Diffuse Leptomeningeal Neuroepithelial Tumor

Abstract

Leptomeningeal dissemination in children is typical of high-grade, and occasionally low-grade, neoplasms. Rare cases of widely disseminated oligodendroglia-like leptomeningeal tumors, sometimes with associated spinal cord lesions, have been described that respond to treatment and follow an indolent course. Whether these lesions represent an established tumor category or are a unique entity remains to be established. We present 9 pediatric cases of such diffuse leptomeningeal neuroepithelial tumors (DLNT), 8 with assessment of 2 common genetic alterations seen in oligodendrogliomas, 1p and 19q chromosomal deletions and isocitrate dehydrogenase-1 (IDH1) R132H mutations. Four patients were male and 5 female, with a mean age at presentation of 4 years (range, 2 to 7 y). All presented with signs of increased intracranial pressure and diffuse contrast enhancement of the leptomeninges by magnetic resonance imaging. Three had a cervical or upper thoracic spinal cord tumor, and another had a small cerebellar lesion. Leptomeningeal biopsies showed a thickened and fibrotic arachnoid infiltrated by monotonous cells with round nuclei and prominent perinuclear clearing. All cases were strongly immunoreactive for S100 protein, and most showed faint granular synaptophysin reactivity. Six of 8 cases showed deletions of chromosome arm 1p by fluorescence in situ hybridization, 2 of which also had loss of 19q. None of the lesions reacted with IDH1-R132H antibodies. Although the clinicopathologic features show overlap of these DLNT lesions with oligodendroglioma and extraventricular neurocytoma, they do not exactly match either one, suggesting that DLNTs are a distinct tumor entity.

Clinicopathologic Features of Pediatric Oligodendrogliomas

“…49–53 Also OLIG2 positive, it has in some cases clear neuronal differentiation, although this in itself does not necessarily exclude oligodendroglioma as the parent neoplasm. A frequent isolated 1p deletion appears to individualize the disseminated tumor; however, some such leptomeningeal lesions have the 1p19q codeletion typical of adult oligodendroglioma.…”

“…51–54 Mutant IDH1/2 immunostaining has been negative. 52,53 We did not include this type of tumor in the present study.…”

Primary Leptomeningeal Oligodendroglioma, IDH-Mutant, 1p/19q-Codeleted

“…The other entity in the differential diagnosis is diffuse leptomeningeal glioneuronal tumor (DLGT), which very rarely can show combined 1p/19q codeletion (isolated 1p deletion is more common). IDH mutations have not been described in DLGT (2, 5–7). In contrast, DLGT or disseminated oligodendroglioma-like leptomeningeal neoplasms (DOLN) have been shown to frequently carry the BRAF-KIAA1549 fusion/tandem duplication at 7q34 (6).…”

Newly Identified Characteristics and Suggestions for Diagnosis and Treatment of Diffuse Leptomeningeal Glioneuronal/Neuroepithelial Tumors

“…It has also been termed “diffuse leptomeningeal neuroepithelial tumor.” 1 It does not fit into the current World Health Organization classification system, which describes mixed glioneuronal tumors as having elements of both glial and neuronal differentiation in mixed cell populations. Mixed glioneuronal tumors are characteristically biphasic.…”

“…2 However, diffuse leptomeningeal glioneuronal tumor is comprised of 1 cell population that variably stains for both glial and neuronal components. 1 This tumor was described as a distinct entity for the first time in 2010; 3 however, it has likely been encountered before, diagnosed as other known tumors. These diagnoses include diffuse leptomeningeal oligodendrogliomatosis, leptomeningeal oligodendroglioma, central neurocytoma with uncharacteristically aggressive features, ganglioneurocytomas, gliomatosis cerebri, and glioneuronal tumors with neuropil-like islands.…”