HGG-38. Gliomatosis cerebri/Glioblastoma with discordant histological and molecular profiles - treatment and outcome of a pediatric patient

Abstract

Gliomatosis cerebri is no longer recognized as a distinctive pathological diagnosis, but a manifestation of diffuse glioma involving at least three cerebral lobes. Lack of understanding in this manifestation of CNS neoplasms limits treatment for this aggressive disease. Here we present a case of stabilization of disease in a pediatric patient with unusual molecular profiles normally associated with aggressive tumor behavior. A nine-year-old male presented with acute onset of right-sided vision changes, headache and numbness of the left arm and leg for one day. He also had a three-month history of an asymptomatic bump on the right temporal skull bone. MRI of the brain was significant for diffuse thickening of the cortex of the entire right hemisphere (temporal>frontal>parietal lobes). No specific enhancing lesion or restricted diffusion was noted. Histologically, the tissue had findings of diffuse low-grade astrocytoma. Molecular genetic testing was notable for TERT and EGFR mutations which are more consistent with adult type high-grade astrocytic tumors. MGMT promoter methylation array was negative. Final diagnosis was glioblastoma, IDH and H3 wildtype. All the molecular features of this tumor were high-grade with an average progression free survival of less than 12 months. Despite the lack of methylation, we opted to include alkylating agents in a maintenance chemotherapy treatment plan following radiation therapy with concurrent temozolomide. Despite poor prognostic factors, the patient is alive without signs of progression 2.5 years post-diagnosis. Targeted agents were not used in upfront treatment for this patient. This is a rare case of stabilization of disease with conventional treatment in a very aggressive tumor. This case is a rare constellation of an ‘adult-type’ molecular profile in a pediatric patient with a low grade, less aggressive behavior profile, and highlights the need to better understand this rare subtype of tumors in children.