Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Epidemiology and risk factors for skin cancer in solid organ transplant recipients

Thomas Stasko, MD
Allison M Hanlon, MD
Section Editor
June K Robinson, MD
Deputy Editor
Rosamaria Corona, MD, DSc


The long-term immunosuppressive therapy required to maintain host tolerance of a transplanted organ contributes to an increased risk for malignancy in organ transplant recipients. Skin is the most common site for the development of malignancy; in particular, cutaneous squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) are frequently detected [1]. A variety of factors, including the intensity and duration of immunosuppression, patient ethnic background, patient sun exposure history, and geographic location, can influence the likelihood for the development of skin cancer in these patients.

The most common skin cancers that develop in solid organ transplant recipients will be reviewed here. The management of skin cancer in solid organ transplant recipients and information on other malignancies in organ transplant recipients are discussed elsewhere. (See "Prevention and management of skin cancer in solid organ transplant recipients" and "Development of malignancy following solid organ transplantation" and "Epidemiology, clinical manifestations, and diagnosis of post-transplant lymphoproliferative disorders".)


Skin cancers account for almost 40 percent of malignancies in organ transplant recipients, and develop in more than 50 percent of white organ transplant recipients [2,3]. The most commonly reported skin cancers in this population include squamous cell carcinoma (SCC), basal cell carcinoma (BCC), melanoma, and Kaposi sarcoma [2,4-6].

Although the pathways that lead to an elevated risk for cutaneous malignancy in organ transplant recipients are not fully understood, it generally is accepted that immunosuppressive medications used to induce tolerance to the donor organ play an important role. Proposed mechanisms through which immunosuppression may contribute to the development of skin cancer include [7]:

Reduced immune surveillance, thereby facilitating the survival and proliferation of atypical cells.


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Aug 23, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Vajdic CM, van Leeuwen MT. Cancer incidence and risk factors after solid organ transplantation. Int J Cancer 2009; 125:1747.
  2. Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N Engl J Med 2003; 348:1681.
  3. Greenberg JN, Zwald FO. Management of Skin Cancer in Solid-organ Transplant Recipients: A Multidisciplinary Approach. Dermatol Clin 2011; 29:231.
  4. Moloney FJ, Comber H, O'Lorcain P, et al. A population-based study of skin cancer incidence and prevalence in renal transplant recipients. Br J Dermatol 2006; 154:498.
  5. Moosa MR. Racial and ethnic variations in incidence and pattern of malignancies after kidney transplantation. Medicine (Baltimore) 2005; 84:12.
  6. España A, Martínez-González MA, García-Granero M, et al. A prospective study of incident nonmelanoma skin cancer in heart transplant recipients. J Invest Dermatol 2000; 115:1158.
  7. Athar M, Walsh SB, Kopelovich L, Elmets CA. Pathogenesis of nonmelanoma skin cancers in organ transplant recipients. Arch Biochem Biophys 2011; 508:159.
  8. Ducloux D, Carron PL, Racadot E, et al. CD4 lymphocytopenia in long-term renal transplant recipients. Transplant Proc 1998; 30:2859.
  9. Ulrich C, Kanitakis J, Stockfleth E, Euvrard S. Skin cancer in organ transplant recipients--where do we stand today? Am J Transplant 2008; 8:2192.
  10. Chockalingam R, Downing C, Tyring SK. Cutaneous Squamous Cell Carcinomas in Organ Transplant Recipients. J Clin Med 2015; 4:1229.
  11. Bouwes Bavinck JN, Hardie DR, Green A, et al. The risk of skin cancer in renal transplant recipients in Queensland, Australia. A follow-up study. Transplantation 1996; 61:715.
  12. Ramsay HM, Fryer AA, Hawley CM, et al. Non-melanoma skin cancer risk in the Queensland renal transplant population. Br J Dermatol 2002; 147:950.
  13. Caforio AL, Fortina AB, Piaserico S, et al. Skin cancer in heart transplant recipients: risk factor analysis and relevance of immunosuppressive therapy. Circulation 2000; 102:III222.
  14. Harwood CA, Proby CM, McGregor JM, et al. Clinicopathologic features of skin cancer in organ transplant recipients: a retrospective case-control series. J Am Acad Dermatol 2006; 54:290.
  15. Brewer JD, Colegio OR, Phillips PK, et al. Incidence of and risk factors for skin cancer after heart transplant. Arch Dermatol 2009; 145:1391.
  16. Krynitz B, Olsson H, Lundh Rozell B, et al. Risk of basal cell carcinoma in Swedish organ transplant recipients: a population-based study. Br J Dermatol 2016; 174:95.
  17. Moosa MR, Gralla J. Skin cancer in renal allograft recipients--experience in different ethnic groups residing in the same geographical region. Clin Transplant 2005; 19:735.
  18. Glover MT, Deeks JJ, Raftery MJ, et al. Immunosuppression and risk of non-melanoma skin cancer in renal transplant recipients. Lancet 1997; 349:398.
  19. Park GH, Chang SE, Won CH, et al. Incidence of primary skin cancer after organ transplantation: An 18-year single-center experience in Korea. J Am Acad Dermatol 2014; 70:465.
  20. Berg D, Otley CC. Skin cancer in organ transplant recipients: Epidemiology, pathogenesis, and management. J Am Acad Dermatol 2002; 47:1.
  21. Mithoefer AB, Supran S, Freeman RB. Risk factors associated with the development of skin cancer after liver transplantation. Liver Transpl 2002; 8:939.
  22. Ramsay HM, Fryer AA, Hawley CM, et al. Factors associated with nonmelanoma skin cancer following renal transplantation in Queensland, Australia. J Am Acad Dermatol 2003; 49:397.
  23. Ramsay HM, Fryer AA, Reece S, et al. Clinical risk factors associated with nonmelanoma skin cancer in renal transplant recipients. Am J Kidney Dis 2000; 36:167.
  24. Fortina AB, Piaserico S, Caforio AL, et al. Immunosuppressive level and other risk factors for basal cell carcinoma and squamous cell carcinoma in heart transplant recipients. Arch Dermatol 2004; 140:1079.
  25. Wisgerhof HC, Edelbroek JR, de Fijter JW, et al. Subsequent squamous- and basal-cell carcinomas in kidney-transplant recipients after the first skin cancer: cumulative incidence and risk factors. Transplantation 2010; 89:1231.
  26. Euvrard S, Kanitakis J, Decullier E, et al. Subsequent skin cancers in kidney and heart transplant recipients after the first squamous cell carcinoma. Transplantation 2006; 81:1093.
  27. Gogia R, Binstock M, Hirose R, et al. Fitzpatrick skin phototype is an independent predictor of squamous cell carcinoma risk after solid organ transplantation. J Am Acad Dermatol 2013; 68:585.
  28. Kang W, Sampaio MS, Huang E, Bunnapradist S. Association of Pretransplant Skin Cancer With Posttransplant Malignancy, Graft Failure and Death in Kidney Transplant Recipients. Transplantation 2016.
  29. Tessari G, Naldi L, Boschiero L, et al. Incidence and clinical predictors of a subsequent nonmelanoma skin cancer in solid organ transplant recipients with a first nonmelanoma skin cancer: a multicenter cohort study. Arch Dermatol 2010; 146:294.
  30. Jiyad Z, Olsen CM, Burke MT, et al. Azathioprine and Risk of Skin Cancer in Organ Transplant Recipients: Systematic Review and Meta-Analysis. Am J Transplant 2016.
  31. Robbins HA, Clarke CA, Arron ST, et al. Melanoma Risk and Survival among Organ Transplant Recipients. J Invest Dermatol 2015; 135:2657.
  32. Clarke CA, Robbins HA, Tatalovich Z, et al. Risk of merkel cell carcinoma after solid organ transplantation. J Natl Cancer Inst 2015; 107.
  33. Jensen P, Hansen S, Møller B, et al. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol 1999; 40:177.
  34. Wisgerhof HC, van der Boog PJ, de Fijter JW, et al. Increased risk of squamous-cell carcinoma in simultaneous pancreas kidney transplant recipients compared with kidney transplant recipients. J Invest Dermatol 2009; 129:2886.
  35. Rashtak S, Dierkhising RA, Kremers WK, et al. Incidence and risk factors for skin cancer following lung transplantation. J Am Acad Dermatol 2015; 72:92.
  36. Perera GK, Child FJ, Heaton N, et al. Skin lesions in adult liver transplant recipients: a study of 100 consecutive patients. Br J Dermatol 2006; 154:868.
  37. Laing ME, Dicker P, Moloney FJ, et al. Association of methylenetetrahydrofolate reductase polymorphism and the risk of squamous cell carcinoma in renal transplant patients. Transplantation 2007; 84:113.
  38. Nindl I, Gottschling M, Stockfleth E. Human papillomaviruses and non-melanoma skin cancer: basic virology and clinical manifestations. Dis Markers 2007; 23:247.
  39. Connolly K, Manders P, Earls P, Epstein RJ. Papillomavirus-associated squamous skin cancers following transplant immunosuppression: one Notch closer to control. Cancer Treat Rev 2014; 40:205.
  40. Neale RE, Weissenborn S, Abeni D, et al. Human papillomavirus load in eyebrow hair follicles and risk of cutaneous squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 2013; 22:719.
  41. Mühleisen B, Petrov I, Frigerio S, et al. Pronounced allelic imbalance at D9S162 in skin squamous cell carcinoma of organ transplant recipients. Arch Dermatol 2012; 148:697.
  42. de Graaf YG, Rebel H, Elghalbzouri A, et al. More epidermal p53 patches adjacent to skin carcinomas in renal transplant recipients than in immunocompetent patients: the role of azathioprine. Exp Dermatol 2008; 17:349.
  43. Green AC, Olsen CM. Increased risk of melanoma in organ transplant recipients: systematic review and meta-analysis of cohort studies. Acta Derm Venereol 2015; 95:923.
  44. Hollenbeak CS, Todd MM, Billingsley EM, et al. Increased incidence of melanoma in renal transplantation recipients. Cancer 2005; 104:1962.
  45. Vajdic CM, van Leeuwen MT, Webster AC, et al. Cutaneous melanoma is related to immune suppression in kidney transplant recipients. Cancer Epidemiol Biomarkers Prev 2009; 18:2297.
  46. Xiao D, Craig JC, Chapman JR, et al. Donor cancer transmission in kidney transplantation: a systematic review. Am J Transplant 2013; 13:2645.
  47. Krynitz B, Rozell BL, Lyth J, et al. Cutaneous malignant melanoma in the Swedish organ transplantation cohort: A study of clinicopathological characteristics and mortality. J Am Acad Dermatol 2015; 73:106.
  48. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008; 319:1096.
  49. Imko-Walczuk B, Kryś A, Lizakowski S, et al. Sebaceous carcinoma in patients receiving long-term immunosuppresive treatment: case report and literature review. Transplant Proc 2014; 46:2903.
  50. Harwood CA, McGregor JM, Swale VJ, et al. High frequency and diversity of cutaneous appendageal tumors in organ transplant recipients. J Am Acad Dermatol 2003; 48:401.
  51. Seçkin D, Barete S, Euvrard S, et al. Primary cutaneous posttransplant lymphoproliferative disorders in solid organ transplant recipients: a multicenter European case series. Am J Transplant 2013; 13:2146.
  52. Belloni-Fortina A, Montesco MC, Piaserico S, et al. Primary cutaneous CD30+ anaplastic large cell lymphoma in a heart transplant patient: case report and literature review. Acta Derm Venereol 2009; 89:74.
  53. Spence-Shishido A, Streicher JL, George RP, et al. Folliculotropic Mycosis Fungoides as a Posttransplant Lymphoproliferative Disorder. Pediatrics 2015; 136:e701.
  54. Baer LN, Savage DG, Hibshoosh HH, Kalinsky K. Concomitant angiosarcoma and lymphoproliferative disorder in solid organ transplant recipients. Clin Sarcoma Res 2014; 4:15.
  55. Blackmon J, Rajpara A, Patel V, et al. Primary scalp angiosarcoma with metastasis to the liver in an orthotopic liver transplant patient. Exp Clin Transplant 2014; 12:269.
  56. Kanitakis J, Chouvet B, Roussoulières A, Euvrard S. Postirradiation cutaneous angiosarcoma mimicking a cyst in a heart transplant recipient. Transplantation 2014; 97:e68.
  57. McCoppin HH, Christiansen D, Stasko T, et al. Clinical spectrum of atypical fibroxanthoma and undifferentiated pleomorphic sarcoma in solid organ transplant recipients: a collective experience. Dermatol Surg 2012; 38:230.
  58. Bhatia K, Shiels MS, Berg A, Engels EA. Sarcomas other than Kaposi sarcoma occurring in immunodeficiency: interpretations from a systematic literature review. Curr Opin Oncol 2012; 24:537.
  59. Mukai HY, Kojima H, Suzukawa K, et al. Nasal natural killer cell lymphoma in a post-renal transplant patient. Transplantation 2000; 69:1501.
  60. Gallagher MP, Kelly PJ, Jardine M, et al. Long-term cancer risk of immunosuppressive regimens after kidney transplantation. J Am Soc Nephrol 2010; 21:852.
  61. Marcén R, Galeano C, Fernández-Rodriguez A, et al. Effects of the new immunosuppressive agents on the occurrence of malignancies after renal transplantation. Transplant Proc 2010; 42:3055.
  62. Einollahi B, Nemati E, Lessan-Pezeshki M, et al. Skin cancer after renal transplantation: Results of a multicenter study in Iran. Ann Transplant 2010; 15:44.
  63. Taylor AE, Shuster S. Skin cancer after renal transplantation: the causal role of azathioprine. Acta Derm Venereol 1992; 72:115.
  64. Doesch AO, Müller S, Konstandin M, et al. Malignancies after heart transplantation: incidence, risk factors, and effects of calcineurin inhibitor withdrawal. Transplant Proc 2010; 42:3694.
  65. Dantal J, Hourmant M, Cantarovich D, et al. Effect of long-term immunosuppression in kidney-graft recipients on cancer incidence: randomised comparison of two cyclosporin regimens. Lancet 1998; 351:623.
  66. Kelly GE, Meikle W, Sheil AG. Effects of immunosuppressive therapy on the induction of skin tumors by ultraviolet irradiation in hairless mice. Transplantation 1987; 44:429.
  67. Brem R, Li F, Karran P. Reactive oxygen species generated by thiopurine/UVA cause irreparable transcription-blocking DNA lesions. Nucleic Acids Res 2009; 37:1951.
  68. Zhang X, Jeffs G, Ren X, et al. Novel DNA lesions generated by the interaction between therapeutic thiopurines and UVA light. DNA Repair (Amst) 2007; 6:344.
  69. Ren X, Xu YZ, Karran P. Photo-oxidation of 6-thioguanine by UVA: the formation of addition products with low molecular weight thiol compounds. Photochem Photobiol 2010; 86:1038.
  70. O'Donovan P, Perrett CM, Zhang X, et al. Azathioprine and UVA light generate mutagenic oxidative DNA damage. Science 2005; 309:1871.
  71. Yarosh DB, Pena AV, Nay SL, et al. Calcineurin inhibitors decrease DNA repair and apoptosis in human keratinocytes following ultraviolet B irradiation. J Invest Dermatol 2005; 125:1020.
  72. Norman KG, Canter JA, Shi M, et al. Cyclosporine A suppresses keratinocyte cell death through MPTP inhibition in a model for skin cancer in organ transplant recipients. Mitochondrion 2010; 10:94.
  73. Wu X, Nguyen BC, Dziunycz P, et al. Opposing roles for calcineurin and ATF3 in squamous skin cancer. Nature 2010; 465:368.
  74. Salgo R, Gossmann J, Schöfer H, et al. Switch to a sirolimus-based immunosuppression in long-term renal transplant recipients: reduced rate of (pre-)malignancies and nonmelanoma skin cancer in a prospective, randomized, assessor-blinded, controlled clinical trial. Am J Transplant 2010; 10:1385.
  75. Euvrard S, Morelon E, Rostaing L, et al. Sirolimus and secondary skin-cancer prevention in kidney transplantation. N Engl J Med 2012; 367:329.
  76. Campbell SB, Walker R, Tai SS, et al. Randomized controlled trial of sirolimus for renal transplant recipients at high risk for nonmelanoma skin cancer. Am J Transplant 2012; 12:1146.
  77. Knoll GA, Kokolo MB, Mallick R, et al. Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data. BMJ 2014; 349:g6679.
  78. Karia PS, Azzi JR, Heher EC, et al. Association of Sirolimus Use With Risk for Skin Cancer in a Mixed-Organ Cohort of Solid-Organ Transplant Recipients With a History of Cancer. JAMA Dermatol 2016; 152:533.
  79. Asgari MM, Arron ST, Warton EM, et al. Sirolimus use and risk of cutaneous squamous cell carcinoma (SCC) in solid organ transplant recipients (SOTRs). J Am Acad Dermatol 2015; 73:444.
  80. Williams K, Mansh M, Chin-Hong P, et al. Voriconazole-associated cutaneous malignancy: a literature review on photocarcinogenesis in organ transplant recipients. Clin Infect Dis 2014; 58:997.
  81. Mansh M, Binstock M, Williams K, et al. Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma, Aspergillus Colonization, Invasive Aspergillosis and Death in Lung Transplant Recipients. Am J Transplant 2016; 16:262.