S9C23P14-1: In this field of a lesion of granuloma annulare, a basic quality, focality, is clearly evident. There are two foci represented, one outlined by blue arrows and the other outlined by green arrows. Within the central areas of each focus, the matrix is less structured; two pale collagen bundles near the extremity of the dark arrow on the right are better defined (among the green arrows). There is a peripheral palisaded zone that is hypercellular; the respective cells of the cellular zones are epithelioid histiocytes (the lesions are granulomatous by virtue of the peripheral shells; they are relatively structureless and are acellular centrally). The combination of features qualifies the lesion as a palisaded granuloma; the focality of the process would be in keeping with a lesion of granuloma annulare (focal, granulomatous collagenosis). Perivascular infiltrates in lesions of granuloma annulare are non-specific; they usually do not contain plasma cells. Occasionally, eosinophils are a feature.

S9C23P14-2: At higher magnification, the palisaded granuloma shows zonal patterns, with some loss of structure centrally. Epithelioid histiocytes, in palisades, form a peripheral shell. The histiocytes of the peripheral shell are mostly immunoreactive for KP1 (CD68), a marker for lysomal activity. Histiocytes, immunoreactive for factor XIIIa, also are to be found in the peripheral shell. It is a stretch of the morphologic criteria, in the definition of a vasculitis, to attribute vasculitic qualities to this distinctive portion of the lesion.

The perivenular components, by the definitions in this contribution, qualify as a lymphocytic vasculitis. Such a characterization would be expected to offend those whose definition of vasculitis requires evidence of both a neutrophilic infiltrate and leukocytoclasia. In practice, some of those observers who, though rigid in their definition of vasculitis, readily accept the perivenular lymphocytic infiltrates of granuloma annulare as evidence of a vasculitis. Being committed to a concept that granuloma annulare is a vasculitis, they are obliged to make accommodations for conceptual conflicts. They then extend the definition of vasculitis to include the interstitial infiltrates of histiocytes and the altered connective tissue.

It may well be that antigen-antibody complexes have been deposited in the central region of palisaded granulomas. Their presence, in the interstitial tissue, may well have initiated the reaction. Perhaps, the complexes are relatively insoluble and provide the antigenic stimulus leading to the local accummulation of histiocytes. Granuloma annulare is a granulomatous assault on dense fibrous tissue mediated at the level of activated, phagocytic histiocytes.

S9C23P14-3: The locus of a palisaded granuloma is characterized by a central nidus of mucinous (blue) material (colloidal iron stain). Cells (including histiocytes) and elastic fibers are yellow. Centrally, the enzymes of activated histiocytes have digested connective tissue fibers, particularly collagen bundles. As new histiocytes are recuited to the peripheral shell, older generations of histiocytes in the vicinity of the mucinous zone die. Cellular and fibrous debris are digested. The lesion has a tendency to spread from a central nidus in a centrifugal direction.

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