Novel three-way complex rearrangement of TRPM1-PUM1-LCK in a case of agminated Spitz nevi arising in a giant congenital hyperpigmented macule

Pigment Cell Melanoma Res. 2020 Sep;33(5):767-772. doi: 10.1111/pcmr.12884. Epub 2020 Jun 4.

Abstract

The genetic anomalies associated with the agminated variant of Spitz nevus have so far been limited to HRAS G13R mutations, especially when arising within a nevus spilus. A previous report exposed the case of a man with a giant pigmented macule involving his upper right limb and trunk. Since childhood, Spitz nevi have been periodically arising, within the pigmented area. The histopathology of several lesions displayed the usual criteria of junctional, compound, or intradermal Spitz nevi with a diversity of cytomorphological and architectural features. Some lesions spontaneously regressed. Genetic studies confirmed in three lesions an identical translocation involving TRPM1, PUM1, and LCK. No mutations in HRAS, NRAS, BRAF, or other known fusion genes linked to Spitz nevus were detected. LCK break-apart fluorescence in situ hybridization confirmed the rearrangement was present not only in the melanocytic proliferation but also in the surrounding non-spitzoid melanocytes. This report expands the list of genetic alterations involved both in giant congenital macules and in agminated Spitz nevi, and also extends the concept of mosaicism in melanocytes to gene translocations.

Keywords: LCK; PUM1; TRPM1; Spitz nevus; agminated Spitz nevi.

Publication types

  • Case Reports

MeSH terms

  • Base Sequence
  • Gene Rearrangement*
  • Humans
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics*
  • Male
  • Middle Aged
  • Nevus, Epithelioid and Spindle Cell / genetics*
  • Nevus, Epithelioid and Spindle Cell / pathology
  • Nevus, Pigmented / genetics*
  • Nevus, Pigmented / pathology
  • RNA-Binding Proteins / genetics*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • TRPM Cation Channels / genetics*

Substances

  • PUM1 protein, human
  • RNA-Binding Proteins
  • TRPM Cation Channels
  • TRPM1 protein, human
  • LCK protein, human
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)

Supplementary concepts

  • Melanocytic nevus syndrome, congenital