Multinodular and Vacuolating Neuronal Tumors of the Cerebrum: 10 Cases of a Distinctive Seizure‐Associated Lesion

Abstract

We report 10 cases of a non-neurocytic, purely neuronal tumor affecting adults. Situated in the cerebral hemispheres, with 7 of 10 confined to the temporal lobes, most presented with seizures as their principal clinical manifestations. On magnetic resosnance imaging (MRI), the tumors generally appeared solid and non-contrast enhancing with minimal diffuse infiltration, edema, or mass effect. Six examples demonstrated internal nodularity. Microscopically, the tumor cells were largely distributed into discrete and coalescent nodules exhibiting varying degrees of matrix vacuolization, principally within the deep cortical ribbon and superficial subcortical white matter. Populating elements ranged from morphologically ambiguous to recognizably neuronal, with only two cases manifesting overt ganglion cell cytology. In all cases, tumor cells exhibited widespread nuclear immunolabeling for the HuC/HuD neuronal antigens, although expression of other neuronal markers, including synaptophysin, neurofilament and chromogranin was variable to absent. Tumor cells also failed to express GFAP, p53, IDH1 R132H, or CD34, although CD34-labeling ramified neural elements were present in the adjoining cortex of seven cases. Molecular analysis in a subset of cases failed to reveal DNA copy number abnormalities or BRAF V600E mutation. Follow-up data indicate that this unusual neuronal lesion behaves in benign, World Health Organization (WHO) grade I fashion and is amenable to surgical control.

Two cases of multinodular and vacuolating neuronal tumour

“…There was also no chromogranin or neurofilament positivity in the cytoplasm of those cells but axonal immunoreactivity with neurofilament was detected in the axons running through the lesion. We were able to confirm consistent labelling of the vacuolated cells by HuC/HuD as reported by Huse et al [2]. In addition we also noted immunoreactivity in small round nuclei being present not only in the lesion but also in the normal white matter, suggesting labelling of some of the normal oligodendroglial cells.…”

“…We have described two cases, a surgical resection and the other an autopsy specimen, with histological features similar to those recently described as MVNT by Huse et al [2]. The radiological features were also similar, showing lesions with T2 signal hyperintensity and increased signal in FLAIR in the subcortical white matter; being subtle in Case 1 and extensively involving the posterior part of the temporal lobe in Case 2.…”

“…Huse et al described OLIG2 expression in all of their lesions [2]. We also detected increased a number of oligodendroglial-like cells and oligodendrocytes within and sometimes at the border of the nodules.…”

“…The discrete and coalescing grey nodules abutted on the deep cortex although most lesions were subcortical. This type of localisation may also occur in DNT but appears also to be characteristic of MVNT [2]. …”

“…Most epileptogenic neuroepithelial tumours present in childhood but may not get surgical treatment until adulthood due to their indolent clinical behaviour. Recently, a non-neurocytic, purely neuronal lesion affecting adults with epilepsy has been described, in which there was striking vacuolation of the neuronal cytoplasm, referred to as multinodular and vacuolating neuronal tumour (MVNT) [2]. We report two cases with similar histological features, one from a surgical resection to treat chronic seizures, and the other from an autopsy specimen without a history of epilepsy, with MRIs in both cases suggesting a diagnosis of DNT.…”