Medulloblastoma（MB）是童年最常见的恶性脑肿瘤，很少见于成人。基于转录组谱系，MB目前被分类为四大分子类别，反映了相当大的生物异质性：WNT活化、SHH活化、3号组和4号组。最近，DNA甲基化分析确定了四大分子组中的其他亚组，这些亚组与不同的临床病理和分子特征相关联。同工酶异柠檬酸脱氢酶-1和2（IDH1和IDH2）突变已在多种肿瘤中报道，包括胶质瘤，而在MB中很少报告，也不常规调查。通过磁共振磁共振（MRS），我们明确评估了成人MB的癌代谢物D-2-羟基戊二酸（2HG）的存在，这是IDH1和IDH2突变的标志物。免疫表型工作和甲基化分析确定了MB为SHH-A亚型，分子检测显示存在非经典体细胞IDH1（p.R132C）突变和另一个GNAS突变，这在MB中也很少见。据我们所知，这是首次报道MB同时携带这两种突变的案例。值得注意的是，肿瘤表现出异质性表型，有一个肿瘤成分显示胶质分化，具有强大的GFAP表达，和一个具有常规MB特征和选择性存在GNAS突变的成分，表明存在两个不同的主要肿瘤亚克隆。这些发现引起了对需要更深入的MB基因特征描述的关注，以便了解它们的生物学并改善患者的分层和临床管理。此外，我们的结果强调了在非胶质瘤中进行MRS以识别IDH突变的重要性。利用高通量分子谱系分析和先进的医学影像技术无疑将增加发现罕见分子变异肿瘤实体的频率。这些发现是否具有特定的治疗意义或预后相关性需要进一步研究。 ©2023.作者（们）。

Medulloblastoma (MB) is the most common malignant brain tumor occurring in childhood and rarely found in adults. Based on transcriptome profile, MB are currently classified into four major molecular groups reflecting a considerable biological heterogeneity: WNT-activated, SHH-activated, group 3 and group 4. Recently, DNA methylation profiling allowed the identification of additional subgroups within the four major molecular groups associated with different clinic-pathological and molecular features. Isocitrate dehydrogenase-1 and 2 (IDH1 and IDH2) mutations have been described in several tumors, including gliomas, while in MB are rarely reported and not routinely investigated. By means of magnetic resonance spectroscopy (MRS), we unequivocally assessed the presence the oncometabolite D-2-hydroxyglutarate (2HG), a marker of IDH1 and IDH2 mutations, in a case of adult MB. Immunophenotypical work-up and methylation profiling assigned the diagnosis of MB, subclass SHH-A, and molecular testing revealed the presence of the non-canonical somatic IDH1(p.R132C) mutation and an additional GNAS mutation, also rarely described in MB. To the best of our knowledge, this is the first reported case of MB simultaneously harboring both mutations. Of note, tumor exhibited a heterogeneous phenotype with a tumor component displaying glial differentiation, with robust GFAP expression, and a component with conventional MB features and selective presence of GNAS mutation, suggesting co-existence of two different major tumor subclones. These findings drew attention to the need for a deeper genetic characterization of MB, in order to get insights into their biology and improve stratification and clinical management of the patients. Moreover, our results underlined the importance of performing MRS for the identification of IDH mutations in non-glial tumors. The use of throughput molecular profiling analysis and advanced medical imaging will certainly increase the frequency with which tumor entities with rare molecular alterations will be identified. Whether these findings have any specific therapeutic implications or prognostic relevance requires further investigations.© 2023. The Author(s).