Fibrosis in regressing melanoma versus nonfibrosis in halo nevus upon melanocyte disappearance: Could it be related to a different cytokine microenvironment?

Abstract

It is not clear why melanocyte disappearance occurs without fibrotic evolution in halo nevus and with fibrotic evolution in regressing melanoma. Six halo nevi, seven regressing primary melanomas, and seven primary melanoma (PM) without regression were studied using immunohistochemistry for the phenotype of inflammatory infiltrate and the expression of cytokines involved in fibrogenesis or macrophage regulation. Melanocytes were also evaluated using electron microscopy. CD8(+) lymphocytes predominated in halo nevus, whereas CD4(+) lymphocytes prevailed in melanoma; a few macrophages were only found in melanoma. Fibrogenic cytokines, IL-6, platelet-derived growth factor, and transforming growth factor-beta were only expressed in melanoma, whereas basic fibroblastic growth factor was also expressed in halo nevus. Antifibrotic cytokine tumor necrosis factor (TNF)-alpha was expressed at a higher degree in halo nevus. Cytokines involved in macrophage regulation were only expressed in melanoma. Fibrogenic cytokines were more frequently expressed in melanoma than in halo nevus, irrespective of regression. At ultrastructural level, melanocytes showed a more activated status in regressing melanoma than in halo nevus, in compliance with a milieu richer in cytokines. Although the cytokine microenvironment does not completely justify the fibrotic evolution in regressing PM, the higher TNF-alpha expression in halo nevus suggests a possible role in nonfibrotic evolution of this lesion.