From the Department of Pathology, Albert Einstein College of Medicine, and the Department of Neuropathology, Montefiore Medical Center, Bronx, New York.
Arch Pathol Lab Med. 2018 Jul;142(7):804-814. doi: 10.5858/arpa.2017-0449-RA. Epub 2018 May 18.
Diffuse gliomas comprise the bulk of "brain cancer" in adults. The recent update to the 4th edition of the World Health Organization's classification of tumors of the central nervous system reflects an unprecedented change in the landscape of the diagnosis and management of diffuse gliomas that will affect all those involved in the management and care of patients. Of the recently discovered gene alterations, mutations in the Krebs cycle enzymes isocitrate dehydrogenases (IDHs) 1 and 2 have fundamentally changed the way the gliomas are understood and classified. Incorporating information on a few genetic parameters (IDH, ATRX and/or p53, and chromosome 1p19q codeletion), a relatively straightforward diagnostic algorithm has been generated with robust and reproducible results that correlate with patients' survival far better than relying on conventional histology alone. Evidence also supports the conclusion that the vast majority of diffuse gliomas without IDH mutations (IDH-wild-type astrocytomas) behave like IDH-wild-type glioblastomas ("molecular GBM"). Together, these changes reflect a big shift in the practice of diagnostic neuropathology in which tumor risk stratification aligns better with molecular information than histology/grading. The purpose of this review is to provide the readers with a brief synopsis of the changes in the 2016 World Health Organization update with an emphasis on diffuse gliomas and to summarize key gene abnormalities on which these classifications are based. Practical points involved in day-to-day diagnostic workup are also discussed, along with a comparison of the various diagnostic tests, including immunohistochemistry, with an emphasis on targeted next-generation sequencing panel technology as a future universal approach.
弥漫性神经胶质瘤构成了成人“脑癌”的主体。世界卫生组织（WHO）中枢神经系统肿瘤分类第四版的最新更新反映了弥漫性神经胶质瘤诊断和管理领域前所未有的变化，这将影响到所有参与患者管理和护理的人员。在最近发现的基因改变中，克雷布斯循环酶异柠檬酸脱氢酶（IDH）1 和 2 的突变从根本上改变了人们对神经胶质瘤的理解和分类方式。纳入少数遗传参数（IDH、ATRX 和/或 p53 以及 1p19q 染色体缺失）的信息，生成了一个相对简单的诊断算法，其结果具有强大的可重复性，与患者的生存相关性远优于单纯依赖传统组织学。证据还支持这样的结论，即绝大多数没有 IDH 突变的弥漫性神经胶质瘤（IDH 野生型星形细胞瘤）表现得像 IDH 野生型胶质母细胞瘤（“分子 GBM”）。这些变化共同反映了诊断神经病理学实践中的重大转变，即肿瘤风险分层与分子信息的相关性优于组织学/分级。本文的目的是为读者简要概述 2016 年世界卫生组织更新中的变化，重点介绍弥漫性神经胶质瘤，并总结这些分类所依据的关键基因异常。本文还讨论了日常诊断工作中的实际问题，并比较了各种诊断测试，包括免疫组织化学，重点介绍了靶向下一代测序面板技术作为未来的通用方法。
