Abstract
Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic disease in which various neoplastic lesions occur in multiple organs. Reported here is a case of VHL disease with concurrent renal cell carcinoma and endocrine pancreatic cancer. The patient was a 43-year old woman. On this occasion, the patient had sought treatment from her local physician, complaining chiefly of yellowing of the skin and bulbar conjunctiva. Abdominal ultrasound and computed tomography scans revealed a mass in the right kidney and a mass in the pancreatic head. Peripheral blood genetic analysis revealed an Arg/stop heteroconjugative mutation in codon 113 in exon 1 of the VHL gene on the short arm of chromosome 3 (p25–26). After various tests were performed, the patient was diagnosed with right renal cell carcinoma, malignant tumor of the pancreatic head, and multiple pancreatic cysts accompanying von Hippel-Lindau disease. Right nephrectomy and pancreatoduodenectomy were performed. Based on the histopathological results, the patient was diagnosed with right renal cell carcinoma and highly differentiated endocrine pancreatic cancer. Immunohistologically, a large number of atypical cells were found to be positive for both anti-chromogranin and anti-synaptophysin antibodies in the endocrine tumor. Immunostaining for each type of gut hormone was also performed, but all results were negative. Based on the above findings, nonfunctioning, highly differentiating endocrine cancer was diagnosed. This is the first confirmed case of renal cell carcinoma and endocrine pancreatic cancer occurring concurrently with VHL. This is an important case, so it is presented here along with a short discussion of the literature.
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References
DM Hough DH Stephens CD Johnson LA Binkovitz (1994) ArticleTitlePancreatic lesions in von Hippel-Lindau disease: prevalence, clinical significance, and CT findings Am J Roentgenol 162 1091–4 Occurrence Handle1:STN:280:ByuB3MbjtVE%3D
PR Hammel V Vilgrain B Terris A Penfornis A Sauvanet JM Correas et al. (2000) ArticleTitlePancreatic involvement in von Hippel-Lindau disease Gastroenterology 119 1087–95 Occurrence Handle10.1053/gast.2000.18143 Occurrence Handle1:STN:280:DC%2BD3cvptFSjsA%3D%3D Occurrence Handle11040195
KR Loughlin RF Gittes (1986) ArticleTitleUrological management of patients with von Hippel-Lindau's disease J Urol 136 789–91 Occurrence Handle1:STN:280:BiiD3M7otVM%3D Occurrence Handle3761431
JM Lamiell FG Salazar YE Hsia (1989) ArticleTitleVon Hippel-Lindau disease affecting 43 menbers of a single kindred Medicine (Baltimore) 68 1–29 Occurrence Handle1:STN:280:BiaD1c3jtFc%3D
HP Neumann E Dinkel H Brambs B Wimmer H Friedburg B Volk et al. (1991) ArticleTitlePancreatic lesions in the von Hippel-Lindau syndrome Gastroenterology 101 465–71 Occurrence Handle1:STN:280:By6B1MzltFQ%3D Occurrence Handle2065922
LA Binkovitz CD Johnson DH Stephens (1990) ArticleTitleIslet cell tumors in von Hippel-Lindau disease: increased prevalence and relationship to the multiple endocrine neoplasias Am J Roentgenol 155 501–5 Occurrence Handle1:STN:280:By%2BA2M%2FmtV0%3D
SK Libutti PL Choyke DL Bartlett H Vargas M Walther I Lubensky et al. (1998) ArticleTitlePancreatic neuroendocrine tumors associated with von Hippel-Lindau disease: diagnostic and management recommendations Surgery 124 153–9 Occurrence Handle10.1067/msy.1998.91823
AL Cubilla SI Hajdu (1975) ArticleTitleIslet cell carcinoma of the pancreas Arch Pathol 99 204 Occurrence Handle1:STN:280:CSqC3cflsVw%3D Occurrence Handle163633
WA Horton V Wong R Eldridge (1976) ArticleTitleVon Hippel-Lindau disease: clinical and pathological manifestations in nine families with 50 affected members Arch Intern Med 136 769 Occurrence Handle10.1001/archinte.136.7.769 Occurrence Handle1:STN:280:CSmB3s%2FmslY%3D Occurrence Handle945722
A Anderson Bergdahl (1976) ArticleTitleInsulomas and multiple endocrine neoplasia Acta Chir Scand 142 297
A Probst M Lotz P Heitz (1978) ArticleTitleVon Hippel-Lindau's disease, syringomyelia and multiple endocrine tumors: a complex neuroendocrinopathy Virchows Arch A Path Anat Histol 378 265 Occurrence Handle1:STN:280:CSeB3s%2FjsV0%3D
MT Hull KA Warfel J Muller JT Higgins (1979) ArticleTitleFamilial islet cell tumors in von Hippel-Lindau's disease Cancer 44 1523 Occurrence Handle1:STN:280:Bi%2BD2cvls1A%3D Occurrence Handle227568
D Cornish A Pont D Minor JL Coombs Bennington (1984) ArticleTitleMetastatic islet cell tumor in von Hippel-Lindau disease Am J Med 77 147 Occurrence Handle10.1016/0002-9343(84)90450-9 Occurrence Handle1:STN:280:BiuB2MznvFw%3D Occurrence Handle6331159
JL Mulshine R Tubbs LR Sheeler RW Gifford (1984) ArticleTitleCase report: clinical significance of the association of the von Hippel-Lindau disease with pheochromocytroma and pancreatic apudoma Am J Med Sci 288 212 Occurrence Handle1:STN:280:BiqD1MvjsFY%3D Occurrence Handle6517090
P Hardwig DM Robertson (1984) ArticleTitleVon Hippel-Lindau disease: a familial, often lethal, multi-system phakomatosis Ophthalmology 91 263 Occurrence Handle1:STN:280:BiuC1M3ks1E%3D Occurrence Handle6538954
AM Jennings C Smith DR Cole et al. (1988) ArticleTitleVon Hippel-Lindau disease in a large British family: clinicopathological features and recommendations for screening and follow-up Q J Med 66 233 Occurrence Handle1:STN:280:BiaD2s3gtlM%3D Occurrence Handle3200963
CA Clelland CS Treip (1989) ArticleTitleHistological differentiation of metastatic renal carcinoma in the cerebellum from cerebellar haemangioblastoma in von Hippel-Lindau's disease J Neurol Neurosurg Psychiatry 52 162 Occurrence Handle1:STN:280:BiaC1MfpvFI%3D Occurrence Handle2467965
I Ikami M Munakata H Tsuchida K Matsumoto H Yodono S Takekawa (1991) ArticleTitleNonfunctioning islet cell carcinoma of the von Hippel-Lindau disease: report of a case (in Japanese) Gazo Shindan 11 1460
N Karsdorp A Elderson D Wittebol-Post et al. (1994) ArticleTitleVon Hippel-Lindau disease: new strategies in early detection and treatment Am J Med 97 158 Occurrence Handle10.1016/0002-9343(94)90026-4 Occurrence Handle1:STN:280:ByuA3sjnvVc%3D Occurrence Handle8059782
MM Walther PL Choyke G Weiss et al. (1995) ArticleTitleParenchymal sparing surgery in patients with hereditary renal cell carcinoma J Urol 153 913 Occurrence Handle1:STN:280:ByqC2MnmslU%3D Occurrence Handle7853573
SL Mount DL Weaver DJ Taatjes WC McKinnon JC Hebert (1995) ArticleTitleVon Hippel-Lindau disease presenting as pancreatic neuroendocrine tumour Virchows Arch 426 523 Occurrence Handle10.1007/BF00193177 Occurrence Handle1:STN:280:ByqA28%2FislI%3D Occurrence Handle7633663
M Maki Y Kaneko Y Ohta T Nakamura R Machinami K Kurokawa (1995) ArticleTitleSomatostatinoma of the pancreas associated with von Hippel-Lindau disease Intern Med 34 661 Occurrence Handle1:STN:280:BymD3sjit1Q%3D Occurrence Handle7496080
N Mizuno S Naruse M Kitagawa et al. (1998) ArticleTitleIslet cell tumor in von Hippel-Lindau Disease Intern Med 37 295–9 Occurrence Handle1:STN:280:DyaK1c3nvVChug%3D%3D Occurrence Handle9617866
M Kogire R Hosotani M Kondo K Itoh R Doi T Terachi et al. (2000) ArticleTitlePancreatic lesions in von Hippel-Lindau syndrome: the coexistence of metastatic tumors from renal cell carcinoma and multiple cysts Surg Today 30 380–2 Occurrence Handle10.1007/s005950050605 Occurrence Handle1:STN:280:DC%2BD3c3lsVyqsw%3D%3D Occurrence Handle10795874
TP Chambers EK Fishman RB Hruban (1997) ArticleTitlePancreatic metastasis from renal cell carcinoma in von Hippel-Lindau disease Clin Imaging 21 40–2 Occurrence Handle10.1016/0899-7071(95)00066-6 Occurrence Handle1:STN:280:ByiC1c%2Fksl0%3D Occurrence Handle9117930
M Sugiyama M Katsura K Yamamoto et al. (1999) ArticleTitlePancreatic metastasis from renal cell carcinoma causing massive gastrointestinal hemorrhape in von Hippel-Lindau disease Hepato-Gastroenterology 46 1199–201 Occurrence Handle1:STN:280:DyaK1M3pvVyhuw%3D%3D Occurrence Handle10370691
IA Lubensky S Pack D Ault AO Vortmeyer SK Libutti PL Choyke et al. (1998) ArticleTitleMultiple neuroendocrine tumors of the pancreas in von Hippel-Lindau disease patients. Histopathological and molecular genetic analysis Am J Pathol 153 223–31 Occurrence Handle1:STN:280:DyaK1czivVChsg%3D%3D Occurrence Handle9665483
LA Guarda EG Silva NG Ordonez B Mackay ML Ibanez (1983) ArticleTitleClear cell islet cell tumor Am J Clin Pathol 79 512–7 Occurrence Handle1:STN:280:BiyC2srlt1I%3D Occurrence Handle6188363
NG Ordonez EG Silva (1997) ArticleTitleIslet cell tumor with vacuolated lipid-rich cytoplasm: a new histological variant of islet cell tumor Histopathology 31 157–60 Occurrence Handle1:STN:280:ByiH38rltFM%3D Occurrence Handle9279567
BR Seizinger GA Rouleau LJ Ozelius AH Lane GE Farmer JM Lamiell et al. (1988) ArticleTitleVon Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma Nature 332 268–9 Occurrence Handle10.1038/332268a0 Occurrence Handle1:CAS:528:DyaL1cXhs1Gmsro%3D Occurrence Handle2894613
F Latif K Tory J Gnarra M Yao FM Duh ML Orcutt et al. (1993) ArticleTitleIdentification of the von Hippel-Lindau disease tumor suppressor gene Science 260 1317–20 Occurrence Handle1:CAS:528:DyaK3sXks12htbc%3D Occurrence Handle8493574
T Shuin K Kondo S Torigoe T Kishida Y Kubota M Hosaka et al. (1994) ArticleTitleFrequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas Cancer Res 54 2852–5 Occurrence Handle1:CAS:528:DyaK2cXksl2rsLo%3D Occurrence Handle8187067
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Osawa, A., Sumiyama, Y., Watanabe, M. et al. Single case of renal cell carcinoma and endocrine pancreatic head cancer occurring with von Hippel-Lindau disease. J Hepatobiliary Pancreat Surg 13, 174–180 (2006). https://doi.org/10.1007/s00534-005-1041-9
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DOI: https://doi.org/10.1007/s00534-005-1041-9