C2 neurofibromas in neurofibromatosis type 1: genetic and imaging characteristics

Object. C2 nerve root neurofibromas have been reported frequently in patients with neurofibromatosis type 1 (NF1), though their genetic and imaging characteristics are unexplored. The aim of this study was to characterise genetic and spinal imaging findings in a large cohort of NF1 patients with C2 neurofibromas. Methods. Review of national NF1 referrals 2009-2016. Inclusion criteria: at least one C2 root neurofibroma; MRI cervical spine/whole spine available for analysis. Blinded imaging review by a neuroradiologist with interest in NF1. Results. 54 patients with 106 C2 neurofibromas were included. The median age was 32.5 years (range 15-61 years) and there was a slight male excess (M:F, 33:21). Splice-site (30%) and missense variants (20%) were frequent. Spinal neurofibromas were distributed in all spine regions (65%) or the cervical spine alone (22%). Most (93%) C2 neurofibromas were visible on MRI head scans. Intradural invasion and cord compression in the cervical spine included the C2 level in 95% and 80% of patients, respectively. Compared to all other cervical spine neurofibromas, C2 neurofibromas had higher rates of intraspinal extension (75% vs. 32%; OR=6.20, 95% CI 3.85-9.97; p<0.001), intradural invasion (53% vs. 26%; OR=3.20, 95% CI 2.08-4.92; p<0.001) and cord compression (25% vs. 13%; OR=2.26, 95% CI 1.35-3.79; p=0.002). However, C2 neurofibromas had lower rates of extraforaminal growth beyond the transverse process (12% vs. 62%; OR=0.09, 95% CI 0.05-0.16; p<0.001). Conclusions. C2 neurofibromas are associated with an aggressive intraspinal phenotype, limited growth outside the spinal canal and uncommon genetic profile. These observations require future study.