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

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Saraggi D, Salmaso R, Zamuner C, Munari G, Lanza C, Alaibac MS, Bassetto F, Rugge M, Montesco MC, Cerroni L, Fassan M.

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

 

Abstract

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.

Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

 

 

Pubmed: https://www.ncbi.nlm.nih.gov/pubmed/29920315