多结节和空泡状神经元肿瘤的临床和病理学特征分析

Analysis of clinical and pathological features of multinodular and vacuolating neuronal tumors

目的探讨多结节和空泡状神经元肿瘤(MVNT)的临床和病理学特征。方法回顾性分析2019年1月至2022年6月经北京市神经外科研究所,首都医科大学附属北京天坛医院神经病理中心诊断的4例MVNT患者的临床资料。4例患者均接受手术治疗,术后根据头颅MRI判断肿瘤切除程度。术后随访患者的症状改善情况、有无放化疗及肿瘤复发情况。对肿瘤组织标本行HE染色、免疫组织化学染色及基因测序。结果4例患者的中位年龄为38.5岁(24~42岁),男性为主(3/4),症状以头痛、头晕为主,可有癫痫发作;中位病程为2年(3个月至10年)。4例病变均位于颞叶和海马,肿瘤最大径为2.5~4.0 cm,主要累及大脑皮质深部,影像学可见特征性的"串珠状"或"簇状"异常信号。增强扫描显示无强化(2/4)或轻度不均匀强化(2/4)。4例患者的肿瘤均为全切除,术后均未行放化疗。4例患者的中位随访时间为12个月(3~43个月)。至末次随访,4例患者的术前症状均得到明显改善;影像学显示均无复发迹象。4例患者肿瘤组织的病理学检查显示,大体标本可见多个离散或合并的灰色结节,累及皮质深部、灰白质交界区和皮质下白质。HE染色显示,MVNT由小至中等大小的神经元细胞组成,排列成结节状,背景基质及肿瘤细胞胞质内可见明显的空泡形成。免疫组织化学染色结果显示,相对于正常皮质区,结节内髓磷脂碱性蛋白(MBP)呈弱阳性,使结节状病灶呈"虫蚀样"外观;微管相关蛋白(MAP2)呈不同程度阳性、突触素(Syn)呈颗粒状弱阳性,神经纤维(NF)和神经元特异性核蛋白(NeuN)呈阴性。胶质纤维酸性蛋白(GFAP)显示背景中反应性星形胶质细胞呈"蜘蛛样"表达。CD34在肿瘤细胞中表达阴性,但在邻近的发育异常的大脑皮质神经元成分中呈"分枝状"表达。4例患者的二代测序结果显示,FGFR4 P400移码突变及BRAF A34插入缺失1例,NOTCH1 L188V突变1例;其中3例行焦磷酸测序,显示O6-甲基鸟嘌呤DNA甲基转移酶(MGMT)均未发生甲基化。结论MVNT好发于成人,多见于颞叶和海马,MRI可见特征性的"串珠状"或"簇状"异常信号,特异性病理学表现为多结节、空泡样改变,可通过手术全切除,预后好。

Objective To explore the clinical and pathological features of multinodular and vacuolating neuronal tumors(MVNT).Methods A retrospective analysis was conducted on the clinical data of 4 patients with MVNT diagnosed by the Neuropathology Center of Beijing Institute of Neurosurgery,Beijing Tiantan Hospital Affiliated to Capital Medical University from January 2019 to June 2022.Four patients underwent tumor resection,and postoperative re-examination of head MRI was performed to determine the extent of tumor resection.All patients were followed up and inquired about their symptom improvement,radiotherapy,chemotherapy and tumor recurrence.HE staining,immunohistochemical staining and gene sequencing were performed on tumor tissue samples.Results The median age of the 4 patients was 38.5 years old(24-42 years old)who were mostly males(3/4).The symptoms were mainly headache and dizziness,with or without epileptic seizure.The median course of disease was 2 years(3 months to 10 years).Four patients′lesions were all located in the temporal lobe and hippocampus.The largest diameter of the tumor was 2.5-4.0 cm.The tumors mainly involved the deep cerebral cortex showing characteristic"beadlike"or"nodular"abnormal signals.The scan showed no(2/4)or mild(2/4)uneven enhancement.The tumors of all 4 patients were completely resected,and none of them received radiotherapy or chemotherapy after surgery.The median follow-up time of the 4 patients was 12 months(3-43 months).At the last follow-up,the preoperative symptoms of all 4 patients were significantly improved and MRI showed no signs of recurrence.Macroscopically,multiple discrete or coalesced gray nodules involved deep cortex,gray matter-white matter junction,and subcortical white matter.HE staining showed that MVNT consisted of small-to-medium-sized neuronal cells arranged in nodules,with obvious vacuoles in the background stroma and in the cytoplasm of tumor cells.The results of immunohistochemical staining showed that myelin basic protein(MBP)in the nodule was weakly positive compared with the normal cortex,giving the nodular lesions a"wormlike"appearance.Microtubule association protein 2(MAP2)was positive expression in varying degrees,and synaptophysin(Syn)was granularly and weakly positive.Neurofilament(NF)and neuro-specific nuclear protein(NeuN)were negative.Glial fibrillary acidic protein(GFAP)showed"spider-like"expression of reactive astrocytes in the background.CD34 expression was negative in tumor cells,but ramified in neural elements of the adjacent dysplastic cerebral cortex.The next-generation sequencing results of 4 patients showed that there was 1 case of FGFR4 P400 frameshift mutation and BRAF A34 indel,and 1 case of NOTCH1 L188V mutation.Three of 4 patients underwent pyrosequencing which showed no methylation of O6-methylguanine DNA methyltransferase(MGMT).Conclusions MVNT is more common in adults and mainly involves temporal lobe and hippocampus.It shows characteristic"beaded"or"nodular"abnormal signals in MRI and unique multinodular and vacuolar pathological features.MVNT can be totally resected by surgery and has good prognosis.