{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:46:46Z","timestamp":1791586006766,"version":"4.3.4"},"reference-count":33,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T00:00:00Z","timestamp":1636934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer AG","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Diatech Pharmacogenetics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Atypical Spitz tumors (AST) deviate from stereotypical Spitz nevi for one or more atypical features and are now regarded as an intermediate category of melanocytic tumors with uncertain malignant potential. Activating NTRK1\/NTRK3 fusions elicit oncogenic events in Spitz lesions and are targetable with kinase inhibitors. However, their prevalence among ASTs and the optimal approach for their detection is yet to be determined. A series of 180 ASTs were screened with pan-TRK immunohistochemistry and the presence of NTRK fusions was confirmed using FISH, two different RNA-based NGS panels for solid tumors, and a specific real time RT-PCR panel. Overall, 26 ASTs showed pan-TRK immunostaining. NTRK1 fusions were detected in 15 of these cases showing cytoplasmic immunoreaction, whereas NTRK3 was detected in one case showing nuclear immunoreaction. Molecular tests resulted all positive in only two ASTs (included the NTRK3 translocated), RNA-based NGS and real time RT-PCR were both positive in three cases, and FISH and real time RT-PCR in another two cases. In seven ASTs NTRK1 fusions were detected only by FISH and in two cases only by real time RT-PCR. The frequency of NTRK fusions in ASTs is 9%, with a clear prevalence of NTRK1 compared to NTRK3 alterations. Pan-TRK immunohistochemistry is an excellent screening test. Confirmation of NTRK fusions may require the use of different molecular techniques.<\/jats:p>","DOI":"10.3390\/ijms222212332","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T20:46:47Z","timestamp":1637009207000},"page":"12332","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["NTRK Gene Fusion Detection in Atypical Spitz Tumors"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0480-3412","authenticated-orcid":false,"given":"Rocco","family":"Cappellesso","sequence":"first","affiliation":[{"name":"Pathological Anatomy Unit, University Hospital of Padua, 35121 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Nozzoli","sequence":"additional","affiliation":[{"name":"Section of Anatomic Pathology, Department of Health Sciences, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Zito Marino","sequence":"additional","affiliation":[{"name":"Pathology Unit, University of Campania \u201cL. Vanvitelli\u201d, 80129 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6145-8275","authenticated-orcid":false,"given":"Sara","family":"Simi","sequence":"additional","affiliation":[{"name":"Section of Anatomic Pathology, Department of Health Sciences, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1696-5651","authenticated-orcid":false,"given":"Francesca","family":"Castiglione","sequence":"additional","affiliation":[{"name":"Section of Anatomic Pathology, Careggi University Hospital, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6531-7998","authenticated-orcid":false,"given":"Vincenzo","family":"De Giorgi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Cota","sequence":"additional","affiliation":[{"name":"Unit of Dermatopathology, San Gallicano Dermatological Institute, 00153 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Senetta","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Oncology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giosu\u00e8","family":"Scognamiglio","sequence":"additional","affiliation":[{"name":"Pathology Unit, Istituto Nazionale Tumori-IRCCS -Fondazione G Pascale, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Anniciello","sequence":"additional","affiliation":[{"name":"Pathology Unit, Istituto Nazionale Tumori-IRCCS -Fondazione G Pascale, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Cesinaro","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Azienda Ospedaliero-Universitaria di Modena, 41122 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8846-8959","authenticated-orcid":false,"given":"Mario","family":"Mandal\u00e0","sequence":"additional","affiliation":[{"name":"Unit of Medical Oncology, University of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2303-7394","authenticated-orcid":false,"given":"Andrea","family":"Gianatti","sequence":"additional","affiliation":[{"name":"Pathology Unit, ASST-Papa Giovanni XXIII, 24127 Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Gabriella","family":"Valente","sequence":"additional","affiliation":[{"name":"Department of Pathology, San Gerardo Hospital, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Valeri","sequence":"additional","affiliation":[{"name":"Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela Rita","family":"Sementa","sequence":"additional","affiliation":[{"name":"Pathology Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7254-4195","authenticated-orcid":false,"given":"Costantino","family":"Ricci","sequence":"additional","affiliation":[{"name":"Pathology Unit, Ospedale Maggiore, 40133 Bologna, Italy"},{"name":"Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6555-6227","authenticated-orcid":false,"given":"Barbara","family":"Corti","sequence":"additional","affiliation":[{"name":"Pathology Unit, IRCCS University Hospital of Bologna, 40133 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giandomenico","family":"Roviello","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo Paolo","family":"Dei Tos","sequence":"additional","affiliation":[{"name":"Pathological Anatomy Unit, University Hospital of Padua, 35121 Padua, Italy"},{"name":"Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8340-3184","authenticated-orcid":false,"given":"Renato","family":"Franco","sequence":"additional","affiliation":[{"name":"Pathology Unit, University of Campania \u201cL. Vanvitelli\u201d, 80129 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Massi","sequence":"additional","affiliation":[{"name":"Section of Anatomic Pathology, Department of Health Sciences, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.pathol.2015.12.003","article-title":"The complex management of atypical Spitz tumours","volume":"48","author":"Massi","year":"2016","journal-title":"Pathology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.5826\/dpc.0501a06","article-title":"Hypopigmented atypical Spitzoid neoplasms (atypical Spitz nevi, atypical Spitz tumors, Spitzoid melanoma): A clinicopathological update","volume":"30","author":"Ferrara","year":"2015","journal-title":"Derm. Pr. 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