A case series of Diffuse Glioneuronal Tumours with Oligodendroglioma-like features and Nuclear Clusters (DGONC)

Abstract

In this study, we report three paediatric cases of Diffuse Glioneuronal Tumours with Oligodendroglioma-like features and Nuclear Clusters (DGONC).

Keywords: DNA methylation classification; brain tumour; glioneuronal tumour; monosomy 14; paediatric.

FIGURE 1

Summary of presenting features in three paediatric DGONC. (A) DNA methylation profiling of the new DGONC cases with existing reference cohorts available online via Heidelberg Molecular Neuropathology platform, https://www.molecularneuropathology.org/mnp and those held locally with a confirmed molecular classification (calibrated score using MNPb11v6 >0.9). FS and DTWJ kindly provided reference DGONC samples. Samples are coloured according to their methylation class. t‐SNE parameters: perplexity = 20, theta = 0.5, dims = 2. (B) Representative copy number plot (DGONC_3) showing previously described features of DGONC: monosomy of chr14, gains in 1p and 17p. Additionally, we noted focal losses in 1p and 3p that were common in our cases series. (C) Radiological features (DGONC_3) of an 11‐year‐old boy presenting with a mass in the right medial frontal lobe, heterogeneously hyperintense on T2‐ and FLAIR‐weighted sequences with some internal cysts, poorly enhancing with contrast, and rather heterogeneous on diffusion, with a small focus of low ADC values. The CT scan (not shown) revealed calcification in the wall of the cystic area. (D–I) Representative histopathological features observed. Predominant features included rounded nuclei with perinuclear haloes (D–E), clear cell morphology, vascular proliferation and frequent areas of neutrophil (D–G). We observed nuclear aggregation (E, arrows), giant cells and large foamy cells (G). DGONC were negative for glial markers, for example, GFAP (H) and positive for neuronal and oligodendrocyte markers, for example, OLIG2 (I). See extended data for summary table of immunohistochemistry available and additional radiology. Abbreviations (A): CN: central neurocytoma, DGONC: Diffuse Glioneuronal tumour with Oligodendroglioma‐like features and Nuclear Clusters, DLGNT: diffuse leptomeningeal glioneuronal tumour, DMG K27: diffuse midline glioma with H3 K27M mutation; EFT CIC: Ewings‐like family tumour with CIC alteration; GBM RTKI: glioblastoma receptor tyrosine kinase I group; HGNET BCOR: high‐grade neuroepithelial tumour with BCOR alteration; HGNET MN1: high‐grade neuroepithelial tumour with MN1 alteration; LGG DNT: low‐grade glioma, dysembryoplastic neuroepithelial tumour; LGG MYB: low‐grade glioma MYB/MYB1; LGG PA/GG ST: low‐grade glioma, hemispheric pilocytic astrocytoma and ganglioglioma; NB FOXR2: neuroblastoma with FOXR2 alteration; O IDH: IDH glioma, 1q/19q codeleted oligodendroglioma; DGONC (GOSH): DGONC cases identified at our centre (DGONC_1 to DGONC_3, includes DGONC_1R)