ETMR-15. Central Nervous System Embryonal Tumor with EWSR1 translocation: Evolving changes in histology, sequencing, and epigenetics at relapse in 2 patients and potential treatment implications

Abstract INTRODUCTION: Histologically diagnosed embryonal tumors (ET) of the central nervous system (CNS) in pediatric population represent a group aggressive malignancies with historically poor prognoses. Immunohistochemistry (IHC) and cytogenetics refined tumor classification improved treatment strategies. Modern advancements molecular methods including methylation profiling provide further delineation distinct ET subclasses. CASE DESCRIPTION: We present two cases initial diagnosis CNS EWSR1 rearrangement. Relapsed tissue both displayed acquisition INI-1 loss consistent atypical teratoid/rhabdoid (AT/RT). The first case presented at 14 months age vomiting altered mental status. Imaging revealed right frontal lobe hemorrhagic mass signs increased intracranial pressure; pathology returned as EWSR1-PLAGL1 translocation. Patient ultimately experienced multiple relapses sample each loss. second 11 new onset seizures was found to have tumor; recurrence original bed malignant Methylation for diagnostic samples patients not otherwise specified, while relapsed AT/RT. translocation persistent from samples. CONCLUSION/DISCUSSION: These illustrate need ongoing analysis primitive neuroectodermal rearrangements, unique role studies tissue. emergence resistance subpopulation cells more AT/RT suggests these could benefit upfront experimental approaches