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

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