Multinodular and vacuolating neuronal tumor

Multinodular and vacuolating neuronal tumors (MVNT) are lesions with distinct cytoarchitectural patterns. 

Radiologically, MVNTs appear as small "bubbly" indolent subcortical tumors that sometimes present with seizures. These tumors have been most frequently identified in the temporal lobe, although that is likely to be due to that location being more likely to result in seizures than necessarily a predilection for that lobe ^1-4.

Terminology

Lesions with identical imaging features have been described in the cerebellum but have not been histologically confirmed and have, therefore, prudently been named multinodular and vacuolating posterior fossa lesions of unknown significance (MV-PLUS) ⁷.

Epidemiology

The true epidemiology of these tumors is unknown as they have only been relatively recently described and most are asymptomatic, so are likely undiagnosed or misdiagnosed as other lesions (see differential diagnosis below) further confounding epidemiology.

Reported cases are mostly in young to middle-aged individuals with adult-onset epilepsy, or identified incidentally ^1-4,7. 

Clinical presentation

Other than some of these lesions being epileptogenic, it is likely that most are asymptomatic as presenting symptoms are usually difficult to reconcile with the lesion location ^1-4,7.

Pathology

MVNTs are considered as one of the glioneuronal and neuronal tumors in the current (2021) WHO classification of CNS tumors ⁹.

Microscopic appearance

The histopathological hallmark of MVNT is of neuroepithelial cells with conspicuous stromal vacuolation arranged in nodules principally within the deep cortical ribbon and superficial subcortical white matter ^1-3. 

Immunophenotype

Immunostaining is positive for synaptophysin, HuC/HuD neuronal antigens and p62 but negative for other markers (e.g. IDH1, nestin, NeuN, neurofilament, GFAP, and CD34) ^1-4. 

Genetics

Alterations in the MAPK pathway are important molecular characteristics ⁹. 

Radiographic features

CT

Smaller lesions are difficult to identify, but if seen will appear as non-enhancing low attenuation lesions deep to the cortex in the subcortical white matter. 

MRI

These tumors appear as a cluster of well-circumscribed high T2 signal "bubbles" located predominantly in the subcortical white matter but can involve the overlying cortex ^1,3,4. 

• T1: hypointense to adjacent gray and white matter

• T1 C+ (Gd)

  • usually no enhancement

  • some faint focal enhancement may be seen ^3,4

• T2

  • hyperintense to grey and white matter, almost as high as CSF

  • occasional central hypointense dot (also hypointense on FLAIR) ^7,8

• FLAIR: does not suppress (remains high signal)

In the cerebellum (MV-PLUS) these lesions most commonly involve the vermis, often extending cerebellar hemispheres, but not the brainstem ⁷. 

Treatment and prognosis

MVNTs appear to be benign tumors with very indolent biological behavior which can, if asymptomatic, be followed by imaging alone. In symptomatic patients (where the MVNT is causing seizures) surgical resection often controls seizures, with no tumor regrowth reported ^1-4. 

History and etymology

MVNTs were first described in 2013 ³ and included in the 2016 revised 4^th edition of the WHO classification of CNS tumors as an "architectural pattern" but recognized as a distinct entity in the 2021 5^th edition ⁹.

Differential diagnosis

Possible considerations include:

• dysembryoplastic neuroepithelial tumor (DNET)

  • can appear similar with a soap bubble appearance but usually is mostly cortical (rather than subcortical)

  • often has bright FLAIR rim

• focal cortical dysplasia (type II) 

  • high T2 signal deep to the cortex is in the same location but is usually associated with a radial glial band (transmantle sign) and with thickened abnormal overlying cortex

• perivascular spaces

  • location can be similar

  • usually more elongated along vessel long axis

  • fully attenuating on FLAIR

• gangliocytoma

• encephalomalacia and gliosis