Abstract：
OBJECTIVE: Anaplastic ganglioglioma is a rare tumour, and diagnosis has been based on histological criteria. The 5th edition of the World Health Organization Classification of Tumours of the Central Nervous System (CNS WHO) does not list anaplastic ganglioglioma as a distinct diagnosis due to lack of molecular data in previous publications. We retrospectively compiled a cohort of 54 histologically diagnosed anaplastic gangliogliomas to explore whether the molecular profiles of these tumours represent a separate type or resolve into other entities.
METHODS: Samples were subjected to histological review, desoxyribonucleic acid (DNA) methylation profiling and next-generation sequencing. Morphological and molecular data were summarised to an integrated diagnosis.
RESULTS: The majority of tumours designated as anaplastic gangliogliomas resolved into other CNS WHO diagnoses, most commonly pleomorphic xanthoastrocytoma (16/54), glioblastoma, isocitrate dehydrogenase protein (IDH) wild type and diffuse paediatric-type high-grade glioma, H3 wild type and IDH wild type (11 and 2/54), followed by low-grade glial or glioneuronal tumours including pilocytic astrocytoma, dysembryoplastic neuroepithelial tumour and diffuse leptomeningeal glioneuronal tumour (5/54), IDH mutant astrocytoma (4/54) and others (6/54). A subset of tumours (10/54) was not assignable to a CNS WHO diagnosis, and common molecular profiles pointing to a separate entity were not evident.
CONCLUSIONS: In summary, we show that tumours histologically diagnosed as anaplastic ganglioglioma comprise a wide spectrum of CNS WHO tumour types with different prognostic and therapeutic implications. We therefore suggest assigning this designation with caution and recommend comprehensive molecular workup.
METHODS: Samples were subjected to histological review, desoxyribonucleic acid (DNA) methylation profiling and next-generation sequencing. Morphological and molecular data were summarised to an integrated diagnosis.
RESULTS: The majority of tumours designated as anaplastic gangliogliomas resolved into other CNS WHO diagnoses, most commonly pleomorphic xanthoastrocytoma (16/54), glioblastoma, isocitrate dehydrogenase protein (IDH) wild type and diffuse paediatric-type high-grade glioma, H3 wild type and IDH wild type (11 and 2/54), followed by low-grade glial or glioneuronal tumours including pilocytic astrocytoma, dysembryoplastic neuroepithelial tumour and diffuse leptomeningeal glioneuronal tumour (5/54), IDH mutant astrocytoma (4/54) and others (6/54). A subset of tumours (10/54) was not assignable to a CNS WHO diagnosis, and common molecular profiles pointing to a separate entity were not evident.
CONCLUSIONS: In summary, we show that tumours histologically diagnosed as anaplastic ganglioglioma comprise a wide spectrum of CNS WHO tumour types with different prognostic and therapeutic implications. We therefore suggest assigning this designation with caution and recommend comprehensive molecular workup.
摘要：
目的：间变性神经节胶质瘤是一种罕见的肿瘤，和诊断是基于组织学标准。世界卫生组织第5版中枢神经系统肿瘤分类（CNSWHO）未将间变性神经节胶质瘤列为独特的诊断，因为以前的出版物中缺乏分子数据。我们回顾性地编制了54例经组织学诊断的间变性神经节胶质瘤的队列，以探索这些肿瘤的分子谱是否代表单独的类型或解析为其他实体。
方法：对样本进行组织学检查，脱氧核糖核酸（DNA）甲基化分析和下一代测序。将形态学和分子数据总结为综合诊断。
结果：大多数被指定为间变性神经节胶质瘤的肿瘤在其他中枢神经系统WHO诊断中消退，最常见的多形性黄色星形细胞瘤（16/54），胶质母细胞瘤,异柠檬酸脱氢酶蛋白（IDH）野生型和弥漫性儿科型高级别神经胶质瘤，H3野生型和IDH野生型（11和2/54），其次是低级别的神经胶质或神经胶质细胞瘤，包括毛细胞星形细胞瘤，胚胎发育不良神经上皮肿瘤和弥漫性软脑膜神经胶质瘤（5/54），IDH突变型星形细胞瘤(4/54)等(6/54)。一部分肿瘤（10/54）不能分配给中枢神经系统WHO诊断，和指向单独实体的共同分子谱并不明显。
结论：总之，我们表明,组织学诊断为间变性神经节胶质瘤的肿瘤包括广泛的CNSWHO肿瘤类型,具有不同的预后和治疗意义.因此，我们建议谨慎分配此名称，并建议进行全面的分子检查。
方法：对样本进行组织学检查，脱氧核糖核酸（DNA）甲基化分析和下一代测序。将形态学和分子数据总结为综合诊断。
结果：大多数被指定为间变性神经节胶质瘤的肿瘤在其他中枢神经系统WHO诊断中消退，最常见的多形性黄色星形细胞瘤（16/54），胶质母细胞瘤,异柠檬酸脱氢酶蛋白（IDH）野生型和弥漫性儿科型高级别神经胶质瘤，H3野生型和IDH野生型（11和2/54），其次是低级别的神经胶质或神经胶质细胞瘤，包括毛细胞星形细胞瘤，胚胎发育不良神经上皮肿瘤和弥漫性软脑膜神经胶质瘤（5/54），IDH突变型星形细胞瘤(4/54)等(6/54)。一部分肿瘤（10/54）不能分配给中枢神经系统WHO诊断，和指向单独实体的共同分子谱并不明显。
结论：总之，我们表明,组织学诊断为间变性神经节胶质瘤的肿瘤包括广泛的CNSWHO肿瘤类型,具有不同的预后和治疗意义.因此，我们建议谨慎分配此名称，并建议进行全面的分子检查。
