Epithelioid glioblastoma (E‐GBM) was recently designated as a subtype of glioblastoma (GBM) by the World Health Organization (2016). E‐GBM is an aggressive and rare variant of GBM that primarily occurs in children and young adults. Although most characterized cases of E‐GBM harbor a mutation of the BRAF gene in which valine (V) is substituted by glutamic acid (E) at amino acid 600 (BRAF‐V600E), in addition to telomerase reverse transcriptase promoter mutations and homozygous CDKN2A/B deletions, the origins and cellular nature of E‐GBM remain uncertain. Here, we present a case of E‐GBM that exhibits antigenic and functional traits suggestive of microglia. Although no epithelial [e.g., CKAE1/3, epithelial membrane antigen (EMA)] or glial (e.g., GFAP, Olig2) markers were detected by immunohistochemical staining, the microglial markers CD68 and Iba1 were readily apparent. Furthermore, isolated E‐GBM‐derived tumor cells expressed microglial/macrophage‐related genes including cytokines, chemokines, MHC class II antigens, lysozyme and the critical functional receptor, CSF‐1R. Isolated E‐GBM‐derived tumor cells were also capable of phagocytosis and cytokine production. Treating E‐GBM‐derived tumor cells with the BRAF‐V600E inhibitor, PLX4032 (vemurafenib), resulted in a dose‐dependent reduction in cell viability that was amplified by addition of the CSF‐1R inhibitor, BLZ945. The present case provides insight into the cellular nature of E‐GBM and introduces several possibilities for effective targeted therapy for these patients.

中文翻译：

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具有小胶质细胞特征的上皮样胶质母细胞瘤：新疗法的潜力。

上皮样胶质母细胞瘤（E-GBM）最近被世界卫生组织（2016）指定为胶质母细胞瘤（GBM）的一个亚型。E-GBM 是一种侵袭性的、罕见的 GBM 变体，主要发生在儿童和年轻人身上。尽管大多数特征性 E-GBM 病例包含 BRAF 基因突变，其中除了端粒酶逆转录酶启动子突变和纯合CDKN2A外，缬氨酸 (V) 在氨基酸 600 处被谷氨酸 (E) 取代 (BRAF-V600E) /BE-GBM 的起源和细胞性质仍然不确定。在这里，我们介绍了一个 E-GBM 的案例，它表现出暗示小胶质细胞的抗原和功能特征。尽管通过免疫组织化学染色未检测到上皮 [例如 CKAE1/3、上皮膜抗原 (EMA)] 或神经胶质（例如 GFAP、Olig2）标志物，但小胶质细胞标志物 CD68 和 Iba1 很明显。此外，分离的 E-GBM 衍生的肿瘤细胞表达小胶质细胞/巨噬细胞相关基因，包括细胞因子、趋化因子、MHC II 类抗原、溶菌酶和关键功能受体 CSF-1R。分离的 E-GBM 衍生的肿瘤细胞也能够吞噬和产生细胞因子。用 BRAF-V600E 抑制剂 PLX4032 (vemurafenib) 处理 E-GBM 衍生的肿瘤细胞，通过添加 CSF-1R 抑制剂 BLZ945，导致细胞活力的剂量依赖性降低。本案例提供了对 E-GBM 细胞性质的深入了解，并介绍了对这些患者进行有效靶向治疗的几种可能性。