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Diagnosis and Management of Malignant Tumours in NF1: Evolution from Atypical Neurofibroma to Malignant Peripheral Nerve Sheath Tumour and Treatment Options

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Multidisciplinary Approach to Neurofibromatosis Type 1

Abstract

Individuals with Neurofibromatosis 1 have a 15.8% lifetime risk of developing malignant peripheral nerve sheath tumour (MPNST), which usually arises within a plexiform neurofibroma, is difficult to diagnosis and treat and often has a poor prognosis. A family history of MPNST, prior treatment with radiotherapy, a large disease burden, nodular neurofibromas, NF1 microdeletion, atypical neurofibromas and neurofibromatous neuropathy are risk factors requiring heightened surveillance. The cardinal symptoms of MPNST are rapid neurofibroma growth, persistent pain, hard texture and neurological deficit. Magnetic resonance imaging and 18F fluorodeoxyglucose positron emission tomography computerised tomography may assist the diagnosis. However, diagnostic biopsy for high grade lesions and excision biopsy (without wide margins) for atypical neurofibroma/low grade MPNST is the gold standard. The aim of treatment for high grade MPNST is surgery with wide margins, radiotherapy may be helpful for local control and chemotherapy metastasis but neither is curative.

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References

  1. Ferner RE, Gutmann DH. Neurofibromatosis type 1 (NF1): diagnosis and management. Handb Clin Neurol. 2013;115:939–55.

    Article  Google Scholar 

  2. Uusitalo E, Leppavirta J, Koffert A, Suominen S, Vahtera J, Vahlberg T, et al. Incidence and mortality of neurofibromatosis: a total population study in Finland. J Invest Dermatol. 2015;135(3):904–6.

    Article  CAS  Google Scholar 

  3. Ferner RE, Gutmann DH. International consensus statement on malignant peripheral nerve sheath tumors in neurofibromatosis. Cancer Res. 2002;62(5):1573–7.

    CAS  Google Scholar 

  4. Reilly KM, Kim A, Blakely J, Ferner RE, Gutmann DH, Legius E, et al. Neurofibromatosis type 1-associated MPNST state of the science: outlining a research agenda for the future. J Natl Cancer Inst. 2017;109(8):djx124.

    Article  Google Scholar 

  5. CLINICAL LECTURE ON MOLLUSCUM. Lancet. 1841;36(924):256–60.

    Google Scholar 

  6. Malbari F, Spira M, Knight PB, Zhu C, Roth M, Gill J, et al. Malignant peripheral nerve sheath tumors in neurofibromatosis: impact of family history. J Pediatr Hematol Oncol. 2018;40(6):e359–e63.

    Article  Google Scholar 

  7. Evans DG, Birch JM, Ramsden RT, Sharif S, Baser ME. Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes. J Med Genet. 2006;43(4):289–94.

    Article  CAS  Google Scholar 

  8. Kehrer-Sawatzki H, Mautner VF, Cooper DN. Emerging genotype-phenotype relationships in patients with large NF1 deletions. Hum Genet. 2017;136(4):349–76.

    Article  CAS  Google Scholar 

  9. De Raedt T, Brems H, Wolkenstein P, Vidaud D, Pilotti S, Perrone F, et al. Elevated risk for MPNST in NF1 microdeletion patients. Am J Hum Genet. 2003;72(5):1288–92.

    Article  Google Scholar 

  10. Mautner VF, Kluwe L, Friedrich RE, Roehl AC, Bammert S, Hogel J, et al. Clinical characterisation of 29 neurofibromatosis type-1 patients with molecularly ascertained 1.4 Mb type-1 NF1 deletions. J Med Genet. 2010;47(9):623–30.

    Article  CAS  Google Scholar 

  11. De Raedt T, Beert E, Pasmant E, Luscan A, Brems H, Ortonne N, et al. PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature. 2014;514(7521):247–51.

    Article  Google Scholar 

  12. Zhang M, Wang Y, Jones S, Sausen M, McMahon K, Sharma R, et al. Somatic mutations of SUZ12 in malignant peripheral nerve sheath tumors. Nat Genet. 2014;46(11):1170–2.

    Article  CAS  Google Scholar 

  13. Mautner VF, Asuagbor FA, Dombi E, Funsterer C, Kluwe L, Wenzel R, et al. Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1. Neuro-Oncology. 2008;10(4):593–8.

    Article  Google Scholar 

  14. Ferner RE, Hughes RA, Hall SM, Upadhyaya M, Johnson MR. Neurofibromatous neuropathy in neurofibromatosis 1 (NF1). J Med Genet. 2004;41(11):837–41.

    Article  CAS  Google Scholar 

  15. Higham CS, Dombi E, Rogiers A, Bhaumik S, Pans S, Connor SEJ, et al. The characteristics of 76 atypical neurofibromas as precursors to neurofibromatosis 1 associated malignant peripheral nerve sheath tumors. Neuro-Oncology. 2018;20(6):818–25.

    Article  Google Scholar 

  16. Miettinen MM, Antonescu CR, Fletcher CDM, Kim A, Lazar AJ, Quezado MM, et al. Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1-a consensus overview. Hum Pathol. 2017;67:1–10.

    Article  CAS  Google Scholar 

  17. Beert E, Brems H, Daniels B, De Wever I, Van Calenbergh F, Schoenaers J, et al. Atypical neurofibromas in neurofibromatosis type 1 are premalignant tumors. Genes Chromosomes Cancer. 2011;50(12):1021–32.

    Article  CAS  Google Scholar 

  18. Ahlawat S, Fayad LM, Khan MS, Bredella MA, Harris GJ, Evans DG, et al. Current whole-body MRI applications in the neurofibromatoses: NF1, NF2, and schwannomatosis. Neurology. 2016;87(7 Suppl 1):S31–9.

    Article  Google Scholar 

  19. Demehri S, Belzberg A, Blakeley J, Fayad LM. Conventional and functional MR imaging of peripheral nerve sheath tumors: initial experience. AJNR Am J Neuroradiol. 2014;35(8):1615–20.

    Article  CAS  Google Scholar 

  20. Ferner RE, Golding JF, Smith M, Calonje E, Jan W, Sanjayanathan V, et al. [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) as a diagnostic tool for neurofibromatosis 1 (NF1) associated malignant peripheral nerve sheath tumours (MPNSTs): a long-term clinical study. Ann Oncol. 2008;19(2):390–4.

    Article  CAS  Google Scholar 

  21. Warbey VS, Ferner RE, Dunn JT, Calonje E, O’Doherty MJ. [18F]FDG PET/CT in the diagnosis of malignant peripheral nerve sheath tumours in neurofibromatosis type-1. Eur J Nucl Med Mol Imaging. 2009;36(5):751–7.

    Article  CAS  Google Scholar 

  22. Bredella MA, Torriani M, Hornicek F, Ouellette HA, Plamer WE, Williams Z, et al. Value of PET in the assessment of patients with neurofibromatosis type 1. AJR Am J Roentgenol. 2007;189(4):928–35.

    Article  Google Scholar 

  23. Higham CS, Steinberg SM, Dombi E, Perry A, Helman LJ, Schuetze SM, et al. SARC006: phase II trial of chemotherapy in sporadic and neurofibromatosis type 1 associated chemotherapy-naive malignant peripheral nerve sheath tumors. Sarcoma. 2017;2017:8685638.

    Article  Google Scholar 

  24. Ferner RE, Thomas M, Mercer G, Williams V, Leschziner GD, Afridi SK, et al. Evaluation of quality of life in adults with neurofibromatosis 1 (NF1) using the impact of NF1 on Quality Of Life (INF1-QOL) questionnaire. Health Qual Life Outcomes. 2017;15(1):34.

    Article  Google Scholar 

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Acknowledgements

I am very grateful to the patients within our national neurofibromatosis service, my colleagues in the NF1 and sarcoma units and NHS England for funding the clinical service.

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Authors and Affiliations

  1. National Neurofibromatosis Service, Department of Neurology, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK

    Rosalie E. Ferner

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  1. Rosalie E. Ferner
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Correspondence to Rosalie E. Ferner .

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Editors and Affiliations

  1. Center for Inherited Cutaneous Diseases, University of Milan, Milan, Milano, Italy

    Gianluca Tadini

  2. Center for Human Genetics, Universitaire Ziekenhuizen Leuven Center for Human Genetics, Leuven, Oost-Vlaanderen, Belgium

    Eric Legius

  3. Department of Human Genetics, KU Leuven, Leuven, Belgium

    Hilde Brems

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Ferner, R.E. (2020). Diagnosis and Management of Malignant Tumours in NF1: Evolution from Atypical Neurofibroma to Malignant Peripheral Nerve Sheath Tumour and Treatment Options. In: Tadini, G., Legius, E., Brems, H. (eds) Multidisciplinary Approach to Neurofibromatosis Type 1. Springer, Cham. https://doi.org/10.1007/978-3-319-92450-2_12

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  • DOI: https://doi.org/10.1007/978-3-319-92450-2_12

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-92449-6

  • Online ISBN: 978-3-319-92450-2

  • eBook Packages: MedicineMedicine (R0)

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