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Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical <jats:italic>ETV6::NTRK3<\/jats:italic> fusion identified more than 20\u2009years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring <jats:italic>NTRK<\/jats:italic> or other kinase alterations, including tumours with an infantile fibrosarcoma\u2010like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma\u2010like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including <jats:italic>NTRK1\/2\/3<\/jats:italic>, <jats:italic>RET<\/jats:italic>, <jats:italic>MET<\/jats:italic>, <jats:italic>RAF1<\/jats:italic>, <jats:italic>BRAF<\/jats:italic>, <jats:italic>ALK<\/jats:italic>, <jats:italic>EGFR<\/jats:italic> and <jats:italic>ABL1<\/jats:italic> fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with <jats:italic>NTRK<\/jats:italic> and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications.<\/jats:p>","DOI":"10.1111\/his.14443","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T18:31:04Z","timestamp":1640629864000},"page":"4-18","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Mesenchymal neoplasms with NTRK and other kinase gene alterations"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2725-1518","authenticated-orcid":false,"given":"Jessica L","family":"Davis","sequence":"first","affiliation":[{"name":"Department of Pathology Oregon Health &amp; Science University Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1769-7839","authenticated-orcid":false,"given":"Alyaa","family":"Al\u2010Ibraheemi","sequence":"additional","affiliation":[{"name":"Department of Pathology Boston Children\u2019s Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin R","family":"Rudzinski","sequence":"additional","affiliation":[{"name":"Department of Laboratories Seattle Children\u2019s Hospital Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea F","family":"Surrey","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine The Children\u2019s Hospital of Philadelphia Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198810133191506"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5846"},{"key":"e_1_2_11_4_1","unstructured":"HowladerN NooneAM KrapchoMet\u00a0al. eds.SEER cancer statistics review 1975\u20132018.Bethesda MD:National Cancer Institute based on November 2020 SEER data submission posted to the SEER website April 2021. 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