中枢神经系统(CNS)胚胎性肿瘤代表了一组异质性的高侵袭性肿瘤,优先发生在儿童中,但也发生在青少年和成人中。2021年,中枢神经系统世界卫生组织(WHO)的分类大大改变了其他中枢神经系统胚胎肿瘤的诊断,包括新的组织分子肿瘤类型。这里,我们报告了一例儿科病例,在其他中枢神经系统胚胎肿瘤中,一种新的肿瘤类型被归类为甲基化类别“BRD4-LEUTX融合中枢神经系统胚胎肿瘤”。患者是一名4岁女孩,以前没有疾病史。几周来,她头痛,呕吐和轻度发烧与虚弱和体重减轻有关,导致全球健康恶化。MRI脑部检查显示,位于左顶叶的肿瘤肿块病变,对侧脑积水和中线移位。显微镜检查显示具有多态性的高度细胞肿瘤。大多数肿瘤具有神经外胚层特征,由小细胞组成,细胞质很少,核与小的“髓母细胞瘤样”细胞相关,其特征是合胞体排列和局灶性流动模式。肿瘤细胞对突触素呈弥漫性阳性,CD56、INI1和SMARCA4与GFAP的阴性相关,OLIG-2EMA,BCOR,LIN28A和MIC-2。其他的IHC特征包括在超过10%的肿瘤细胞中表达p53蛋白,非常有趣的是,H3K27me3表达缺失。海德堡DNA甲基化分类器将此病例分类为“具有BRD4:LEUTX融合的CNS胚胎肿瘤”。RNA测序分析证实了BRD4(外显子13)-LEUTX(外显子2)融合,没有通过DNA测序发现的其他分子改变。我们的病例报告证实了一个新的CNS胚胎性肿瘤亚组具有高侵袭潜力,H3K27me3蛋白表达缺失,BRDA4-LEUTX融合,命名为“BRD4-LEUTX融合的胚胎性中枢神经系统肿瘤”,必须被纳入新的CNSWHO分类。
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.