Etmr-15. Reclassification of Childhood Central Nervous System Primitive Neuroectodermal Tumor: Clinical Features and Outcome

Abstract BACKGROUND The “central nervous system primitive neuroectodermal tumor” (CNS-PNET) nosology was removed from the World Health Organization (WHO) classification after DNA methylation profiling and new tumor entities characterized by specific recurrent genetic alterations were described. The aim of this study was to re-evaluate the diagnosis of CNS-PNET and to describe their clinical characteristics. METHODS Patients aged 18 years with CNS-PNET or unclassified tumor, who were treated at Gustave Roussy between 1999 and 2019 or enrolled in the PNET HR trial were retrospectively identified. The study included all patients with sufficient archival material for diagnosis re-evaluation. RESULTS Sixty-two patients were eligible for the current analysis. The central histopathological review proposed a diagnosis according to the WHO classification in 58 cases. Out of these cases, 34 embryonal tumors were identified: 22 Embryonal Tumors with Multilayered Rosettes (ETMR), 4 CNS neuroblastomas with FOXR2 activation (CNS NB-FOXR2), 4 CNS high-grade neuroepithelial tumors with BCOR alteration (CNS HGNET-BCOR), 4 medulloblastomas. Another 24 tumors were classified as non embryonal tumors: 11 high-grade gliomas, 5 ependymomas, 4 pineoblastomas, 2 teratomas, one desmoplastic small round cell tumor, and one pilocytic astrocytoma. Four tumors without suspected diagnosis after first analysis remain unclassified after DNA methylation profiling. The 5-year event-free survival and overall survival for patients with ETMR were 14% (95% CI, 4.7-39%) and 27% (95% CI, 14-54%) respectively. For patients with CNS HGNET-BCOR and CNS NB-FOXR2 the median time to relapse was respectively 11 months (range, 0.5 to 1.3 year) and 3.1 years (range 1.7 to 4.4 years). CONCLUSIONS This study confirmed that the former nosology of CNS PNET does not correspond to a homogenous class but encompasses a diversity of rare histomolecular entities with specific clinical characteristics and outcomes.