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Case Report
A Case of Von Hippel-Lindau Disease Presented with Multiple Pancreatic Cysts and Medullary Hemangioblastoma
Clin Pediatr Hematol Oncol 2020;27:67-71.
Published online April 30, 2020
© 2020 Korean Society of Pediatric Hematology-Oncology

Young Hyun Kim, Hye Lim Jung, Aram Yang, Ji Hee Kwak, Deok Soo Kim, Jung Yeon Shim and Jae Won Shim

Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
Correspondence to: Hye Lim Jung
Department of Pediatrics, Kangbuk Samsung Hospital, 29 Saemunanro, Jongro-gu, Seoul 03181, Korea
Tel: +82-2-2001-2483
Fax: +82-2-2001-1922
Received March 30, 2020; Revised April 21, 2020; Accepted April 24, 2020.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Von Hippel-Lindau (VHL) disease is a rare inherited cancer predisposition syndrome characterized by benign and malignant tumors in multiple organs, especially cerebellar hemangioblastomas, retinal angiomas, renal-cell carcinoma, and pheochromocytomas. Clinically, VHL disease also presents an increased risk for developing multiple visceral cysts in the pancreas, liver, and kidneys. Regular surveillance for VHL disease-associated tumors after early diagnosis is necessary for better outcomes in VHL disease. An 11-year-old girl was admitted with prolonged fever lasting for more than 10 days and cervical lymphadenopathy. She did not have a family history of cysts or malignancy. Initial blood tests showed mild leukopenia and moderate elevation in aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, but with normal amylase and lipase. Hepatobiliary ultrasonography and magnetic resonance cholangiopancreatography were done and revealed multiple cysts involving the whole pancreas with cyst sizes up to 1.6 cm, indicating VHL disease. Direct sequencing of the VHL gene showed a heterozygous duplication at codon 384 (c.384dup), which is predicted to cause a frameshift of the reading frame (p.Leu129Serfs*3). This was a novel pathogenic variant VHL gene. We carried out the surveillance protocol for VHL disease-associated tumors, and found a hemangioblastoma in the medulla of the brainstem. We are reporting an 11-year-old female patient of VHL disease with brainstem hemangioblastoma who could be suspected and diagnosed of VHL disease in asymptomatic state due to incidentally found multiple pancreatic cysts.
Keywords: Von Hippel-Lindau disease, Pancreatic cyst, Hemangioblastoma
  1. Keutgen XM, Hammel P, Choyke PL, Libutti SK, Jonasch E, Kebebew E. Evaluation and management of pancreatic lesions in patients with von Hippel-Lindau disease. Nat Rev Clin Oncol 2016;13:537-49.
    Pubmed CrossRef
  2. Sharma A, Mukewar S, Vege SS. Clinical profile of pancreatic cystic lesions in von Hippel-Lindau disease: A series of 48 patients seen at a tertiary institution. Pancreas 2017;46:948-52.
    Pubmed CrossRef
  3. Bhuyan M, Dutta D, Baishya BK, Hussain Z. Cerebellospinal hemangioblastoma with bilateral pheochromocytoma and hepatic cyst: a rare entity. Asian J Neurosurg 2016;11:311.
    Pubmed KoreaMed CrossRef
  4. Ayloo S, Molinari M. Pancreatic manifestations in von Hippel-Lindau disease: a case report. Int J Surg Case Rep 2016;21:70-2.
    Pubmed KoreaMed CrossRef
  5. Findeis-Hosey JJ, McMahon KQ, Findeis SK. Von Hippel-Lindau disease. J Pediatr Genet 2016;5:116-23.
    Pubmed KoreaMed CrossRef
  6. Richards FM, Payne SJ, Zbar B, Affara NA, Ferguson-Smith MA, Maher ER. Molecular analysis of de novo germline mutations in the von Hippel-Lindau disease gene. Hum Mol Genet 1995;4:2139-43.
    Pubmed CrossRef
  7. Lonser RR, Glenn GM, Walther M, et al. von Hippel-Lindau disease. Lancet 2003;361:2059-67.
    Pubmed CrossRef
  8. Wilding A, Ingham SL, Lalloo F, et al. Life expectancy in hereditary cancer predisposing diseases: an observational study. J Med Genet 2012;49:264-9.
    Pubmed CrossRef
  9. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405-24.
    Pubmed KoreaMed CrossRef
  10. van Asselt SJ, de Vries EG, van Dullemen HM, et al. Pancreatic cyst development: insights from von Hippel-Lindau disease. Cilia 2013;2:3.
    Pubmed KoreaMed CrossRef
  11. 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:e68-e75.
    Pubmed CrossRef
  12. Ganeshan D, Menias CO, Pickhardt PJ, et al. Tumors in von Hippel-Lindau syndrome: from head to toe-comprehensive state-of-the-art review. Radiographics 2018;38:849-66.
    Pubmed CrossRef
  13. Hwang S, Ku CR, Lee JI, et al. Germline mutation of Glu70Lys is highly frequent in Korean patients with von Hippel-Lindau (VHL) disease. J Hum Genet 2014;59:488-93.
    Pubmed CrossRef
  14. Lee JS, Lee JH, Lee KE, et al. Genotype-phenotype analysis of von Hippel-Lindau syndrome in Korean families: HIF-α binding site missense mutations elevate age-specific risk for CNS hemangioblastoma. BMC Med Genet 2016;17:48.
    Pubmed KoreaMed CrossRef

April 2020, 27 (1)
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  • Hye Lim Jung