Histopathologically dysplastic neurofibromas in neurofibromatosis 1: diagnostic criteria, prevalence and clinical significance.

BACKGROUND

Malignant peripheral nerve sheath tumours (MPNSTs) correspond to the most frequent and aggressive neoplasic complications associated with poor prognosis in neurofibromatosis 1.

OBJECTIVES

To define the dysplastic neurofibroma potentially at risk of transformation and evaluate its prevalence and incidence.

METHODS

According to our database, we retrospectively included, between 1 March 2000 and 31 August 2004, all patients who had subcutaneous and/or plexiform neurofibromas removed surgically. Tumour specimens were systematically reviewed; dysplastic neurofibroma was defined by the association of high cellularity and the presence of atypical cells. Clinically atypical and histopathologically dysplastic neurofibromas were analysed using Fisher's exact test. In addition, three high-grade MPNSTs were analysed retrospectively for the presence of associated histopathologically dysplastic neurofibroma.

RESULTS

Among the 89 plexiform and/or subcutaneous neurofibromas surgically removed, high cellularity and cytonuclear atypia were observed in 19% and 17% of cases, respectively. Both criteria were associated in 8.9% of cases (n=8); Mib-1 immunostaining was negative in all cases (n=7). In univariate analysis, only neurological symptoms were significantly associated with dysplasia (P=0.02). Interestingly, dysplastic neurofibroma areas could be identified within or at the periphery of two MPNSTs.

CONCLUSIONS

The association of hypercellularity and cytonuclear atypia could be considered as a potential histological prognostic factor of transformation leading to increased surveillance.