Pineal region glioblastomas display features of diffuse midline and non-midline gliomas

Pineal region glioblastomas (GBM) are very rare, with approximately 46 cases described in the literature. The epidemiology, pathogenesis, and treatment of these lesions are poorly characterized. We identified all cases of pineal region GBM treated surgically at our institution between 1990 and 2017. Demographic and clinical follow-up data were extracted from the medical records for all cases. Pathology was reviewed and classified according to 2016 World Health Organization (WHO) criteria. Specific attention was given to the frequency of histone H3 K27M mutations in these midline gliomas. Eight patients (seven men, one woman) with pineal region GBM, WHO grade IV, were identified. The most common presenting symptoms were headache (75%), vision changes (75%), and gait imbalance/ataxia (50%). Median age at diagnosis was 48.5 years (range 36-74 years). Radical subtotal resection, via a supracerebellar infratentorial approach, was achieved in 75% of patients. Review of the surgical pathology revealed seven primary GBMs (including one giant cell GBM) and one pineal region GBM that developed three years after resection of a pineal parenchymal tumor of intermediate differentiation. No cases demonstrated evidence of IDH-1 R132H mutation (N = 6) or 1p/19q co-deletion (N = 3). One case tested positive for the histone H3 K27M-mutation. Targeted exome sequencing of 467 cancer-related genes revealed nonsense mutations in ATRX and NF1. Adjuvant radiation and chemotherapy was employed in 87.5% and 75.0% of patients, respectively. Median overall survival (OS) was 15 months (range 2-24 months) from GBM diagnosis. This study expands the clinical and pathologic spectrum of pineal region GBM, and provides the first report of the genetic landscape of these tumors.