CNS & pituitary tumors
Gliomas, glioneuronal tumors and neuronal tumors
Neuronal and mixed neuronal-glial tumors
Multinodular and vacuolating neuronal tumor (MVNT)
Editorial Board Member: Valeria Barresi, M.D., Ph.D.
Deputy Editor-in-Chief: Chunyu Cai, M.D., Ph.D.
Last author update: 15 October 2024
Last staff update: 15 October 2024
Copyright: 2024, PathologyOutlines.com, Inc.
PubMed Search: Multinodular and vacuolating neuronal tumor
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: d'Amati A, Gianno F, Antonelli M. Multinodular and vacuolating neuronal tumor (MVNT). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/CNStumorMVNT.html. Accessed December 22nd, 2024.
Definition / general
- Neuronal tumor composed of multiple nodules of monomorphic neurons, with vacuolar changes in the cytoplasm and matrix
Essential features
- Multinodular tumor with neuronal differentiation and vacuolation
- No mitotic activity
- MAPK pathway activating alterations
- CNS WHO grade 1
Terminology
- Diffuse gangliocytoma (not recommended by CNS WHO 2021)
ICD coding
Epidemiology
- Population based incidence data are currently not available
- Mainly encountered in adults; rare in the pediatric population (Brain Pathol 2013;23:515, Brain Pathol 2018;28:155, Acta Neuropathol 2018;135:485, Hum Pathol 2019;86:203)
- Median age: 42 years; age range: 5 - 71 years
- M:F = 1.5:1
Sites
- Supratentorial tumor, involving deep gray and superficial white matter (Brain Pathol 2013;23:515, Brain Pathol 2018;28:155, Acta Neuropathol 2018;135:485, Hum Pathol 2019;86:203)
- Temporal lobe is the most common location (75 - 80%)
- Frontal (10 - 15%), parietal and occipital lobes are also possible
- Single case reported in basal ganglia (J Neurosci Rural Pract 2020;11:214)
Pathophysiology
- Probable origin from developmentally dysregulated, partially arrested neuronal or glioneuronal precursors located in deep cortical layers (Brain Pathol 2018;28:155)
- MAPK pathway activating alterations (Acta Neuropathol 2018;135:485)
- Recurrent mutations in MAP2K1 and BRAF (excluding p.V600E mutation, which has not been documented in this tumor)
Etiology
- Predisposing factors have not been identified
- Single radiologically suspected case (without histological examination) reported in a patient with Klinefelter syndrome (Neuroradiology 2017;59:1187)
Clinical features
- Clinical signs and symptoms depend on tumor location (Acta Neuropathol Commun 2014;2:7, Surg Neurol Int 2018;9:63)
- Seizures are the most common manifestation (60%)
- Headache, dizziness and episodic confusion have also been reported
- May be asymptomatic and incidentally discovered
Diagnosis
- Magnetic resonance imaging (MRI), followed by stereotactic brain biopsy or surgical resection
- CNS WHO 2021 diagnostic criteria
- Essential
- Multinodularity
- Neuronal cytological features or tumor cell immunoreactivity for synaptophysin, HuC / HuD or nonphosphorylated 200 kDa NFP
- Absence of mitotic activity
- Tumor cell / matrix vacuolation (also minimal)
- Desirable
- Immunoreactivity for Olig2 and internexin A
- Absence of NeuN or chromogranin expression
- MAPK pathway activating abnormalities
- Essential
Radiology description
- Highly characteristic on MRI (Brain Pathol 2013;23:515, Brain Pathol 2018;28:155, Acta Neuropathol 2018;135:485, Hum Pathol 2019;86:203)
- Clustering of coalescent or discrete T2 FLAIR hyperintense nodules in deep cortex and superficial white matter
- No mass effect, edema, restricted diffusion or contrast enhancement
- Stable on surveillance imaging
Radiology images
Contributed by Patrizia Cenni, M.D. and Daniela Bartolini, M.D.
Flair MRI of brain
T2 MRI of brain
Prognostic factors
- MVNTs are benign and stable lesions
- Recurrence or progression has not been described (Brain Pathol 2013;23:515, Brain Pathol 2018;28:155, Hum Pathol 2019;86:203)
- Can also be safely followed by imaging without recourse to biopsy (AJNR Am J Neuroradiol 2017;38:1899, Neuroradiology 2017;59:873)
Case reports
- 5 year old boy with a longstanding history of cerebral palsy, spastic gait and toe walking (J Neurosci Rural Pract 2020;11:214)
- 34 year old man with psychiatric history presented with lesion on MRI (Interdisciplinary Neurosurgery 2020;19:100556)
- 34 year old woman with multiple small T2 weighted hyperintense lesions and 71 year old woman with a lesion in the left lateral temporal lobe (Acta Neuropathol Commun 2014;2:7)
- 52 year old woman with cerebellar lesion (Front Neurol 2024;14:1309209)
- 60 year old man with left frontal intracerebral lesion (Surg Neurol Int 2018;9:63)
Treatment
- Complete surgical resection, particularly for symptomatic cases
- Asymptomatic cases with characteristic neuroradiological features may be followed without recourse to biopsy (AJNR Am J Neuroradiol 2017;38:1899, Neuroradiology 2017;59:873)
Gross description
- Multiple discrete or coalescent gray nodules, located at the gray-white matter junction (Brain Pathol 2013;23:515, Acta Neuropathol Commun 2014;2:7)
Microscopic (histologic) description
- Neoplastic neuronal elements haphazardly distributed within multiple pale, hypomyelinated nodules (Brain Pathol 2013;23:515, Acta Neuropathol Commun 2014;2:7, Neuropathology 2015;35:561, Brain Pathol 2018;28:155)
- Tumor cells are monomorphic neuronal element of intermediate / large size, with vesicular round nuclei and distinct nucleoli
- Vacuolar changes
- Cytoplasm of neoplastic neuronal elements
- Pericellular
- Delicate fibrillar matrix of nodules
- Dysmorphic and multinucleated neuronal forms, Rosenthal fibers, eosinophilic granular bodies, myxoid microcysts and microcalcifications are typically absent
- High grade histological features (mitotic figures, vascular proliferation, necrosis) have not been identified
- Can be associated with regional cortical disorganization and hippocampal sclerosis (Brain Pathol 2013;23:515, Brain Pathol 2018;28:644)
Microscopic (histologic) images
Contributed by Francesca Gianno, M.D., Ph.D. and Chiara Cavatorta, M.D.
Multinodular aspect
Nodular aspect
Neoplastic cells
Neuronal cells with eosinophilic cytoplasm
Vacuolar changes
GFAP
Olig2
Synaptophysin
Low Ki67
CD34
Positive stains
- Olig2
- HuC / HuD
- Nonphosphorylated NFP
- Doublecortin
- Alpha internexin (strong matrix labeling) (Neuropathology 2015;35:561, Brain Pathol 2018;28:155)
- MAP2 (often)
- Synaptophysin (weak) (Brain Pathol 2013;23:515, Neuropathology 2015;35:561, Brain Pathol 2018;28:155, Hum Pathol 2019;86:203)
Negative stains
- Phosphorylated NFP
- NeuN
- Chromogranin A
- GFAP
- References: Neuropathology 2015;35:561, Brain Pathol 2018;28:155
Electron microscopy description
- Not routinely used for diagnostic purposes
Molecular / cytogenetics description
- MAPK pathway activating alterations (Acta Neuropathol 2018;135:485, Hum Pathol 2019;86:203)
- Small indels and hotspot mutations in MAPK21 (most common)
- BRAF mutations (excluding p.V600E)
- FGFR2 fusions
Sample pathology report
- Brain, left temporal lobe, resection:
- Integrated diagnosis: multinodular and vacuolating neuronal tumor (MVNT), CNS WHO grade 1
- Histologic diagnosis: glioneuronal / neuronal tumor, favor MVNT
- Immunohistochemical results
- MAP2+
- Olig2+
- Synapthophysin+
- Nonphopsphorylated NFP+
- GFAP-
- Chromogranin-
- Phosphorylated NFP-
- CNS WHO grade: 1
- Molecular information
- MAPK21 hotspot mutation
Differential diagnosis
- Ganglioglioma:
- Biphasic tumor with admixture of neuronal and glial elements
- Neuronal elements are large and dysmorphic (i.e., ganglion cells)
- Eosinophilic granular bodies are frequently encountered
- Neuronal elements express synaptophysin, chromogranin, NFP
- Frequent BRAF p.V600E mutation
- Gangliocytoma:
- Gangliocytoma is composed of numerous dysplastic ganglion cells, positive for synaptophysin, chromogranin A, NeuN and NFP (similar to ganglioglioma but without the glial component)
- Dysembryoplastic neuroepithelial tumor:
- Multinodular intracortical growth with pathognomonic glioneuronal elements; columns formed by axons lined by oligo-like cells, with neurons floating in a mucoid matrix
- Oligo-like component: Olig2 positive, GFAP negative
- Floating neuronal elements: NeuN positive, chromogranin negative
- Frequent BRAF p.V600E mutation or FGFR1 alterations
Additional references
Board review style question #1
A 34 year old man presented with seizures. Magnetic resonance imaging (MRI) reveals a multinodular lesion in the right temporal lobe. Histologic features are shown in the image above. Immunohistochemistry revealed synaptophysin and Olig2 positivity and chromogranin, GFAP and NeuN negativity. What is the most likely diagnosis?
- Gangliocytoma
- Ganglioglioma
- Multinodular and vacuolating neuronal tumor (MVNT)
- Pilocytic astrocytoma
- Pleomorphic xanthoastrocytoma
Board review style answer #1
C. Multinodular and vacuolating neuronal tumor (MVNT). The image shows a neuronal tumor with a multinodular appearance and vacuolar changes in the cytoplasm of neoplastic neuronal elements and in the fibrillar matrix of the nodules. Answer D is incorrect because pilocytic astrocytoma has a completely different radiological presentation and morphological appearance, characterized by elongated glial neoplastic elements immersed in a fibrillary or loose background, usually associated with the presence of Rosenthal fibers. Answer B is incorrect because ganglioglioma shows larger neoplastic neurons (i.e., dysplastic ganglion cells), has a different immunohistochemical phenotype (positive for synaptophysin, chromogranin A, NeuN and NFP) and has a glial component. Answer A is incorrect because gangliocytoma is composed of numerous dysplastic ganglion cells, positive for synaptophysin, chromogranin A, NeuN and NFP (similar to ganglioglioma but without the glial component). Answer E is incorrect because pleomorphic xanthoastrocytoma shows a different clinical and histological appearance, characterized by pleomorphic neoplastic elements with spindle or epithelioid morphology, frequently with xanthomatous cytoplasm.
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Board review style question #2
Which of the following is an essential criterion to confirm a diagnosis of multinodular and vacuolating neuronal tumor (MVNT)?
- Biphasic tumor composed of neuronal and glial elements
- BRAF p.V600E mutation
- MAPK pathway activating alterations
- Neuronal cytological features or immunoreactivity for specific neuronal markers
- Olig2 positivity
Board review style answer #2
D. Neuronal cytological features or immunoreactivity for specific neuronal markers. According to the 2021 CNS WHO criteria, demonstration of neuronal cytology or immunoreactivity for specific neuronal markers (synaptophysin, HuC / HuD or nonphosphorylated 200 kDa NFP) is mandatory to confirm a diagnosis of MVNT. Answers C and E are incorrect because MAPK pathway activation alterations and Olig2 positivity are desirable but not essential criteria. Answer B is incorrect because BRAF p.V600E mutation has not been documented in MVNT, unlike other BRAF alterations. Answer A is incorrect because MVNT is only composed of neoplastic neuronal elements, without any associated neoplastic glial component.
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