Identification of Factor XIIIa in cutaneous tissue

Sir: In a recent issue of Histopathology, Adany & Muszbek (1987) outlined their findings on the immunophenotypic characterization of spindle or stellate-shaped, Factor XIIIa-containing cells in human connective tissue. They disagreed with Reid e t a / . (1986), who interpreted these cells as fibroblasts. Employing macrophage markers (RFD7, Leu M3 and Dako anti-macrophage), Adany & Muszbek (1987) suggested that the cells were tissue macrophages. We have utilized Factor XIIIa to investigate normal skin and fibroproliferative lesions of the skin. In normal skin, positively labelled cells were confined to fixed connective tissue cells exhibiting a stellate or dendritic morphology, which were especially prominent around vessels and in the papillary dermis. On morphological appearances alone, they would have been previously regarded as fibroblasts. They stained for vimentin but were negative for S-100 protein and Mac 387, a monocyte-derived macrophage marker (Flavell, Jones & Wright 1987). However, we have observed Factor XIIIa labelling of melanin-containing dermal phagocytes but not of epithelioid cells or foreign body type giant cells. Moreover, cultured fibroblasts also remained unlabelled. Immunohistochemical studies demonstrated a positive reaction for Factor XIIIa in 3@70% of the constituent cells of 30 histiocytomas (dermatofibromas) which we have investigated but there was negative labelling for 16 dermatofibrosarcomas, three scars, three keloids and single cases of Dupuytren’s contracture. nodular fasciitis and dermoid tumour. Factor XIIIa immunoreactivity was strongest at the periphery of the histiocytomas but weaker labelling occurred in areas of fibroplasia. Mac 387 could be identified in haernosiderin-containing and foamy macrophages but these made up less than 5% of the constituent cells of the histiocytomas. Our results demonstrated that Factor XIlIa does not label cutaneous fibroproliferative lesions except for the consistent labelling of histiocytomas. However, less immunoreactivity was seen in older histiocytomas exhibiting fibroplasia. This supports the interpretation of Adany & Muszbek (1987) that Factor XIIIa does not identify collagen-producing fibroblasts. However, it is difficult to reconcile our findings in the skin with the claims of Muszbek et al. (1985) and Adany et al. (1985, 1987) that human monocytes, and lymph node and peritoneal macrophages are Factor XIIIa positive. For instance, we have found that cells such as multinucleate giant cells, histiocytes in granuloma annulare and foamy macrophages are Mac 387 positive, suggesting their macrophage/monocyte lineage, but these same cells are Factor XIIIa negative. In the skin our findings indicate that the fixed dermal connective tissue cells are Factor XlIIa positive, cells that Headington (1986) has proposed renaming dermal dendrocytes. His studies suggest that these cells are not actively fibroblastic but stem cells. These stem cells, under the appropriate stimulus, can differentiate into collagen-producing cells and non-monocyte-derived mononuclear phagocytes. Perhaps histiocytoma represents a hyperplasia of Factor XIIIa-containing ‘dermal dendrocytes’ which can differentiate towards fibroblasts, subsequently losing their antigenicity. Our studies have demonstrated that Factor XIIIa is not only of theoretical interest but may be of important practical interest. The antibody can successfully label routine paraffin sections, essential for conventional diagnostic dermatopathology. Furthermore, our studies have shown that i t may help to differentiate histiocytoma from dermatofibrosarcoma.