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To date, only two cases of mesothelioma harboring <jats:italic>EWSR1::YY1<\/jats:italic> fusions have been described. We present three additional cases of <jats:italic>EWSR1::YY1\u2010<\/jats:italic>fused peritoneal mesotheliomas, two localized and one diffuse, all occurring in the peritoneum of middle\u2010aged adults (2 females and 1 male), and discovered incidentally by imaging or during surgery performed for unrelated reasons. None presented with symptoms or had a known history of asbestos exposure. All three cases were cellular epithelioid neoplasms with heterogeneous architectural patterns comprising mostly solid nests and sheets with variably papillary and trabecular areas against collagenous stroma. Cytologically, the cells were monomorphic, polygonal, epithelioid cells with dense eosinophilic cytoplasm and centrally located nuclei. Overt mitotic activity or tumor necrosis was absent. All cases showed strong diffuse immunoreactivity for pancytokeratin, CK7, and nuclear WT1, patchy to negative calretinin, retained BAP1 expression, and were negative for Ber\u2010EP4 and MOC31. RNA\u2010sequencing confirmed in\u2010frame gene fusion transcripts involving <jats:italic>EWSR1<\/jats:italic> exon 7\/8 and <jats:italic>YY1<\/jats:italic> exon 2\/3. By unsupervised clustering analysis, the methylation profiles of <jats:italic>EWSR1::YY1<\/jats:italic>\u2010fused mesotheliomas clustered similarly with <jats:italic>EWSR1\/FUS::ATF1<\/jats:italic>\u2010fused mesotheliomas and conventional mesotheliomas, suggesting a mesothelioma epigenetic signature. All three patients underwent surgical resection or cytoreductive surgery of the masses. On follow\u2010up imaging, no recurrence or progression of disease was identified. Our findings suggest that <jats:italic>EWSR1::YY1\u2010<\/jats:italic>fusion defines a small subset of peritoneal epithelioid mesothelioma in middle\u2010aged adults without history of asbestos exposure.<\/jats:p>","DOI":"10.1002\/gcc.23074","type":"journal-article","created":{"date-parts":[[2022,6,4]],"date-time":"2022-06-04T13:28:42Z","timestamp":1654349322000},"page":"592-602","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["<i><scp>EWSR1<\/scp>::<scp>YY1<\/scp><\/i> fusion positive peritoneal epithelioid mesothelioma harbors mesothelioma epigenetic signature: Report of 3 cases in support of an emerging entity"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1139-2914","authenticated-orcid":false,"given":"Josephine K.","family":"Dermawan","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York 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