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

J Cutan Pathol. 2020 Dec;47(12):1164-1169. doi: 10.1111/cup.13802. Epub 2020 Aug 11.

Abstract

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 overexpression of p16 protein. While these data need to be confirmed in larger cases series, our results show that NGS could be an additional genetic diagnostic tool in DDM-GCN.

Keywords: TP53 mutation; giant congenital nevus; melanoma; proliferative nodules.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Biopsy
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Dermis / pathology
  • Female
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Immunohistochemistry / methods
  • Lymph Nodes / pathology
  • Male
  • Melanoma / diagnosis
  • Melanoma / genetics*
  • Melanoma / pathology
  • Melanoma / surgery
  • Mutation
  • Nevus, Pigmented / diagnosis
  • Nevus, Pigmented / genetics*
  • Nevus, Pigmented / pathology
  • Nevus, Pigmented / surgery
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Skin Neoplasms / surgery
  • Tumor Suppressor Protein p53 / genetics*
  • Young Adult

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • TP53 protein, human
  • Tumor Suppressor Protein p53

Supplementary concepts

  • Melanocytic nevus syndrome, congenital