{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T02:46:04Z","timestamp":1791427564087,"version":"4.3.3"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The mammalian Vestigial\u2010like (VGLL) transcriptional cofactor family of proteins VGLL1\u20104 has recently emerged as an important player in the tumorigenesis of diverse neoplasms. The role of <jats:italic>VGLL3<\/jats:italic> in soft tissue tumors is exemplified by its amplification in myxoinflammatory fibroblastic sarcoma and its rearrangement (fused to <jats:italic>CHD7, CHD9<\/jats:italic>, or <jats:italic>MAMLD1<\/jats:italic>) in hybrid schwannoma\u2010perineurioma. This study characterizes a distinctive low\u2010grade myogenic neoplasm with a striking predilection for the head and neck, characterized by <jats:italic>VGLL3<\/jats:italic> fusions. The study includes five males and one female patient, aged 30\u201371\u2009years (median, 56). Three tumors originated in the tongue, with one case each in the nasopharynx, oral cavity, and oropharynx. The <jats:italic>VGLL3<\/jats:italic> fusion partners included <jats:italic>TCF12<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u20093), <jats:italic>EP300<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u20092), and <jats:italic>PPARGC1A<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u20091). The tumor size range was 0.8\u20131.6\u00a0cm (all, but one, was &lt;1\u00a0cm). Histologically, all tumors displayed bland spindle to ovoid cells arranged into vague fascicular and diffuse patterns. Mitotic activity ranged from 1 to 7 per 10 HPFs. Five tumors were muscle\u2010centered and infiltrative, and one was centered beneath nasopharyngeal mucosa. Immunohistochemistry revealed consistent expression of desmin (diffuse in four and patchy in two cases) associated with patchy smooth muscle actin expression (4\/6), and focal reactivity for myogenin (5\/6) and myoD1 (1\/3). All patients were managed surgically; one patient each received adjuvant radio\u2010 or chemotherapy. Three patients with follow\u2010up were without disease at 8, 19, and 60\u2009months and one was alive with unknown disease status at 24\u2009months. All <jats:italic>VGLL3<\/jats:italic> fusions were in\u2010frame and involved exon 2, fused with either <jats:italic>TCF12<\/jats:italic> exon 16, <jats:italic>EP300<\/jats:italic> exon 31, or <jats:italic>PPARGC1A<\/jats:italic> exon 5, respectively. This series characterizes a distinctive subset of spindle cell rhabdomyosarcoma (RMS) with a predilection for the head and neck in adults, defined by <jats:italic>VGLL3<\/jats:italic> fusions, likely indolent behavior and limited rhabdomyoblastic differentiation. Further delineation of this entity and differentiation from more aggressive molecular subtypes of spindle cell RMS is mandatory to define the most appropriate therapeutic strategy and avoid overtreatment.<\/jats:p>","DOI":"10.1002\/gcc.23083","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T14:55:44Z","timestamp":1656514544000},"page":"701-709","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Recurrent <i>VGLL3<\/i> fusions define a distinctive subset of spindle cell rhabdomyosarcoma with an indolent clinical course and striking predilection for the head and neck"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0445-8161","authenticated-orcid":false,"given":"Abbas","family":"Agaimy","sequence":"first","affiliation":[{"name":"Institute of Pathology, Erlangen University Hospital, Comprehensive Cancer Center, European Metropolitan Area Erlangen\u2010Nuremberg, Friedrich Alexander University of Erlangen\u2010Nuremberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1139-2914","authenticated-orcid":false,"given":"Josephine K.","family":"Dermawan","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iona","family":"Leong","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry University of Toronto  Toronto Ontario Canada"},{"name":"Department of Pathology &amp; 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