{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:43:09Z","timestamp":1791499389294,"version":"4.3.4"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P50 CA097257"],"award-info":[{"award-number":["P50 CA097257"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["DP5 OD021403"],"award-info":[{"award-number":["DP5 OD021403"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\u2018Intracranial mesenchymal tumor, FET\u2010CREB fusion\u2010positive\u2019 occurs primarily in children and young adults and has previously been termed intracranial angiomatoid fibrous histiocytoma (AFH) or intracranial myxoid mesenchymal tumor (IMMT). Here we performed genome\u2010wide DNA methylation array profiling of 20 primary intracranial mesenchymal tumors with FET\u2010CREB fusion to further study their ontology. These tumors resolved into two distinct epigenetic subgroups that were both divergent from all other analyzed intracranial neoplasms and soft tissue sarcomas, including meningioma, clear cell sarcoma of soft tissue (CCS), and AFH of extracranial soft tissue. The first subgroup (Group A, 16 tumors) clustered nearest to but independent of solitary fibrous tumor and AFH of extracranial soft tissue, whereas the second epigenetic subgroup (Group B, 4 tumors) clustered nearest to but independent of CCS and also lacked expression of melanocytic markers (HMB45, Melan A, or MITF) characteristic of CCS. Group A tumors most often occurred in adolescence or early adulthood, arose throughout the neuroaxis, and contained mostly <jats:italic>EWSR1<\/jats:italic>\u2010<jats:italic>ATF1<\/jats:italic> and <jats:italic>EWSR1<\/jats:italic>\u2010<jats:italic>CREB1<\/jats:italic> fusions. Group B tumors arose most often in early childhood, were located along the cerebral convexities or spinal cord, and demonstrated an enrichment for tumors with <jats:italic>CREM<\/jats:italic> as the fusion partner (either <jats:italic>EWSR1<\/jats:italic>\u2010<jats:italic>CREM<\/jats:italic> or <jats:italic>FUS<\/jats:italic>\u2010<jats:italic>CREM<\/jats:italic>). Group A tumors more often demonstrated stellate\/spindle cell morphology and hemangioma\u2010like vasculature, whereas Group B tumors more often demonstrated round cell or epithelioid\/rhabdoid morphology without hemangioma\u2010like vasculature, although robust comparison of these clinical and histologic features requires future study. Patients with Group B tumors had inferior progression\u2010free survival relative to Group A tumors (median 4.5 vs. 49\u00a0months, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.001). Together, these findings confirm that intracranial AFH\u2010like neoplasms and IMMT represent histologic variants of a single tumor type (\u2018intracranial mesenchymal tumor, FET\u2010CREB fusion\u2010positive\u2019) that is distinct from meningioma and extracranial sarcomas. Additionally, epigenomic evaluation may provide important prognostic subtyping for this unique tumor entity.<\/jats:p>","DOI":"10.1111\/bpa.13037","type":"journal-article","created":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T09:47:34Z","timestamp":1637920054000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Intracranial mesenchymal tumors with FET\u2010CREB fusion are composed of at least two epigenetic subgroups distinct from meningioma and extracranial sarcomas"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7268-2712","authenticated-orcid":false,"given":"Emily A.","family":"Sloan","sequence":"first","affiliation":[{"name":"Department of Pathology University of California, San Francisco  San Francisco California USA"},{"name":"Department of Pathology and Laboratory Medicine MedStar Georgetown University Hospital  Washington D.C. 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