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

Deborah Saraggi, Roberto Salmaso, Carolina Zamuner, Giada Munari, Cristiano Lanza, Mauro Salvatore Alaibac, Franco Bassetto, Massimo Rugge, Maria Cristina Montesco, Lorenzo Cerroni, Matteo Fassan

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)728-735
Number of pages8
JournalJournal of the American Academy of Dermatology
Volume79
Issue number4
DOIs
Publication statusPublished - Oct 1 2018

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Epithelioid and Spindle Cell Nevus
Fluorescence In Situ Hybridization
Genes
Melanoma
Neoplasms
Tropomyosin
Proto-Oncogenes
Gene Rearrangement
Gene Fusion
Protein-Serine-Threonine Kinases
Extremities
Staining and Labeling
Biopsy
Mutation
Growth

Keywords

  • ALK
  • atypical Spitz tumor
  • plexiform melanocytic lesions

ASJC Scopus subject areas

  • Dermatology

Cite this

Prevalence of ALK gene alterations among the spectrum of plexiform spitzoid lesions. / Saraggi, Deborah; Salmaso, Roberto; Zamuner, Carolina; Munari, Giada; Lanza, Cristiano; Alaibac, Mauro Salvatore; Bassetto, Franco; Rugge, Massimo; Montesco, Maria Cristina; Cerroni, Lorenzo; Fassan, Matteo.

In: Journal of the American Academy of Dermatology, Vol. 79, No. 4, 01.10.2018, p. 728-735.

Research output: Contribution to journalArticle

Saraggi, Deborah ; Salmaso, Roberto ; Zamuner, Carolina ; Munari, Giada ; Lanza, Cristiano ; Alaibac, Mauro Salvatore ; Bassetto, Franco ; Rugge, Massimo ; Montesco, Maria Cristina ; Cerroni, Lorenzo ; Fassan, Matteo. / Prevalence of ALK gene alterations among the spectrum of plexiform spitzoid lesions. In: Journal of the American Academy of Dermatology. 2018 ; Vol. 79, No. 4. pp. 728-735.
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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.",
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AU - Saraggi, Deborah

AU - Salmaso, Roberto

AU - Zamuner, Carolina

AU - Munari, Giada

AU - Lanza, Cristiano

AU - Alaibac, Mauro Salvatore

AU - Bassetto, Franco

AU - Rugge, Massimo

AU - Montesco, Maria Cristina

AU - Cerroni, Lorenzo

AU - Fassan, Matteo

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AB - 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.

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