Department of Pathology, Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Erasme University Hospital, Brussels, Belgium.
Department of Neurosurgery, Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Erasme University Hospital, Brussels, Belgium.
Acta Neuropathol Commun. 2023 Mar 18;11(1):46. doi: 10.1186/s40478-023-01549-2.
Central Nervous System (CNS) embryonal tumors represent a heterogeneous group of highly aggressive tumors occurring preferentially in children but also described in adolescents and adults. In 2021, the CNS World Health Organization (WHO) classification drastically changed the diagnosis of the other CNS embryonal tumors including new histo-molecular tumor types. Here, we report a pediatric case of a novel tumor type among the other CNS embryonal tumors classified within the methylation class "CNS Embryonal Tumor with BRD4-LEUTX Fusion". The patient was a 4-year girl with no previous history of disease. For a few weeks, she suffered from headaches, vomiting and mild fever associated with increasing asthenia and loss of weight leading to a global deterioration of health. MRI brain examination revealed a large, grossly well-circumscribed tumoral mass lesion located in the left parietal lobe, contralateral hydrocephalus and midline shift. Microscopic examination showed a highly cellular tumor with a polymorphic aspect. The majority of the tumor harbored neuroectodermal features composed of small cells with scant cytoplasm and hyperchromatic nuclei associated with small "medulloblastoma-like" cells characterized by syncytial arrangement and focally a streaming pattern. Tumor cells were diffusely positive for Synaptophysin, CD56, INI1 and SMARCA4 associated with negativity for GFAP, OLIG-2, EMA, BCOR, LIN28A and MIC-2. Additional IHC features included p53 protein expression in more than 10% of the tumor's cells and very interestingly, loss of H3K27me3 expression. The Heidelberg DNA-methylation classifier classified this case as "CNS Embryonal Tumor with BRD4:LEUTX Fusion". RNA-sequencing analyses confirmed the BRD4 (exon 13)-LEUTX (exon 2) fusion with no other molecular alterations found by DNA sequencing. Our case report confirmed that a new subgroup of CNS embryonal tumor with high aggressive potential, loss of H3K27me3 protein expression, BRDA4-LEUTX fusion, named "Embryonal CNS tumor with BRD4-LEUTX fusion", has to be considered into the new CNS WHO classification.
中枢神经系统 (CNS) 胚胎肿瘤是一组高度侵袭性肿瘤，主要发生在儿童中，但也有青少年和成人发病的报道。2021 年，CNS 世界卫生组织 (WHO) 分类方案对其他 CNS 胚胎肿瘤的诊断进行了重大改变，包括新的组织分子肿瘤类型。在这里，我们报告了一个新的肿瘤类型病例，该病例属于新的 CNS WHO 分类中的“BRD4-LEUTX 融合的 CNS 胚胎肿瘤”甲基化亚类。患者为 4 岁女孩，无既往疾病史。数周以来，她一直遭受头痛、呕吐和轻度发热，伴有逐渐虚弱和体重减轻，导致整体健康状况恶化。脑部 MRI 检查显示左顶叶有一个大的、大体边界清楚的肿瘤肿块病变，伴有对侧脑积水和中线移位。显微镜下检查显示肿瘤细胞高度增生，形态多样。肿瘤的大部分具有神经外胚层特征，由小细胞组成，细胞质稀少，核染色质深，伴有小的“髓母细胞瘤样”细胞，表现为合胞体排列，局部呈流状排列。肿瘤细胞弥漫性表达突触素、CD56、INI1 和 SMARCA4，同时表达 GFAP、OLIG-2、EMA、BCOR、LIN28A 和 MIC-2 阴性。额外的免疫组织化学特征包括 p53 蛋白在肿瘤细胞中的表达超过 10%，并且非常有趣的是，H3K27me3 表达缺失。海德堡 DNA 甲基化分类器将该病例归类为“BRD4：LEUTX 融合的 CNS 胚胎肿瘤”。RNA 测序分析证实存在 BRD4（外显子 13）-LEUTX（外显子 2）融合，DNA 测序未发现其他分子改变。我们的病例报告证实，一种新的具有高侵袭性潜能、H3K27me3 蛋白表达缺失、BRDA4-LEUTX 融合的 CNS 胚胎肿瘤亚组，命名为“BRD4-LEUTX 融合的 CNS 胚胎肿瘤”，需要被纳入新的 CNS WHO 分类。
