Hemangioblastoma diagnosis and surveillance in von Hippel–Lindau disease: a consensus statement

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  • 1 Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Ohio State University, Columbus, Ohio;
  • | 2 Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia;
  • | 3 Department of Neurology, Lou and Jean Malnati Brain Tumor Institute, Northwestern University, Chicago, Illinois;
  • | 4 Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas; and
  • | 5 Division of Ocular Oncology and Pathology, Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, Tennessee
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OBJECTIVE

Hemangioblastomas are a frequent underlying cause of neurological morbidity and death in patients with von Hippel–Lindau disease (VHL). Although these benign tumors can cause significant neurological debility when undetected and untreated, unified evidence-based surveillance recommendations for VHL patients have not been established. To develop consensus recommendations, the VHL Alliance established an expert committee, named the International VHL Surveillance Guidelines Consortium, to define surveillance recommendations.

METHODS

The Central Nervous System (CNS) Hemangioblastoma Subcommittee of the Guidelines Consortium was formed as a multidisciplinary team of experts in the diagnosis and management of hemangioblastomas. Recommendations were formulated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) and National Comprehensive Cancer Network Categories of Evidence and Consensus categorization after a comprehensive literature review.

RESULTS

Published studies (n = 49) that discussed age at onset, MRI frequency, natural history of VHL, and the risks and benefits of surveillance were analyzed. Based on this analysis, the authors recommend that clinical evaluation (yearly) be used as the primary screening tool for hemangioblastomas in VHL. The subcommittee suggests that screening be performed between the ages of 11 and 65 years, or with the onset of symptoms, for synchronicity with other testing regimens in VHL. The subcommittee also recommends that baseline MRI be first performed at the age of 11 years (suggested 2B, level of evidence D) or after identification of neurological symptoms or signs (if earlier) and continue every 2 years (recommended 2A, level of evidence A).

CONCLUSIONS

The CNS Hemangioblastoma Subcommittee of the International VHL Surveillance Guidelines Consortium here proposes guidelines that aim to increase the early detection of VHL-associated hemangioblastomas to reduce their morbidity and mortality.

ABBREVIATIONS

CNS = central nervous system; GRADE = Grading of Recommendations, Assessment, Development and Evaluation; VHL = von Hippel–Lindau disease.

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  • 1

    Lonser RR, Butman JA, Huntoon K, et al. Prospective natural history study of central nervous system hemangioblastomas in von Hippel-Lindau disease. J Neurosurg. 2014;120(5):10551062.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Huntoon K, Wu T, Elder JB, et al. Biological and clinical impact of hemangioblastoma-associated peritumoral cysts in von Hippel-Lindau disease. J Neurosurg. 2016;124(4):971976.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Huntoon K, Lonser RR. Findings from the natural history of central nervous system hemangioblastomas in von Hippel-Lindau disease. Neurosurgery. 2014;61(suppl 1):N159N162.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Zhou B, Wang J, Liu S, et al. Hemangioblastoma instead of renal cell carcinoma plays a major role in the unfavorable overall survival of Von Hippel-Lindau disease patients. Front Oncol. 2019;9:1037.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5

    Lonser RR, Butman JA, Kiringoda R, et al. Pituitary stalk hemangioblastomas in von Hippel-Lindau disease. J Neurosurg. 2009;110(2):350353.

  • 6

    Barrett R, Meyer D, Boulos A, et al. Optic nerve hemangioblastoma. Ophthalmology. 2008;115(11):2095.

  • 7

    Rasulic L, Samardzic M, Bascarevic V, et al. A rare case of peripheral nerve hemangioblastoma—case report and literature review. Neurosurg Rev. 2015;38(1):205209.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Koo HW, Park JE, Cha J, et al. Hemangioblastomas with leptomeningeal dissemination: case series and review of the literature. Acta Neurochir (Wien). 2016;158(6):11691178.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Maher ER, Yates JR, Harries R, et al. Clinical features and natural history of von Hippel-Lindau disease. Q J Med. 1990;77(283):11511163.

  • 10

    Maddock IR, Moran A, Maher ER, et al. A genetic register for von Hippel-Lindau disease. J Med Genet. 1996;33(2):120127.

  • 11

    Byun J, Yoo HJ, Kim JH, et al. Growth rate and fate of untreated hemangioblastomas: clinical assessment of the experience of a single institution. J Neurooncol. 2019;144(1):147154.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Feletti A, Anglani M, Scarpa B, et al. Von Hippel-Lindau disease: an evaluation of natural history and functional disability. Neuro Oncol. 2016;18(7):10111020.

  • 13

    Vergauwen E, Steiert C, Krüger MT, et al. Cumulative surgical morbidity in patients with multiple cerebellar and medullary hemangioblastomas. Clin Neurol Neurosurg. 2020;197:106111.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Binderup ML, Bisgaard ML, Harbud V, et al. Von Hippel-Lindau disease (vHL). National clinical guideline for diagnosis and surveillance in Denmark. 3rd edition. Dan Med J. 2013;60(12):B4763.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Rednam SP, Erez A, Druker H, et al. Von Hippel-Lindau and hereditary pheochromocytoma/paraganglioma syndromes: clinical features, genetics, and surveillance recommendations in childhood. Clin Cancer Res. 2017;23(12):e68e75.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Choyke PL, Glenn GM, Walther MM, et al. von Hippel-Lindau disease: genetic, clinical, and imaging features. Radiology. 1995;194(3):629642.

  • 17

    Atkins D, Best D, Briss PA, et al. Grading quality of evidence and strength of recommendations. BMJ. 2004;328(7454):1490.

  • 18

    VHL Alliance. VHLA Suggested Active Surveillance Guidelines. Revised May 20, 2016.Accessed May 6, 2021. https://www.vhl.org/wp-content/uploads/2019/11/Active-Surveillance-Guidelines.pdf

    • Search Google Scholar
    • Export Citation
  • 19

    Lonser RR, Glenn GM, Walther M, et al. von Hippel-Lindau disease. Lancet. 2003;361(9374):20592067.

  • 20

    Butman JA, Linehan WM, Lonser RR. Neurologic manifestations of von Hippel-Lindau disease. JAMA. 2008;300(11):13341342.

  • 21

    Ho VB, Smirniotopoulos JG, Murphy FM, Rushing EJ. Radiologic-pathologic correlation: hemangioblastoma. AJNR Am J Neuroradiol. 1992;13(5):13431352.

  • 22

    Nguyen HS, Doan NB, Gelsomino M, et al. Intracranial hemangioblastoma—a SEER-based analysis 2004-2013. Oncotarget. 2018;9(46):2800928015.

  • 23

    Elster AD, Arthur DW. Intracranial hemangioblastomas: CT and MR findings. J Comput Assist Tomogr. 1988;12(5):736739.

  • 24

    Klingler JH, Gläsker S, Bausch B, et al. Hemangioblastoma and von Hippel-Lindau disease: genetic background, spectrum of disease, and neurosurgical treatment. Childs Nerv Syst. 2020;36(10):25372552.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Vanbinst AM, Brussaard C, Vergauwen E, et al. A focused 35-minute whole body MRI screening protocol for patients with von Hippel-Lindau disease. Hered Cancer Clin Pract. 2019;17:22.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Nielsen SM, Rhodes L, Blanco I, et al. Von Hippel-Lindau disease: genetics and role of genetic counseling in a multiple neoplasia syndrome. J Clin Oncol. 2016;34(18):21722181.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27

    Launbjerg K, Bache I, Galanakis M, et al. von Hippel-Lindau development in children and adolescents. Am J Med Genet A. 2017;173(9):23812394.

  • 28

    Wang Q, Meng S, Cheng J, et al. Central nervous system hemangioblastomas: an age-stratified analysis. Clin Neurol Neurosurg. 2020;199:106281.

  • 29

    Wang Q, Cheng J, Zhang S, et al. Central nervous system hemangioblastomas in the elderly (over 65 years): Clinical characteristics and outcome analysis. Clin Neurol Neurosurg. 2020;189:105622.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Poulsen ML, Budtz-Jørgensen E, Bisgaard ML. Surveillance in von Hippel-Lindau disease (vHL). Clin Genet. 2010;77(1):4959.

  • 31

    Meister M, Choyke P, Anderson C, Patel U. Radiological evaluation, management, and surveillance of renal masses in Von Hippel-Lindau disease. Clin Radiol. 2009;64(6):589600.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Vergauwen E, Vanbinst AM, Brussaard C, et al. Central nervous system gadolinium accumulation in patients undergoing periodical contrast MRI screening for hereditary tumor syndromes. Hered Cancer Clin Pract. 2018;16:2.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Ye DY, Bakhtian KD, Asthagiri AR, Lonser RR. Effect of pregnancy on hemangioblastoma development and progression in von Hippel-Lindau disease. J Neurosurg. 2012;117(5):818824.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Binderup ML, Budtz-Jørgensen E, Bisgaard ML. New von Hippel-Lindau manifestations develop at the same or decreased rates in pregnancy. Neurology. 2015;85(17):15001503.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35

    Othmane IS, Shields C, Singh A, et al. Postpartum cerebellar herniation in von Hippel-Lindau syndrome. Am J Ophthalmol. 1999;128(3):387389.

  • 36

    Capone F, Profice P, Pilato F, et al. Spinal hemangioblastoma presenting with low back pain in pregnancy. Spine J. 2013;13(12):e27e29.

  • 37

    Merhi B, Miller M, Lanis A, et al. Management of uncommon disorders in pregnancy: Von Hippel-Lindau disease, Gitelman syndrome, and Nutcracker syndrome. Obstet Med. 2017;10(3):138141.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Ma XJ, Zhang GB, Guo TX, et al. Management and outcomes of pregnant patients with central nervous system hemangioblastoma. J Clin Neurosci. 2018;57:126130.

  • 39

    Yoon JY, Gao A, Das S, Munoz DG. Epidemiology and clinical characteristics of hemangioblastomas in the elderly: An update. J Clin Neurosci. 2017;43:264266.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Kanno H, Kuratsu J, Nishikawa R, et al. Clinical features of patients bearing central nervous system hemangioblastoma in von Hippel-Lindau disease. Acta Neurochir (Wien). 2013;155(1):17.

    • Crossref
    • Search Google Scholar
    • Export Citation

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