Growth dynamics of plexiform neurofibromas: a retrospective cohort study of 201 patients with neurofibromatosis 1

Orphanet Journal of Rare Diseases

Victor-Felix Mautner⁵  Jan M Friedman²  Lan Kluwe³  Carsten Fuensterer¹  Jeffrey Solomon⁶  Brigitte C Widemann⁶  Eva Dombi⁶  Rosa Nguyen⁴ 

[1]Department of Radiology, MRI Institute Hamburg Othmarschen, Hamburg, Germany

[2]Department of Medical Genetics, University of British Columbia, Vancouver, Canada

[3]Department of Maxillo-Facial-Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany

[4]Department of Pediatrics, University of Maryland, 22 South Greene Street, Baltimore, MD, 21201, USA

[5]Department of Neurology, University Hospital Hamburg-Eppendorf, Hamburg, Germany

[6]Pediatric Oncology Branch, National Cancer Institute, Bethesda, USA

关键词: Tumour burden;    Neurofibromatosis 1;    Plexiform;    Neurofibroma;    MRI scan;   

Others  :  864195
DOI  :  10.1186/1750-1172-7-75

 received in 2012-08-28, accepted in 2012-10-01,  发布年份 2012

【 摘 要 】

Background

To examine the natural growth dynamics of internal plexiform neurofibromas (PNs) in patients with neurofibromatosis 1 (NF1).

Methods

Two hundred and one NF1 patients underwent whole body MRI (WBMRI). Tumour burden was estimated volumetrically. Non-parametric Spearman’s rho correlation coefficients were used to analyse the relationship of growth rate to tumour volume and age. Chi-squared and Mann–Whitney U tests were used for analysing the association of tumour occurrence with sex or age. Chi-squared tests were used to analyse the association of tumour growth with age group.

Results

Seventy-one of 171 patients with serial WBMRI exams had internal PNs (median follow up 2.2 years[1.1 to 4.9 years]). Median whole body tumour volume was 86.4 mL [5.2 to 5878.5 mL]) with a median growth rate of 3.7%/year (−13.4 to 111%/year) that correlated with larger whole body tumour volume (P<0.001) and lower age (P=0.004). No new PNs developed in 273.0 patient-years among patients without tumours. Rate of new tumour development among patients with PNs was 0.6%/year (95% confidence interval 0.02 to 3.4%). Twenty-seven (13.5%) tumours increased significantly and were more frequent among children (P<0.001). Growth rate of tumours was inversely correlated with age (Spearman’s rho=−0.330, P<0.001). Seventy-one (35.5%) tumours had smaller volumes on follow up (median −3.4%/year [−0.07% to −35.9%/year]).

Conclusion

Children with NF1 and internal PNs are at risk for tumour growth. Most PNs grow slowly or not at all, and some decrease in size. New tumours are infrequent in NF1 patients with PNs and unlikely in patients without PNs.

【 授权许可】

   
2012 Nguyen et al.; licensee BioMed Central Ltd.

【 图 表 】

Fig. 7.

【 参考文献 】

• [1]Huson SM, Compston DA, Clark P, Harper PS: A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. J Med Gen 1989, 26:704-711.
• [2]Tonsgard JH, Kwak SM, Short MP, Dachman AH: CT imaging in adults with neurofibromatosis-1: frequent asymptomatic plexiform lesions. Neurol 1998, 50:1755-1760.
• [3]Mautner VF, Asuagbor FA, Dombi E, Fuensterer C, Kluwe L, Wenzel R, Widemann BC, Friedman JM: Assessment of benign tumour burden by whole-body MRI in patients with neurofibromatosis 1. Neuro-Oncol 2008, 10:593-598.
• [4]Nguyen R, Kluwe L, Fuensterer C, Kentsch M, Friedrich RE, Mautner VF: Plexiform neurofibromas in children with neurofibromatosis type 1: frequency and associated clinical deficits. J Pediatr 2011, 159:652-5. e2
• [5]Mautner VF, Hartmann M, Kluwe L, Friedrich RE, Fuensterer C: MRI growth patterns of plexiform neurofibromas in patients with neurofibromatosis type 1. Neuroradiol 2006, 48:160-165.
• [6]Evans DG, Baser ME, McGaughran J, Sharif S, Howard E, Moran A: Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Gen 2002, 39:311-314.
• [7]Tucker T, Friedman JM, Friedrich RE, Wenzel R, Fuensterer C, Mautner VF: Longitudinal study of neurofibromatosis 1 associated plexiform neurofibromas. J Med Gen 2009, 46:81-85.
• [8]Dombi E, Solomon J, Gillespie AJ, Fox E, Balis FM, Patronas N, Korf BR, Babovic-Vuksanovic D, Packer RJ, Belasco J, Goldman S, Jakacki R, Kieran M, Steinberg SM, Widemann BC: NF1 plexiform neurofibroma growth rate by volumetric MRI: relationship to age and body weight. Neurol 2007, 68:643-647.
• [9]Solomon J, Warren K, Dombi E, Patronas N, Widemann B: Automated detection and volume measurement of plexiform neurofibromas in neurofibromatosis 1 using magnetic resonance imaging. Comput Med Imaging Graph 2004, 28:257-265.
• [10]Stumph DA: Neurofibromatosis. Conference statement. National institutes of health consensus development conference. Arch Neurol 1988, 45(5):575-578.
• [11]Friedrich RE, Korf B, Fuensterer C, Mautner VF: Growth type of plexiform neurofibromas in NF1 determined on magnetic resonance images. Anticancer Res 2003, 23:949-952.
• [12]Friedrich RE, Schmelzle R, Hartmann M, Fuensterer C, Mautner VF: Resection of small plexiform neurofibromas in neurofibromatosis type 1 children. World J Surg Oncol 2005, 3:6. BioMed Central Full Text
• [13]Needle MN, Cnaan A, Dattilo J, Chatten J, Phillips PC, Shochat S, Sutton LN, Vaughan SN, Zackai EH, Zhao H, Molloy PT: Prognostic signs in the surgical management of plexiform neurofibroma: the Children’s hospital of Philadelphia experience, 1974–1994. J Pediatr 1997, 131:678-82.
• [14]Brenner W, Friedrich RE, Gawad KA, Hagel C, von Deimling A, de Wit M, Buchert R, Clausen M, Mautner VF: Prognostic relevance of FDG PET in patients with neurofibromatosis type-1 and malignant peripheral nerve sheath tumour. Eur J Nucl Med Mol Imaging 2006, 33:428-32.
• [15]Riccardi VM: Neurofibromatosis: phenotype, natural history, and pathogenesis. Baltimore: Johns Hopkins University Press; 1992.
• [16]Waggoner DJ, Towbin J, Gottesman G, Gutmann DH: Clinic-based study of plexiform neurofibromas in neurofibromatosis 1. Am J Med Gen 2000, 92:132-135.