CD163+ Foamy Macrophages Are Associated with the Morphogenesis of Oral Verruciform Xanthoma through Angiogenesis by VEGF Expression: An Immunohistochemical Study

Abstract

Oral verruciform xanthoma (OVX) is an uncommon benign lesion that is characterized histologically by the accumulation of several foamy macrophages in the lamina propria papillae. The pathogenesis of OVX has not been completely elucidated, although the significance of macrophage polarization (M1, tumor suppression; and M2, tumor promotion) and the contribution of M2 macrophages to angiogenesis are well established. This study investigated the role of foamy macrophages in OVX, with a focus on angiogenesis. Four patients who underwent surgical excision or total excisional biopsy for OVXs were enrolled in this study. We evaluated the expression of the macrophage markers CD68 (broad) and CD163 (M2) and the CD34-positive microvessel density (MVD) of OVXs. The foamy macrophages of all patients exhibited positivity to CD68 and CD163. We evaluated the MVD and the expression of the vascular endothelial growth factor (VEGF) based on histological architecture. The MVD of all OVX cases was significantly higher than that of the corresponding normal epithelia. Interestingly, the MVD of verrucous-type OVX cases was higher than that of the other type. VEGF was expressed on foamy macrophages in all cases. Overall, the foamy macrophages expressing CD163 were associated with the morphogenesis of OVX through the process of angiogenesis by VEGF expression.

Vascular endothelial growth factor-mediated peritoneal neoangiogenesis in peritoneal dialysis

“…105 Macrophages can be divided into two sub-types: classically activated macrophages (M1 macrophages) and alternatively activated macrophages (M2 macrophages), and the latter are responsible for angiogenesis and vascularization. 107,108 The proangiogenic function of M2-polarized macrophage is based on the production of angiogenic cytokines, such as VEGF, TGF-b and matrix metalloprotein-9. 109 Multiple IL factors (i.e.…”

Alteration of Macrophage Infiltrating Compartment: A Novel View on Oral Carcinogenesis

“…In oral candidiasis, oral lichen planus, and aphthous stomatitis, CD163 + macrophages were present in the subepithelial area but not in the epithelial area [84]. In oral verruciform xanthoma, which is a rare reactive lesion characterized by accumulation of foamy macrophages in the stroma, it was suggested that foamy Pathobiology 2021;88:327-337 DOI: 10.1159/000515922 cells express the M2 marker CD163 + and may be involved in morphogenesis by vascular endothelial growth factor expression-mediated angiogenesis [85]. These findings stress that it is difficult to establish a discrimination system of M1 and M2 macrophage phenotypes in oral mucosal lesions based only on macrophage markers.…”