{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:49:05Z","timestamp":1778644145753,"version":"3.51.4"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100018935","name":"Universit\u00e4tsklinikum Erlangen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018935","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>VG<\/jats:italic>\n                    <jats:italic>L<\/jats:italic>\n                    <jats:italic>L3<\/jats:italic>\n                    (encoding the mammalian Vestigial-like 3 transcriptional cofactor) has emerged as a fusion partner in hybrid nerve sheath tumors and in rare spindle cell rhabdomyosarcomas (RMS) of the head and neck. We herein describe a new\n                    <jats:italic>EP300::VGLL3<\/jats:italic>\n                    RMS and review\/update reported cases (total: 6) to reappraise their outcome. All six reported\n                    <jats:italic>EP300::VGLL3<\/jats:italic>\n                    fusion RMS cases originated exclusively in the tongue musculature of adult males at a median age of 48\u00a0years (range, 36\u201359). Nonradical surgery was the initial treatment in most cases, followed by variable re-excisions in most. Incomplete adjuvant chemotherapy was given to one patient. No metastases were recorded, and all patients with follow-up were disease-free at last follow-up (12, 34, 36, and 48\u00a0months). Histologically, all tumors displayed bland spindled to ovoid plump cells lacking clear-cut rhabdomyoblastic features and disposed into fascicular and storiform patterns. The tumor margins were infiltrating with entrapment of skeletal muscle fibers. Overtly malignant cytology, brisk mitotic activity, necrosis, lymphovascular, and perineural invasion were absent. Immunohistochemistry was consistently positive for desmin (6\/6), and variably myogenin (6\/6), myoD1 (4\/4), and SMA (5\/6). Fusion breakpoints were identical among all cases (\n                    <jats:italic>EP300ex31::VGLL3ex2<\/jats:italic>\n                    ). Given their indolent course after local excision alone, the noncommitted term\n                    <jats:italic>EP300::VGLL3-fused rhabdomyoblastic tumor<\/jats:italic>\n                    might be more appropriate for these tumors than the original RMS terminology to avoid overprognostication\/overtreatment that the \u201crhabdomyosarcoma\u201d label would imply. Reporting more cases is mandatory to elucidate the full anatomic and biological spectrum of this morphologically, anatomically, and genetically unique entity.\n                  <\/jats:p>","DOI":"10.1007\/s00428-026-04433-1","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T04:10:26Z","timestamp":1770351026000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["EP300::VGLL3 fused rhabdomyoblastic tumor revisited: Is the label \u201crhabdomyosarcoma\u201d justified?"],"prefix":"10.1007","author":[{"given":"Abbas","family":"Agaimy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khin","family":"Thway","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyril","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"4433_CR1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.225946","volume":"132","author":"N Figeac","year":"2019","unstructured":"Figeac N, Mohamed AD, Sun C, Sch\u00f6nfelder M, Matallanas D, Garcia-Munoz A, Missiaglia E, Collie-Duguid E, De Mello V, Pobbati AV, Pruller J, Jaka O, Harridge SDR, Hong W, Shipley J, Vargesson N, Zammit PS, Wackerhage H (2019) VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle. J Cell Sci 132:jcs225946","journal-title":"J Cell Sci"},{"key":"4433_CR2","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1097\/PAS.0000000000000538","volume":"40","author":"R Alaggio","year":"2016","unstructured":"Alaggio R, Zhang L, Sung YS, Huang SC, Chen CL, Bisogno G, Zin A, Agaram NP, LaQuaglia MP, Wexler LH, Antonescu CR (2016) A molecular study of pediatric spindle and sclerosing rhabdomyosarcoma: identification of novel and recurrent VGLL2-related fusions in infantile cases. Am J Surg Pathol 40:224\u2013235","journal-title":"Am J Surg Pathol"},{"key":"4433_CR3","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1097\/PAS.0000000000001702","volume":"45","author":"J Cyrta","year":"2021","unstructured":"Cyrta J, Gauthier A, Karanian M, Vieira AF, Cardoen L, Jehanno N, Bouvet M, Bouvier C, Komuta M, Le Loarer F, Orbach D, Rome A, Minard-Colin V, Brichard B, Pluchart C, Thebaud E, Renard M, Pannier S, Brisse H, Petit P, Benoist C, Schleiermacher G, Geoerger B, Vincent-Salomon A, Fr\u00e9neaux P, Pierron G (2021) Infantile rhabdomyosarcomas with VGLL2 rearrangement are not always an indolent disease: a study of 4 aggressive cases with clinical, pathologic, molecular, and radiologic findings. Am J Surg Pathol 45:854\u2013867","journal-title":"Am J Surg Pathol"},{"key":"4433_CR4","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1038\/s41379-021-00783-0","volume":"34","author":"BC Dickson","year":"2021","unstructured":"Dickson BC, Antonescu CR, Demicco EG, Leong DI, Anderson ND, Swanson D, Zhang L, Fletcher CDM, Hornick JL (2021) Hybrid schwannoma-perineurioma frequently harbors VGLL3 rearrangement. Mod Pathol 34:1116\u20131124","journal-title":"Mod Pathol"},{"key":"4433_CR5","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1097\/PAS.0000000000001858","volume":"46","author":"H Nihous","year":"2022","unstructured":"Nihous H, Baud J, Azmani R, Michot A, Perret R, Mayeur L, de Pinieux G, Milin S, Angot E, Duquenne S, Geneste D, Lucchesi C, Le Loarer F, Bouvier C (2022) Clinicopathologic and molecular study of hybrid nerve sheath tumors reveals their common association with fusions involving VGLL3. 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Informed consent was obtained for publishing this case.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"AA is the Editor-in-Chief of Virchows Archiv. Khin Thway serves on the editorial board of Virchows Archiv. The authors have no financial or non-financial conflicts of interest to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}