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

Sources

• RCPA manual & guidelines (Royal College of Pathologists of Australasia)
• WHO Classification of Tumours (open abstracts)
• CAP Cancer Protocols (College of American Pathologists)