P11.05 Reappraisal of CNS embryonal tumors, not otherwise specified and RELA fusion negative supratentorial ependymomas using immunohistochemistry and sequencing for BCOR

Abstract

Abstract BACKGROUND BCl2 co-repressor (BCOR) gene internal tandem duplications have recently been identified as the defining molecular alteration in a subset of central nervous system (CNS) high grade neuroepithelial tumors (CNS-HGNET). Their clinicopathological profile is yet to be fully elucidated with available data being largely derived from case reports and small case series. Reported cases presented in young children with a male preponderance, were located predominantly in the posterior fossa, and sometimes but not always showed an ependymoma-like morphology. BCOR protein overexpression and exon 15 internal tandem duplications were characteristic. These tumors associated with a poor overall survival. MATERIAL AND METHODS We designed a retrospective study (2002–2019) wherein all cases of CNS embryonal tumors, not otherwise specified (NOS), by definition lacking C19MC locus amplification and Lin28A protein expression, and supratentorial ependymomas (ST-EPN), NOS, lacking RELA and YAP1 fusions and L1CAM protein expression were retrieved and subject to immunohistochemistry for BCOR. Those tumors showing nuclear expression of BCOR were subject to sequencing of exon 15 of BCOR gene. RESULTS A total of 19 CNS embryonal tumors, NOS, constituting 86% of all CNS embryonal tumors other than medulloblastomas and atypical teratoid rhabdoid tumors, and 11 ST-EPN, NOS constituting 30% of all ST EPNs, were included. Diffuse nuclear staining for BCOR was seen in 6 tumors, including two patients with CNS embryonal tumor, NOS (10 year old male with spinal cord mass; 5-year-old female with left frontal mass) and 4 patients with ST-EPN-NOS (median age 15 years, ranging from 10–28 years, all females). While the CNS embryonal tumors showed high grade small round cell morphology, the remaining showed ependymoma-like morphology, but with increased cellularity and focal to diffuse membranous expression of epithelial membrane antigen and cytokeratins unlike ependymomas. Among these four patients, one was disease free at last follow-up at 17 months, while the remaining suffered recurrences within a median time duration of 26 months after diagnosis (24 months - 36 months). CONCLUSION The clinicopathological spectrum of BCOR-altered CNS tumors appears to be wider than that described in literature. We describe BCOR alterations in a subset of ependymoma-like tumors in older children and young adults with a striking female preponderance. BCOR alterations need to be studied on a broad spectrum of pediatric and adults CNS tumors to aid in better understanding of its true prevalence and biological significance.