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In this study, we conducted a comprehensive clinicopathological and molecular analysis of 22 cases of IFS and other kinase gene\u2010altered spindle cell neoplasms affecting both pediatric and adult patients. Follow\u2010up periods for 16 patients ranged in length from 10 to 130\u2009months (mean 38\u2009months). Six patients were treated with targeted therapy, achieving a partial or complete response in five cases. Overall, three cases recurred and one metastasized. Eight patients were free of disease, five were alive with disease, and two patients died. All cases showed previously reported morphological patterns. Based on the cellularity and level of atypia, cases were divided into three morphological grade groups. S100 protein and CD34 were at least focally positive in 12\/22 and 14\/22 cases, respectively. Novel\n                    <jats:italic>PWWP2A::RET<\/jats:italic>\n                    ,\n                    <jats:italic>NUMA1::RET<\/jats:italic>\n                    ,\n                    <jats:italic>ITSN1::RAF1<\/jats:italic>\n                    , and\n                    <jats:italic>CAPZA2::MET<\/jats:italic>\n                    fusions, which we report herein in mesenchymal tumors for the first time, were detected by RNA sequencing. Additionally, the first uterine case with\n                    <jats:italic>BRAF<\/jats:italic>\n                    and\n                    <jats:italic>EGFR<\/jats:italic>\n                    mutations and CD34 and S100 co\u2010expression is described. DNA sequencing performed in 13 cases uncovered very rare additional genetic aberrations. The CNV profiles showed that high\u2010grade tumors demonstrate a significantly higher percentage of copy number gains and losses across the genome compared with low\u2010 and intermediate\u2010grade tumors. Unsupervised clustering of the tumors\u2019 methylation profiles revealed that in 8\/9 cases, the methylation profiles clustered with the IFS methylation class, irrespective of their clinicopathological or molecular features. \u00a9 2024 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6260","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T03:17:22Z","timestamp":1707448642000},"page":"61-73","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Comprehensive clinicopathological, molecular, and methylation analysis of mesenchymal tumors with\n                    <scp>\n                      <i>NTRK<\/i>\n                    <\/scp>\n                    and other kinase gene aberrations"],"prefix":"10.1002","volume":"263","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4407-5544","authenticated-orcid":false,"given":"Nat\u00e1lie","family":"Klub\u00ed\u010dkov\u00e1","sequence":"first","affiliation":[{"name":"Department of Pathology Faculty of Medicine in Pilsen, Charles University  Pilsen Czech Republic"},{"name":"Bioptical Laboratory Ltd  Pilsen Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1139-2914","authenticated-orcid":false,"given":"Josephine K","family":"Dermawan","sequence":"additional","affiliation":[{"name":"Robert J. Tomsich Pathology and Laboratory Medicine Institute Cleveland Clinic  Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaheh","family":"Mosaieby","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Medicine in Pilsen, Charles University  Pilsen Czech Republic"},{"name":"Bioptical Laboratory Ltd  Pilsen Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0276-5771","authenticated-orcid":false,"given":"Petr","family":"Mart\u00ednek","sequence":"additional","affiliation":[{"name":"Bioptical Laboratory Ltd  Pilsen Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1\u0161","family":"Van\u011b\u010dek","sequence":"additional","affiliation":[{"name":"Bioptical Laboratory Ltd  Pilsen Czech 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