Department of Radiological, Oncological and Anatomo-pathological Sciences, University Sapienza of Rome, Rome, Italy.
Department of Hematology/Oncology and Stem Cell Transplantation, IRCCS Bambino Gesù Children Hospital, Rome, Italy.
Indian J Pathol Microbiol. 2022 May;65(Supplement):S73-S82. doi: 10.4103/ijpm.ijpm_1049_21.
Embryonal tumors are a heterogenous group of neoplasms mostly defined by recurrent genetic driver events. They have been, previously, broadly classified as either medulloblastoma or supratentorial primitive neuroectodermal tumors (PNETs). However, the application of DNA methylation/gene expression profiling in large series of neoplasms histologically defined as PNET, revealed tumors, which showed genetic events associated with glial tumors. These findings led to the definitive removal of the term "PNET" in the 2016 World Health Organization (WHO) classification of CNS tumors. Moreover, further studies on a large scale of methylation profiling have allowed the identification of new molecular-defined entities and have largely influenced the 5 edition of the WHO classification of CNS tumors (WHO CNS5) for both medulloblastomas and other CNS embryonal tumors. The importance of molecular characteristics in CNS embryonal tumors is well represented by the identification of different molecular groups and subgroups in medulloblastoma. So, in the CNS5, the emerged group 3 and group 4 belong to the classification, and the four molecular and morphologic types are now combined into a unique section. Among other embryonal tumors, two new recognized entities are introduced in CNS5: CNS neuroblastoma, FOXR2-activated, and CNS tumor with BCOR internal tandem duplication (ITD). Embryonal tumor with multilayered rosettes (ETMR), already present in the previous classification now has a revised nomenclature as a result of the new DICER1 alteration, additional to the formerly known C19MC. Regarding atypical teratoid/rhabdoid tumor (AT/RT), three molecular subgroups are recognized in CNS5. The combination of histopathological and molecular features reflects the complexity of all these tumors and gives critical information in terms of prognosis and therapy. This encourages the use of a layered diagnostic report with the integrated diagnosis at the top, succeeded by layers including the histological, molecular, and other essential details.
胚胎性肿瘤是一组异质性肿瘤，主要由反复发生的遗传驱动事件定义。它们以前被广泛分为髓母细胞瘤或幕上原始神经外胚层肿瘤（PNET）。然而，在一系列组织学上定义为 PNET 的肿瘤中应用 DNA 甲基化/基因表达谱分析，揭示了具有与神经胶质瘤相关遗传事件的肿瘤。这些发现导致在 2016 年世界卫生组织（WHO）中枢神经系统肿瘤分类中明确删除了“PNET”一词。此外，在大规模甲基化谱分析的基础上进行的进一步研究，确定了新的分子定义实体，并在很大程度上影响了第五版 WHO 中枢神经系统肿瘤分类（WHO CNS5），包括髓母细胞瘤和其他中枢神经系统胚胎性肿瘤。在中枢神经系统胚胎性肿瘤中，分子特征的重要性体现在髓母细胞瘤中不同分子亚群和亚组的鉴定上。因此，在 CNS5 中，新出现的第 3 组和第 4 组被归入分类，现在将四种分子和形态学类型合并为一个独特的部分。在其他胚胎性肿瘤中，CNS5 中引入了两个新的实体：FOXR2 激活的中枢神经系统神经母细胞瘤和中枢神经系统肿瘤伴 BCOR 内部串联重复（ITD）。多层玫瑰花结胚胎性肿瘤（ETMR）已经存在于以前的分类中，现在由于新的 DICER1 改变，除了以前已知的 C19MC 外，还有了一个修订后的命名。关于典型的畸胎瘤/横纹肌样瘤（AT/RT），CNS5 中识别出三个分子亚组。组织病理学和分子特征的结合反映了所有这些肿瘤的复杂性，并提供了预后和治疗方面的关键信息。这鼓励使用分层诊断报告，将综合诊断放在最上面，其次是包括组织学、分子和其他必要细节的各个层。
