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. 2018 May 18;20(6):818-825.
doi: 10.1093/neuonc/noy013.

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

Christine S Higham  1   2 , Eva Dombi  1 , Aljosja Rogiers  3 , Sucharita Bhaumik  1   4 , Steven Pans  5 , Steve E J Connor  6 , Markku Miettinen  7 , Raf Sciot  8 , Roberto Tirabosco  9 , Hilde Brems  3 , Andrea Baldwin  1 , Eric Legius  3 , Brigitte C Widemann  1 , Rosalie E Ferner  10
Affiliations

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

Christine S Higham et al. Neuro Oncol. .

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.

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Figures

Fig. 1
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
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.
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Comment in

References

    1. Cawthon RM, Weiss R, Xu GF et al. . A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell. 1990;62(1):193–201. - PubMed
    1. Martin GA, Viskochil D, Bollag G et al. . The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21. Cell. 1990;63(4):843–849. - PubMed
    1. Wallace MR, Marchuk DA, Andersen LB et al. . Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science. 1990;249(4965):181–186. - PubMed
    1. DeBella K, Szudek J, Friedman JM. Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children. Pediatrics. 2000;105(3 Pt 1):608–614. - PubMed
    1. Friedman JM. Neurofibromatosis 1: clinical manifestations and diagnostic criteria. J Child Neurol. 2002;17(8):548–554; discussion 571–572, 646–651. - PubMed

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