C2 neurofibromas in neurofibromatosis type 1: genetic and imaging characteristics

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OBJECTIVE

C2 nerve root neurofibromas have been reported frequently in patients with neurofibromatosis type 1 (NF1), although their genetic and imaging characteristics are unexplored. The aim of this study was to characterize genetic and spinal imaging findings in a large cohort of NF1 patients with C2 neurofibromas.

METHODS

The authors performed a review of national NF1 referrals between 2009 and 2016. Inclusion criteria were at least 1 C2 root neurofibroma and cervical-spine or whole-spine MRI scans available for analysis. Blinded imaging review was performed by a neuroradiologist with an interest in NF1.

RESULTS

Fifty-four patients with 106 C2 neurofibromas were included. The median age was 32.5 years (range 15–61 years), and there were slightly more male patients (33 vs 21 female patients). Splice-site (30%) and missense (20%) variants were frequent. Spinal neurofibromas were distributed in all spine regions (65%) or in the cervical spine alone (22%). Most (93%) C2 neurofibromas were visible on MRI scans of the head. Intradural invasion and cord compression in the cervical spine included the C2 level in 95% and 80% of patients, respectively. Compared with all other cervical spine neurofibromas in these patients, 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 an uncommon genetic profile. These observations require future study.

ABBREVIATIONS NF1 = neurofibromatosis type 1; PFS = progression-free survival.

Article Information

Correspondence Mueez Waqar: Salford Royal NHS Foundation Trust, Manchester, United Kingdom. mwaqar@doctors.org.uk.

INCLUDE WHEN CITING Published online October 19, 2018; DOI: 10.3171/2018.7.SPINE171340.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

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Figures

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    Spine segmental neurofibroma patterns in patients with C2 neurofibromas. A: Intradural invasion patterns. These were similar between the cervical and lumbosacral spine. Intradural invasion was rare in the thoracic spine. B: Cord compression patterns. In general, radiological cord compression was rare outside of the cervical spine.

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    Features in patients with C2 neurofibromas as seen on coronal (A–C) and axial (D and E) images. A: Multilevel segmental spinal neurofibromas were common, as in this 39-year-old man with extensive segmental neurofibromas throughout the whole spine, including plexiform neurofibromatous involvement of the brachial plexi and lumbar and sacral plexi. B: Isolated neurofibromas were rare, as in this 61-year-man male with an isolated, unilateral left-sided C2 neurofibroma (arrow), without neurofibromas elsewhere in the spine. C: Some neurofibromas had intraspinal growth without intradural invasion, as in this 52-year-old woman with an extensive right-sided C2 neurofibroma causing cord compression (arrow). D: Intradural invasion was present in a significant proportion, as in this 45-year-old man with bilateral C2 neurofibromas with intradural invasion (1%–25%; arrow). E: Radiological cord compression was commonly associated with C2 neurofibromas, as in this 19-year-old woman with progressive myelopathy (arrow) due to bilateral C2 neurofibromas. Figure is available in color online only.

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