Pleomorphic Xanthoastrocytoma, Anaplastic Pleomorphic Xanthoastrocytoma, and Epithelioid Glioblastoma: Case Series With Clinical Characteristics, Molecular Features and Progression Relationship

Abstract Background: Pleomorphic xanthoastrocytoma (PXA), anaplastic pleomorphic xanthoastrocytoma (A-PXA), and epithelioid glioblastoma (E-GBM) show overlapping features. However, little is known about their clinical characteristics, molecular features and progression relationship. Methods: Fourteen patients diagnosed at Nanfang Hospital from 2016 to 2019 were enrolled, including eleven PXA patients, two A-PXA patients, and one E-GBM patient. All tumor tissue samples of fourteen patients were examined by immunohistochemistry staining (MGMT, VEGF, BRAF-V600E, etc.). The recurred tumor tissue of the E-GBM patient arising from A-PXA was detected for 11 glioma markers (MGMT, BRAF-V600E, etc.) and chromosome 1p/19q by next generation sequencing (NGS). Results: The mean age of 13 patients with PXA or A-PXA was 25.4 years, twelve of whom were burdened with tumors at supratentorial regions. VEGF showed positive expression in the tumor samples of 13 patients, MGMT positive in 10 patients, and BRAF-V600E positive in 7 patients. As for the tumor sample of the E-GBM patient survived for up to 10 years after the fourth resections, BRAF V600E was wild-type in the sample obtained from the first surgery while it was mutant in the second, third, and fourth surgery. In the contrast, the promoter status of MGMT in four operations were unmethylated. The NGS results showed that the mutation frequencies of BRAF V600E in the second surgery, the third surgery and the fourth surgery were 14.06%, 9.13% and 48.29% respectively. Conclusions: Collectively, the results suggest that patients with A-PXA may relapse multiple times and eventually progress to E-GBM with BRAF-V600E mutation.