PMC9719366_01
Radiologic features of tumor. (A-D) Axial T2, Coronal T1 post contrast, Axial ADC, and Axial SWAN images of the lesion at presentation. (A) Lesion is well defined, encasing the right MCA. (B) Demonstrates no enhancement post contrast administration. (C) No diffusion restriction noted. (D) Central calcifications seen on susceptibility weighted images. (E-H) Follow-up axial T2 images. (E) Subtotal resection of the tumor after first surgery. (F) Small residual component posterior to the MCA after second surgery. (G) Stable residual lesion on follow-up scans at 3 months, and 1-year post-surgery (H).
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F1
The MRI features suggested a low-grade lesion (Figure 1a-d). The patient underwent a frontotemporal craniotomy with a resultant subtotal resection limited due to the MCA (Figure 1e). It took approximately 3 months to obtain a clear and accurate diagnosis due to challenges posed by this rare tumor entity including some high-grade features on histopathology (Supplementary Figure 1). Resection remained subtotal again due to challenges presented by MCA encasement (Figure 1f). Given the stability of the tumor over the initial 3 months between the 2 surgical resections (Figure 1g), the prolonged symptom interval, and that no standard of care is known for DGONC, a watch and wait approach without adjuvant therapy was undertaken. The patient's residual tumor has since been followed and remains stable without growth 14 months from the second surgery and 17 months from original diagnosis (Figure 1h).
Histopathologic features of tumor. (A) Moderately cellular tumor with round nuclei, perinuclear halos, and nuclear clusters (black arrows). (B) Areas of mucinous degeneration with foam cells (black arrow) and scattered microvascular proliferation (white arrow). (C) Areas of confluent apoptosis (black arrow) and associated endothelial proliferation (white arrow). (D) Frequent entrapped normal neurons (black arrow) and mitotic figures (white arrow). (E) Strong diffuse positivity for synaptophysin. (F) Strong diffuse nuclear staining for OLIG2. Scale bar represents 200 microns.
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Histology sections showed a moderately cellular, diffusely infiltrating tumor composed of round cells with variable perinuclear halos (Figure 2a). Areas of myxoid degeneration with foam cells and early cystic change were also noted (Figure 2b). Mitotic figures and single cell necrosis were frequent and occasional microvascular proliferation and confluent necrosis were present (Figure 2c and d). Neuronal markers, such as synaptophysin and NeuN, were strongly and diffusely positive, as was OLIG2 (Figure 2e and f).
Molecular features of tumor. (A) Copy number variation plot showing the characteristic loss of chromosome 14. (B) tSNE embedding of the index case in regard to selected tumor types central neuroblastoma (CN), diffuse glioneuronal tumors with oligodendroglioma-like features and nuclear clusters (DGONC), Diffuse leptomeningeal glioneuronal tumor subgroup 1 and 2 (DLGNT_1 and _2), dysembryoplastic neuroepithelial tumor (DNET), extraventricular neurocytoma (EVNCYT), ganglioglioma (GG), desmoplastic infantile ganglioglioma/astrocytoma (LGG_DIG_DIA), oligodendroglioma (O_IDH), pilocytic astrocytoma cortical, infratentorial and midline (PA_Cort, _INF & _mid), rosette-forming glioneuronal tumor (RGNT).
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Whole chromosomal aberrations showed monosomy 14, mosaic loss of one copy of chromosomes 5, 15, 16, 19, and 22, gain of one copy of chromosomes 2 and 17, and mosaic copy neutral loss of heterozygosity of chromosome 13 (Figure 3a). DNA methylation array at Universitats Klinikum Heidelberg in Germany. DNA methylation using the brain tumor classifier version 12.5 returned showing a calibrated score of 0.93 for a DGONC (Figure 3b).