Plexiform neurofibromas are nerve sheath tumors that grow along the length of nerves and tend to involve multiple branches of a nerve. They represent one of the major sources of morbidity to individuals with NF1, causing disfigurement and impairment of nerve function, and in some cases they develop into malignant peripheral nerve sheath tumors. Plexiform neurofibromas are, therefore, an important target for trials of potential therapeutic agents. Before such trials can be undertaken, however, a reliable scheme will be needed to permit accurate assessment of the size and growth rate of these tumors. Such assessment is made particularly difficult by the irregular size and shape of many plexiform neurofibromas and their apparent unpredictable growth.

The overall goal of this project is to develop such a scheme and to provide a body of normative data on the growth rate of plexiform neurofibromas. It is also intended to develop a consortium of clinical centers supported by statistical, radiological, genetic, and pathological resources that will be in a position to perform clinical trials in the future. The study calls for recruitment of 300 subjects with NF1 and plexiform neurofibromas. These will be distributed into three groups of 100 subjects. Group 1 will include patients with plexiform neurofibroma derived from a cranial nerve; group 2 will be patients with plexiform neurofibroma originating in a spinal nerve root; group 3 will be patients with plexiform neurofibroma of a peripheral nerve not including the nerve root. Each group will include fifty subjects from birth to 18 years of age and fifty over 18 years of age at the time of recruitment into the study. Tumors will be imaged by MRI [magnetic resonance imaging] according to a standard protocol at intervals depending on clinical indications and evidence of tumor growth. At least three data points will be obtained for each subject. MRI data will be subjected to volumetric analysis at a central facility. A standard data entry form will record clinical information about each subject. DNA will be collected for analysis of the NF1 gene mutation. If tumor tissue is obtained in the course of routine clinical care, pathology will be reviewed at a central facility and any available tumor tissue will be processed and stored in a tissue bank for future study. The tissue bank and pathology review will be open to use by the community at large, in order to collect more information on the pathology, genetics, and cell biology of plexiform neurofibromas. It is expected that this study will validate the use of quantitative MRI for the study of plexiform neurofibroma growth rates, provide better characterization of the patterns of neurofibroma growth, and develop an infrastructure to facilitate future clinical trials of potential treatments.