{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T06:10:08Z","timestamp":1780553408344,"version":"3.54.1"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T00:00:00Z","timestamp":1696204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mesenchymal spindle cell tumors with kinase fusions, often presenting in superficial or deep soft tissue locations, may rarely occur in bone. Herein, we describe the clinicopathologic and molecular data of eight bone tumors characterized by various kinase fusions from our files and incorporate the findings with the previously reported seven cases, mainly as single case reports. In the current series all but one of the patients were young children or teenagers, with an age range from newborn to 59\u2009years (mean 19\u2009years). Most tumors (<jats:italic>n<\/jats:italic>\u2009=\u20095) presented in the head and neck area (skull base, mastoid, maxilla, and mandible), and remaining three in the tibia, pelvic bone, and chest wall. The fusions included <jats:italic>NTRK1<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20093), <jats:italic>RET<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20092), <jats:italic>NTRK3<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20092), and <jats:italic>BRAF<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20091). In the combined series (<jats:italic>n<\/jats:italic>\u2009=\u200915), most tumors (73%) occurred in children and young adults (&lt;30\u2009years) and showed a predilection for jaw and skull bones (40%), followed by long and small tubular bones (33%). The fusions spanned a large spectrum of kinase genes, including in descending order <jats:italic>NTRK3<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20096), <jats:italic>NTRK1<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20094), <jats:italic>RET<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20092), <jats:italic>BRAF<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20092), and <jats:italic>RAF1<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20091). All fusions confirmed by targeted RNA sequencing were in\u2010frame and retained the kinase domain within the fusion oncoprotein. Similar to the soft tissue counterparts, most <jats:italic>NTRK3<\/jats:italic>\u2010positive bone tumors in this series showed high\u2010grade morphology (5\/6), whereas the majority of <jats:italic>NTRK1<\/jats:italic> tumors were low\u2010grade (3\/4). Notably, all four tumors presenting in the elderly were high\u2010grade spindle cell sarcomas, with adult fibrosarcoma (FS)\u2010like, malignant peripheral nerve sheath tumor (MPNST)\u2010like and MPNST phenotypes. Overall, 10 tumors had high\u2010grade morphology, ranging from infantile and adult\u2010types FS, MPNST\u2010like, and MPNST, whereas five showed benign\/low\u2010grade histology (MPNST\u2010like and myxoma\u2010like). Immunohistochemically (IHC), S100 and CD34 positivity was noted in 57% and 50%, respectively, while co\u2010expression of S100 and CD34 in 43% of cases. One\u2010third of tumors (4 high grade and the myxoma\u2010like) were negative for both S100 and CD34. IHC for Pan\u2010TRK was positive in all eight <jats:italic>NTRK<\/jats:italic>\u2010fusion positive tumors tested and negative in two tumors with other kinase fusions. Clinical follow\u2010up was too limited to allow general conclusions.<\/jats:p>","DOI":"10.1002\/gcc.23205","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T15:55:10Z","timestamp":1696262110000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Kinase fusion positive intra\u2010osseous spindle cell tumors: A series of eight cases with review of the literature"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1361-9454","authenticated-orcid":false,"given":"Albert J. H.","family":"Suurmeijer","sequence":"first","affiliation":[{"name":"Department of Pathology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4638-9835","authenticated-orcid":false,"given":"Bin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianne","family":"Torrence","sequence":"additional","affiliation":[{"name":"Department of Pathology Northwell Health (Long Island Jewish Medical Center)  New Hyde Park New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2269-6216","authenticated-orcid":false,"given":"Brendan C.","family":"Dickson","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine Mount Sinai Hospital  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9717-8205","authenticated-orcid":false,"given":"Cristina R.","family":"Antonescu","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0298-184"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22846"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000675"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22671"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22767"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001297"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001982"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22877"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/cup.14216"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2021.10.007"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001055"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-0623-z"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3729"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30453-x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14680"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-022-02515-3"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.23089"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14847"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2023.101744"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2020.12.009"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000938"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-021-00806-w"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3109\/15513815.2011.587497"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.23132"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/10668969221080059"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001194"},{"issue":"3","key":"e_1_2_7_28_1","article-title":"Detection of NTRK fusions and TRK expression and performance of pan\u2010TRK immunohistochemistry in routine diagnostics: results from a Nationwide Community\u2010based cohort","volume":"12","author":"Koopman B","year":"2022","journal-title":"Diagnostics (Basel)"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197608)38:2<729::AID-CNCR2820380216>3.0.CO;2-Z"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001203"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001929"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30119-0"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181dbedf1"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.path.2017.04.013"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14602"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2022.02.003"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199711000-00003"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000564"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12797"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.23205","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T13:24:05Z","timestamp":1705584245000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.23205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,2]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/gcc.23205"],"URL":"https:\/\/doi.org\/10.1002\/gcc.23205","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,2]]},"assertion":[{"value":"2023-07-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e23205"}}