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

Maria Thom, Joan Liu, Anika Bongaarts, Roy J. Reinten, Beatrice Paradiso, Hans Rolf Jäger, Cheryl Reeves, Alyma Somani, Shu An, Derek Marsdon, Andrew McEvoy, Anna Miserocchi, Lewis Thorne, Fay Newman, Sorin Bucur, Mrinalini Honavar, Tom Jacques, Eleonora Aronica

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
Pages (from-to)155-171
JournalBrain Pathology
Volume28
Issue number2
DOIs
Publication statusPublished - 2018
Externally publishedYes

Cite this

Thom, M., Liu, J., Bongaarts, A., Reinten, R. J., Paradiso, B., Jäger, H. R., ... Aronica, E. (2018). Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia? Brain Pathology, 28(2), 155-171. https://doi.org/10.1111/bpa.12555
Thom, Maria ; Liu, Joan ; Bongaarts, Anika ; Reinten, Roy J. ; Paradiso, Beatrice ; Jäger, Hans Rolf ; Reeves, Cheryl ; Somani, Alyma ; An, Shu ; Marsdon, Derek ; McEvoy, Andrew ; Miserocchi, Anna ; Thorne, Lewis ; Newman, Fay ; Bucur, Sorin ; Honavar, Mrinalini ; Jacques, Tom ; Aronica, Eleonora. / Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?. In: Brain Pathology. 2018 ; Vol. 28, No. 2. pp. 155-171.
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title = "Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?",
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.",
author = "Maria Thom and Joan Liu and Anika Bongaarts and Reinten, {Roy J.} and Beatrice Paradiso and J{\"a}ger, {Hans Rolf} and Cheryl Reeves and Alyma Somani and Shu An and Derek Marsdon and Andrew McEvoy and Anna Miserocchi and Lewis Thorne and Fay Newman and Sorin Bucur and Mrinalini Honavar and Tom Jacques and Eleonora Aronica",
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Thom, M, Liu, J, Bongaarts, A, Reinten, RJ, Paradiso, B, Jäger, HR, Reeves, C, Somani, A, An, S, Marsdon, D, McEvoy, A, Miserocchi, A, Thorne, L, Newman, F, Bucur, S, Honavar, M, Jacques, T & Aronica, E 2018, 'Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?' Brain Pathology, vol. 28, no. 2, pp. 155-171. https://doi.org/10.1111/bpa.12555

Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia? / Thom, Maria; Liu, Joan; Bongaarts, Anika; Reinten, Roy J.; Paradiso, Beatrice; Jäger, Hans Rolf; Reeves, Cheryl; Somani, Alyma; An, Shu; Marsdon, Derek; McEvoy, Andrew; Miserocchi, Anna; Thorne, Lewis; Newman, Fay; Bucur, Sorin; Honavar, Mrinalini; Jacques, Tom; Aronica, Eleonora.

In: Brain Pathology, Vol. 28, No. 2, 2018, p. 155-171.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?

AU - Thom, Maria

AU - Liu, Joan

AU - Bongaarts, Anika

AU - Reinten, Roy J.

AU - Paradiso, Beatrice

AU - Jäger, Hans Rolf

AU - Reeves, Cheryl

AU - Somani, Alyma

AU - An, Shu

AU - Marsdon, Derek

AU - McEvoy, Andrew

AU - Miserocchi, Anna

AU - Thorne, Lewis

AU - Newman, Fay

AU - Bucur, Sorin

AU - Honavar, Mrinalini

AU - Jacques, Tom

AU - Aronica, Eleonora

PY - 2018

Y1 - 2018

N2 - 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.

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Thom M, Liu J, Bongaarts A, Reinten RJ, Paradiso B, Jäger HR et al. Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia? Brain Pathology. 2018;28(2):155-171. https://doi.org/10.1111/bpa.12555