This case of hereditary leiomyomatosis and renal cell cancer in a young man illustrates the importance of considering a hereditary basis for renal cancer in a young patient, and highlights how targeted therapy underpins modern personalised medicine in renal oncology.
A 25-year-old white man presented with a year-long history of malaise, a palpable right loin mass and a painless nodular rash over his back of indeterminate duration. Computed tomography (CT) showed a right renal mass with para-aortic and retroperitoneal lymphadenopathy. The patient underwent radical nephrectomy and para-aortic lymphadenectomy.
- 1. Merino MJ, Torres-Cabala C, Pinto P, Linehan WM. The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Am J Surg Pathol 2007; 31: 1578-1585.
- 2. Gill AJ, Pachter NS, Clarkson A, et al. Renal tumors and hereditary pheochromocytoma-paraganglioma syndrome type 4. N Engl J Med 2011; 364: 885-886.
- 3. Kloepfer HW, Krafchuk J, Derbes V, Burks J. Hereditary multiple leiomyoma of the skin. Am J Hum Genet 1958; 10: 48-52.
- 4. Launonen V, Vierimaa O, Kiuru M, et al. Inherited susceptibility to uterine leiomyomas and renal cell cancer. Proc Natl Acad Sci USA 2001; 98: 3387-3392.
- 5. Tomlinson IP, Alam NA, Rowan AJ, et al. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet 2002; 30: 406-410.
- 6. Bayley JP, Launonen V, Tomlinson IP. The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency. BMC Med Genet 2008; 9: 20.
- 7. Pithukpakorn M, Wei MH, Toure O, et al. Fumarate hydratase enzyme activity in lymphoblastoid cells and fibroblasts of individuals in families with hereditary leiomyomatosis and renal cell cancer. J Med Genet 2006; 43: 755-762.
- 8. Wei MH, Toure O, Glenn GM, et al. Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer. J Med Genet 2006; 43: 18-27.
- 9. Ylisaukko-oja SK, Kiuru M, Lehtonen HJ, et al. Analysis of fumarate hydratase mutations in a population-based series of early onset uterine leiomyosarcoma patients. Int J Cancer 2006; 119: 283-287.
- 10. Kiuru M, Launonen V. Hereditary leiomyomatosis and renal cell cancer (HLRCC). Curr Mol Med 2004; 4: 869-875.
- 11. Smit DL, Mensenkamp AR, Badeloe S, et al. Hereditary leiomyomatosis and renal cell cancer in families referred for fumarate hydratase germline mutation analysis. Clin Genet 2011; 79: 49-59.
- 12. Isaacs JS, Jung YJ, Mole DR, et al. HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell 2005; 8: 143-153.
- 13. Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008; 372: 449-456.
- 14. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 2011; 378: 1931-1939.
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