Neurofibroma and schwannoma

Neurofibromas and schwannomas are benign peripheral nerve sheath tumours that occur as isolated sporadic lesions, but have their major clinical impact on the neurocutaneous diseases neurofibromatosis 1 and neurofibromatosis 2. The gene products neurofibromin and merlin (schwannomin), respectively, are thought to act as tumour suppressors. The aim of this review is to document recent advances in our understanding of the clinical characteristics and pathogenesis of neurofibromas and schwannomas in the neurofibromatoses.Animal models have shed light on the pathogenesis of neurofibromas confirming that the Schwann cell initiates neurofibroma formation. New data suggest that individuals with neurofibromatosis 1 have a 10% lifetime risk of developing malignant peripheral nerve sheath tumours. Positron emission tomography with the glucose analogue 18-fluorodeoxyglucose might be helpful in the diagnosis of malignant peripheral nerve sheath tumours. Such tumours associated with neurofibromatosis 1 show a loss of neurofibromatosis 1 expression and high levels of Ras, but malignant transformation requires additional genetic events that inactivate key cell cycle regulators. Neurofibromatosis 2-associated vestibular schwannomas have variable growth rates that tend to decline with age. Early microsurgery for small tumours results in optimal preservation of hearing and facial nerve function. Currently, radiosurgery for these lesions produces similar results. Systematic follow-up of both groups will determine the best treatment method. Merlin's function as a tumour suppressor has not been elucidated. The control of cell cycle progression and abnormal intracellular and extracellular signalling could all play a part.Molecular advances will allow a biological approach to targeted therapies for neurofibromas, malignant peripheral nerve sheath tumours and schwannomas. Knowledge of the pathogenesis of these tumours will have implications for our understanding of the neurofibromatoses and of the formation of sporadic tumours.