Spinal ependymomas in neurofibromatosis Type 2: a retrospective analysis of 55 patients

Clinical article

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  • 1 Departments of Neurology and Cancer Center and
  • 3 Neurosurgery, and
  • 2 Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts
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Object

The aim of this paper was to define the clinical characteristics of spinal ependymomas associated with neurofibromatosis Type 2 (NF2).

Methods

The authors retrospectively reviewed the clinical records of patients with NF2 who had imaging findings consistent with ependymomas and were seen at Massachusetts General Hospital between 1994 and 2007. Clinical characteristics of these patients were obtained from hospital records, imaging studies, surgical reports, and pathology reports. Mutational analysis of the NF2 gene was performed in 37 of 44 unrelated patients.

Results

Fifty-five patients met inclusion criteria for the study. The median age at diagnosis of NF2 was 21 years; the median time after diagnosis until identification of ependymomas was 5 years. Multiple ependymomas were present in 58% of patients. The most common site of involvement was the cervical cord or cervicomedullary junction (86% of imaging studies), followed by the thoracic and lumbar cords (62% and 8%, respectively). The majority of patients had no symptoms related to their tumors (42 patients [76%]). After a median follow-up of 50 months, surgery was performed in 11 patients (20%) for symptomatic progression (indications for surgery). Mutational analysis of the NF2 gene detected alterations in 28 (76%) of 37 unrelated patients, with nonsense and frameshift mutations accounting for 64% of detected mutations. The high rate of truncating mutations may help explain the high tumor burden in these patients.

Conclusions

Neurofibromatosis Type 2–related ependymomas exhibit an indolent growth pattern with tumor progression limited to a minority of patients. The authors believe that surveillance is reasonable for asymptomatic ependymomas, including those with cystic areas that expand the cord. For symptomatic tumors, resection may be warranted depending on age, overall clinical status, and ease of resectability.

Abbreviations used in this paper: CMJ = cervicomedullary junction; NF2 = neurofibromatosis Type 2.

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Contributor Notes

Address correspondence to: Scott R. Plotkin, M.D., Ph.D., Yawkey 9E, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114. email: splotkin@partners.org.

Please include this information when citing this paper: published online February 4, 2011; DOI: 10.3171/2010.11.SPINE10350.

  • 1

    Ahronowitz I, , Xin W, , Kiely R, , Sims K, , MacCollin M, & Nunes FP: Mutational spectrum of the NF2 gene: a meta-analysis of 12 years of research and diagnostic laboratory findings. Hum Mutat 28:112, 2007

    • Search Google Scholar
    • Export Citation
  • 2

    Baser ME, , Friedman JM, , Wallace AJ, , Ramsden RT, , Joe H, & Evans DG: Evaluation of clinical diagnostic criteria for neurofibromatosis 2. Neurology 59:17591765, 2002

    • Search Google Scholar
    • Export Citation
  • 3

    Baser ME, , Kuramoto L, , Joe H, , Friedman JM, , Wallace AJ, & Gillespie JE, : Genotype-phenotype correlations for nervous system tumors in neurofibromatosis 2: a population-based study. Am J Hum Genet 75:231239, 2004

    • Search Google Scholar
    • Export Citation
  • 4

    Central Brain Tumor Registry of the United States (CBTRUS): Statistical Report: Primary Brain Tumors in the United States 1998–2002 (http://www.cbtrus.org/reports//2005-2006/2006report.pdf) [Accessed December 7, 2010]

    • Search Google Scholar
    • Export Citation
  • 5

    Dow G, , Biggs N, , Evans G, , Gillespie J, , Ramsden R, & King A: Spinal tumors in neurofibromatosis type 2. Is emerging knowledge of genotype predictive of natural history?. J Neurosurg Spine 2:574579, 2005

    • Search Google Scholar
    • Export Citation
  • 6

    Evans DG, , Huson SM, , Donnai D, , Neary W, , Blair V, & Newton V, : A clinical study of type 2 neurofibromatosis. Q J Med 84:603618, 1992

  • 7

    Gilhuis HJ, , van der Laak J, , Wesseling P, , Boerman RH, , Beute G, & Teepen JL, : Inverse correlation between genetic aberrations and malignancy grade in ependymal tumors: a paradox?. J Neurooncol 66:111116, 2004

    • Search Google Scholar
    • Export Citation
  • 8

    Gutmann DH, , Aylsworth A, , Carey JC, , Korf B, , Marks J, & Pyeritz RE, : The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA 278:5157, 1997

    • Search Google Scholar
    • Export Citation
  • 9

    Jacoby LB, , Jones D, , Davis K, , Kronn D, , Short MP, & Gusella J, : Molecular analysis of the NF2 tumor-suppressor gene in schwannomatosis. Am J Hum Genet 61:12931302, 1997

    • Search Google Scholar
    • Export Citation
  • 10

    Kobata H, , Kuroiwa T, , Isono N, , Nagasawa S, , Ohta T, & Tsutsumi A: Tanycytic ependymoma in association with neurofibromatosis type 2. Clin Neuropathol 20:93100, 2001

    • Search Google Scholar
    • Export Citation
  • 11

    Mautner VF, , Tatagiba M, , Lindenau M, , Fünsterer C, , Pulst SM, & Baser ME, : Spinal tumors in patients with neurofibromatosis type 2: MR imaging study of frequency, multiplicity, and variety. AJR Am J Roentgenol 165:951955, 1995

    • Search Google Scholar
    • Export Citation
  • 12

    Miyazawa N, , Hida K, , Iwasaki Y, , Koyanagi I, & Abe H: MRI at 1.5 T of intramedullary ependymoma and classification of pattern of contrast enhancement. Neuroradiology 42:828832, 2000

    • Search Google Scholar
    • Export Citation
  • 13

    Patronas NJ, , Courcoutsakis N, , Bromley CM, , Katzman GL, , MacCollin M, & Parry DM: Intramedullary and spinal canal tumors in patients with neurofibromatosis 2: MR imaging findings and correlation with genotype. Radiology 218:434442, 2001

    • Search Google Scholar
    • Export Citation
  • 14

    Rennie AT, , Side L, , Kerr RS, , Anslow P, & Pretorius P: Intramedullary tumours in patients with neurofibromatosis type 2: MRI features associated with a favourable prognosis. Clin Radiol 63:193200, 2008

    • Search Google Scholar
    • Export Citation
  • 15

    Schwartz TH, & McCormick PC: Intramedullary ependymomas: clinical presentation, surgical treatment strategies and prognosis. J Neurooncol 47:211218, 2000

    • Search Google Scholar
    • Export Citation
  • 16

    Sun B, , Wang C, , Wang J, & Liu A: MRI features of intramedullary spinal cord ependymomas. J Neuroimaging 13:346351, 2003

  • 17

    Ueki K, , Sasaki T, , Ishida T, & Kirino T: Spinal tanycytic ependymoma associated with neurofibromatosis type 2—case report. Neurol Med Chir (Tokyo) 41:513516, 2001

    • Search Google Scholar
    • Export Citation

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