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Schwannomatosis: Review of Diagnosis and Management

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Diagnostic Assessment and Treatment of Peripheral Nerve Tumors

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Abstract

Schwannomatosis is a relatively new addition to the neurofibromatosis family of disorders. Occurring in only 1 in every 70,000 live births, it is the rarest neurofibromatosis and is characterized by the proliferation of peripheral nerve and spinal schwannomas. Genetic studies have identified SMARCB1 and LZTR1 as playing key roles in the pathogenesis of this disease. Patients most commonly present in the fourth or fifth decade of life with chronic and neuropathic pain, the medical management of which forms the core of therapy in this patient population. Surgical excision appears to have a role in the treatment of medically refractory, radicular, or neuropathic pain that is attributable to the schwannoma. At present no systemic therapies exist, and this remains an area of key interest for investigation.

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Abbreviations

GABA:

γ-Aminobutyric acid

MRI:

Magnetic resonance imaging

NF1:

Neurofibromatosis type 1

NF2:

Neurofibromatosis type 2

NSAID:

Non-steroidal anti-inflammatory drug

VEGF:

Vascular endothelial growth factor

WB-MRI:

Whole-body MRI

References

  1. Koontz NA, Wiens AL, Agarwal A, Hingtgen CM, Emerson RE, Mosier KM. Schwannomatosis: the overlooked neurofibromatosis? Am J Roentgenol. 2013;200:W646–53.

    Article  Google Scholar 

  2. Kresak J, Walsh M. Neurofibromatosis: a review of NF1, NF2, and Schwannomatosis. J Pediatr Genet. 2016;05:98–104.

    Article  CAS  Google Scholar 

  3. Hilton DA, Hanemann CO. Schwannomas and their pathogenesis. Brain Pathol. 2014;24:205–20.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Evans DG, Bowers NL, Tobi S, et al. Schwannomatosis: a genetic and epidemiological study. J Neurol Neurosurg Psychiatry. 2018;89:1215–9.

    Article  PubMed  Google Scholar 

  5. Antinheimo J, Sankila R, Carpen O, Pukkala E, Sainio M, Jaaskelainen J. Population-based analysis of sporadic and type 2 neurofibromatosis-associated meningiomas and schwannomas. Neurology. 2000;54:71–6.

    Article  CAS  PubMed  Google Scholar 

  6. Merker VL, Esparza S, Smith MJ, Stemmer-Rachamimov A, Plotkin SR. Clinical features of Schwannomatosis: a retrospective analysis of 87 patients. Oncologist. 2012;17:1317–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ostrow KL, Bergner AL, Blakeley J, et al. Creation of an international registry to support discovery in schwannomatosis. Am J Med Genet A. 2017;173:407–13.

    Article  CAS  PubMed  Google Scholar 

  8. MacCollin M, Chiocca EA, Evans DG, et al. Diagnostic criteria for schwannomatosis. Neurology. 2005;64:1838–45.

    Article  CAS  PubMed  Google Scholar 

  9. Alaidarous A, Parfait B, Ferkal S, Cohen J, Wolkenstein P, Mazereeuw-Hautier J. Segmental schwannomatosis: characteristics in 12 patients. Orphanet J Rare Dis. 2019;14:207.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kehrer-Sawatzki H, Farschtschi S, Mautner V-F, Cooper DN. The molecular pathogenesis of schwannomatosis, a paradigm for the co-involvement of multiple tumour suppressor genes in tumorigenesis. Hum Genet. 2017;136:129–48.

    Article  CAS  PubMed  Google Scholar 

  11. Chick G, Victor J, Poujade T, Hollevoet N. Sporadic Schwannomatosis: a systematic review following the 2005 consensus statement. J Neurol Surg A Cent Eur Neurosurg. 2018;79:408–15.

    Article  PubMed  Google Scholar 

  12. Plotkin S, Wick A. Neurofibromatosis and Schwannomatosis. Semin Neurol. 2018;38:73–85.

    Article  PubMed  Google Scholar 

  13. Kwon NY, Oh H-M, Ko YJ. Multiple lower extremity mononeuropathies by segmental Schwannomatosis: a case report. Ann Rehabil Med. 2015;39:833–7.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Jia Y, Kraus JA, Reddy H, Groff M, Wong ET. Polyradiculopathies from Schwannomatosis. Open Neuroimaging J. 2011;5:9–13.

    Article  Google Scholar 

  15. Plotkin SR, Bredella MA, Cai W, et al. Quantitative assessment of whole-body tumor burden in adult patients with neurofibromatosis. PLoS One. 2012;7:e35711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mehta GU, Feldman MJ, Wang H, Ding D, Chittiboina P. Unilateral vestibular schwannoma in a patient with schwannomatosis in the absence of LZTR1 mutation. J Neurosurg. 2016;125:1469–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Castellanos E, Bielsa I, Carrato C, et al. Segmental neurofibromatosis type 2: discriminating two hit from four hit in a patient presenting multiple schwannomas confined to one limb. BMC Med Genomics. 2015;8:2.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Leverkus M, Kluwe L, Roll E-M, Becker G, Brocker E-B, Mautner VF, Hamm H. Multiple unilateral schwannomas: segmental neurofibromatosis type 2 or schwannomatosis? Br J Dermatol. 2003;148:804–9.

    Article  CAS  PubMed  Google Scholar 

  19. MacCollin M, Woodfin W, Kronn D, Short MP. Schwannomatosis: a clinical and pathologic study. Neurology. 1996;46:1072–9.

    Article  CAS  PubMed  Google Scholar 

  20. MacCollin M, Willett C, Heinrich B, Jacoby LB, Acierno JS, Perry A, Louis DN. Familial schwannomatosis: exclusion of the NF2 locus as the germline event. Neurology. 2003;60:1968–74.

    Article  CAS  PubMed  Google Scholar 

  21. Gonzalvo A, Fowler A, Cook RJ, Little NS, Wheeler H, McDonald KL, Biggs MT. Schwannomatosis, sporadic schwannomatosis, and familial schwannomatosis: a surgical series with long-term follow-up. J Neurosurg. 2011;114:756–62.

    Article  PubMed  Google Scholar 

  22. Seppälä MT, Sainio MA, Haltia MJJ, Kinnunen JJ, Setälä KH, Jääskeläinen JE. Multiple schwannomas: schwannomatosis or neurofibromatosis type 2? J Neurosurg. 1998;89:36–41.

    Article  PubMed  Google Scholar 

  23. Ahlawat S, Blakeley JO, Langmead S, Belzberg AJ, Fayad LM. Current status and recommendations for imaging in neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis. Skeletal Radiol. 2020;49:199–219.

    Article  PubMed  Google Scholar 

  24. Cai W, Kassarjian A, Bredella MA, Harris GJ, Yoshida H, Mautner VF, Wenzel R, Plotkin SR. Tumor burden in patients with Neurofibromatosis types 1 and 2 and Schwannomatosis: determination on whole-body MR images. Radiology. 2009;250:665–73.

    Article  PubMed  Google Scholar 

  25. Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA. 1997;278:51–7.

    Article  CAS  PubMed  Google Scholar 

  26. Hulsebos TJM, Plomp AS, Wolterman RA, Robanus-Maandag EC, Baas F, Wesseling P. Germline mutation of INI1/SMARCB1 in familial Schwannomatosis. Am J Hum Genet. 2007;80:805–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Smith MJ, Wallace AJ, Bowers NL, Rustad CF, Woods CG, Leschziner GD, Ferner RE, Evans DGR. Frequency of SMARCB1 mutations in familial and sporadic schwannomatosis. Neurogenetics. 2012;13:141–5.

    Article  CAS  PubMed  Google Scholar 

  28. Romero OA, Sanchez-Cespedes M. The SWI/SNF genetic blockade: effects in cell differentiation, cancer and developmental diseases. Oncogene. 2014;33:2681–9.

    Article  CAS  PubMed  Google Scholar 

  29. Dutta A, Sardiu M, Gogol M, Gilmore J, Zhang D, Florens L, Abmayr SM, Washburn MP, Workman JL. Composition and function of mutant Swi/Snf complexes. Cell Rep. 2017;18:2124–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kadoch C, Crabtree GR. Mammalian SWI/SNF chromatin remodeling complexes and cancer: mechanistic insights gained from human genomics. Sci Adv. 2015;1:e1500447.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Wilson BG, Roberts CWM. SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer. 2011;11:481–92.

    Article  CAS  PubMed  Google Scholar 

  32. Guidi CJ, Sands AT, Zambrowicz BP, Turner TK, Demers DA, Webster W, Smith TW, Imbalzano AN, Jones SN. Disruption of Ini1 leads to peri-implantation lethality and tumorigenesis in mice. Mol Cell Biol. 2001;21:3598–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Steklov M, Pandolfi S, Baietti MF, et al. Mutations in LZTR1 drive human disease by dysregulating RAS ubiquitination. Science. 2018;362:1177–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Gutmann DH, Giovannini M. Mouse models of neurofibromatosis 1 and 2. Neoplasia. 2002;4:279–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Piotrowski A, Xie J, Liu YF, et al. Germline loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas. Nat Genet. 2014;46:182–7.

    Article  CAS  PubMed  Google Scholar 

  36. Zhang K, Lin J-W, Wang J, et al. A germline missense mutation in COQ6 is associated with susceptibility to familial schwannomatosis. Genet Med. 2014;16:787–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hadfield KD, Smith MJ, Urquhart JE, Wallace AJ, Bowers NL, King AT, Rutherford SA, Trump D, Newman WG, Evans DG. Rates of loss of heterozygosity and mitotic recombination in NF2 schwannomas, sporadic vestibular schwannomas and schwannomatosis schwannomas. Oncogene. 2010;29:6216–21.

    Article  CAS  PubMed  Google Scholar 

  38. Smith MJ, Walker JA, Shen Y, Stemmer-Rachamimov A, Gusella JF, Plotkin SR. Expression of SMARCB1 (INI1) mutations in familial schwannomatosis. Hum Mol Genet. 2012;21:5239–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Bellampalli SS, Khanna R. Towards a neurobiological understanding of pain in neurofibromatosis type 1: mechanisms and implications for treatment. Pain. 2019;160:1007–18.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Blakeley JO, Plotkin SR. Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis. Neuro Oncol. 2016;18:624–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Levi AD, Ross AL, Cuartas E, Qadir R, Temple HT. The surgical management of symptomatic peripheral nerve sheath tumors. Neurosurgery. 2010;66:833–40.

    Article  PubMed  Google Scholar 

  42. Guha D, Davidson B, Nadi M, et al. Management of peripheral nerve sheath tumors: 17 years of experience at Toronto Western Hospital. J Neurosurg. 2018;128:1226–34.

    Article  PubMed  Google Scholar 

  43. Safaee MM, Lyon R, Barbaro NM, Chou D, Mummaneni PV, Weinstein PR, Chin CT, Tihan T, Ames CP. Neurological outcomes and surgical complications in 221 spinal nerve sheath tumors. J Neurosurg Spine. 2017;26:103–11.

    Article  PubMed  Google Scholar 

  44. Safaee M, Parsa AT, Barbaro NM, Chou D, Mummaneni PV, Weinstein PR, Tihan T, Ames CP. Association of tumor location, extent of resection, and neurofibromatosis status with clinical outcomes for 221 spinal nerve sheath tumors. Neurosurg Focus. 2015;39:E5.

    Article  PubMed  Google Scholar 

  45. Montano N, D’Alessandris QG, D’Ercole M, Lauretti L, Pallini R, Di Bonaventura R, La Rocca G, Bianchi F, Fernandez E. Tumors of the peripheral nervous system: analysis of prognostic factors in a series with long-term follow-up and review of the literature. J Neurosurg. 2016;125:363–71.

    Article  PubMed  Google Scholar 

  46. Fehlings MG, Nater A, Zamorano JJ, et al. Risk factors for recurrence of surgically treated conventional spinal schwannomas. Spine (Phila Pa 1976). 2016;41:390–8.

    Article  Google Scholar 

  47. Pennington Z, Westbroek EM, Ahmed AK, Cottrill E, Lubelski D, Goodwin ML, Sciubba DM (2019) Surgical management of giant presacral schwannoma: systematic review of published cases and meta-analysis. J Neurosurg Spine: 1–12.

    Google Scholar 

  48. Evans DGR, Salvador H, Chang VY, Erez A, Voss SD, Druker H, Scott HS, Tabori U. Cancer and central nervous system tumor surveillance in pediatric Neurofibromatosis 2 and related disorders. Clin Cancer Res. 2017;23:e54–61.

    Article  CAS  PubMed  Google Scholar 

  49. Blakeley JO, Bakker A, Barker A, et al. The path forward: 2015 International Children’s Tumor Foundation conference on neurofibromatosis type 1, type 2, and schwannomatosis. Am J Med Genet A. 2017;173:1714–21.

    Article  PubMed  Google Scholar 

  50. Blakeley JO, Ye X, Duda DG, et al. Efficacy and biomarker study of bevacizumab for hearing loss resulting from neurofibromatosis type 2–associated vestibular schwannomas. J Clin Oncol. 2016;34:1669–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Blakeley J, Schreck KC, Evans DG, Korf BR, Zagzag D, Karajannis MA, Bergner AL, Belzberg AJ. Clinical response to bevacizumab in schwannomatosis. Neurology. 2014;83:1986–7.

    Article  PubMed  PubMed Central  Google Scholar 

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Disclosures

Zach Pennington—None; Daniel Lubelski—None; Ravi Medikonda—None; Allan J. Belzberg—Consultant for Axogen and for AstraZeneca.

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Authors and Affiliations

  1. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Zach Pennington, Daniel Lubelski, Ravi Medikonda & Allan J. Belzberg

Authors
  1. Zach Pennington
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  2. Daniel Lubelski
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  3. Ravi Medikonda
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  4. Allan J. Belzberg
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Corresponding author

Correspondence to Allan J. Belzberg .

Editor information

Editors and Affiliations

  1. WFNS Peripheral Nerve Surgery Committee Division of Neurosurgery, Department of Surgery, Gaffrée e Guinle University Hospital (HUGG) School of Medicine Federal University of Rio de Janeiro State (UNIRIO), Rio de Janeiro, Rio de Janeiro, Brazil

    Fernando Guedes

  2. WFNS Peripheral Nerve Surgery Committee Department of Neurosurgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA

    Eric L. Zager

  3. WFNS Peripheral Nerve Surgery Committee Department of Neurosurgery, Mediclinic Parkview Hospital, Dubai, United Arab Emirates

    Debora Garozzo

  4. WFNS Peripheral Nerve Surgery Committee, Faculty of Medicine University of Belgrade, Clinic for Neurosurgery, University Clinical Center of Serbia, Department of Peripheral Nerve Surgery, Functional Neurosurgery and Pain Management Surgery, Belgrade, Serbia

    Lukas Rasulic

  5. WFNS Peripheral Nerve Surgery Committee Peripheral Nerve & Brachial Plexus Surgery Program Department of Neurosurgery, University of Buenos Aires School of Medicine, Buenos Aires, Argentina

    Mariano Socolovsky

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Pennington, Z., Lubelski, D., Medikonda, R., Belzberg, A.J. (2021). Schwannomatosis: Review of Diagnosis and Management. In: Guedes, F., Zager, E.L., Garozzo, D., Rasulic, L., Socolovsky, M. (eds) Diagnostic Assessment and Treatment of Peripheral Nerve Tumors. Springer, Cham. https://doi.org/10.1007/978-3-030-77633-6_30

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