Multinodular and Vacuolating Neuronal Tumor of the Cerebrum: A New “Leave Me Alone” Lesion with a Characteristic Imaging Pattern

Discussion

MVNTs are distinctive neuronal lesions first described by Huse et al¹ in 2013 in a small case series of 10 patients. Since then, an additional 5 cases have been reported in the neuropathology literature.^3⇓⇓–6 Because so few reported cases were available, the new 2016 World Health Organization Classification of CNS neoplasms recognized MVNT as an entity but provisionally included it as a unique cytoarchitectural pattern of gangliocytoma, noting that it was unclear whether it is a truly neoplastic or dysplastic lesion.² This article examines the imaging and clinical spectrum of a large series of presumed MVNTs and delineates classic imaging findings of MVNT in an effort to prevent misdiagnosis and unnecessary biopsy.

Published cases^{1,3⇓⇓–6} share similar histopathologic features, showing neuroepithelial cells with conspicuous stromal vacuolation arranged in nodules principally within the deep cortical ribbon and superficial subcortical white matter. These dysplastic cells typically orient perpendicular to the cortical surface, which correlates well with the radiologic appearance of clusters or a linear array of juxtacortical nodules. The constituent dysplastic cells exhibit immunopositivity for HuC/HuD and Olig2, associated with neurogenesis at an earlier stage of neuronal development. However, they show negativity or weak positivity for neuronal lineage markers that are present in mature neurons, therefore, revealing an early neuronal immunophenotype. To date, genetic analyses have failed to demonstrate characteristic molecular changes that specify a particular tumor subtype.^{1,3⇓⇓–6} More recently, MVNTs have been shown to demonstrate overexpression of α-internexin, which is a major component of neurofilaments in interneurons and cerebellar granule cells. INA expression is seen in developing immature neurons. Again, these findings support the hypothesis that MVNT may represent a dysplastic early neuronal phenotype and may fall into a category between cortical malformation and harmatomatous lesions, which behave in a benign fashion.^3,6

MVNTs exhibit a highly characteristic appearance on MR imaging. All lesions in our series consist of a cluster of variably sized nodular lesions located on the subcortical ribbon and superficial subcortical white matter following the gyral contour (Fig 6). They appear hyperintense on T2WI, do not suppress on FLAIR, and typically do not enhance or cause mass effect (Figs 2⇑–4). Our findings are in accordance with those in the cases in the pathology literature.^{1,3⇓⇓–6} The nonsuppression on FLAIR and the slightly hypointense signal compared with CSF on T2-weighted sequences observed in this series are possibly related to a high protein or solid component within the vacuolated areas. In almost half of our patients, the subcortical white matter adjacent to the small nodules are hyperintense on T2/FLAIR; this appearance is likely due to coalescence of many smaller clustered nodules and partial volume averaging (Fig 2), sometimes resembling a mass-like lesion as previously described.^3⇓⇓–6

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Fig 6.

MVNT typical presentation graphic illustration. Schematic coronal view depicts a nodular “bubbly-appearing” lesion located on the inner surface of otherwise normal-appearing left temporal lobe cortex within the deep cortical ribbon and superficial subcortical white matter. Reprinted from Osborn's Brain⁹ with permission from Elsevier.

Most of our cases were imaged before the description of MVNT in the 2016 World Health Organization Classification and were initially diagnosed as enlarged perivascular spaces, focal cortical dysplasia, or dysembryoplastic neuroepithelial tumor (DNET). Although MVNT may have some overlapping imaging features with DNET and other cortically based tumors, the absence of cortical involvement and prominent mass effect and intra- or perilesional tumor nodules help to distinguish MVNTs.^3,6,7 Enlarged perivascular spaces may also have some similar imaging features; however, they typically exhibit CSF-like signal on all sequences, while MVNTs do not suppress on FLAIR. Prominent perivascular spaces that are below the resolution of 1.5 or 3T MR imaging may not suppress on FLAIR, but this pattern is usually described as an abnormal white matter signal surrounding other typical enlarged perivascular spaces, particularly in the anterior temporal region.⁸

While the most common clinical manifestation was an episode of seizure in the neuropathology literature,^{1,3⇓⇓–6} in this series, possible seizure was only observed in a few patients (19%) and the remainder presented with nonspecific, nonfocal clinical manifestations. Most MVNTs are usually an incidental finding on imaging studies and may be more common than other neuronal and mixed glioneuronal tumors. The true prevalence of this lesion in asymptomatic individuals may have been underestimated in the neuropathology literature due to reporting bias because most are probably not resected.

It is still not clear whether multinodular and vacuolating neuronal tumor represents a neoplasm or malformation²; however, on the basis of our results, given the long stability of the imaging findings and clinical course, it is apparent that MVNT behaves in a benign, nonaggressive manner that is more like a hamartomatous lesion than a neoplasm. Imaging findings of MVNT are highly suggestive of the diagnosis. While a few MVNTs may be causative of seizure disorders and therefore require excision for clinical management, akin to DNET, most are asymptomatic lesions that are “leave me alone” entities. These lesions usually do not require biopsy, resection, or follow-up imaging unless and until it can be demonstrated that the visualized lesion is responsible for the symptoms.

Our retrospective study had clear limitations. Only half of our patients had adequate imaging follow-up to confirm stability with time. Another major limitation is that histopathology was only available for 4 cases. Nevertheless, the imaging findings of all presumed MVNTs were strikingly similar to the ones described in the neuropathology literature.