Abstract

A 15-month-old boy presented with four brown-black papules on the right cheek within an irregularly shaped, light-brown patch. Over the subsequent year, similar papules arose within the patch. Biopsies of these pigmented papules revealed compound proliferations of spindled and polygonal melanocytes with abundant cytoplasm and minimal maturation with descent. There were also many bizarre nuclei in junctional and superficial melanocytes and rare dermal mitoses. Despite the concerning cytomorphology and increased mitotic activity, the melanocytes demonstrated expression of p16 and did not overexpress PRAME. Gene panel sequencing of one of the papules demonstrated an activating point mutation in beta-catenin (CTNNB1^S33F); a MAPK activating alteration was not identified. We also noted strong membranous and occasional nuclear expression of beta-catenin by immunohistochemistry in the melanocytes in the papule with the demonstrated beta-catenin mutation. Separate papules had similar beta-catenin expression suggesting that albeit spatially separated, the melanocytic tumors constituting the papules were clonal for CTNNB1^S33F. The histologic, immunophenotypic and genetic features are compatible with an unusual Wnt-activated melanocytoma. While most Wnt-activated melanocytomas have a BRAF^V600E or MAP2K1 insertion/deletion that activates the MAPK pathway in combination with the Wnt-pathway activating mutation, this melanocytoma did not harbor these alterations. We present the unique clinical and histopathologic features of the first reported agminated Wnt-activated melanocytic tumor.