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

Clinical article

Restricted access

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.

Article Information

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.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Imaging characteristics of ependymomas in patients with NF2. A: Sagittal postcontrast MR image of an intramedullary tumor in a symptomatic patient, demonstrating an enhancing lesion at the CMJ. B and C: Axial postcontrast images demonstrating a cyst (B) associated with the enhancing lesion (C). The arrows indicate that this is the same lesion as in A. It is remarkable that neurological function may be preserved even in instances in which only an attenuated rim of spinal cord remains. D: Sagittal postcontrast MR image obtained in an asymptomatic patient, showing multiple intramedullary tumors with the appearance of a “string of pearls” (arrows) found during routine imaging of the cord.

References

1

Ahronowitz IXin WKiely RSims KMacCollin MNunes FP: Mutational spectrum of the NF2 gene: a meta-analysis of 12 years of research and diagnostic laboratory findings. Hum Mutat 28:1122007

2

Baser MEFriedman JMWallace AJRamsden RTJoe HEvans DG: Evaluation of clinical diagnostic criteria for neurofibromatosis 2. Neurology 59:175917652002

3

Baser MEKuramoto LJoe HFriedman JMWallace AJGillespie JE: Genotype-phenotype correlations for nervous system tumors in neurofibromatosis 2: a population-based study. Am J Hum Genet 75:2312392004

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

5

Dow GBiggs NEvans GGillespie JRamsden RKing A: Spinal tumors in neurofibromatosis type 2. Is emerging knowledge of genotype predictive of natural history?. J Neurosurg Spine 2:5745792005

6

Evans DGHuson SMDonnai DNeary WBlair VNewton V: A clinical study of type 2 neurofibromatosis. Q J Med 84:6036181992

7

Gilhuis HJvan der Laak JWesseling PBoerman RHBeute GTeepen JL: Inverse correlation between genetic aberrations and malignancy grade in ependymal tumors: a paradox?. J Neurooncol 66:1111162004

8

Gutmann DHAylsworth ACarey JCKorf BMarks JPyeritz RE: The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA 278:51571997

9

Jacoby LBJones DDavis KKronn DShort MPGusella J: Molecular analysis of the NF2 tumor-suppressor gene in schwannomatosis. Am J Hum Genet 61:129313021997

10

Kobata HKuroiwa TIsono NNagasawa SOhta TTsutsumi A: Tanycytic ependymoma in association with neurofibromatosis type 2. Clin Neuropathol 20:931002001

11

Mautner VFTatagiba MLindenau MFünsterer CPulst SMBaser ME: Spinal tumors in patients with neurofibromatosis type 2: MR imaging study of frequency, multiplicity, and variety. AJR Am J Roentgenol 165:9519551995

12

Miyazawa NHida KIwasaki YKoyanagi IAbe H: MRI at 1.5 T of intramedullary ependymoma and classification of pattern of contrast enhancement. Neuroradiology 42:8288322000

13

Patronas NJCourcoutsakis NBromley CMKatzman GLMacCollin MParry DM: Intramedullary and spinal canal tumors in patients with neurofibromatosis 2: MR imaging findings and correlation with genotype. Radiology 218:4344422001

14

Rennie ATSide LKerr RSAnslow PPretorius P: Intramedullary tumours in patients with neurofibromatosis type 2: MRI features associated with a favourable prognosis. Clin Radiol 63:1932002008

15

Schwartz THMcCormick PC: Intramedullary ependymomas: clinical presentation, surgical treatment strategies and prognosis. J Neurooncol 47:2112182000

16

Sun BWang CWang JLiu A: MRI features of intramedullary spinal cord ependymomas. J Neuroimaging 13:3463512003

17

Ueki KSasaki TIshida TKirino T: Spinal tanycytic ependymoma associated with neurofibromatosis type 2—case report. Neurol Med Chir (Tokyo) 41:5135162001

TrendMD

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 31 31 31
Full Text Views 74 74 38
PDF Downloads 79 79 29
EPUB Downloads 0 0 0

PubMed

Google Scholar