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Clinicopathological and molecular analysis of multinodular and vacuolating neuronal tumors of the cerebrum.
Human Pathology 2018 December 12
Multinodular and vacuolating neuronal tumor (MVNT) of the cerebrum is a recently recognized rare neuronal tumor, and its pathogenesis is unclear. We analyzed 7 cases of histologically typical MVNT: six were adults [mean age: 43.0years (range: 23-56)] and one was a child (10-year-old). The most common symptoms were seizures (n=4) and headache (n=2). The tumors were supratentorial (temporal=5 and frontal lobes=2) in origin as reported. Vacuolated tumor cells were robustly positive for alpha-INA and Olig2 and at least partly positive for synaptophysin and MAP2, but negative for Neu-N. Two cases were positive for nestin and one for CD34. GFAP and vimentin were expressed in reactive astrocytes, but not in tumor cells. Negative results were obtained for p53, IDH-1, BRAFV600E , H3 K27M, EGFR, Lin28A, and L1CAM. ATRX, BRG1, INI-1, and TMHH were retained. The Ki-67 labeling index was very low (<1%) and pHH3 revealed no mitotic figure. Ultrastructural features of tumor cells were comparable with those of immature neuronal cells, with several intracytoplasmic myelin-like autophagosomes and pericellular vacuolization. No IDH1/IDH2 and BRAFV600E mutations were found upon direct sequencing. WES revealed FGFR2-ZMYND11 gene fusion in one case. After gross total resection, all patients were alive without seizures. There was no tumor recurrence during an average time period of 68months (range: 23-101months). The analysis of seven typical cases of MVNT suggested that these lesions may be clonal tumors because FGFR2-ZMYND11 fusion was found (one case).
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