S12C6-Granulomatous Disease

Lipogranulomas:

The lipogranulomatous quality of the rosacea-like tuberculid, and the chalazion has been discussed. Insoluble lipids that gain access to the dermis induce a lipogranulomatous response (Fig. 48). Vaseline applied over granulation tissue may result in the impregnation of lipid in the granulation tissue. The lipids are extracted during routine processing of tissue and their removal is marked by a rounded, clear defect. Epithelioid cells surround the clear space.

In the subcutis, lipids are liberated by the disruption of lipocytes (i.e., in response to trauma or inflammation); the free lipids may form pools, which on histologic sections, present the pattern of a lipogranuloma. Some of the histiocytes bordering the zones of necrosis in the subcutaneous fat acquire xanthomatous qualities.

In some chronic inflammatory processes in the dermis (lichen simplex chronicus or contact dermatitis) the perivascular spaces contain lymphoid cells and closely aggregated, clear, rounded spaces. In some examples, the clear spaces have distinct membranes, clear cytoplasm, and an eccentric nucleus; these cells probably represent lipophages. These lipid-laden cells apparently are histiocytes and are markers for a smoldering, chronic inflammatory process. They are lipophages with cytoplasmic, endogenous lipid. In some examples, the defects cannot be identified as viable cells; they may represent small, lipid-filled cysts. In either case, the process qualifies histologically as lipophagic dermatitis. It may be confused with the effects of the dermajet in which air bubbles disrupt epithelium and connective tissue.

Foreign Body Granulomas: The foreign body granuloma is a histiocytic response to an insoluble, foreign body. Foreign bodies, such as metallic fragments, wood splinters, cactus spines, or suture materials, may be identified in routine sections. As with silica or vegetable fibers, they may be refractile. Crystalline material which is refractile is usually birefringent. If the foreign material is lost during processing of the specimen, its site of residence often persists as an empty defect in the tissue.

The morphologic distinctions between an immune-mediated granuloma and a foreign body granuloma are difficult to define. Even at the experimental level, the distinctions are sometimes contradictory. The reaction to colloidal silica in the skin is attributed to a foreign body response, but pulmonary silicosis is an immunologic disorder. Granulomas in response to foreign bodies may be indistinguishable, by the usual histologic techniques, from immune-mediated granulomas. The macrophage may be activated by specific immune processes and, in addition, by nonspecific physical or chemical agents. In general, granulomatous reactions to particulate, foreign material are classified as foreign body granulomas on the basis of the characteristics of the multinucleated giant cells and the demonstration of a foreign body. Morphologically, the "foreign body giant cell" is not diagnostic and foreign material such as colloidal silica may not be demonstrable with the usual histologic techniques.

In foreign body reactions, the macrophage may acquire epithelioid characteristics, but usually the response is composed of loosely aggregated macrophages and numerous multinucleated giant cells. The giant cells usually contain randomly distributed nuclei. If a foreign body is histologically demonstrable, it may be confined to the cytoplasm of macrophages and giant cells. If it is particulate, it is often birefringent. The reaction in actinic granuloma has features of a foreign body reaction.

Some of the common foreign bodies have distinctive characteristics:

1. The cell wall of a vegetable fiber is rich in polysaccharides [PAS(+)] and is birefringent.

2. Cotton suture in cross section is composed of multiple fibers, each of which is a folded plate with a localized defect that communicates between a central lumen and the external surface. The individual fibers are refractile, birefringent, and PAS(+).

3. Silk sutures are composed of multiple pigmented fibers (greenish black) which are polygonal in cross-section. Acidophilic deposits may form at the periphery of fibers (127).

4. Catgut sutures are single, homogeneous fibers. They are faintly eosinophilic. In well developed reactions, the surface of the suture is scalloped and irregular. These surface defects are produced by the action of phagocytic macrophages.

5. Plastic sutures have variable qualities, but many of the sutures are stranded (composed of multiple filaments).

6. Silica is characteristically needle-like, when a section is examined under polarized light. Large fragments of glass may be refractile, as well as birefringent. Conchoid bodies of sarcoidosis are birefringent, and may be mistaken for a foreign body. Silica-like particles are occasionally identified in the granulomas of sarcoidosis.

7. The most common foreign body reaction is produced by sebum and keratinized debris that has been extruded into the dermis from a ruptured, obstructed pilosebaceous unit. The keratinized debris forms loosely aggregated lamellae in inflamed granulation tissue, or is confined to the cytoplasm of foreign body giant cells. Sebum is granular and either acidophilic or basophilic. It usually induces a lipogranulomatous response.

8. In some tattoos, the metallic pigments evokes a granulomatous response. The exciting agent is a foreign body, but the process expresses altered immunity. Rarely, the reaction is a lichenoid response. Some of the pigment in a tattoo may be birefringent.

If silica is a foreign body, the host response is a pure granuloma in which the changes are indistinguishable from those induced by cellular immune processes. Silica-like particles may be demonstrated in the granulomas under polarized light. The diagnosis of zirconium and beryllium granules requires special analytic techniques and clinicopathologic correlations. The zirconium granuloma is an immune response (2).

Granulomatous sequestration is descriptive of metabolic disorders in which mononuclear cells store metabolic products in their cytoplasms, or concentrate at the interface between a matrix containing crystallized, metabolic products and adjacent uninvolved tissue. The two patterns are not mutually exclusive.

Storage of metabolic products in the cytoplasm of macrophages may be associated with zones of necrosis in which the metabolites form crystalline aggregates. The histiocytic and xanthomatous lesions of the hyperlipidemias are examples of the cytoplasmic storage of circulating metabolites. The palisaded granulomas of gout, chondrocalcinosis, and granulomatous calcinosis are examples of extracellular crystallization of abnormal metabolites. The stored, or crystalline material is in equilibrium with the peripheral blood. An exchange occurs at the interface between the crystalline material and the normal tissue; it is probably mediated by the macrophage. The macrophage may also function as a collagenoclast to prepare a suitable matrix for the crystalline material.

There are similarities between the lesions of granulomatous sequestration and palisaded granulomas, such as rheumatoid nodule or granuloma annulare. Perhaps antigen-antibody complexes are sequestered in some of the palisaded granulomas.

Histiocytoses: Examples of histiocytoses are included in the section on borderline disorders.

 

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