved, the severity of injury, and the host immune status.
• Acute patterns are dominated by vascular changes and neutrophilic exudation; chronic patterns by mononuclear cell infiltration, tissue remodelling, and, in specific circumstances, granuloma formation.
• Pattern recognition allows generation of a meaningful differential diagnosis from morphology alone.

Acute Inflammatory Patterns

The cardinal vascular and cellular responses of acute inflammation (vasodilation, increased permeability, neutrophil recruitment) underlie all acute patterns; specific morphological subtypes are superimposed depending on site and aetiology.

Serous Inflammation

• Definition: Exudation of cell-poor fluid into body cavities or tissue planes, without significant neutrophilic infiltration.
• Mechanism: Increased vascular permeability allows plasma-derived fluid to accumulate; few leukocytes present. Fluid may be derived from plasma or mesothelial secretion.
• Gross: Clear to straw-coloured effusion in pleural, pericardial, or peritoneal spaces; skin blisters.
• Histology: Sparse inflammatory cells; mesothelial reactive changes; no significant fibrin deposition.
• Associations: Early viral infections (e.g. viral pericarditis, mild lymphocytic infiltrate in epipericardial fat), skin blisters, tumour-associated effusions (neoplastic cells may be identified).
• Outcome: Usually resolves without sequelae; organisation to fibrous adhesions is rare.

Fibrinous Inflammation

• Definition: Exudate rich in fibrinogen that polymerises to form fibrin strands on serosal surfaces or within body cavities.
• Mechanism: More severe vascular injury allows high-molecular-weight proteins (including fibrinogen) to escape; local activation of the coagulation cascade.
• Gross: Shaggy "bread-and-butter" appearance on pericardial surfaces; rough, matt pleural surfaces.
• Histology: Eosinophilic meshwork of threads or amorphous coagulum admixed with inflammatory cells; underlying tissue shows congestion and early neutrophilic infiltrate.
• Associations: Acute MI, Dressler syndrome (postinfarction autoimmune pericarditis appearing weeks after MI), uraemia, rheumatic fever, SLE, bacterial pneumonia (fibrinous pleuritis), radiation injury, routine cardiac surgery.
• Outcome: Fibrinolysis → resolution; or organisation by ingrowth of fibroblasts and capillaries → fibrous adhesions, constrictive pericarditis, or pleural symphysis.

Suppurative (Purulent) Inflammation

• Definition: Exudate dominated by neutrophils with liquefactive necrosis, producing pus (neutrophils + cellular debris + proteinaceous fluid).
• Mechanism: Pyogenic bacteria (Staphylococcus aureus, streptococci, gram-negative rods) secrete toxins and enzymes causing liquefactive necrosis; potent chemotactic signals recruit neutrophils.
• Gross: Creamy yellow-green exudate; abscess = walled-off collection of pus with central liquefaction.
• Histology:
  • Diffuse suppurative: Sheets of neutrophils permeating tissue (e.g. acute appendicitis, lobar bronchopneumonia, suppurative pericarditis, acute pyelonephritis with neutrophil casts in tubules).
  • Abscess: Central zone of necrotic leukocytes and debris; surrounding rim of viable neutrophils; outer zone of granulation tissue with vascular dilation and fibroblastic proliferation.
• Associations: S. aureus skin/visceral abscesses; acute appendicitis; bacterial pericarditis (via direct extension from empyema, lobar pneumonia, mediastinal infection, haematogenous seeding, lymphatic extension, or cardiotomy); empyema; pyonephrosis; perinephric abscess; suppurative arthritis.
• Outcome: Spontaneous or surgical drainage; or walling off → chronic abscess with fibrous wall.

Haemorrhagic Inflammation

• Definition: Exudate with prominent red cell extravasation, reflecting severe vascular injury or erosion of vessel walls.
• Histology: Abundant erythrocytes admixed with inflammatory cells; haemosiderin-laden macrophages in resolving lesions.
• Associations: Necrotising fasciitis, anthrax, plague (Yersinia pestis), haemorrhagic pancreatitis, Waterhouse-Friderichsen syndrome (bilateral adrenal haemorrhage in meningococcal sepsis), haemorrhagic viral fevers.

Pseudomembranous Inflammation

• Definition: Necrotic mucosal surface covered by a confluent membrane of fibrin, necrotic epithelium, and neutrophils anchored to the underlying ulcerated base.
• Gross: Grey-white to yellow adherent membrane overlying denuded mucosa; peels away leaving ulcerated base.
• Histology: Superficial mucosal necrosis, neutrophilic infiltrate, fibrin, and cellular debris forming the pseudomembrane.
• Distinction from true membrane: True membranes (diphtheria) incorporate viable host tissue; pseudomembranes consist of exudate adherent to necrotic mucosa.

Summary Table: Acute Inflammation Patterns

Chronic Inflammatory Patterns

• Chronic inflammation is characterised by a predominance of mononuclear cells, macrophages, lymphocytes, and plasma cells, often with concurrent tissue destruction and attempted repair (fibrosis).
• It may follow unresolved acute inflammation or arise de novo as a primary event.

General Chronic Inflammation (Lymphoplasmacytic)

• Histology: Lymphocytes, plasma cells, and macrophages; fibroblasts and new capillaries (granulation tissue); variable degrees of fibrosis. Neutrophil polymorphs are absent or sparse.
• CD4+ T-cell subsets driving chronicity:
  • Th1 → IFN-γ → classical macrophage activation → granulomatous/cell-mediated inflammation
  • Th2 → IL-4, IL-5, IL-13 → eosinophil recruitment; alternative macrophage activation; helminth and allergic responses
  • Th17 → IL-17 → chemokine secretion → neutrophil/monocyte recruitment (acute-on-chronic)
• Examples: Chronic peptic ulcer (base: fibrosis, plasma cells, lymphocytes, residual neutrophils); chronic pyelonephritis (tubular atrophy, interstitial fibrosis, patchy lymphoplasmacytic infiltrate with intervening preserved parenchyma, "jigsaw pattern"); chronic cholecystitis (lymphocytic infiltrate, replacement of muscularis by fibrous tissue, from recurrent acute episodes).

Granulomatous Inflammation

• A morphologically distinct form of chronic inflammation defined by aggregates of activated macrophages (epithelioid histiocytes), accompanied by lymphocytes, variable multinucleated giant cells, and variable necrosis.
• Represents a cellular attempt to contain an agent that resists eradication; requires strong T-cell-mediated (Th1) immunity.

Key cellular components:

• Epithelioid cells: Activated macrophages; abundant pale-pink granular cytoplasm; indistinct cell borders; elongated vesicular nuclei with small nucleoli, resembling epithelial cells. Surrounded by a collar of lymphocytes.
• Langhans giant cells: Fusion of activated macrophages; 40-$50\ \mu\text{m}$ diameter; peripheral horseshoe or ring arrangement of nuclei around abundant cytoplasm.
• Foreign body giant cells: Haphazardly ("scrambled egg") arranged nuclei; response to indigestible foreign material.
• Fibrous rim: Present in older/resolving granulomas.

Caseating vs. non-caseating granulomas:

Causes of granulomatous inflammation, systematic:

Eosinophilic Inflammation

• Mechanism: Th2-driven (IL-4, IL-5, IL-13) eosinophil recruitment; IgE-mediated mast cell degranulation; eosinophil major basic protein causes tissue injury.
• Histology: Sheets or clusters of eosinophils (bilobed nuclei, bright eosinophilic granular cytoplasm); Charcot-Leyden crystals (eosinophil membrane degradation products) may be present.

Plasma Cell-Rich Chronic Inflammation

• Histology: Sheets or aggregates of plasma cells (clock-face/cartwheel chromatin, eccentric nucleus, perinuclear hof); Russell bodies (intracytoplasmic Ig accumulation); Dutcher bodies (intranuclear pseudoinclusions of Ig).

Giant Cell Types and Associated Diseases