Expression of interstitial collagenase, 92-kDa gelatinase, and tissue inhibitor of metalloproteinases-1 in granuloma annulare and necrobiosis lipoidica diabeticorum.

Granuloma annular (GA) and necrobiosis lipoidica diabeticorum (NLD) are disorders characterized by granulomatous inflammation and degenerative changes in collagen and elastic fibers. Because these disorders have often been described as being associated with altered extracellular matrix deposition, we studied the in situ expression of interstitial collagenase, 92-kDa gelatinase, and tissue inhibitor of metalloproteinases (TIMP)-1. Twelve lesions each of GA and NLD of different histopathologic types and durations were examined. Interstitial collagenase mRNA was seen in histiocyte-like cells in one-third of the cases of both diseases, typically in younger lesions. In GA, collagenase mRNA was only detected in lesions of the palisading type. Signal for 92-kDa gelatinase mRNA was observed in eosinophils, which were present in low numbers in five of 12 GA and three of 12 NLD samples. The signal for this enzyme and the presence of eosinophils did not correlate with the age of lesion. TIMP-1 mRNA was consistently expressed by histiocyte-like cells in both disorders. In GA, TIMP-1 mRNA was detected at the outer edge of the palisading granulomas, but in NLD, inhibitor expression was seen in the perivascular and periadnexal accumulation of inflammatory cells. Our data indicate that collagenase and TIMP are expressed early in these disorders and that these proteins may contribute to stromal remodeling associated with necrobiotic lesions. Our results further indicate that the localization of TIMP-1 production may provide a distinction between the two disorders, whereas metalloproteinase expression is not sufficiently specific to aid in the differential diagnosis of GA and NLD.

Differential staining pattern of lysozyme in palisading granulomas: an immunoperoxidase study.

Biopsies from palisading granulomas of granuloma annulare, necrobiosis lipoidica, and rheumatoid nodules were examined for the presence of lysozyme (muramidase). This enzyme was identified in paraffin-embedded tissues using a primary antibody to lysozyme and the peroxidase-antiperoxidase technic. Some inflammatory cells in the infiltrate of granuloma annulare stained abundantly for lysozyme, whereas those of necrobiosis lipoidica and rheumatoid nodule stained minimally and negatively, respectively. This pattern of staining may be of diagnostic value and suggests that the histiocytoid cells constituting the infiltrate of granuloma annulare are in some way different from the similar-appearing cells of necrobiosis lipoidica and rheumatoid nodule.