Solitary (juvenile) xanthogranuloma: A comprehensive immunohistochemical study emphasizing recently developed markers of histiocytic lineage

Summary Solitary (juvenile) xanthogranuloma (SXG) is an uncommon, benign lesion that usually occurs in children. The cell of origin of SXG has been the subject of debate, with hypotheses including endothelium, dermal dendrocytes, dermal indeterminate cells, and the plasmacytoid monocyte, among others. We further characterized the immunophenotype of SXG with an extended immunohistochemical panel, paying special attention to recently described or novel markers of histiocytic lineage. Forty-one SXG and 23 benign fibrous histiocytomas (BFHs) were immunostained for factor XIIIa, CD4, CD11c, CD163, CD31, CD45, lysozyme, and S-100. The mononuclear cells of SXG and the spindled cells of BFH were scored as "negative," "1+" (<10% positive), "2+" (10%-50% positive), and "3+" (>50% positive). SXG immunohistochemistry showed the following: factor XIIIa, 35/40 (88%); CD4, 34/36 (94%); CD11c, 36/37 (97%); CD163, 36/36 (100%); CD31, 14/31 (45%); CD45, 14/32 (44%); lysozyme, 23/30 (77%); and S-100, 0/32 (0%). The 5 factor XIIIa-negative cases all showed 2+-3+ CD4, CD11c, and CD163 expression. In contrast, only 8 (35%) of 23 BFH cases were factor XIIIa positive. All other stains were universally negative in the lesional cells of BFH, although these tumors frequently contained interspersed cells expressing various histiocytic markers. Our results strongly support histiocytic lineage for the mononuclear cells of SXG. CD11c expression has not been previously described in SXG. CD163 expression appears to be characteristic of SXG, as it was not expressed by the lesional cells of BFH, in contrast to previous reports. CD31 expression in SXG represents a potential diagnostic pitfall, as many (dermato)pathologists are unaware of CD31 expression in histiocytes.