Histogenetic Study of Verruciform Xanthoma of the Gingiva

Verruciform xanthoma is characterized macroscopically by papillomatous or verrucous hyperplasia of the mucosal epithelium and histopathologically by papillary epithelial hyperplasia and foam cell accumulation in the lamina propria between epithelial processes. This relatively rare lesion does not appear to be a true tumor, but rather an inflammatory event. Here, verruciform xanthoma of the gingiva was subjected to histopathological and immunohistochemical analyses. Notably, the cortical layer of the lesion exhibited a verrucous and granular outer surface, similar to a papilloma. Within the lesion, keratinized stratified squamous epithelium and epithelial process extensions were observed, and the connective tissue between clubbed epithelial processes was filled with foam cells. These foam cells exhibited strong cytoplasmic and membrane expression of CD68, α1-antitrypsin, and macrophage scavenger receptor-1 (MSR-1), as well as human leukocyte antigen (HLA)-DR and oxidized low-density lipoprotein cholesterol (ox-LDL). The epithelial cells also expressed HLA-DR in the cytoplasm and cell membrane. By contrast, the expression of S-100 and CD1a in Langerhans cells was clearly reduced in the epithelium of the verruciform xanthoma, while the inflammatory infiltrating cell population comprised of mainly CD3- or CD8-positive cells, with few CD20- or CD4-positive cells. The increased lipid content of the cell membrane and concomitant epithelial hyperplasia causes cellular injury and leakage into the connective tissue consistent with dysregulated cellular immunity in the stratified squamous epithelium. Accordingly, it may be concluded that macrophages phagocytose these lipids and differentiate to foam cells.