The characteristics of 76 atypical neurofibromas as precursors to neurofibromatosis 1 associated malignant peripheral nerve sheath tumors

Abstract

Background: Neurofibromatosis 1 (NF1) leads to the development of benign and malignant peripheral nerve sheath tumors (MPNST). MPNST have been described to develop in preexisting benign plexiform neurofibromas (PN) and have a poor prognosis. Atypical neurofibromas (ANF) were recently described as precursor lesions for MPNST, making early detection and management of ANF a possible strategy to prevent MPNST. We aimed to clinically characterize ANF and identify management approaches.

Methods: We analyzed clinical, imaging, and pathology findings of all patients with NF1 and ANF at 3 institutions.

Results: Sixty-three patients had 76 ANF (32M/31F; median age 27.1 y). On MRI, most ANF appeared as distinct nodular lesions and were 18F-fluorodeoxyglucose (FDG) avid. Forty-six ANF were associated with pain, 19 with motor weakness, 45 were palpable or visible, and 13 had no clinical signs. Completely resected ANF (N = 57) have not recurred (median follow-up, 4.1 y; range, 0-14 y). Four ANF transformed into MPNST and 17 patients had a history of MPNST in a different location than was their ANF.

Conclusions: Growth of distinct nodular lesions, pain, and FDG-PET avidity should raise concern for ANF in NF1. Patients with ANF are at greater risk for development of MPNST. Complete resection of ANF may prevent development of MPNST.

Figures

Fig. 1

(A) Location of atypical neurofibromas. (B) Location of atypical neurofibromas in fascial plane. (C) Symptoms related to atypical neurofibromas. (D) Texture on palpation of atypical neurofibromas.

Fig. 2

Kaplan–Meier curve: proportion of patients with disease manifestations: age in years at first ANF, first MPNST, and death. All MPNST were included: MPNST prior to diagnosis of ANF or after diagnosis of ANF, whether transformed or developed in a different location.