Abstract IA16: Natural history of peripheral nerve sheath tumors in NF1: Identification and characterization of malignant precursor lesions

Abstract

Abstract Neurofibromatosis type 1 (NF1) is a common (incidence 1:2,700) inherited disorder characterized by the development of peripheral nerve sheath tumors, including plexiform neurofibromas (PN) and malignant peripheral nerve sheath tumors (MPNST). While PN are histologically benign they can result in substantial morbidity including pain, disfigurement, and neurologic or functional deficits. Importantly, PN are at risk for transformation to MPNST with a lifetime incidence in NF1 of 15.8%. We are evaluating the natural history of NF1 PN in children enrolled on an NCI natural history study. Patients undergo detailed clinical evaluations and longitudinal evaluation with whole body MRI to assess total body tumor burden. Our studies confirm that PN grow most rapidly in young children and that substantial PN growth in patients ≥15 years old is infrequent and should raise concern for malignant transformation. We also identified the development of distinct nodular lesions (DNL) on MRI. These lesions appear after early childhood, frequently grow more rapidly than the surrounding PN, show a growth rate independent of age, and are avid for fluorodexyglucose on positron emission tomography. On biopsy, some of these lesions were identified as atypical neurofibromas (ANF), which were recently identified as precursor lesions to MPNST, and are characterized by CDKN2A/B loss. We have confirmed that patients with ANF are at greater risk for MPNST and are developing strategies for the evaluation and management of patients with ANF. Surgical resection of ANF, when safely feasible, may reduce the risk for MPNST development. We recently identified that MEK inhibition results in shrinkage of most PN and are expanding our efforts to evaluate the effect of MEK inhibition on DNL and ANF. Citation Format: Brigitte C. Widemann. Natural history of peripheral nerve sheath tumors in NF1: Identification and characterization of malignant precursor lesions [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr IA16.