Symptoms associated with malignancy of peripheral nerve sheath tumours:: a retrospective study of 69 patients with neurofibromatosis 1

Background Neurofibromatosis 1 (NF1) is a common genetic disorder with variable clinical manifestations and an unpredictable course. Plexiform neurofibromas are common complications of NF1. Their malignant transformation is the main cause of mortality in adult patients with NF1. Objectives To identify clinical factors associated with malignant transformation of plexiform neurofibromas. Methods Using the database of our neurofibromatosis clinic we included in a retrospective study all patients with NF1 having at least one peripheral nerve sheath tumour for which they underwent surgery or surgical biopsy. Predictive values for malignant transformation of three clinical symptoms, i.e. pain, enlargement of mass and neurological symptoms, were evaluated in association with histological parameters. Results Of 69 patients studied, 48 had at least one plexiform neurofibroma and 21 had a malignant peripheral nerve sheath tumour. Only enlargement of the tumour had high negative and positive predictive values for malignant transformation: 0.92 and 0.95, respectively. In multivariate analysis, tumour enlargement was independently associated with malignant transformation (odds ratio 167.8, 95% confidence interval 14.0-2012.1). Conclusions From a practical point of view, pain, neurological deficit and enlargement of a pre-existing peripheral nerve sheath tumour in NF1 must lead to deep surgical biopsy to rule out malignant transformation.