Inflammatory Cell Immunophenotypes in Regressing Melanomas and Halo Nevi: Possible Keys to Distinguish Intensely Inflamed Tumors.

Abstract

Introduction: The immunophenotypic analysis of inflammatory cells in the tumor microenvironment of regressing melanomas is object of ongoing debate. On the other hand, benign halo nevi paradigmatically show marked inflammation. Characterizing these immune profiles can provide insights into the local immune response, its pathogenesis, and differential diagnosis.

Methodology: A cohort of 16 clinically atypical Sutton nevi from Hospital Clínic de Barcelona, Spain, and 70 regressing melanomas from Turin University Hospital, Italy, were evaluated. Histological assessments analyzed inflammation density, location, fibrosis, and markers like CD3, CD4, CD8, CD25, FOXP3, and PD1.

Results: Sutton nevi showed higher inflammation density than regressing melanomas, but similar location and quantity of fibrosis. Sutton nevi had higher CD8/CD3 ratios and melanomas, higher CD4/CD3 and CD4/CD8 ratios. Markers such as CD25/CD4, FOXP3/CD4, and PD1/CD4 were more common in Sutton nevi.

Conclusion: Results indicate a stronger cytotoxic reaction and consequently a regulatory mechanism in halo nevi, characterized by increased PD1, FOXP3, and CD25. This research further characterizes halo nevi and regressing melanomas, and shows possible clues to distinguish those challenging inflamed melanocytic tumors from melanomas.