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

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.