Description

A previously healthy 9-year-old girl presented to otolaryngology clinic due to new onset bilateral sensorineural hearing loss. An MRI brain was ordered as part of her routine workup, and she was found to have an incidental 1.3 cm non-enhancing T1 hypointense, T2 hyperintense mass in the right occipital lobe just superior to the tentorium without associated diffusion restriction. The patient otherwise denied any problems with vision, nausea, vomiting or seizures. Her neurological examination was normal other than the sensorineural hearing loss confirmed on audiometry, which was likely unrelated to the imaging findings. Given the imaging appearance, a low-grade glioma was suspected, and she was monitored closely with sequential MRI. However, follow-up imaging 2 years later showed a slight increase in tumour size with new heterogeneous enhancement (figure 1). At that time, the patient underwent gross total resection. Permanent sections showed a proliferation of bland, occasionally process-forming cells in a largely myxoid background with microcyst formation, scattered ‘floating’ neurons within pools of mucin and increased mitotic activity. Findings were most consistent with a dysembryoplastic neuroepithelial tumour (DNET).1 Immunohistochemistry demonstrated NeuN-positive scattered neurons corresponding to the floating neurons noted on H&E staining, diffusely positive glial fibrillar acidic protein (GFAP) staining and 3%–5% Ki67 positivity (figure 2). Next-generation sequencing with solid tumour mutation panel analysis revealed a GNAi1-BRAF fusion, and a microarray demonstrated chromothripsis of chromosome 7 with nine segmental gains and breakages at 7q34 in KIAA1549.

• Download figure
• Open in new tab
• Download powerpoint

Figure 1

MRI brain demonstrates a well-circumscribed, T2 hyperintense (A) and T2 FLAIR hyperintense (B) mass in the right occipital lobe, with post-contrast showing heterogeneous enhancement (C), and fractional anisotropy on diffusion tensor imaging showing fibre displacement of the right optic radiation on both sides of the lesion (D).

• Download figure
• Open in new tab
• Download powerpoint

Figure 2

H&E stained sections showing a proliferation predominantly of bland, occasionally process-forming cells in a largely myxoid background with microcyst formation and scattered ‘floating’ neurons with mitotic activity noted (A), and Ki-67 staining showing ~3%–5% nuclear labelling (B).

DNETs are WHO grade I low-grade gliomas more commonly seen in children that often present with focal epilepsy.2 BRAF p.V600E mutations, FGFR1 alterations and BRAF-KIAA1549 fusion are more commonly reported, although the incidences vary among different studies.3–5 In addition, copy number alterations, most frequently copy number gains in chromosomes 5 and 7, are reported in DNETs, although they do not correlate with specific histological subtypes.1 6 We report an unusual occipital low-grade glioma with histological characteristics of a DNET and genetics demonstrating a GNAi1- BRAF fusion which has been reported at very low frequencies compared with the more common KIAA1549-BRAF fusions in cerebellar juvenile pilocytic astrocytoma. However, our reported case of GNAi1-BRAF has not been previously described in DNETs. The rare GNAi1-BRAF fusion represents an activating mutation that may potentially be amenable to targeted therapies.7 Thus, molecular stratification with next-generation sequencing can aid in tumour classification and further characterise phenotype–genotype correlation to better guide clinical management.