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.
Highlights
Indolent cortical lesions provoking focal refractory epilepsy often bridge a gap between focal developmental anomalies and low grade tumors
We present a series of ten cases and compare their pathological and genetic features to better characterized epilepsyassociated malformations including focal cortical dysplasia type II (FCDII) and low-grade epilepsy-associated tumors (LEAT)
Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology
Summary
Indolent cortical lesions provoking focal refractory epilepsy often bridge a gap between focal developmental anomalies and low grade tumors. Many hamartomatous or developmental ‘overgrowth’ lesions, the mTORopathies [13] or those associated with mutations in the PI3K–AKT signaling pathway [21], are characterized by abnormal cortical architecture with excessive cell size and tumor-like mass effect, such as tuberous sclerosis. In 2007, we reported a unique case of a ‘diffuse gangliocytoma’ involving the temporal lobe in a patient with late onset epilepsy which posed such a diagnostic conundrum [45]. Pathology examination of an MRI visible lesion disclosed diffuse involvement of the white matter by nodules of vacuolated ganglion cells; malformations as focal cortical dysplasia (FCD), mild malformation of cortical development, nodular heterotopia were diagnoses considered in addition to a neuronal tumour.
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