{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T08:35:31Z","timestamp":1794040531820,"version":"4.8.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">VGLL2<\/jats:italic>\n                    -rearranged rhabdomyosarcomas (RMS) are rare low-grade tumors with only favorable outcomes reported to date. We describe 4 patients with\n                    <jats:italic toggle=\"yes\">VGLL2<\/jats:italic>\n                    -rearranged RMS confirmed by molecular studies, who experienced local progression and distant metastases, including 2 with fatal outcomes. Tumors were diagnosed at birth (n=3) or at 12 months of age (n=1), and were all localized at initial diagnosis, but unresectable and therefore managed with chemotherapy and surveillance. Metastatic progression occurred from 1 to 8 years from diagnosis (median, 3.5\u2009y). Three patients experienced multimetastatic spread and one showed an isolated adrenal metastasis. At initial diagnosis, 3 tumors displaying bland morphology were misdiagnosed as fibromatosis or infantile fibrosarcoma and initially managed as such, while 1 was a high-grade sarcoma. At relapse, 3 tumors showed high-grade morphology, while 1 retained a low-grade phenotype. Low-grade primary tumors showed only very focal positivity for desmin, myogenin, and\/or MyoD1, while high-grade tumors were heterogenously or diffusely positive. Whole-exome sequencing, performed on primary and relapse samples for 3 patients, showed increased genomic instability and additional genomic alterations (eg,\n                    <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">CDKN2A\/B<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">FGFR4<\/jats:italic>\n                    ) at relapse, but no recurrent events. RNA sequencing confirmed that high-grade tumors retained\n                    <jats:italic toggle=\"yes\">VGLL2<\/jats:italic>\n                    fusion transcripts and transcriptomic profiles consistent with\n                    <jats:italic toggle=\"yes\">VGLL2<\/jats:italic>\n                    -rearranged RMS. High-grade samples showed a high expression of genes encoding cell cycle proteins, desmin, and some developmental factors. These 4 cases with distinct medical history imply the importance of complete surgical resection, and suggest that RMS-type chemotherapy should be considered in unresectable cases, given the risk of high-grade transformation. They also emphasize the importance of correct initial diagnosis.\n                  <\/jats:p>","DOI":"10.1097\/pas.0000000000001702","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T20:13:28Z","timestamp":1617826408000},"page":"854-867","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":29,"title":["Infantile Rhabdomyosarcomas With VGLL2 Rearrangement Are Not Always an Indolent Disease"],"prefix":"10.1097","volume":"45","author":[{"given":"Joanna","family":"Cyrta","sequence":"first","affiliation":[{"name":"Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Gauthier","sequence":"additional","affiliation":[{"name":"Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Karanian","sequence":"additional","affiliation":[{"name":"Department of Pathology, Lyon University Hospital, Lyon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre F.","family":"Vieira","sequence":"additional","affiliation":[{"name":"Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesbeth","family":"Cardoen","sequence":"additional","affiliation":[{"name":"Imaging"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Jehanno","sequence":"additional","affiliation":[{"name":"Nuclear Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9gane","family":"Bouvet","sequence":"additional","affiliation":[{"name":"Genetics Unit, Department of Tumor Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Bouvier","sequence":"additional","affiliation":[{"name":"Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Komuta","sequence":"additional","affiliation":[{"name":"Pathology"},{"name":"Department of Pathology, School of Medicine, Keio University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Le Loarer","sequence":"additional","affiliation":[{"name":"Department of Pathology, Bergoni\u00e9 Institute, Bordeaux"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Orbach","sequence":"additional","affiliation":[{"name":"SIREDO Oncology Center (Care, Innovation and Research for Children and AYA With Cancer), Curie Institute, PSL Research University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9lique","family":"Rome","sequence":"additional","affiliation":[{"name":"Pediatric and Adolescent Hematogy and Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Minard-Colin","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Campus, INSERM U1015, Paris-Saclay University, Villejuif"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Brichard","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\/Oncology, University Hospital Saint-Luc, Catholic University of Leuven, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Pluchart","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology\/Hematology, American Hospital, University Hospital of Reims, Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Thebaud","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-oncology, University Hospital of Nantes, Nantes"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen","family":"Renard","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\/Oncology, University Hospital Saint-Luc, Catholic University of Leuven, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Pannier","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, University Hospital Necker-Enfants-Malades, Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Brisse","sequence":"additional","affiliation":[{"name":"Imaging"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Petit","sequence":"additional","affiliation":[{"name":"Radiology, La Timone Hospital, Aix Marseille University, Marseille"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Benoist","sequence":"additional","affiliation":[{"name":"Biopathology and Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun","family":"Schleiermacher","sequence":"additional","affiliation":[{"name":"SIREDO Oncology Center (Care, Innovation and Research for Children and AYA With Cancer), 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