S100A6 preferentially labels type C nevus cells and nevic corpuscles: additional support for Schwannian differentiation of intradermal nevi

Background: Melanocytic nevi typically show a morphologic sequence of maturation from epithelioid type A cells to fusiform, Schwann cell-like type C cells with dermal descent. Nevi may also produce Wagner-Meissner-like structures (nevic corpuscles). Previous studies have shown that this maturation of intradermal nevi recapitulates intermediate stages in Schwann cell development. In intradermal nevi, we have evaluated the pattern of S100A6 protein, a form of S100 found in Schwann cells. Methods: Formalin-fixed, paraffin-embedded archival tissues were evaluated by immunohistochemistry using antibodies specific for S100A6 and S100B in 38 intradermal nevi (IDN). Ten neurofibromas (NF), 3 Schwannomas (SCH), 2 palisaded and encapsulated neuromas (PEN), and 2 granular cell tumors (GCT) were included as positive controls since these lesions have large numbers of Schwann cells. Results: Melanocytic nevi demonstrated preferential and-S100A6 staining of type C cells (36/38; 28 strong, 8 weak) and nevic corpuscles (25/38; 19 strong, 6 weak) compared to type A cells (17/38; 17 weak) and type B cells (17/38; 4 strong, 13 weak). All NF, SCH, and PEN stained strongly with anti-S100A6. Both GCT were negative with anti-S100A6 but positive with anti-S100B. Conclusions: The pattern of SI00A6 expression in intradermal nevi further supports the hypothesis that maturation in these lesions recapitulates features of Schwann cell differentiation. The lack of S100A6 expression by both GCT suggests that these lesions have lost this feature of Schwann cells, which may play a role in their peculiar phenotypic appearance.