Non infectious Granulomas

1. NON INFECTIOUS
GRANULUMA
Prepared By :DR Monther Fadel Nagi

2. GRANULOMA
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What is Granuloma?
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• Cutaneous granuloma (granulomatous dermatitis) is a histopathological
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term referring to a chronic inflammatory condition o f the skin in which
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histiocytes (tissue macrophages) are the predominant cells with / without
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other inflammatory cells (i.e. epithelioid histiocytes, multi-nucleated giant
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cells, lymphocytes, neutrophils, fibroblasts and / or plasma cells)

3. STEPS OF GRANULOMA FORMATION
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• Granuloma develops as an immune response to a persistent
nondegradable (indigestible) antigen.
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• The inciting antigens may be infectious (including live or dead
microorganisms), drugs (and / or their metabolites), foreign body or result
from innate host pathology (e.g. connective tissue disease, vasculitis, or
cancerous antigens).
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• After engulfing the antigen, histiocytes lose their mobility
“immobilization” and accumulate at site of inflammation.

4. STPS OF GRANULOMA FORMATION
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Histiocytes undergo structural Granuloma formation and components,
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changes (larger with abundant cytoplasm and aggregate together). They are
called “epithelioid histiocytes” i.e. resembling epithelial cells (keratinocytes).
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These epithelioid histiocytes may fuse together to form “multi-nucleated
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giant cells”.
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The whole granuloma may be surrounded with lymphocytes or fibroblasts.
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The center o f the granuloma may undergo caseation necrosis.

5. STEPS OF GRANULOMA FORMATION
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Giant cells
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• Large cells formed by fusion o f multiple epithelioid histiocytes.
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• There are different types o f giant cells that differ according to the number
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and arrangement o f their nuclei, and the nature o f their inclusion bodies.
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• Although none of these giant cells is pathognomonic or exclusive to just
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one disease, some disorders are characterized by the predominant presence
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o f one or more o f these cells.

6. CLASSIFICATIONS OF GRANULOMA
(A) According to aetiology
• Infectious e.g. tuberculosis, leprosy, leishmaniasis, syphilis .
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* Non-infectious e.g. granuloma annulare, Sarcoidosis,Granuloma
annular,Annular elastolytic giant cell granuloma,Necrobiosis
lipoidica,Cutaneous Crohn disease,Foreign body granulomas Interstitial
granulomatous dermatitis and palisaded neutrophilic and
granulomatous dermatitis.

7. CLASSIFICATION OF GRANULOMA
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(B)Histopathological classification:
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» Nodular: histiocytes (and other cells) are arranged in discrete
collections or aggregations.
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* Diffuse: histiocytes (and other cells) are scattered diffusely
throughout the dermis.

8. HISTOLOGICAL CLASSIFICATION

9. NOTE
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Whether nodular or diffuse, granulomas may be classified into
either of the following types (patterns) according to type and
characteristics of giant cells, presence or absence of
lymphocytes and other features.

10. TUBERCULOID GRANULOMA
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(1) Tuberculoid granuloma:
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- Composed of epithelioid histiocytes, multi-nucleated giant cells (Langhans
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type), surrounded by a dense rim of lymphocytes. Caseation may be present
centrally.
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- This type o f granuloma is seen in:
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■ Cutaneous tuberculosis
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■ Tuberculoid leprosyTuberculoid granuloma
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c Lupus miliaris disseminatus faciei

11. SARCOIDAL GRANULOMA
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(2) Sarcoidal (Naked) granuloma:
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- Composed of epithelioid histiocytes, multi-nucleated giant cells (containing
asteroid and Schumann inclusion bodies), with only a sparse number of
peripheral lymphocytes (i.e. a “naked” granuloma).
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- This type o f granuloma is seen in:
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* Sarcoidosis
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■ Sarcoidal reaction

12. PALISADING GRANULOMA
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(3) Palisading (Necrobiotic) granuloma:
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® Epithelioid histiocytes are arranged in a rim (palisade-like) around a
central area of necrobiosis.
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Necrobiosis refers to changes/alterations in the connective tissue of the
dermis (collagen, elastin ... etc) with different staining characteristics e.g.
increased basophilia or eosinophilia.

13. PALISADING GRANULOMA
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This type Of granuloma is seen in:-
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- Granuloma annulare (GA)
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- Necrobiosis lipoidica (NBL)
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- Rheumatoid nodule (RN)
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- Annular elastolytic giant-cell granuloma (AEGCG, actinic granuloma)
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- Necrobiotic xanthogranuloma

14. FORIGEN BODY GRANULOMA
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(4) Foreign body granuloma:
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• A granulomatous reaction to foreign bodies whether
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- exogenous e.g. non-absorbable suture material or
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- endogenous e.g. hair, keratin from a ruptured follicle, uric acid in gout.
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• Characterized by the presence of foreign body giant cells. The foreign
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material can be seen with polarization microscopy.