Verruciform xanthoma of the oral cavity: clinicopathological study relating to pathogenesis. Report of three cases.

Verruciform xanthoma is a rare condition that was first reported in the oral cavity in 1971. Its histopathology is distinctive on account of the presence of foamy histiocytes within elongated dermal papillae. Three cases of oral mucosal verruciform xanthoma were studied. Immunohistochemical staining by streptavidin-peroxidase and in situ hybridization to detect human papillomavirus (HPV types 6, 11, 16, 18) DNA and matrix metalloproteinase (MMP-2, -9) RNA were performed to investigate the pathogenesis of verruciform xanthoma. This study showed that the foam cells were strongly positive for CD68 (KP1) and vimentin. Cytokeratin, PCNA and S-100 stained focally negative in foam cells. In situ hybridization failed to detect HPV (types 6, 11, 16, 18) in any of the three cases. Based on our findings we conclude that verruciform xanthoma is most likely not a human papillomavirus-associated lesion; the foam cells, as a histological hallmark of the lesion, are most likely derived from the monocyte-macrophage lineage, and verruciform xanthoma is, at least partly, mediated by an immune mechanism. MMPs degrade basilar membrane that promotes the reciprocal induction between epithelium and mesenchyme. However, as yet unrecognized factors may play a role in the development of epithelium-mesenchyme reciprocal induction.