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.

Introduction

Solitary xanthogranuloma (SXG), also known as juvenile xanthogranuloma and archaically as “nevoxanthoendothelioma,” is an uncommon non–Langerhans cell histiocytosis that most often occurs in children. SXG usually involves the skin and subcutis, but can rarely involve the viscera and bones [1]. Originally regarded as a neoplasm of endothelial cell lineage [2], hypotheses regarding the SXG cell of origin have included macrophages [3], dermal dendrocytes [4], dermal indeterminate cells [5], and, most recently, CD4⁺ plasmacytoid monocytes [6]. The World Health Organization's Committee on Histiocytic/Reticulum Cell Proliferations currently classifies SXG as a dendritic cell–related histiocytic disorder, based in part on expression of factor XIIIa in the lesional cells [7].

Although a number of previous studies have evaluated the immunophenotype of SXG [4], [6], [8], [9], [10], [11], [12], [13], [14], [15], they focused on a limited number of macrophage markers and have not, for the most part, investigated the expression of more recently described macrophage markers, such as CD11c [16], CD163 [17], and CD31 [18]. We studied a large series of well-characterized SXG with an extended immunohistochemical panel, including factor XIIIa, CD4, CD11c, CD163, CD31, CD45, lysozyme, and S-100, to better define the immunophenotype of this lesion and evaluate its utility in the distinction of SXG from potential mimics, in particular benign fibrous histiocytoma/dermatofibroma (BFH). We did not evaluate SXG for CD68 expression, as CD68 is now widely appreciated to be a highly nonspecific lysosomal marker, rather than a histiocyte-specific marker [19].