CEREBELLAR DIFFUSE MIDLINE GLIOMA, H3K27M ALTERED IN A FIFTY-FIVE-YEAR-OLD PATIENT

Abstract

Abstract H3 K27M mutations were first identified in Pediatric Diffuse Intrinsic Pontine Glioma and are now recognized in gliomas occurring in other midline locations such as the thalamus, spinal cord and cerebellum. These gliomas were renamed to Diffuse Midline Glioma (DMG) H3 K27-altered in the 2021 WHO classification due to the discovery of alternate mechanisms of H3 K27 loss. These gliomas are more commonly found in children but also occur in adolescents and young adults. We present the case of a 55- year-old woman who presented with a 2.5-month history of nausea, vomiting and gait impairment. Imaging revealed a partially cystic, enhancing lesion in the midline of the cerebellum. She had a gross total resection with pathology revealing Diffuse Midline Glioma, H3K27 altered, subgroup DMG, H3 wildtype with EZHIP over-expression, WHO grade 4. The patient completed chemoradiation with temozolomide with plans to enroll in a clinical trial upon progression. However due to loss of ambulation and function she was admitted to hospice. The patient survived 24 months after her surgery, a period longer than the reported median overall survival in DMG with EZIP overexpression which is 16 months. This case illustrates the importance of considering DMG H3K27- altered glioma in adults older than 40 years who present with infiltrative IDH wildtype glioma in midline locations. Recognition of this diagnosis may allow enrollment in clinical trials and should prompt molecular testing for concurrent targetable alterations in the RAS-MAPK-pathway (e.g., mutations in BRAF V600E, FGFR1, NF1 and NTRK) and PI3K-mTOR pathway (e.g., PIK3CA mutation).