Infantile Rhabdomyosarcomas With VGLL2 Rearrangement Are Not Always an Indolent Disease

作者：Joanna Cyrta, Arnaud Gauthier, Marie Karanian, André Filipe Vieira, Liesbeth Cardoen, Nina Jehanno, Mégane Bouvet, Corinne Bouvier, Mina Komuta, François Le Loarer, Daniel Orbach, Angélique Rome, Véronique Minard‐Colin, Bénédicte Brichard, Claire Pluchart, Estelle Thébaud, Marleen Renard, Stéphanie Pannier, Hervé J. Brisse, Philippe Petit, Camille Benoist, Gudrun Schleiermacher, Birgit Geoerger, Anne Vincent‐Salomon, Paul Fréneaux, Gaëlle Pierron · 发表于：The American Journal of Surgical Pathology · 年份：2021 · DOI：10.1097/pas.0000000000001702 · 被引用次数：29 · 研究领域：Sarcoma Diagnosis and Treatment、Tumors and Oncological Cases、Soft tissue tumor case studies

VGLL2-rearranged rhabdomyosarcomas (RMS) are rare low-grade tumors with only favorable outcomes reported to date. We describe 4 patients with VGLL2-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 y). 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, TP53, CDKN2A/B, FGFR4) at relapse, but no recurrent events. RNA sequencing confirmed that high-grade tumors retained VGLL2 fusion transcripts and transcriptomic profiles consistent with VGLL2-rearranged RMS. High-grade samples showed a high expression o...