J Korean Med Sci.  2009 Dec;24(6):1145-1149. 10.3346/jkms.2009.24.6.1145.

Clinical Characteristics of Renal Cell Carcinoma in Korean Patients with von Hippel-Lindau Disease Compared to Sporadic Bilateral or Multifocal Renal Cell Carcinoma

• Kim WT
• Ham WS
• Ju HJ
• Lee JS
• Lee JS
• Choi YD

• KMID: 1783146
• DOI: http://doi.org/10.3346/jkms.2009.24.6.1145

Abstract

This study was done to analyze the clinical characteristics of renal cell carcinoma (RCC) in Korean patients with von Hippel-Lindau (VHL) disease. Between January 1996 and July 2008, 1,514 patients were diagnosed with RCC and 24 patients were diagnosed with VHL disease at our institute. We analyzed the clinical characteristics of the 24 patients diagnosed with VHL. The mean age of patients with VHL was 39.2+/-12.6 yr; the mean age of patients with both VHL and RCC was 42.5+/-10.3 yr. Among the 24 patients with VHL, 7 patients had retinal angiomas, 11 had RCC, 16 had renal lesions, 18 had pancreatic lesions and 21 had cerebellar hemangioblastomas. There was no significant difference between survival rates of patients with VHL alone and those with VHL and RCC. However, cancer-specific survival rates were significantly different between patients with both VHL and RCC and patients with sporadic bilateral or multifocal RCC. In our Korean study, the incidence of RCC in patients with VHL disease is 45.8% and the incidence of VHL disease in patients with RCC is 0.73%. Due to the low overall incidence of VHL in Korea, extended multi-institutional studies are needed to establish the true characteristics of VHL disease.

Keyword

Von Hippel-Lindau Disease; Carcinoma, Renal Cell; Incidence

MeSH Terms

Adolescent
Adult
Aged
*Carcinoma, Renal Cell/pathology/physiopathology
Diagnosis, Differential
Female
Humans
*Kidney Neoplasms/pathology/physiopathology
Male
Middle Aged
Prognosis
Survival Rate
Young Adult
*von Hippel-Lindau Disease/pathology/physiopathology

Figure

• 

  Fig. 1 Overall disease-specific survival rates for patients with von Hippel-Lindau (VHL) disease only, and VHL with and without renal cell carcinoma (RCC).

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  Fig. 2 Cancer-specific survival rates of patients with both von Hippel- Lindau (VHL) disease and RCC, versus patients with sporadic bilateral or multifocal RCC.

Reference

1. Lonser RR, Glenn GM, Walther M, Chew EY, Libutti SK, Linehan WM, Oldfield EH. von Hippel-Lindau disease. Lancet. 2003. 361:2059–2067.

2. Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L. Identification of the von Hippel-Lindau disease tumour suppressor gene. Science. 1993. 260:1317–1320.

3. Maher ER, Iselius L, Yates JR, Littler M, Benjamin C, Harris R, Sampson J, Williams A, Ferguson-Smith MA, Morton N. Von Hippel-Lindau disease: a genetic study. J Med Genet. 1991. 28:443–447.

4. Kim DS, Kim JJ, Yoon DK, Koh SK, Won NH. A case of von Hippel-Lindau disease diagnosed by initial symptoms of urologic manifestation. Korean J Urol. 1987. 28:126–132.

5. Kang IS, Lee YI, Seo IY, Jeong HJ, Rim JS. Renal cell carcinoma associated with von Hippel-Lindau disease treated by wedge resection. Korean J Urol. 2004. 45:495–497.

6. Kim JH, Cheon SH, Oh CS, Kim YM, Park RJ. Cystic renal cell carcinoma associated with von Hippel-Lindau disease treated by nephron sparing surgery. Korean J Urol. 2005. 46:93–95.

7. Klein B, Weirich G, Brauch H. DHPLC-based germline mutation screening in the analysis of the VHL tumor suppressor gene: usefulness and limitations. Hum Genet. 2001. 108:376–384.

8. Chen F, Kishida T, Yao M, Hustad T, Glavac D, Dean M, Gnarra JR, Orcutt ML, Duh FM, Glenn G, Hsia YE, Lamiell J, Li H, Wei MH, Schmidt L, Tory K, Kuzmin I, Stackhouse T, Latif F, Linehan WM, Lerman M, Zbar B. Germline mutations in the von Hippel-Lindau disease tumor suppressor gene: correlations with phenotype. Hum Mutat. 1995. 5:66–75.

9. Richards FM, Webster AR, McMahon R, Woodward ER, Rose S, Maher ER. Molecular genetic analysis of von Hippel-Lindau disease. J Intern Med. 1998. 243:527–533.

10. Rocha JC, Silva RL, Mendonca BB, Marui S, Simpson AJ, Camargo AA. High frequency of novel germline mutations in the VHL gene in the heterogeneous population of Brazil. J Med Genet. 2003. 40:e31.

11. Neumann HP, Wiestler OD. Clustering of features of von Hippel-Lindau syndrome: evidence for a complex genetic locus. Lancet. 1991. 337:1052–1054.

12. Maddock IR, Moran A, Maher ER, Teare MD, Norman A, Payne SJ, Whitehouse R, Dodd C, Lavin M, Hartley N, Super M, Evans DG. A genetic register for von Hippel-Lindau disease. J Med Genet. 1996. 33:120–127.

13. Friedrich CA. Von Hippel-Lindau syndrome. A pleomorphic condition. Cancer. 1999. 86:Suppl 2. 2478–2482.

14. Richard S, Campello C, Taillandier L, Parker F, Resche F. French VHL study Group. Haemangioblastoma of the central nervous system in von Hippel-Lindau disease. J Intern Med. 1998. 243:547–553.

15. Maher ER, Yates JR, Harries R, Benjamin C, Harris R, Moore AT, Ferguson-Smith MA. Clinical features and natural history of von Hippel-Lindau disease. Q J Med. 1990. 77:1151–1163.

16. Hes FJ, Slootweg PJ, van Vroonhoven TJ, Hene RJ, Feldberg MA, Zewald RA, Ploos van Amstel JK, Hoppener JW, Pearson PL, Lips CJ. Management of renal cell carcinoma in von Hippel-Lindau disease. Eur J Clin Invest. 1999. 29:68–75.

17. Neumann HP, Bender BU, Berger DP, Laubenberger J, Schultze-seemann W, Wetterauer U, Ferstl FJ, Herbst EW, Schwarzkopf G, Hes FJ, Lips CJ, Lamiell JM, Masek O, Riegler P, Mueller B, Glavac D, Brauch H. Prevalence, morphology and biology of renal cell carcinoma in von Hippel-Lindau disease compared to sporadic renal cell carcinoma. J Urol. 1998. 160:1248–1254.

18. Ishikawa I, Kovacs G. High incidence of papillary renal cell tumours in patients on chronic haemodialysis. Histopathology. 1993. 22:135–139.

19. Steinbach F, Novick AC, Zincke H, Miller DP, Williams RD, Lund G, Skinner DG, Esriq D, Richie JP, deKernion JB, Marshall F, Marsh CL. Treatment of renal cell carcinoma in von Hippel-Lindau disease: a multicenter study. J Urol. 1995. 153:1812–1816.

20. Walther MM, Choyke PL, Weiss G, Manolatos C, Long J, Reiter R, Alexander RB, Linehan WM. Parenchymal sparing surgery in patients with hereditary renal cell carcinoma. J Urol. 1995. 153:913–916.

21. Ploussard G, Droupy S, Ferlicot S, Ples R, Rocher L, Richard S, Benoit G. Local recurrence after nephron-sparing surgery in von Hippel-Lindau disease. Urology. 2007. 70:435–439.