Von Hippel–Lindau Disease (VHL): Characteristic Lesions with Classic Imaging Findings

Main Article Content

Suryansh Bajaj
Darshan Gandhi
Divya Nayar
Ali Serhal


carcinoma, cysts, hemangioblastoma, insulinoma, renal cell, Von Hippel–Lindau disease


Von Hippel–Lindau disease (VHL) is a multisystem cancer syndrome caused by the inactivation of the VHL tumor suppressor gene and involves various organ systems including the central nervous system (CNS), endocrine system, and the kidneys. Tumors seen in patients with VHL disease can be benign or malignant and are usually multifocal, bilateral, and hypervascular in nature. As most lesions associated with VHL are asymptomatic initially, early diagnosis and the institution of an evidence-based surveillance protocol are of paramount importance. Screening, surveillance, and genetic counseling are key aspects in the management of patients diagnosed with VHL disease and often require a multidisciplinary approach and referral to specialized centers. This article will discuss the characteristic lesions seen with VHL disease, their diagnosis, screening protocols and management strategies, as well as an illustrative case to demonstrate the natural progression of the disease with classic imaging findings.

Abstract 494 | PDF Downloads 916 HTML Downloads 39 XML Downloads 18


1. 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(11):2139–43. 10.1093/hmg/4.11.2139

2. Maher ER, Neumann HP, Richard S. Von Hippel–Lindau disease: A clinical and scientific review. Eur J Hum Genet. 2011;19(6):617–23. 10.1038/ejhg.2010.175

3. Maher ER, Iselius L, Yates JR, Littler M, Benjamin C, Harris R, et al. Von Hippel–Lindau disease: A genetic study. J Med Genet. 1991;28(7):443–7. 10.1136/jmg.28.7.443

4. Nielsen SM, Rhodes L, Blanco I, Chung WK, Eng C, Maher ER, et al. Von Hippel–Lindau disease: Genetics and role of genetic counseling in a multiple neoplasia syndrome. J Clin Oncol. 2016;34(18):2172–81. 10.1200/JCO.2015.65.6140

5. Barontini M, Dahia PL. VHL disease. Best Pract Res Clin Endocrinol Metab. 2010;24(3):401–13. 10.1016/j.beem.2010.01.002

6. Ganeshan D, Menias CO, Pickhardt PJ, Sandrasegaran K, Lubner MG, Ramalingam P, et al. Tumors in Von Hippel–Lindau syndrome: From head to toe-comprehensive state-ofthe-art review. Radiographics. 2018;38(3):849–66. 10.1148/rg.2018170156

7. Filling-Katz MR, Choyke PL, Patronas NJ, Gorin MB, Barba D, Chang R, et al. Radiologic screening for Von Hippel–Lindau disease: The role of Gd-DTPA enhanced MR imaging of the CNS. J Comput Assist Tomogr. 1989;13(5):743–55. 10.1097/00004728-198909000-00001

8. Kanno H, Yamamoto I, Nishikawa R, Matsutani M, Wakabayashi T, Yoshida J, et al. Spinal cord hemangioblastomas in Von Hippel–Lindau disease. Spinal Cord. 2009;47(6):447–52. 10.1038/sc.2008.151

9. Chittiboina P, Lonser RR. Von Hippel–Lindau disease. Handb Clin Neurol. 2015;132:139–56. 10.1016/B978-0-444-62702-5.00010-X

10. Lonser RR, Glenn GM, Walther M, Chew EY, Libutti SK, Linehan WM, et al. Von Hippel–Lindau disease. Lancet. 2003;361(9374):2059–67. 10.1016/S0140-6736(03)13643-4

11. Maher ER, Yates JR, Harries R, Benjamin C, Harris R, Moore AT, et al. Clinical features and natural history of Von Hippel–Lindau disease. Q J Med. 1990;77(283):1151–63. 10.1093/qjmed/77.2.1151

12. Farhadi F, Nikpanah M, Paschall AK, Shafiei A, Tadayoni A, Ball MW, et al. Clear cell renal cell carcinoma growth correlates with baseline diffusion-weighted MRI in Von Hippel–Lindau disease. 2020;295(3):583–90. 10.1148/radiol.2020191016

13. Louise MBM, Smerdel M, Borgwadt L, Beck Nielsen SS, Madsen MG, Møller HU, et al. Von Hippel–Lindau disease: Updated guideline for diagnosis and surveillance. Eur J Med Genet. 2022;65(8):104538. 10.1016/j.ejmg.2022.104538

14. Cassol C, Mete O. Endocrine manifestations of Von Hippel–Lindau disease. Arch Pathol Lab Med. 2015;139(2):263–8. 10.5858/arpa.2013-0520-RS

15. Binderup ML, Bisgaard ML, Harbud V, Møller HU, Gimsing S, Friis-Hansen L, 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.

16. Iacovelli R, Arduini D, Ciccarese C, Pierconti F, Strusi A, Piro G, et al. Targeting hypoxia-inducible factor pathways in sporadic and Von Hippel–Lindau syndrome-related kidney cancers. Crit Rev Oncol Hematol. 2022;176:103750. 10.1016/j.critrevonc.2022.103750

17. Toledo RA, Jimenez C. Hypoxia-inducible factor 2 alpha (HIF2α) inhibitors: Targeting genetically driven tumor hypoxia. Endocr Rev. 2023;44(2):312–22. 10.1210/endrev/bnac025

18. Choueiri TK, Bauer TM, Papadopoulos KP, Plimack ER. Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: A phase 1 trial and biomarker analysis. Nat Med. 2021;27(5):802–5. 10.1038/s41591-021-01324-7

19. Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, et al. Belzutifan for renal cell carcinoma in Von Hippel–Lindau disease. N Engl J Med. 2021;385(22):2036–46. 10.1056/NEJMoa2103425

20. Weerakkody YSL, Yap J, et al. Von Hippel–Lindau disease. Radiopaedia. 2023. Available from https://radiopaedia.org/articles/von-hippel-lindau-disease-5?lang=us

21. Ho VB, Smirniotopoulos JG, Murphy FM, Rushing EJ. Radiologic-pathologic correlation: Hemangioblastoma. AJNR Am J Neuroradiol. 1992;13(5):1343–52.

22. Zhang TJ, Yue Q, Lui S, Wu QZ, Gong QY. MRI findings of choroid plexus tumors in the cerebellum. Clin Imaging. 2011;35(1):64–7. 10.1016/j.clinimag.2010.02.010

23. Tang X, Ji HM, Li WW, Ding ZX, Ye SL. Imaging features of retinal hemangioblastoma: A case report. World JClinCases. 2023;11(3):692–9. 10.12998/wjcc.v11.i3.692

24. Patel NP, Wiggins RH, 3rd, Shelton C. The radiologic diagnosis of endolymphatic sac tumors. Laryngoscope. 2006;116(1):40–6. 10.1097/01.mlg.0000185600.18456.36

25. Goyal A, Sharma R, Bhalla AS, Gamanagatti S, Seth A. Diffusion-weighted MRI in inflammatory renal lesions: All that glitters is not RCC! Eur Radiol. 2013;23(1):272–9. 10.1007/s00330-012-2577-0

26. Israel GM, Hindman N, Hecht E, Krinsky G. The use of opposed-phase chemical shift MRI in the diagnosis of renal angiomyolipomas. AJR Am J Roentgenol. 2005;184(6):1868–72. 10.2214/ajr.184.6.01841868

27. Nandra G, Duxbury O, Patel P. Technical and interpretive pitfalls in adrenal imaging. Radiographics. 2020;40(4):1041–60. 10.1148/rg.2020190080

28. Blake MA, Kalra MK, Maher MM, Sahani DV, Sweeney AT, Mueller PR, et al. Pheochromocytoma: An imaging chameleon. Radiographics. 2004;24 Suppl 1:S87–99. 10.1148/rg.24si045506

29. Lewis RB, Lattin GE, Jr., Paal E. Pancreatic endocrine tumors: Radiologic-clinicopathologic correlation. Radiographics. 2010; 30(6):1445–64. 10.1148/rg.306105523

30. Mergo PJ, Helmberger TK, Buetow PC, Helmberger RC, Ros PR. Pancreatic neoplasms: MR imaging and pathologic correlation. Radiographics. 1997;17(2):281–301. 10.1148/radiographics.17.2.9084072

31. Horton KM, Bluemke DA, Hruban RH, Soyer P, Fishman EK. CT and MR imaging of benign hepatic and biliary tumors. Radiographics. 1999;19(2):431–51. 10.1148/radiographics.19.2.g99mr04431

32. Funk KC, Heiken JP. Papillary cystadenoma of the broad ligament in a patient with Von Hippel–Lindau disease. Am J Roentgenol. 1989;153(3):527–8. 10.2214/ajr.153.3.527