Cutaneous Melanocytoma With CRTC1-TRIM11 Fusion: Report of 5 Cases Resembling Clear Cell Sarcoma

Am J Surg Pathol. 2018 Mar;42(3):382-391. doi: 10.1097/PAS.0000000000000996.

Abstract

We report 5 cases of primary intradermal nodular unpigmented tumors with a melanocytic immunophenotype associated with a novel CRTC1-TRIM11 fusion. Clinically, the cutaneous nodules were slowly growing in 3 women and 2 men (25 to 82 y old, median, 28 y) with no specific topography. Lesion size ranged from 4 to 12 mm (median, 5 mm). The tumors were strictly located in the dermis with a nodular pattern. The cells were arranged in confluent nests and fascicules. Central fibronecrotic areas were present in 2 cases. Cells were medium to large, sometimes multinucleated, and presented a spindled and epithelioid cytology with prominent nucleoli. Cytonuclear atypia was constant, and mitotic activity in hotspot areas ranged from 1 to 5/mm². Immunohistochemistry found a constant positivity with S100, MiTF, and Sox10, and a heterogenous staining by MelanA or HMB45. NTRK1 was strongly positive in 3 cases. In all cases, RNA sequencing found an invariable CRTC1(e1)-TRIM11(e2) fusion, confirmed by fluorescent in situ hybridization techniques with a TRIM11 break-apart probe. In 4/4 cases, nuclear TRIM11 expression was positive by immunohistochemistry. Fluorescent in situ hybridization techniques showed no rearrangement of NTRK1 or EWSR1, and array-comparative genomic hybridization displayed no alteration (1 case) or only a whole chromosome 7 gain (2 cases) when performed. No relapse or metastatic event was observed during follow-up [3 to 72 months (median, 14 mo)]. Cutaneous clear cell sarcoma was the main differential diagnosis. Overlapping morphologic features previously described in primary dermal melanomas and paraganglioma-like melanocytic tumors were present. The CRTC1-TRIM11 fusion appears to be specific of an unpigmented nodular tumor combining a melanocytic phenotype and low-grade tumor behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Diagnosis, Differential
  • Female
  • Gene Fusion*
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Melanocytes* / chemistry
  • Melanocytes* / pathology
  • Middle Aged
  • Neoplasm Grading
  • Phenotype
  • Predictive Value of Tests
  • Sarcoma, Clear Cell / chemistry
  • Sarcoma, Clear Cell / genetics*
  • Sarcoma, Clear Cell / pathology
  • Skin Neoplasms / chemistry
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Skin Neoplasms / surgery
  • Transcription Factors / genetics*
  • Tripartite Motif Proteins / genetics*
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • Biomarkers, Tumor
  • CRTC1 protein, human
  • Transcription Factors
  • Tripartite Motif Proteins
  • TRIM11 protein, human
  • Ubiquitin-Protein Ligases