Next generation sequencing revealing TP53 mutation as potential genetic driver in dermal deep-seated melanoma arising in giant congenital nevus in adult patients: a unique case report and review of the literature.

Melanoma in giant congenital nevus (M-GCN) is a rare and potentially lethal neoplasm. In children M-GCN appears as a dermal/deep-seated melanoma (DDM-GCN) with histopathologic features difficult to distinguish from proliferative nodules (PNs-GCN). DDM-GCN in adults is an anecdotal entity and only 8 cases have been described and genetically characterized. We report the first case of DDM-GCN in a 34-year-old man characterized with a large-panel next-generation sequence (NGS) highlighting a TP53 mutation with a UV-signature (C > T substitution) in DDM but not in PNs-GCN and GCN. Curiously, DDM showed an aberrant p16 overexpression without detection of CDKN2A mutation at NGS. In line with previous studies, it supports a different pathway in children and adults: UV-induced mutations may be involved in the latter not only by CDKN2A but also by TP53 mutations, with a potentially confusing over-expression of p16-protein. Besides, even if this data needs to be confirmed in larger cases series, our results show that NGS could be an additional genetic diagnostic tool in DDM-GCN. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.