{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T06:46:47Z","timestamp":1792392407209,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Endometrial stromal sarcomas (ESSs) comprise a heterogeneous group of uterine mesenchymal tumors characterized by diverse morphological features and recurrent molecular alterations. Although molecular classification has substantially improved ESS diagnosis, the relationship between specific genetic alterations and morphological phenotypes remains incompletely understood. We performed an integrated molecular and histopathological analysis of ESS to investigate genotype\u2013phenotype correlations and refine tumor classification. A total of 61 patients with histologically suspected ESSs were initially enrolled, and 51 successfully underwent targeted RNA sequencing, followed by comprehensive morphological reassessment, immunohistochemical evaluation, molecular validation, and clinicopathological correlation. Molecularly confirmed ESSs demonstrated distinct genotype\u2010associated morphological patterns.\n                    <jats:italic>PHF1<\/jats:italic>\n                    \u2010rearranged low\u2010grade ESSs showed a strong association with hypocellular growth and prominent collagenized stroma. Quantitative cellularity analysis further demonstrated significantly lower tumor cellularity in\n                    <jats:italic>PHF1<\/jats:italic>\n                    \u2010rearranged low\u2010grade ESSs compared with\n                    <jats:italic>JAZF1<\/jats:italic>\n                    ::\n                    <jats:italic>SUZ12<\/jats:italic>\n                    \u2010rearranged tumors (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). High\u2010grade ESSs with\n                    <jats:italic>YWHAE<\/jats:italic>\n                    ::\n                    <jats:italic>NUTM2<\/jats:italic>\n                    and\n                    <jats:italic>BCOR<\/jats:italic>\n                    ::\n                    <jats:italic>ZC3H7B<\/jats:italic>\n                    alterations showed higher mitotic activity than low\u2010grade ESSs and demonstrated tongue\u2010like infiltration patterns in both primary and metastatic lesions, indicating that this growth pattern, traditionally emphasized in low\u2010grade ESSs, may represent a broader morphological feature of ESSs. Molecular reassessment led to the reclassification of 10 cases (19.6%, 10\/51), identifying tumors with alternative molecular alterations that were initially diagnosed as ESSs based on morphology alone. Among these cases, a uterine sarcoma harboring a novel\n                    <jats:italic>GATA6<\/jats:italic>\n                    ::\n                    <jats:italic>SRF<\/jats:italic>\n                    fusion exhibited a low\u2010grade ESS\u2010like morphological phenotype but lacked the characteristic molecular alterations of conventional ESSs, suggesting a potential molecularly defined uterine sarcoma subtype requiring further investigation. Our findings demonstrate that integrated molecular and histopathological analysis extends beyond diagnostic refinement by revealing genotype\u2013phenotype relationships, expanding the molecular spectrum of ESSs and ESS\u2010like uterine sarcomas, and providing new insights into the biological heterogeneity of these rare tumors. \u00a9 2026 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70144","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T06:28:11Z","timestamp":1792391291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated molecular and histopathological analysis reveals genotype\u2013phenotype correlations and diagnostic challenges in endometrial stromal sarcoma"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9566-3761","authenticated-orcid":false,"given":"Yumeng","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Molecular Pathology Research Centre Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longyun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Molecular Pathology Research Centre Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaimi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Molecular Pathology Research Centre Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyi","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Molecular Pathology Research Centre Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Molecular Pathology Research Centre Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinbo","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Molecular Pathology Research Centre Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yining","family":"Zhen","sequence":"additional","affiliation":[{"name":"Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Molecular Pathology Research Centre Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianlong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Molecular Pathology Research Centre Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Molecular Pathology Research Centre Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4787-2925","authenticated-orcid":false,"given":"Zhiyong","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Molecular Pathology Research Centre Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5007-5540","authenticated-orcid":false,"given":"Xiaohua","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Molecular Pathology Research Centre Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/gcc.22907","article-title":"Molecular pathogenesis and prognostication of \u2018low\u2010grade\u2019 and \u2018high\u2010grade\u2019 endometrial stromal sarcoma","volume":"60","author":"Micci F","year":"2021","journal-title":"Genes Chromosomes 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