ETMR-03. Unique Case of Pontine CNS tumor with BCOR internal tandem duplication (ITD) in an Infant

Central nervous system (CNS) tumors with BCOR ITD represent a new molecularly-defined entity which typically originate in cerebellar or cerebral hemispheres, but can rarely occur in the brainstem. Herein we present a case of a 17-month-old infant who presented with left hemiparesis, ataxia, and facial asymmetry, with imaging demonstrating an expansile T2-hyperintense pontine mass with avid diffusion restriction; he was referred with question of DIPG though given his young age and tumor’s atypical diffusion restriction, biopsy was recommended. Pathology was consistent with a high-grade neuroepithelial tumor, not classic by histology or immunohistochemistry (IHC) for one diagnosis (eg, negative H3K27M-mutant IHC, retained H3K27me3). Methylation confidently matched (99% probability) to CNS tumor with BCOR ITD; BCOR ITD was confirmed on RNA fusion panel. Tumor/normal whole exome sequencing did not identify other somatic alterations but interestingly revealed germline tumor predisposition variants in MSH6 (c.1912del) [associated with Lynch syndrome (though there is not a second somatic alteration nor hypermutant state] and SMARCE1 (c.751C>T) [associated with meningiomas]. The patient underwent chemotherapy per ACNS0334 regimen A (induction chemotherapy followed by high-dose chemotherapy with autologous stem cell rescue) with further consolidation with focal proton radiation (54Gy) with very favorable imaging and clinical response. After the first induction cycle, there was significant tumor shrinkage with resolution of diffusion restriction, and pre-treatment sensorineural hearing loss (related to pontine disease) normalized. The patient is now undergoing off-therapy surveillance with no radiographic evidence of viable or recurrent tumor. This case highlights the importance of biopsy and subsequent comprehensive histologic/molecular profiling for pontine tumors in young patients with atypical imaging features to guide precise understanding of diagnosis, prognosis, and treatment. Furthermore, this case provides further evidence that CNS tumors with BCOR ITD can rarely present in the brainstem and despite inability to fully resect, can respond favorably to multimodal therapy.