Department of Neurosurgery, University Hospital Group (GHU) Paris-Sainte-Anne Hospital, Paris, France.
Paris Descartes University, Sorbonne Paris Cité, Paris, France.
Neuro Oncol. 2020 Aug 17;22(8):1190-1202. doi: 10.1093/neuonc/noaa024.
Considering that pediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs).
We performed a multicentric retrospective study of 112 AYAs from adult and pediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyze their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25 years, histopathological HGG diagnosis, available clinical data, and preoperative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next-generation sequencing, whole exome sequencing, and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 World Health Organization (WHO) classification.
Based on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of pediatric subtypes (histone H3-mutants, 40%) but also adult subtypes (isocitrate dehydrogenase [IDH] mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH mutants, and 1p/19q codeletion and the relative high frequency of "rare adult IDH mutations" (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to what is observed in children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance.
HGGs in AYAs could benefit from a specific classification, driven by molecular subtyping rather than age group. Collaborative efforts are needed from pediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.
考虑到儿科高级别神经胶质瘤（HGG）在生物学上与成人 HGG 不同，本研究旨在定义青少年和年轻成人（AYA）中 HGG 的特征。
我们对来自成人和儿科法兰西岛神经外科单位的 112 名 AYA 进行了多中心回顾性研究，这些患者于 1998 年至 2013 年接受治疗，以分析其临床放射影像学和组织分子特征。纳入标准为年龄 15 至 25 岁，组织病理学 HGG 诊断，有临床数据和术前及随访 MRI。MRI 和肿瘤样本进行了中心审查。进行免疫组织化学和互补分子技术，如靶向/下一代测序、全外显子组测序和 DNA 甲基化分析，以根据 2016 年世界卫生组织（WHO）分类进行综合诊断。
基于 80 名有记录的 AYA 患者，HGG 构成了异质的临床病理和分子群体，以儿科亚型（组蛋白 H3 突变，40%）为主，但也包括成人亚型（异柠檬酸脱氢酶 [IDH] 突变，28%），其特点是少突胶质细胞瘤、IDH 突变和 1p/19q 缺失以及相对较高频率的“罕见成人 IDH 突变”（20%）。H3G34 突变（14%）是 AYA 中最具特异性的亚组。在 H3K27 突变亚组中，非脑桥弥漫中线胶质瘤比弥漫性内在脑桥胶质瘤更常见（66.7%比 23.8%），与儿童观察到的情况相反。我们发现，WHO 分级没有预后价值，但分子亚组对预后有重要影响。
AYA 中的 HGG 可能受益于特定的分类，由分子亚型驱动，而不是年龄组。需要儿科和成人神经肿瘤学团队的合作，以改善 AYA 中 HGG 的治疗。
