Granulomatous inflammation: formation and morphology
THE CONTEXT
Granulomatous inflammation is a form of chronic inflammation characterized by collections of activated macrophages, often accompanied by T lymphocytes and sometimes central necrosis.
Why granulomas form
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Granulomatous inflammation usually attempts to contain agents that are difficult to eradicate and induce strong T cell-mediated immune responses, such as persistent microbes.
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Indigestible foreign bodies can also produce granulomas without T cell-mediated immune responses. These materials are not immunogenic but are too large for macrophages to phagocytose, causing persistent macrophage activation.
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Examples include talc associated with intravenous drug use, sutures, and other fibers. Foreign material can usually be identified in the granuloma center by microscopy, particularly when it is refractile in polarized light.
Cellular appearance
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Activated macrophages in granulomas have pink granular cytoplasm and indistinct cell boundaries. They are called epithelioid cells because they resemble epithelial cells.
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Aggregates of epithelioid macrophages are often surrounded by a collar of lymphocytes. Older granulomas may have a rim of fibroblasts and connective tissue.
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Multinucleated Langhans giant cells are frequent but not invariably present. They have abundant cytoplasm and arise through fusion of numerous activated macrophages.
Necrosis and healing
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In granulomas associated with certain infections, classically Mycobacterium tuberculosis, hypoxia and free radical-mediated injury produce central necrosis.
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The granular, cheesy gross appearance gives rise to the term caseous necrosis. Microscopically, the necrotic material consists of amorphous, structureless, eosinophilic granular debris.
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Granulomas in Crohn disease, sarcoidosis, and foreign body reactions usually lack necrotic centers and are termed noncaseating.
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Granulomas heal with fibrosis, which may be extensive.