Abstract
BACKGROUND: Brain intraparenchymal schwannoma is a rare clinical entity, generally curable with adequate resection. METHODS AND RESULTS: We describe a case in a male patient first presenting at 19 months of age, the youngest reported age for this lesion. It also appears to be the first case connected to a germline TSC2 p.1510del mutation in a patient with autism-like symptoms. Although tuberous sclerosis is generally not associated with increased risk of schwannoma, mTORC1 activity, which is inhibited by intact TSC1/TSC2 complex, is involved in schwannoma progression. This patient's tumor also harbored a CHD7::VGLL3 fusion consistent with its genomic DNA methylation classification of CNS Schwannoma, VGLL-fused. The Hippo pathway, mTORC1, and VGLL3 all negatively regulate the YAP1/TEAD cotranscriptional complex. We hypothesize that this schwannoma may have arisen because of increased VGLL3 functional activity from the CHD7::VGLL3 fusion and, perhaps, increased mTORC1 activity due to TSC2 mutation, and their combined effects on the balance between YAP1/TEAD- and VGLL3/TEAD-mediated transcriptional programs. CONCLUSIONS: We present a frontal lobe intra-axial parenchymal schwannoma containing a CHD7::VGLL3 gene fusion presenting in a 19 month-old male, the youngest patient yet reported for this lesion.