BERKELEY, CA (UroToday.com) - Multiple primary malignancies are a well-recognised phenomenon and an increased incidence of subsequent non-cutaneous primary cancers in melanoma patients is well documented. The most frequent are female breast cancer, prostate cancer and non-Hodgkin’s lymphoma. However other cancers with increased reported frequency include neuroectodermal tumours e.g., brain, ocular melanoma, bladder cancer, pancreatic cancer, and hormone-related cancers e.g., thyroid, bone and joint cancers). An elevated frequency of renal carcinoma in males with melanoma is reported,[1, 2, 3] although there has been no clinicopathological review of such cases. We recognised that there was an increased association of these two cancers and have reported the clinicopathological findings of five cases of synchronous renal cell carcinoma of clear-cell subtype (RCC) identified following routine radiological staging for cutaneous melanoma presenting over a two-year period.[4] In all cases, no family history of melanoma or renal cell carcinoma was identified.
It is also possible that the detection of renal tumours in our series was coincidental. Increased medical surveillance is recognised to result in an increased detection of incidental renal cell carcinoma in asymptomatic patients.[3] Whilst the simultaneous occurrence of renal cell carcinoma and melanoma may be coincidental, there appear to be a number of plausible links. Exposure to mutual carcinogens or other shared environmental risk factors such as obesity [5]could be one explanation -- although none of the patients in our series had a BMI exceeding 30. A shared genetic susceptibility has been reported;[6, 7] the CDKN2A gene encoding p16INK4a, may be altered in both renal cancer and melanoma and there is increased association of familial renal cell carcinoma and melanoma;[8] more recently a germline missense mutation in microphthalmia-associated transcription factor (MITF) was reported to predispose to both cancer types.[6] None of our patients gave a positive family history of either cancer, and an increased risk of renal cell carcinoma has not been reported in CDKN2A melanoma-prone families.[9] Furthermore, alteration in the MAP kinase pathway has been reported in both tumours, with therapies developed against targets within the pathway achieving variable success in each cancer.
Evidence of a shared carcinogenesis could also result from an aberration of cell-mediated immunity. Evidence for the role of pro-inflammatory cytokines in the progression of both cancers has arisen from an increasing number of clinical and translational studies; high dose interleukin-2 is approved for the treatment of both metastatic melanoma and renal cell carcinoma and modulation of the tumour necrosis factor-alpha was recently also proposed as a treatment for both [10] suggesting that similar immunological mechanisms are likely to occur predisposing patients to developing both these tumours.
Approximately 30% of adults diagnosed with renal cell carcinoma present with metastatic disease, and, therefore, early identification of renal carcinoma affects prognosis by providing the best chance for long-term survival .[11] Although historically it might be considered that the patients in our series were over-treated for tumours that would have grown very slowly without altering their life expectancy, it appears that a significant proportion of incidental renal tumours can result in death, in particular patients with a tumour diameter exceeding 4 cm.[12]
In summary, although the numbers in our series are small and cannot definitively confirm a true association between RCC and melanoma, we believe that there are sufficient plausible molecular mechanisms for this to justify further investigation. Analysis of a larger series of synchronous melanoma and RCC may provide aetiological and therapeutic insights for these two important tumours.
References:
- Crocetti, E., et al., The risk of developing a second, different, cancer among 14 560 survivors of malignant cutaneous melanoma: a study by AIRTUM (the Italian Network of Cancer Registries). Melanoma Research, 2008. 18(3): p. 230-4.
- Schmid-Wendtner, M.H., et al., Risk of second primary malignancies in patients with cutaneous melanoma. Br J Dermatol, 2001. 145(6): p. 981-5.
- Tsui, K.H., et al., Renal cell carcinoma: prognostic significance of incidentally detected tumors. Journal of Urology, 2000. 163(2): p. 426-30.
- Matin, R.N., et al., Synchronous melanoma and renal carcinoma: a clinicopathological study of five cases. Clinical and Experimental Dermatology, 2013. 38(1): p. 47-9.
- Renehan, A.G., et al., Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet, 2008. 371(9612): p. 569-78.
- Bertolotto, C., et al., A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma. Nature, 2011. 480(7375): p. 94-8.
- Maubec, E., et al., Characteristics of the coexistence of melanoma and renal cell carcinoma. Cancer, 2010. 116(24): p. 5716-24.
- Liu, H., J. Sundquist, and K. Hemminki, Familial Renal Cell Carcinoma from the Swedish Family-Cancer Database. European Urology, 2011.
- de Snoo, F.A., et al., Increased risk of cancer other than melanoma in CDKN2A founder mutation (p16-Leiden)-positive melanoma families. Clin Cancer Res, 2008. 14(21): p. 7151-7.
- Brown, E.R., et al., A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer. Ann Oncol, 2008. 19(7): p. 1340-6.
- Klatte, T., et al., Surveillance for renal cell carcinoma: why and how? When and how often? Urologic Oncology, 2008. 26(5): p. 550-4.
- Bensalah, K., et al., Prognostic variables to predict cancer-related death in incidental renal tumours. BJU Int, 2008. 102(10): p. 1376-80.
Written by:
Rubeta N. Matin, PhD, BSc (HONS), MBBS, MRCP as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Dermatology Department, Churchill Hospital, Oxford University Hospitals NHS Trust, Old Road, Headington, Oxford, OX3 7LJ
Synchronous melanoma and renal carcinoma: A clinicopathological study of five cases - Abstract
More Information about Beyond the Abstract