{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:39:24Z","timestamp":1791823164860,"version":"4.3.4"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Ovarian Sertoli\u2013Leydig cell tumor (SLCT) with heterologous rhabdomyosarcoma (RMS) is exceptionally rare. While the presence of heterologous elements in SLCT is highly predictive of an underlying\n                      <jats:italic>DICER1<\/jats:italic>\n                      mutation, the molecular alterations in these tumors, including in SLCTs with heterologous RMS, remain largely unknown. In this study, we aimed to characterize the clinicopathologic features of these rare tumors, and in a subset of cases, we analyzed in detail their molecular changes to investigate potential recurrent and component\u2010specific genetic alterations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We report clinicopathologic features of 11 ovarian SLCTs with heterologous RMS (positivity for desmin and myogenin); 10 were in keeping with embryonal and 1 with pleomorphic RMS. The patients showed a bimodal age distribution: seven patients (64%) were aged 33\u2009years or younger (mean 20) and four patients (36%) were aged 52\u2009years or older (mean 60). All tumors were unilateral. In addition to the RMS components, 8 of 11 cases (73%) contained other heterologous elements, including gastrointestinal\u2010type mucinous epithelium (5 cases) and immature cartilage (3 cases). Seven of 11 cases (64%) underwent next\u2010generation sequencing analysis. All tumors tested molecularly (7\/7, 100%) harbored hotspot\n                      <jats:italic>DICER1<\/jats:italic>\n                      mutations. Of these, six cases (86%) also carried a second nonsense or frameshift loss\u2010of\u2010function\n                      <jats:italic>DICER1<\/jats:italic>\n                      mutation. One case had only a p.D1810Y hotspot mutation and consisted of high\u2010grade sarcoma with focal rhabdomyoblastic differentiation (focal expression of desmin and myogenin) in keeping with pleomorphic RMS; the pleomorphic sarcoma component also exhibited mutation\u2010type p53 expression. In addition to\n                      <jats:italic>DICER1<\/jats:italic>\n                      mutations,\n                      <jats:italic>TERT<\/jats:italic>\n                      c.\u2010124C&gt;T promoter (4 cases) or\n                      <jats:italic>TP53<\/jats:italic>\n                      mutations (3 cases) were present in all cases and were mutually exclusive. Component\u2010specific analysis in two cases revealed shared common\n                      <jats:italic>DICER1<\/jats:italic>\n                      hotspot mutations in both the SLCT and RMS components, supporting a clonal origin. In 1 case, a\n                      <jats:italic>TERT<\/jats:italic>\n                      promoter c.\u2010124C&gt;T somatic mutation was present only in the RMS component. In the other case, the\n                      <jats:italic>TERT<\/jats:italic>\n                      promoter mutation was found in both components, while a\n                      <jats:italic>BRAF<\/jats:italic>\n                      p.V600E mutation was exclusive to the RMS component.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study demonstrates that the majority (86%) of SLCTs with heterologous RMS harbor double\n                      <jats:italic>DICER1<\/jats:italic>\n                      mutations (a hotspot mutation and a nonsense or frameshift loss\u2010of\u2010function mutation), supporting the existing knowledge on\n                      <jats:italic>DICER1<\/jats:italic>\n                      mutations associated with RMS heterologous elements, the presence of which should trigger genetic counselling. Our findings also suggest that molecular alterations other than\n                      <jats:italic>DICER1<\/jats:italic>\n                      , namely,\n                      <jats:italic>TERT<\/jats:italic>\n                      promoter and\n                      <jats:italic>TP53<\/jats:italic>\n                      mutations, may contribute to component\u2010specific oncogenic transformation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.70058","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T11:04:40Z","timestamp":1765796680000},"page":"985-1002","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Ovarian Sertoli\u2013Leydig cell tumors with heterologous rhabdomyosarcoma: Clinicopathologic features and molecular analysis highlighting recurrent genetic alterations"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2787-1917","authenticated-orcid":false,"given":"Ying S.","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Pathology The Johns Hopkins Medical Institutions  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanobar Yasmeen","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Department of Pathology The Johns Hopkins Medical Institutions  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology The Johns Hopkins Medical Institutions  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7426-3458","authenticated-orcid":false,"given":"Nooshin K.","family":"Dashti","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Dartmouth\u2010Hitchcock Medical Center  Lebanon New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colton","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pathology The Johns Hopkins Medical Institutions  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology The Johns Hopkins Medical Institutions  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7255-7743","authenticated-orcid":false,"given":"Russell","family":"Vang","sequence":"additional","affiliation":[{"name":"Department of Pathology The Johns Hopkins Medical Institutions  Baltimore Maryland USA"},{"name":"Department of Gynecology and Obstetrics The Johns Hopkins Medical Institutions  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9178-4370","authenticated-orcid":false,"given":"W. 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