To explore the clinical and pathological features of multinodular and vacuolating neuronal tumors (MVNT).

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.

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).

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.

Brain neoplasms; Disease attributes; Pathology; Prognosis; Multinodular and vacuolating neuronal tumors