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Clinicopathological, Immunohistochemical and Molecular Genetic Study on Epithelioid Glioblastoma: A Series of Fifteen Cases with Literature Review

Authors Zeng Y, Zhu X, Wang Y, Liu B, Yang X, Wang Q, Du J, Ma Y, Lin L, Fu P, Xiao H, Guo QN

Received 11 February 2020

Accepted for publication 19 April 2020

Published 8 May 2020 Volume 2020:13 Pages 3943—3952

DOI https://doi.org/10.2147/OTT.S249317

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Nicola Silvestris


Ying Zeng,1,2 Xiangfeng Zhu,2 Yali Wang,1 Bo Liu,1 Xin Yang,2 Qiushi Wang,2 Juan Du,2 Yu Ma,2 Li Lin,2 Ping Fu,2 Hualiang Xiao,2 Qiao-Nan Guo1

1Department of Pathology, Second Affiliated Hospital, Amy Medical University (Third Military Medical University), Chongqing 400037, People’s Republic of China; 2Department of Pathology, Daping Hospital, Amy Medical University (Third Military Medical University), Chongqing 400042, People’s Republic of China

Correspondence: Qiao-Nan Guo; Hualiang Xiao Email qiaonan85@263.net; dpbl_xhl@126.com

Purpose: To observe the clinicopathological, immunohistochemical, and molecular genetic features of epithelioid glioblastoma (E-GBM), and identify tumor-associated prognostic factors.
Patients and Methods: The clinical and radiological data of fifteen cases of E-GBM were collected, and their pathological, immunohistochemical, and molecular features were examined. A 1p/19q analysis via FISH, MGMT promoter methylation by MS-PCR, and IDH1 and BRAF V600E mutation analysis by HRM-PCR were performed. The level of EZH2 expression was valuated by immunohistochemistry in 15 E-GBM cases, and the prognostic factors were analyzed in E-GBM patients. Fifteen non-E-GBM cases were used as a control.
Results: The fifteen cases of E-GBM included twelve males and three females, with fourteen cases supratentorially located. Headache was the main symptom. Microscopy revealed that the tumors were composed of epithelioid cells and some rhabdoid cells. The epithelioid and rhabdoid cells displayed focal discohesion, scant intervening neuropil, a distinct cell membrane, eosinophilic cytoplasm, and a laterally positioned nucleus. Most tumors showed high mitosis, zonal necrosis, and microvascular hyperplasia. Immunohistochemical findings included epithelioid cells positive for GFAP, vimentin, nestin, S-100, and INI-1. The molecular findings included no deletions of 1p/19q, EGFR amplifications, or IDH1 mutations in any case, a methylated MGMT promoter in 46.7% (7/15) cases, and a BRAFV600E mutation in 46.7% (7/15) cases. EZH2 overexpression occurred in 60.0% (9/15) of E-GBM cases. E-GBM patients with OS (≤ 12 months) exhibited extensive necrosis (6/6), EZH2 overexpression (6/6), MGMT promoter unmethylation (5/6), BRAFV600E mutation (3/6), and treatment (surgery4/6). E-GBM patients with OS (> 12 months) exhibited focal or limited necrosis, low or negative EZH2 expression, MGMT promoter methylation (2/3), BRAFV600E mutation (3/3), and treatment (surgery+radiotherapy/chemo-radiotherapy, 2/3).
Conclusion: E-GBM was a rare variant of glioblastoma, with histological epithelioid features and poor prognosis. Extensive necrosis, MGMT promoter unmethylation, EZH2 overexpression, and lack of adjuvant chemo-radiotherapy may indicate a poor prognosis.

Keywords: central nervous system tumor, epithelioid glioblastoma, immunohistochemistry, clinicopathological features, molecular genetics, differential diagnosis


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