{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:02:07Z","timestamp":1791478927912,"version":"4.3.4"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"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":[[2025,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Perivascular epithelioid cell tumours (PEComas) show variable smooth muscle and melanocytic differentiation and mostly harbour mTOR pathway activation via <jats:italic>TSC2<\/jats:italic> inactivation. Five\u201310% of sporadic PEComas instead harbour fusions involving <jats:italic>TFE3<\/jats:italic>, an\u00a0vmTOR pathway target. Malignancy in <jats:italic>TSC2<\/jats:italic>\/<jats:italic>1<\/jats:italic>\u2010inactivated PEComa correlates with <jats:italic>TP53<\/jats:italic>, <jats:italic>RB1<\/jats:italic> or <jats:italic>ATRX<\/jats:italic> inactivation. Here, we investigated genetic correlates of malignancy in <jats:italic>TFE3<\/jats:italic>\u2010rearranged PEComa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>Fourteen <jats:italic>TFE3<\/jats:italic>\u2010rearranged PEComas, confirmed by FISH and\/or sequencing, occurred in 11 females (79%) and 3 males aged 9\u201364\u2009years (median: 31.5\u2009yr). Body sites were uterus (3 tumours), extremities (3), colon (2), nasal cavity (2), neck (1), retroperitoneum (1), bladder (1) and ovary (1). Nine tumours (64%) lacking cytologic atypia were diagnosed prospectively as benign, and five cytologically atypical tumours were diagnosed prospectively as malignant.<\/jats:p><jats:p>By immunohistochemistry, tumours expressed SMA (6\/13; 46%), HMB\u201045 (5\/13; 38%), desmin (3\/13; 23%) and melan\u2010A (2\/13; 15%), and not MITF (10 tumours), S\u2010100 (7), SOX10 (4), pan\u2010K (5) or EMA (3). By DNA sequencing, all nine benign tumours lacked complex copy number alterations (CNAs) or inactivation of <jats:italic>TP53<\/jats:italic>, <jats:italic>ATRX<\/jats:italic> or <jats:italic>RB1<\/jats:italic>. In contrast, three of four (75%) assessable malignant tumours showed complex CNAs, and only one of five malignant PEComas (20%) harboured <jats:italic>TP53<\/jats:italic> inactivation. Among eight patients with follow\u2010up (57%), all four benign PEComas neither recurred nor metastasized (median: 5.0\u2009yr; range: 3.3\u20138.1\u2009yr), while all four malignant tumours metastasized.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We conclude that malignant <jats:italic>TFE3<\/jats:italic>\u2010rearranged PEComas frequently harbour complex CNAs, which could be of diagnostic utility. Malignant <jats:italic>TFE3\u2010<\/jats:italic>rearranged PEComas lacked highly recurrent alterations in <jats:italic>TP53<\/jats:italic>, <jats:italic>RB1<\/jats:italic> or <jats:italic>ATRX<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.15476","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T01:29:13Z","timestamp":1749000553000},"page":"436-445","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Genetic correlates of malignancy in <scp><i>TFE3<\/i><\/scp>\u2010rearranged <scp>PEComa<\/scp>: a series of 14 cases"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7746-3546","authenticated-orcid":false,"suffix":"Jr.","given":"David J","family":"Papke","sequence":"first","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital, and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8073-8803","authenticated-orcid":false,"given":"Igor","family":"Odintsov","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital, and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6805-8861","authenticated-orcid":false,"given":"Navin R","family":"Mahadevan","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital, and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher DM","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital, and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2964-1058","authenticated-orcid":false,"given":"John","family":"Hanna","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital, and Harvard Medical School  Boston Massachusetts 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