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.

Keywords: HuC/HuD; developmental tumor; eliptogenic tumor; gangliocytoma; multinodular; vacuolating neuronal tumor.

Figure 1

T₂ –weighted (A), fluid attenuated inversion recovery (FLAIR B) and contrast‐enhanced (C) MR images from case 1. Note manner in which this solid, non‐enhancing lesion conforms to the contours of the right medial temporal lobe without significant tissue expansion or mass effect. T_2/FLAIR‐ hyperintense, the lesion exhibits a subtle internal nodularity most evident in the FLAIR sequence.

Figure 2

Conspicuous lesion multinodularity is apparent in fluid attenuated inversion recovery images from cases 3 (A) and 6 (B). Note the superficial location and manner in which underlying gyral conformations are preserved without mass effects. A tumor nodule spans the grey‐white junction in a gross photograph of the neurosurgical specimen from case 6 (at arrowheads, C).

Figure 3

Multinodular tumor architecture is demonstrated in whole mount hematoxylin and eosin‐stained sections from cases 6 (A) and 5 (B) and in an anti‐synaptophysin immunohistochemical preparation from case 4 (C). Note distribution of nodules within cortex and at grey matter junction and greatly diminished intratumoral expression of synaptophysin in (C). Discrete tumor nodules surrounded by gliotic white matter are apparent at higher magnification (case 6; D). Note vacuolar alterations. Tumor (white arrows) abuts cortex (black arrows) exhibiting architectural disarray (case 6; E).

Figure 4

The cytologic variability of tumor cells is demonstrated in sections, all at the same magnification, from cases 5 (A), 4 (B), 1 (C) and 6 (D). These range from relatively small in size with eosinophilic cytoplasm (A) to large and overtly ganglion cell‐like (D). For comparative purposes, native neurons are included in B (arrows). Note vacuolar changes.

Figure 5

Immunohistochemical features of the cases illustrated in Figure 3 are shown (case 4: A–D; case 5: E–H; case 6: I–L; case 1: M–P). Regardless of cytologic presentation, shared immunophenotypic features include GFAP‐negativity (only the cell bodies and processes of reactive astrocytes are labeled) and nuclear as well as cytoplasmic expression of HuC/HuD in the absence of nuclear of NeuN labeling. Cytoplasmic reactivity for synaptophysin ranges from absent (B) to conspicuous (J, N) without surface perikaryal accentuation.

Figure 6

Nuclear OLIG2 expression, a feature of all examples studied, is depicted in fields from cases 1 (A), 5 (B) and 6 (C).

Figure 7

Ramified, CD34‐labeling neural elements are depicted from cases 5 (A) and 6 (B). Tumor cells are non‐reactive.