Oral verruciform xanthoma (OVX) represents a rare, nonmalignant mucosal disorder histologically distinguished by numerous lipid-laden (foamy) macrophages within the papillary layer of the lamina propria. Although the exact mechanism underlying OVX formation remains unclear, prior evidence has demonstrated that macrophage polarization—namely, M1 with antitumor functions and M2 with protumor and angiogenic activity—plays a crucial biological role. The present investigation aimed to clarify the participation of foamy macrophages in OVX development, emphasizing their involvement in angiogenesis. Four patients who underwent complete surgical removal or total excisional biopsy of OVX lesions were included. Immunohistochemical analysis was conducted to assess macrophage-related markers CD68 (general macrophage marker) and CD163 (M2 subtype), as well as CD34-positive microvessel density (MVD) within the lesions. In every case, foamy macrophages showed strong reactivity for both CD68 and CD163. Microvessel density and vascular endothelial growth factor (VEGF) expression were further analyzed in relation to tissue morphology. The MVD in OVX lesions was markedly greater than that observed in adjacent healthy mucosa. Notably, the verrucous-type OVX exhibited higher MVD compared with the other morphological variants. VEGF immunoreactivity was consistently detected in the foamy macrophages across all specimens. Collectively, these findings suggest that CD163-positive foamy macrophages may contribute to OVX formation through VEGF-mediated angiogenic mechanisms.
