PATH-04 - Transformation of grade 2 oligodendroglioma to gliosarcoma with rapid and extensive progression: case report.

Transition of WHO grade 2 oligodendroglioma to gliosarcoma is rare. We report a case of a 40 year-old gentleman with WHO grade 2 oligodendroglioma, isocitrate dehydrogenase enzyme (IDH)-mutant, 1p/19q co-deletion positive, O⁶-methylguanine-DNA methyltransferase (MGMT) promoter methylated, tumor mutational burden of 5 mutations/megabase, with microsatellite stability. He underwent rapid and extensive transformation to WHO grade 4 glioblastoma with gliosarcomatous features, mesenchymal subclass on DNA methylation, IDH-wild type, 1p/19q co-deletion negative, MGMT promoter methylated. He was diagnosed with bi-hemispheric multifocal partially enhancing, T2-FLAIR hyperintense lesions. Pathology revealed WHO grade 2 oligodendroglioma. He enrolled on a clinical trial to receive proton radiation (45 Gray in 25 fractions) to the involved tumor sites. Three weeks after initiation of radiation, he developed headache, imbalance, and confusion. MRI brain 3 weeks after completion of radiation revealed worsening enhancement, edema, and a new region of non-enhancing T2-FLAIR hyperintensity. Bevacizumab was added for presumed pseudo-progression; followed by chemotherapy with procarbazine and lomustine (PC). Four cycles of PC were completed with observations of gradual clinical and radiographic worsening after each cycle. Re-resection of multifocal tumor for tissue diagnosis and tumor debulking revealed progression to WHO grade 3 oligodendroglioma with high mitotic activity and regions of palisading necrosis. Two weeks postoperatively, malignant cerebral edema developed, requiring left sided decompressive craniectomy. Despite early introduction of 2^nd-line chemotherapy with temozolomide, his disease continued to progress and he succumbed 1.5 years after initial diagnosis. Autopsy revealed extensive bi-hemispheric involvement of WHO grade 4 glioblastoma. Our patient demonstrated unusually rapid clinical and radiographic progression within one month after completion of radiation. Other reported cases in the literature have documented progression at 1 to 5 years after initial treatment. Both IDH mutation and 1p19q co-deletion were lost in the gliosarcomatous transformation. This tumor did not respond to alkylating agents despite the MGMT promoter-methylated status.