The PERISCOPE Cohort: A Retrospective Study of Clinicopathological and TRAF7 Genetic Findings in Intraneural...

Intraneural perineurioma (INP) is a rare, benign peripheral nerve sheath tumour that typically presents in adolescence or early adulthood as a slowly progressive, motor-predominant mononeuropathy or plexopathy. Although its clinicoradiological and histopathological features are well characterised, the genetic basis remains incompletely defined.

We retrospectively analysed 10 patients with histologically confirmed INP diagnosed between February 2015 and December 2024. Demographic and clinical data, MRI/MR neurography findings and histopathology (immunohistochemistry and electron microscopy) were analysed. Targeted Sanger sequencing of TRAF7 exons 17-18 (WD40 domain) was performed. Interphase FISH with an EWSR1 (22q12) probe was performed on archival FFPE tissue in a subset.

All patients exhibited progressive motor deficits, with at least one muscle group graded ≤ 2 on the MRC scale. Sensory symptoms were present in 8/10 and pain in 4/10. MRI demonstrated fusiform nerve enlargement and homogeneous gadolinium enhancement in all cases, with T2 hyperintensity in 9/10. A pathogenic TRAF7 p.His521Arg variant was identified in 2/9 evaluable tumours (22.2%). Tendon transfer was performed in 7/10 patients as a reconstructive strategy to improve motor function, resulting in heterogeneous functional outcomes.

The MRI triad of fusiform enlargement, T2 hyperintensity and homogeneous enhancement strongly supports INP diagnosis and may obviate biopsy in typical cases. Our hotspot-limited assay detected TRAF7 mutations in only 22.2%, underscoring methodological limitations and probable genetic heterogeneity. Despite an indolent imaging appearance, INP frequently causes severe functional impairment requiring reconstructive surgery. Early recognition, structured functional monitoring and risk-adapted intervention are essential to optimise outcomes.