Neuroendocrine Transdifferentiation in Cutaneous Melanoma: A Case Report and Review of the Literature

Am J Dermatopathol. 2023 Apr 1;45(4):264-268. doi: 10.1097/DAD.0000000000002377. Epub 2023 Feb 17.

Abstract

Neuroendocrine transdifferentiation refers to the progressive transformation of a nonneuroendocrine tumor to the one showing evidence of neuroendocrine differentiation on morphological and immunohistochemical grounds. Although this phenomenon has been well-documented in certain malignancies, particularly prostatic adenocarcinoma after androgen deprivation, cases of neuroendocrine transdifferentiation in melanomas are exceptionally rare. Herein, we report a case of a conventional superficial spreading melanoma occurring on the skin of the leg in a young male which showed progressive neuroendocrine transdifferentiation as it progressed through 2 in-transit metastases and a nodal metastatic deposit over a 4-year period. The tumor retained the BRAF V600E mutation throughout the disease process, and disease control was achieved through dual BRAF inhibition therapy. The possibility of melanoma masquerading as a high-grade neuroendocrine malignancy when investigating tumors of unknown primary should be kept in the mind of clinicians and histopathologist alike as a potential diagnostic pitfall, thus helping avoid misdiagnosis and guide appropriate treatment strategies.

Publication types

  • Review
  • Case Reports

MeSH terms

  • Androgen Antagonists
  • Cell Transdifferentiation
  • Humans
  • Immunohistochemistry
  • Male
  • Melanoma* / genetics
  • Melanoma* / pathology
  • Melanoma* / therapy
  • Melanoma, Cutaneous Malignant
  • Mutation
  • Prostatic Neoplasms*
  • Proto-Oncogene Proteins B-raf / genetics
  • Skin Neoplasms* / pathology

Substances

  • Proto-Oncogene Proteins B-raf
  • Androgen Antagonists