大脑多结节和空泡变性神经元肿瘤的临床病理及分子特征

Clinicopathological and molecular features of multinodular and vacuolating neuronal tumors of the cerebrum

目的探讨大脑多结节和空泡变性神经元肿瘤(multinodular and vacuolating neuronal tumor,MVNT)的临床病理特征,并探讨其免疫表型、分子特征及预后。方法收集解放军南部战区总医院2013—2021年间4例大脑MNVT病例和广东省惠州市第一人民医院1例的临床和影像学资料。复习5例MVNT患者的临床资料,光镜下观察其组织学特点和免疫表型,综合分子改变和随访结果评估患者预后。结果5例患者,女性4例,男性1例;年龄17~51岁(平均42岁);临床4例以癫痫为首发症状,1例表现为头部不适感。术前影像显示颞叶(4例)或额叶(1例)皮质深层和/或白质浅层处无明显强化、T2像呈高信号的多结节状病变。镜下观察病变位于皮质下白质和/或皮质深层,呈多发离散或聚集的结节改变。结节主要由不成熟的神经元样细胞组成,核空泡状,核仁突出,胞质嗜酸性或空亮,核偏位,细胞周围可见大小不一的偏心空泡,未见细胞多形性和核分裂象。免疫组织化学空泡状肿瘤细胞HuC/HuD、SOX2和Olig2均阳性,突触素、神经丝蛋白和MAP2部分阳性,但NeuN、胶质纤维酸性蛋白、p53、H3K27M、IDH1 R132H、ATRX、BRG1、INI1和BRAF V600E阴性。2例行二代测序(含131个中枢神经系统肿瘤诊断和预后相关基因),未检测到异常的分子改变。5例均行病灶切除术,术后未行辅助性放化疗,随访6个月至8年,均未见肿瘤进展。结论MVNT多见于成人,是一种惰性神经元肿瘤,WHO分级1级,肿瘤即使不全切除病变亦无进展,如无临床症状,可选择保守治疗。

Objective To investigate clinicopathological features of multinodular and vacuolar neurodegenerative tumor(MVNT)of the cerebrum,and to investigate its immunophenotype,molecular characteristics and prognosis.Methods Four cases were collected at the General Hospital of Southern Theater Command,Guangzhou,China and one case was collected at the First People′s Hospital of Huizhou,China from 2013 to 2021.Clinical,histological,immunohistochemical and molecular characteristics of these five cases were analyzed.Follow-up was carried out to evaluate their prognoses.Results There were four females and one male,with an average age of 42 years(range,17 to 51 years).Four patients presented with seizures,while one presented with discomfort on the head.Pre-operative imaging demonstrated non-enhancing,T2-hyperintense multinodular lesions in the deep cortex and superficial white matter of the frontal(n=1)or temporal lobes(n=4).Microscopically,the tumor cells were mostly arranged in discrete and coalescent nodules primarily within the deep cortical ribbon and superficial subcortical white matter.The tumors were composed of large cells with ganglionic morphology,vesicular nuclei,prominent nucleoli and amphophilic or lightly basophilic cytoplasm.They exhibited varying degrees of matrix vacuolization.Vacuolated tumor cells did not show overt cellular atypia or any mitotic activities.Immunohistochemically,tumor cells exhibited widespread nuclear staining for the HuC/HuD neuronal antigens,SOX10 and Olig2.Expression of other neuronal markers,including synaptophysin,neurofilament and MAP2,was patchy to absent.The tumor cells were negative for NeuN,GFAP,p53,H3K27M,IDH1 R132H,ATRX,BRG1,INI1 and BRAF V600E.No aberrant molecular changes were identified in case 3 and case 5 using next-generation sequencing(including 131 genes related to diagnosis and prognosis of central nervous system tumors).All patients underwent complete or substantial tumor excision without adjuvant chemoradiotherapy.Post-operative follow-up information over intervals of 6 months to 8 years was available for five patients.All patients were free of recurrence.Conclusions MVNT is an indolent tumor,mostly affecting adults,which supports classifying MVNT as WHO grade 1.There is no tumor recurrence even in the patients treated with subtotal surgical excision.MVNTs may be considered for observation or non-surgical treatments if they are asymptomatic.