{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T02:01:02Z","timestamp":1785031262263,"version":"3.55.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Guangdong Medical Science and Technology Research Foundation","award":["A2023377"],"award-info":[{"award-number":["A2023377"]}]},{"DOI":"10.13039\/501100010256","name":"Guangzhou Science and Technology Plan","doi-asserted-by":"publisher","award":["2024A03J0521"],"award-info":[{"award-number":["2024A03J0521"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>YAP1 fusions are well documented in pediatric central nervous system (CNS) tumors, particularly in supratentorial ependymomas and meningiomas where they are generally associated with a favorable prognosis. Outside these entities, YAP1 fusions have rarely been reported in gliomas or other high-grade neuroepithelial tumors. Here, we describe 2 high-grade neuroepithelial tumors harboring a recurrent YAP1::MAML2 fusion. Comprehensive histopathologic evaluation, immunohistochemistry, whole-exome sequencing using the SimcereDx neuro-oncology panel, and DNA methylation profiling were performed. Both tumors were IDH- and H3-wildtype and lacked canonical alterations in the RTK, TP53, or MAPK pathways. DNA methylation profiling did not match any established CNS tumor class. Histologically, both tumors demonstrated rhabdoid morphology accompanied by a prominent inflammatory microenvironment enriched in CD68- and CD163-positive macrophages. Despite sharing the same fusion event, the 2 tumors exhibited divergent morphologic and immunophenotypic features, indicating substantial heterogeneity. These findings suggest a potentially distinct, molecularly defined tumor subgroup characterized by YAP1::MAML2 fusion, high-grade neuroepithelial morphology, rhabdoid features, and an inflammatory microenvironment. They highlight the limitations of current methylation-based classification for such rare entities. Accurate diagnosis requires an integrated approach incorporating histologic features, clinical context, immunophenotype, and molecular alterations.<\/jats:p>","DOI":"10.1093\/jnen\/nlag069","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T11:20:52Z","timestamp":1781695252000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>YAP1::MAML2<\/i>\n                    fusion-positive high-grade neuroepithelial tumors with rhabdoid morphology and inflammatory microenvironment: Implications for integrated diagnosis"],"prefix":"10.1093","author":[{"given":"Hainan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pathology, Guangdong Sanjiu Brain Hospital, JiNan University , Guangzhou, Guangdong,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemin","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pathology, Guangdong Sanjiu Brain Hospital, JiNan University , Guangzhou, Guangdong,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd , Nanjing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shenzhen University General Hospital , Shenzhen,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongzhu","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Guangdong Sanjiu Brain Hospital, JiNan University , Guangzhou, Guangdong,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Kong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd , Nanjing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd , Nanjing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd , Nanjing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shenzhen University General Hospital , Shenzhen,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University , Guangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,26]]},"reference":[{"key":"2026072521443818300_nlag069-B1","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1101\/gad.338681.120","article-title":"Comparison of tumor-associated YAP1 fusions identifies a recurrent set of functions critical for oncogenesis","volume":"34","author":"Szulzewsky","year":"2020","journal-title":"Genes Dev"},{"key":"2026072521443818300_nlag069-B2","doi-asserted-by":"crossref","first-page":"3787","DOI":"10.1016\/j.celrep.2018.04.099","article-title":"A de novo mouse model of c11orf95-rela fusion-driven ependymoma identifies driver functions in addition to NF-\u03baB","volume":"23","author":"Ozawa","year":"2018","journal-title":"Cell Rep"},{"key":"2026072521443818300_nlag069-B3","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/s40478-024-01862-4","article-title":"Non-supratentorial YAP1-fused ependymomas: report of two cases","volume":"12","author":"Wang","year":"2024","journal-title":"Acta Neuropathol Commun"},{"key":"2026072521443818300_nlag069-B4","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1007\/s10014-022-00439-0","article-title":"A novel YAP1-MAML2 fusion in an adult supra-tentorial ependymoma, YAP1-fused","volume":"39","author":"Tauzi\u00e8de-Espariat","year":"2022","journal-title":"Brain Tumor Pathol"},{"key":"2026072521443818300_nlag069-B5","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00401-019-02095-9","article-title":"YAP1-fusions in pediatric NF2-wildtype meningioma","volume":"139","author":"Sievers","year":"2020","journal-title":"Acta Neuropathol"},{"key":"2026072521443818300_nlag069-B6","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1111\/bpa.12866","article-title":"cIMPACT-NOW update 7: advancing the molecular classification of ependymal tumors","volume":"30","author":"Ellison","year":"2020","journal-title":"Brain Pathol"},{"key":"2026072521443818300_nlag069-B7","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/bpa.12659","article-title":"Childhood supratentorial ependymomas with YAP1-MAMLD1 fusion: an entity with characteristic clinical, radiological, cytogenetic and histopathological features","volume":"29","author":"Andreiuolo","year":"2019","journal-title":"Brain Pathol"},{"key":"2026072521443818300_nlag069-B8","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.ccell.2015.04.002","article-title":"Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age 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