Presence of cytogenetic abnormalities in Spitz naevi: a diagnostic challenge for fluorescence in-situ hybridization analysis

Histopathology. 2012 Jan;60(2):336-46. doi: 10.1111/j.1365-2559.2011.04087.x.

Abstract

Aims: Spitz naevi are difficult to diagnose, because of significant overlap with melanomas. It has been recently demonstrated that the LSI RREB1(6p25)/LSI MYB(6q23)/LSI CCND1(11q13)/CEP6 fluorescence in-situ hybridization (FISH) assay is a reliable tool with which to distinguish benign naevi and melanomas. Little is known about its diagnostic usefulness in Spitz naevi.

Methods and results: We investigated 51 patients with Spitz naevi and long-term median follow-up (8.18 years) with the multicolour FISH probe. Control groups included 11 benign naevi and 14 melanomas. Spitz naevi from 32 (63%) patients did not show cytogenetic abnormalities (FISH-). In contrast, Spitz naevi from 19 (37%) patients showed changes in the investigated loci (FISH+). Spitz naevi with the FISH+ profile showed chromosome X polysomy in 14/18 (78%) patients. All Spitz naevi with the FISH- profile were disomic. All melanomas displayed a FISH+ profile, and 4/11 (36%) showed chromosome X polysomy. No differences in clinicopathological features were detected between Spitz naevi with and without genetic abnormalities.

Conclusions: The presence of gene copy number changes in Spitz naevi as detected by FISH is higher than expected, and Spitz naevi at the genetic level represent a heterogeneous group. The findings of similar cytogenetic alterations in Spitz naevi and melanomas suggest that there should be cautious interpretation of FISH analysis in this setting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biopsy
  • Child
  • Child, Preschool
  • Chromosome Aberrations*
  • Chromosomes, Human, X*
  • Cyclin D1 / genetics
  • DNA-Binding Proteins / genetics
  • Diagnosis, Differential
  • Female
  • Follow-Up Studies
  • Gene Dosage / genetics
  • Humans
  • In Situ Hybridization, Fluorescence*
  • Male
  • Melanoma / diagnosis
  • Melanoma / genetics
  • Melanoma / pathology
  • Middle Aged
  • Nevus, Epithelioid and Spindle Cell / diagnosis*
  • Nevus, Epithelioid and Spindle Cell / genetics*
  • Nevus, Epithelioid and Spindle Cell / pathology
  • Oncogene Proteins v-myb / genetics
  • Retrospective Studies
  • Skin / pathology
  • Skin Neoplasms / diagnosis*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Transcription Factors / genetics
  • Young Adult

Substances

  • CCND1 protein, human
  • DNA-Binding Proteins
  • Oncogene Proteins v-myb
  • RREB1 protein, human
  • Transcription Factors
  • Cyclin D1