Utility of next-generation sequencing in the diagnosis of metastatic melanoma: A case report

J Cutan Pathol. 2024 Sep;51(9):644-648. doi: 10.1111/cup.14660. Epub 2024 May 16.

Abstract

During routine dermatologic examination, a 77-year-old male was noted to have a firm blue subcutaneous nodule on his right lateral upper back. His past medical history included metastatic melanoma of unknown primary involving right and left axillary lymph nodes, treated with ipilimumab/nivolumab with complete response, and subsequent primary uveal melanoma. The subcutaneous nodule was located near his previous right axillary scar for metastatic melanoma. Excision of the nodule showed a plexiform neoplasm involving mid and deep dermis composed of spindle and epithelioid atypical cells admixed with numerous melanophages. Central necrosis was present. Immunohistochemical studies revealed the tumor cells to be diffusely positive for HMB45, with retained expression of BAP1 and p16. The tumor cells were negative for PRAME, nuclear expression of β-catenin, LEF1, and BRAF V600E. Molecular studies demonstrated BAP1 and GNA11 somatic mutations, a profile different from that exhibited by his prior melanoma. Collectively, these data were interpreted as a metastasis from uveal melanoma and not a recurrence of his metastatic likely cutaneous melanoma after complete response to immunotherapy. This case emphasizes the importance of molecular studies for definitive diagnosis in challenging clinical situations, especially when there is discordance among histopathological, immunohistochemical, and molecular studies. Integration of clinical, histopathological, and molecular features is warranted.

Keywords: NGS; melanoma; uvea.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • GTP-Binding Protein alpha Subunits / genetics
  • High-Throughput Nucleotide Sequencing* / methods
  • Humans
  • Male
  • Melanoma* / diagnosis
  • Melanoma* / genetics
  • Melanoma* / pathology
  • Melanoma* / secondary
  • Mutation
  • Neoplasms, Unknown Primary / diagnosis
  • Neoplasms, Unknown Primary / genetics
  • Neoplasms, Unknown Primary / pathology
  • Nivolumab / therapeutic use
  • Skin Neoplasms* / diagnosis
  • Skin Neoplasms* / genetics
  • Skin Neoplasms* / metabolism
  • Skin Neoplasms* / pathology
  • Skin Neoplasms* / secondary
  • Tumor Suppressor Proteins / genetics
  • Ubiquitin Thiolesterase* / genetics
  • Ubiquitin Thiolesterase* / metabolism
  • Uveal Neoplasms* / diagnosis
  • Uveal Neoplasms* / genetics
  • Uveal Neoplasms* / metabolism
  • Uveal Neoplasms* / pathology
  • Uveal Neoplasms* / secondary

Substances

  • BAP1 protein, human
  • Ubiquitin Thiolesterase
  • Tumor Suppressor Proteins
  • GNA11 protein, human
  • GTP-Binding Protein alpha Subunits
  • Nivolumab

Supplementary concepts

  • Uveal melanoma