Multinodular and vacuolating neuronal tumor: 4 histopathologically diagnosed cases and systematic review of the literature

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ID: 338668
2026
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Abstract
Abstract Multinodular and vacuolating neuronal tumor (MVNT) is an incompletely understood CNS neoplasm due to its recent recognition and infrequent surgical sampling. This study characterizes MVNT through an institutional case series and systematic review. Four histopathologically confirmed MVNTs were retrospectively identified from our institution, and a PRISMA-guided systematic review of PubMed, Embase, Scopus, and Web of Science for radiologically or pathologically indicated MVNTs was performed. Two institutional patients presented with seizures and T2-hyperintense nodules on MRI (2/2, 100.0%). Histology revealed vacuolated neuronal cells within vacuolated stroma, with strong OLIG2 (3/3, 100.0%) and retained ATRX (2/2, 100.0%) immunoreactivity. Next-generation sequencing identified a pathogenic MAP2K1 deletion (p.Q56_V60del) in one case. The systematic review identified 310 MVNTs across 49 studies. Frequent presentations included headaches (87/310, 28.1%) and seizures (69/310, 22.3%) in patients with T2-hyperintense lesions (289/289, 100.0%). Reported immunohistochemical findings varied, although MAP2 (12/13, 92.3%) and OLIG2 (19/29, 65.5%) were frequently positive. MAP2K1 alterations including microdeletions associated with pathway activation were the most frequent oncogenic mutations. Radiologic progression was rare (1/294, 0.3%). In conclusion, MVNTs are radiologically distinct lesions that are often discovered in individuals with headaches or seizures. Histopathology reinforces a benign glioneuronal origin, and recurrent MAPK pathway alterations suggest a shared mechanism of tumorigenesis.
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Authors Austin Carmichael, Daniel Martinez Heinemann, Umar Arshad, Anita L. Kalluri, Sai Chandan Reddy, Megan Parker, Praneethkumar Madhu, Dhairya A. Lakhani, Haris Iqbal Sair, Karisa C. Schreck, Shanshan Jiang, George I. Jallo, Chetan Bettegowda, Ignacio González-Gómez, Calixto-Hope G. Lucas, Jordina Rincón-Torroella
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Journal Journal of Neuropathology & Experimental Neurology
Year 2026
DOI
10.1093/jnen/nlag071
URL
https://doi.org/10.1093/jnen/nlag071
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