{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T01:13:25Z","timestamp":1789866805577,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"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":["Histopathology"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p><jats:italic>NTRK<\/jats:italic>\u2010rearranged sarcomas of the female genital tract mainly occur in the uterus (more commonly cervix than corpus) and are characterized by a \u201cfibrosarcoma\u2010like\u201d morphology and <jats:italic>NTRK<\/jats:italic> gene rearrangements. These neoplasms may exhibit histological overlap with other entities and can present diagnostic difficulties without molecular confirmation. Pan\u2010TRK immunohistochemistry was developed to identify tumours harbouring <jats:italic>NTRK<\/jats:italic> rearrangements. The aim of this study was to characterize pan\u2010TRK immunohistochemical expression in a large cohort of gynaecological mesenchymal neoplasms and investigate the utility of pan\u2010TRK immunohistochemistry to\u00a0distinguish <jats:italic>NTRK<\/jats:italic>\u2010rearranged sarcoma from its mimics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>A total of 473 gynaecological mesenchymal tumours (461 without known <jats:italic>NTRK<\/jats:italic> fusions and 12 <jats:italic>NTRK<\/jats:italic>\u2010rearranged sarcomas) were selected. Pan\u2010TRK immunohistochemistry (EPR17341, Abcam) was performed on whole tissue sections and tissue microarrays. Molecular interrogation of pan\u2010TRK positive tumours was performed by RNA sequencing or fluorescence <jats:italic>in situ<\/jats:italic> hybridization (FISH). Of the 12 <jats:italic>NTRK<\/jats:italic>\u2010rearranged sarcomas, 11 (92%) exhibited diffuse (\u226570%) cytoplasmic pan\u2010TRK staining with moderate\/marked intensity, while the other was\u00a0negative. Eleven (2.4%) additional tumours also exhibited pan\u2010TRK immunohistochemical expression: three low\u2010grade endometrial stromal sarcomas, seven high\u2010grade endometrial stromal sarcomas, and an undifferentiated uterine sarcoma. Molecular confirmation of the absence of <jats:italic>NTRK<\/jats:italic> rearrangements was possible in nine of these tumours. Of these nine neoplasms, seven exhibited focal\/multifocal (&lt;70%) pan\u2010TRK cytoplasmic staining with weak\/moderate intensity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Even though pan\u2010TRK immunohistochemical expression is not entirely sensitive or specific for <jats:italic>NTRK<\/jats:italic>\u2010rearranged sarcomas, these neoplasms tend to exhibit diffuse staining of moderate\/strong intensity, unlike its mimics. Pan\u2010TRK should be performed in monomorphic uterine (corpus and cervix) spindle cell neoplasms that are negative for smooth muscle markers and hormone receptors and positive for CD34 and\/ or S100. Ultimately, the diagnosis requires molecular confirmation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.15082","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T19:48:28Z","timestamp":1700682508000},"page":"451-462","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["<scp>Pan\u2010TRK<\/scp> immunohistochemistry in gynaecological mesenchymal tumours: diagnostic implications and pitfalls"],"prefix":"10.1111","volume":"84","author":[{"given":"Madalena Souto","family":"Moura","sequence":"first","affiliation":[{"name":"Department of Pathology Portuguese Institute of Oncology\u2014Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9506-9662","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Pathology Portuguese Institute of Oncology\u2014Porto  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