摘要：

目的 回顾分析1 例存在BRAF V600E 突变的混合性多形性黄色星形细胞瘤和节细胞胶质瘤患儿的临床病理学和分子遗传学特征。 方法与结果 男性患儿，14 岁，临床表现为发作性意识丧失伴四肢抽搐6 年，头部MRI 显示左侧颞叶海马类圆形异常信号，考虑占位性病变。手术全切除肿瘤，术中可见颞叶深部局部脑回粉红色，肿瘤组织呈灰红、灰白色，质地较韧，内有钙化，伴囊性变，血供较丰富，无包膜，与周围脑组织界限清晰。组织学形态表现为肿瘤细胞弥漫性生长，肿瘤具有异质性：部分区域呈节细胞胶质瘤结构，部分区域呈多形性黄色星形细胞瘤结构。免疫组织化学染色和特殊染色，节细胞胶质瘤区域胶质纤维酸性蛋白（GFAP）和神经微丝蛋白（NF）散在阳性，神经节细胞样细胞微管相关蛋白-2 和神经元核抗原阳性，Ki-67 抗原标记指数约2%；多形性黄色星形细胞瘤区域梭形肿瘤细胞GFAP 和NF 散在阳性，黄瘤样细胞CD163 和CD68 阳性，Ki-67 抗原标记指数3% ~ 5%，网织纤维丰富。基因检测显示两部分区域均存在BRAF V600E 突变。术后未予放射治疗和药物化疗，口服抗癫痫药物（丙戊酸钠1.20 g/次、2 次/d 和左乙拉西坦0.50 g/次、2 次/d）1 年，临床症状明显改善。随访18 个月未见肿瘤复发。 结论 混合性多形性黄色星形细胞瘤和节细胞胶质瘤是临床少见的中枢神经系统肿瘤，具有多形性黄色星形细胞瘤和节细胞胶质瘤的组织学形态特征，但具有BRAF V600E 突变的相同分子遗传学特征。该病例对混合性胶质瘤和混合性神经元-胶质肿瘤的组织学形态、组织来源和分子遗传学研究具有很好的提示意义。

关键词: 星形细胞瘤, 神经节神经胶质瘤, 原癌基因蛋白质B-raf, 突变, 病理学, 免疫组织化学

Abstract:

Objective  To investigate the clinicopathological and molecular genetic features of one case of mixed pleomorphic xanthoastrocytoma (PXA) and ganglioglioma (GG) with BRAF V600E mutation.  Methods and Results  A 14-year-old boy mainly presented paroxymal loss of consciousness and tic of limbs for 6 years. Head MRI displayed circular abnormal signal on the hippocampus of left temporal lobe, considering space-occupying lesion. The patient underwent operation, and the lesion was totally removed. Pink gyri in deep temporal lobe could be seen during the operation. The tumor tissue was red grey, tough, nonencapsulated, with calcification, cystic degeneration, rich blood supply and clear boundary. Morphology showed the tumor grew diffusely and was heterogeneous: some areas showed the structure of GG and others showed the structure of PXA. Immunohistochemical staining and special staining showed in the region of GG, the tumor was scatteredly positive for glial fibrillary acidic protein (GFAP) and neurofilament protein (NF), gangliocyte-like cells were positive for microtubule associated protein-2 (MAP-2) and neuronal nuclei (NeuN), Ki-67 labeling index was 2%; in the region of PXA, spindle tumor cells were scatteredly positive for GFAP and NF, xanthomatoid cells were positive for CD163 and CD68, Ki-67 labeling index was 3%-5%, reticular fibers were abundant. Molecular detection showed that BRAF V600E mutation existed in both parts of the tumor. The patient was not treated by postoperative radiotherapy or chemotherapy. He took antiepileptic drugs (AEDs) orally [sodium valproate 1.20 g (twice a day) and levetiracetam 0.50 g (twice a day)] for one year, and the symptoms were greatly improved. He had no evidence of tumor recurrence in the 18-month follow-up period.  Conclusions  Combined PXA and GG is a rare tumor of the central nervous system (CNS). The tumor showed different morphological features of PXA and GG, but with the same BRAF V600E mutation molecular characteristics. This case may support the study on morphology, histological origin and molecular genetics for PXA and GG.

Key words: Astrocytoma, Ganglioglioma, Proto-oncogene proteins B-raf, Mutation, Pathology, Immunohistochemistry