Primary and metastatic melanoma with NTRK fusions Journal Article


Authors: Lezcano, C.; Shoushtari, A. N.; Ariyan, C.; Hollmann, T. J.; Busam, K. J.
Article Title: Primary and metastatic melanoma with NTRK fusions
Abstract: A number of oncogenic driver mutations have been identified in melanocytic nevi and melanoma, but translocations also play a role in tumorigenesis and provide potential therapeutic targets for malignant lesions. Various translocations, such as those involving the anaplastic lymphoma kinase (ALK), neurotrophic tropomyosin receptor kinase 1 (NTRK1), and NTRK3 have been reported in spitzoid melanocytic neoplasms leading to kinase-fusion proteins that result in immunohistochemically detectable ALK or NTRK expression. We have previously reported that ALK expression can be found in nonspitzoid primary and metastatic cutaneous melanomas. In this study we report that nonspitzoid metastasizing melanomas of adults may also harbor NTRK fusions and that NTRK expression can be immunohistochemically detected in these tumors. Of 751 melanomas analyzed by next-generation sequencing, 4 metastatic melanomas were identified with NTRK fusions, 3 involving NTRK1, 1 involving NTRK2. They occurred in 3 women and 1 man. Two of the corresponding primary tumors were from the trunk, 1 from an extremity and 1 tumor arose in anal skin. One primary tumor displayed features of superficial spreading melanoma and 3 were nodular melanomas. All tumors were cytologically characterized by the presence of large epithelioid melanocytes. All tumors were immunoreactive with anti-Trk antibody. Next-generation sequencing documented that the NTRK1 fusion partners included TRIM63, DDR2, and GON4L. One tumor harbored an NTRK2-TRAF2 fusion. Thus, our findings document that NTRK kinase fusions can occur in nonspitzoid metastasizing melanomas of adults. The presence of an NTRK family fusion in these tumors may provide a therapeutic opportunity in a small subset of patients with metastatic melanoma. © 2018 Wolters Kluwer Health, Inc. All rights reserved.
Keywords: immunohistochemistry; melanoma; pathology; ntrk
Journal Title: American Journal of Surgical Pathology
Volume: 42
Issue: 8
ISSN: 0147-5185
Publisher: Lippincott Williams & Wilkins  
Date Published: 2018-08-01
Start Page: 1052
End Page: 1058
Language: English
DOI: 10.1097/pas.0000000000001070
PROVIDER: scopus
PMCID: PMC6041134
PUBMED: 29683819
DOI/URL:
Notes: Article -- Export Date: 1 August 2018 -- Source: Scopus
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MSK Authors
  1. Charlotte Eielson Ariyan
    75 Ariyan
  2. Klaus J Busam
    533 Busam