DNAR-10. HETEROGENEOUS MGMT PROMOTER METHYLATION IN A MULTIFOCAL GLIOBLASTOMA: A CASE REPORT

Abstract

Abstract MGMT promoter methylation status is an important predictive biomarker for treatment response in glioblastoma. MGMT unmethylated glioblastoma has elevated levels of MGMT which ultimately leads to chemoresistance. Clinicians consider the MGMT methylation status when treatment recommendations are given, and clinical trials use this marker for the selection of a homogenous group of glioblastoma patients based on prognosis. Here, we present a case of multifocal glioblastoma with heterogeneous MGMT methylation status. A 56-year-old male presented with left leg weakness for 2 months and left arm weakness for 1 month. Imaging revealed a calcified, rim enhancing right temporoparietal cystic lesion and a heterogeneously enhancing right parietal mass. Perilesional edema surrounded and connected the two lesions. The patient underwent gross total resection of the parietal mass and pathology revealed a WHO grade 4 glioblastoma, IDH wildtype, unmethylated tumor. Postoperatively, the patient was neurologically intact. He completed a 6-week long course of concomitant chemoradiation without any significant side effects. Two weeks later the patient developed rapidly worsening headaches, nausea, vomiting, dizziness, and left side weakness. Imaging revealed significant enlargement of the previously unresected temporoparietal cystic lesion with marked increase in surrounding edema and a 2-3 mm right to left midline shift. Patient underwent craniotomy with cyst drainage and tumor resection of the right cystic temporoparietal lesion, demonstrating a WHO grade 4 glioblastoma, IDH wildtype, methylated tumor. Post-operatively the patient was again neurologically intact and started adjuvant temozolomide. MGMT methylation status of glioblastoma can alter recommendations for chemotherapy with temozolomide. MGMT methylation status might vary in distinct parts of the tumor as molecular heterogeneity is a hallmark of glioblastoma. This heterogeneity should be considered by clinicians when treatments are recommended and by clinical trials for glioblastoma patients, especially when multifocal lesions have a distinct radiographic appearance.