Longitudinal study of intraneural perineurioma--a benign, focal hypertrophic neuropathy of youth

Abstract

The natural history of intraneural perineurioma has been inadequately studied. The aim of this study was to characterize the clinical presentation, electrophysiologic and imaging features and outcome of intraneural perineurioma. We ask if intraneural perineurioma is a pure motor syndrome that remains confined to one nerve and should be treated by surgical resection. We examined the nerve biopsies of cases labelled perineurioma and selected those with diagnostic features. Thirty-two patients were identified; 16 children and 16 adults; 16 males and 16 females. Median age of onset of neurological symptoms was 14 years (range 0.5-55 years) and median age at evaluation was 17 years (range 2-56 years). All patients had motor deficits; however, mild sensory symptoms or signs were experienced by 27 patients; 'prickling' or 'asleep numbness' in 20, mild pain in 13 and sensory loss in 23. The sciatic nerve or its branches was most commonly affected in 15, followed by brachial plexus, radial nerve and ulnar nerve (four each). Magnetic resonance imaging demonstrated nerve enlargement (29/32), T1 isointensity (27/32), T2 hyperintensity (25/32) and contrast enhancement (20/20). Diagnoses were made based on targeted biopsy of the focal nerve enlargement identified by imaging. Neurological impairment was of a moderate severity (median Neuropathy Impairment Score was 12 points, range 2-49 points). All patients had focal involvement with 27 involving one nerve and five involving a plexus (one bilateral). Long-term follow-up was possible by telephone interview for 23 patients (median 36 months, range 2-177 months). Twelve patients also had follow-up neurologic evaluation (median 45 months, range 10-247 months). The median Neuropathy Impairment Score had changed from 12.6 to 15.4 points (P = 0.19). In all cases, the distribution of neurologic findings remained unchanged. Median Dyck Disability Score was 3 (range 2-5) indicating a mild impairment without interfering with activities of daily living. Ten patients judged their symptoms unchanged, nine slightly worse and four slightly better. We conclude intraneural perineurioma is a benign hypertrophic (non onion bulb) peripheral nerve tumour that presents insidiously in young people and is motor predominant with mild sensory involvement. It is most often a mononeuropathy, but a plexopathy can occur. Diagnosis of this condition requires clinical suspicion, imaging, targeted fascicular biopsy of the lesion and expertise of nerve pathologists. As these tumours are static or slowly progressive, remain confined to their original distribution and have low morbidity, they probably should not be resected routinely. Because intensive evaluation is needed for diagnosis, intraneural perineurioma is probably under-recognized.

Figure 1

Pathological features of perineurioma. Patient 1: serial transverse sections: Arrowheads indicate pseudo-onion bulb leaflets. (A) H&E section demonstrates diffuse pseudo-onion bulb formation. (B) Epoxy section at a similar level demonstrates thinly myelinated fibres at the centre of pseudo-onion bulbs. (C) Schwann cell preparation (S-100) demonstrates reactivity of the myelinated fibres at the centre and absence of reactivity of the surrounding pseudo-onion bulbs. (D) Reactivity of pseudo-onion bulb leaflets with epithelial membrane antigen (EMA) confirming these are of perineurial origin. These findings taken together are diagnostic of perineurioma.

Figure 2

Immunohistochemistry and ultrastructural features of perineurioma. Patient 3: These pathological features are typical of intraneural perineurioma. In contrast the clinical features of this case are very unusual as this young child has bilateral disease involving multiple nerves over a long distance (see Case 2). (A) S-100 preparation demonstrates reactivity of the myelinated fibres at the centre and absence of reactivity of the surrounding pseudo-onion bulbs (arrowheads). (B) Reactivity of pseudo-onion bulb leaflets with epithelial membrane antigen (EMA) confirming these are of perineurial origin (arrowheads). (C) Electron micrograph of Patient 4 and (D) electron micrograph of Patient 8 demonstrate dense concentrically arranged cellular processes around thinly myelinated axons typical of perineurioma.

Figure 3

MRI characteristics of perineurioma. Patient 5: (A) 3.0-T axial T₁-weighted fast spin echo (FSE) image shows marked enlargement of the individual fascicles of the tibial division of the sciatic nerve in the mid thigh (arrow). The peroneal division is unaffected (arrowhead). (B) Axial T₂-weighted FSE image with fat suppression at the same level demonstrates very mild T₂ hyperintensity in the tibial division of the sciatic nerve (arrow). (C) Axial T₁-weighted spoiled gradient recalled (SPGR) image with fat suppression after contrast administration at the same level shows prominent enhancement of individual fascicles within the tibial division of the nerve (arrow). Patient 3: (D) 1.5-T axial T₁-weighted FSE image shows marked enlargement of the femoral nerve (rightmost arrow with respect to the patient), lumbosacral plexus (middle arrow) and the S1 root (left-most arrow with respect to the patient). (E) Axial T₂-weighted FSE image shows mild T₂ hyperintensity of the nerves (arrows). (F) Axial T₁-weighted FSE image after contrast administration shows mild hyperintensity and avid enhancement of the nerves. There is oedema within the atrophied gluteus muscles on the right consistent with a combination of subacute and chronic denervation (asterisk).

Figure 4

Patient 2. (A) Photograph of the feet demonstrating atrophy and inversion of the affected foot due to chronic sciatic neuropathy (arrow). (B) Intra-operative photograph demonstrating focal fusiform enlargement of the tibial division (arrow) of the sciatic nerve (asterisk).