Prevalence of ALK gene alterations among the spectrum of plexiform spitzoid lesions

J Am Acad Dermatol. 2018 Oct;79(4):728-735. doi: 10.1016/j.jaad.2018.06.018. Epub 2018 Jun 18.


Background: ALK receptor tyrosine kinase gene (ALK) rearrangements have been described in spitzoid lesions with a plexiform growth pattern.

Objective: To investigate the prevalence of ALK alterations in a large series of spitzoid lesions.

Methods: ALK immunohistochemical and fluorescence in situ hybridization analyses of 78 spitzoid plexiform lesions including 41 Spitz nevi, 29 atypical Spitz tumors (ASTs), and 8 spitzoid melanomas.

Results: ALK immunohistochemical staining was observed in 14.6% of Spitz nevi (6 of 41) and 13.8% of ASTs (4 of 29); the spitzoid melanomas were ALK negative. Fluorescence in situ hybridization confirmed ALK translocation in 9 cases and amplification in 1 case. In 2 of the translocated cases it was possible to determine the fusion partner gene (ie, tropomyosin 3 gene [TPM3] or dynactin 1 gene [DCTN1]). Of the 4 cases of AST examined, 2 carried the B-Raf proto-oncogene, serine/threonine kinase gene (BRAF) V600E mutation. The 10 patients had a mean age of 18.7 years (range, 1-39) and a female predominance (female-to-male ratio, 7:3). Seven lesions arose on the extremities; the 2 lesions occurring in infants were located on the face. The lesions' mean diameter was 6.2 mm (range, 3-13), and their mean Breslow thickness was 1.83 mm (range, 0.6-3.6). The results of sentinel node biopsy were negative in 2 ASTs.

Limitations: BRAF status was tested in only 4 of 10 samples because of the limited amount of material.

Conclusion: ALK alterations characterize a significant subset of spitzoid lesions.

Keywords: ALK; atypical Spitz tumor; plexiform melanocytic lesions.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Anaplastic Lymphoma Kinase / genetics*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease / epidemiology*
  • Genetic Variation
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Mutation
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Nevus, Epithelioid and Spindle Cell / genetics*
  • Nevus, Epithelioid and Spindle Cell / pathology*
  • Nevus, Epithelioid and Spindle Cell / surgery
  • Prognosis
  • Real-Time Polymerase Chain Reaction / methods
  • Retrospective Studies
  • Sentinel Lymph Node Biopsy
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / surgery
  • Young Adult


  • ALK protein, human
  • Anaplastic Lymphoma Kinase