Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?

Thom, M., Liu, J., Bongaarts, A., Reinten, R., Paradiso, B., Jäger, H., Reeves, C., Somani, A., An, S., Marsdon, D., McEvoy, A., Miserocchi, A., Thorne, L., Newman, F., Bucur, S., Honavar, M., Jacques, T. and Aronica, E. 2018. Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia? Brain Pathology. 28 (2), pp. 155-171. https://doi.org/10.1111/bpa.12555

TitleMultinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?
TypeJournal article
AuthorsThom, M., Liu, J., Bongaarts, A., Reinten, R., Paradiso, B., Jäger, H., Reeves, C., Somani, A., An, S., Marsdon, D., McEvoy, A., Miserocchi, A., Thorne, L., Newman, F., Bucur, S., Honavar, M., Jacques, T. and Aronica, E.
Abstract

Multinodular and vacuolating neuronal tumor (MVNT) is a new pattern of neuronal tumour included in the recently revised WHO 2016 classification of tumors of the CNS. There are 15 reports in the literature to date. They are typically associated with late onset epilepsy and a neoplastic vs. malformative biology has been questioned. We present a series of ten cases and compare their pathological and genetic features to better characterized epilepsy-associated malformations including focal cortical dysplasia type II (FCDII) and low-grade epilepsy-associated tumors (LEAT). Clinical and neuroradiology data were reviewed and a broad immunohistochemistry panel was applied to explore neuronal and glial differentiation, interneuronal populations, mTOR pathway activation and neurodegenerative changes. Next generation sequencing was performed for targeted multi-gene analysis to identify mutations common to epilepsy lesions including FCDII and LEAT. All of the surgical cases in this series presented with seizures, and were located in the temporal lobe. There was a lack of any progressive changes on serial pre-operative MRI and a mean age at surgery of 45 years. The vacuolated cells of the lesion expressed mature neuronal markers (neurofilament/SMI32, MAP2, synaptophysin). Prominent labelling of the lesional cells for developmentally regulated proteins (OTX1, TBR1, SOX2, MAP1b, CD34, GFAPδ) and oligodendroglial lineage markers (OLIG2, SMI94) was observed. No mutations were detected in the mTOR pathway genes, BRAF, FGFR1 or MYB. Clinical, pathological and genetic data could indicate that MVNT aligns more with a malformative lesion than a true neoplasm with origin from a progenitor neuro-glial cell type showing aberrant maturation.

KeywordsMultinodular
epilepsy
neuronal
tumour
vacuolating
JournalBrain Pathology
Journal citation28 (2), pp. 155-171
ISSN1015–6305
Year2018
PublisherWiley
Publisher's version
License
CC BY 4.0
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.1111/bpa.12555
Publication dates
Published online19 Aug 2017
Published in printMar 2018

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