The Role of the Transplant Physician in the Management of Skin Cancers After Organ Transplantation

  • Emmanuel Morelon
  • Emmanuel Mahe
  • Jean-Louis Touraine
Part of the Cancer Treatment and Research book series (CTAR, volume 146)

Although prognosis in organ transplantation has significantly improved with the development of new immunosuppressive therapies that have dramatically reduced the incidence of acute rejection, post-transplant malignancies are still one of the main complications that may occur after organ transplantation. Most of these malignancies are skin cancers, which are not only frequent, but also multiple, recurrent, and aggressive [1]. In kidney transplant recipients, the overall incidence is 20 times higher for squamous cell carcinoma and 10 times higher for basal cell carcinoma than in the general population [2]. Thus, about 50% of kidney transplant patients develop some form of skin cancer after transplantation and 5% of these skin cancer patients die of their malignancies [3].


Skin Cancer Acute Rejection Renal Transplant Recipient mTOR Inhibitor Calcineurin Inhibitor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N Engl J Med 2003; 348(17):1681–91.PubMedCrossRefGoogle Scholar
  2. 2.
    Kasiske BL, Snyder JJ, Gilbertson DT, Wang C. Cancer after kidney transplantation in the United States. Am J Transplant 2004; 4(6):905–13.PubMedCrossRefGoogle Scholar
  3. 3.
    Kasiske BL, Vazquez MA, Harmon WE, et al. Recommendations for the outpatient surveillance of renal transplant recipients. American Society of Transplantation. J Am Soc Nephrol 2000; 11(Suppl 15):S1–86.Google Scholar
  4. 4.
    Traywick C, O’Reilly FM. Management of skin cancer in solid organ transplant recipients. Dermatol Ther 2005; 18(1):12–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Gerlini G, Romagnoli P, Pimpinelli N. Skin cancer and immunosuppression. Crit Rev Oncol Hematol 2005; 56(1):127–36.PubMedCrossRefGoogle Scholar
  6. 6.
    Stasko T, Brown MD, Carucci JA, et al. Guidelines for the management of squamous cell carcinoma in organ transplant recipients. Dermatol Surg 2004; 30(4 pt 2):642–50.PubMedCrossRefGoogle Scholar
  7. 7.
    Ismail F, Mitchell L, Casabonne D, et al. Specialist dermatology clinics for organ transplant recipients significantly improve compliance with photoprotection and levels of skin cancer awareness. Br J Dermatol 2006; 155(5):916–25.PubMedCrossRefGoogle Scholar
  8. 8.
    Donovan JC, Rosen CF, Shaw JC. Evaluation of sun-protective practices of organ transplant recipients. Am J Transplant 2004; 4(11):1852–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Mahe E, Morelon E, Fermanian J, et al. Renal-transplant recipients and sun protection. Transplantation 2004; 78(5):741–4.PubMedCrossRefGoogle Scholar
  10. 10.
    Moloney FJ, Almarzouqi E, O’Kelly P, Conlon P, Murphy GM. Sunscreen use before and after transplantation and assessment of risk factors associated with skin cancer development in renal transplant recipients. Arch Dermatol 2005; 141(8):978–82.PubMedCrossRefGoogle Scholar
  11. 11.
    Ahlers C, Kreideweiss S, Nordheim A, Ruhlmann A. Cyclosporin A inhibits Ca2+-mediated upregulation of the DNA repair enzyme DNA polymerase beta in human peripheral blood mononuclear cells. Eur J Biochem 1999; 264(3):952–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Dummer R, Maier T. UV protection and skin cancer. Recent Results Cancer Res 2002; 160:7–12.PubMedGoogle Scholar
  13. 13.
    Autier P, Dore JF, Reis AC, et al. Sunscreen use and intentional exposure to ultraviolet A and B radiation: a double blind randomized trial using personal dosimeters. Br J Cancer 2000; 83(9):1243–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Bech-Thomsen N, Wulf HC. Sunbathers’ application of sunscreen is probably inadequate to obtain the sun protection factor assigned to the preparation. Photodermatol Photoimmunol Photomed 1992; 9(6):242–4.PubMedGoogle Scholar
  15. 15.
    Stokes R, Diffey B. How well are sunscreen users protected? Photodermatol Photoimmunol Photomed 1997; 13(5–6):186–8.PubMedGoogle Scholar
  16. 16.
    Bagot M, Revuz J. High-risk behaviour. Lancet 2000; 355(9214):1555–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Clowers-Webb HE, Christenson LJ, Phillips PK, et al. Educational outcomes regarding skin cancer in organ transplant recipients: randomized intervention of intensive vs standard education. Arch Dermatol 2006; 142(6):712–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Robson R, Cecka JM, Opelz G, Budde M, Sacks S. Prospective registry-based observational cohort study of the long-term risk of malignancies in renal transplant patients treated with mycophenolate mofetil. Am J Transplant 2005; 5(12):2954–60.PubMedCrossRefGoogle Scholar
  19. 19.
    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(9103):623–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Otley CC, Berg D, Ulrich C, et al. Reduction of immunosuppression for transplant-associated skin cancer: expert consensus survey. Br J Dermatol 2006; 154(3):395–400.PubMedCrossRefGoogle Scholar
  21. 21.
    Guba M, Graeb C, Jauch KW, Geissler EK. Pro- and anti-cancer effects of immunosuppressive agents used in organ transplantation. Transplantation 2004; 77(12):1777–82.PubMedCrossRefGoogle Scholar
  22. 22.
    Andre N, Roquelaure B, Conrath J. Molecular effects of cyclosporine and oncogenesis: a new model. Med Hypotheses 2004; 63(4):647–52.PubMedCrossRefGoogle Scholar
  23. 23.
    Tiu J, Li H, Rassekh C, van der Sloot P, Kovach R, Zhang P. Molecular basis of posttransplant squamous cell carcinoma: the potential role of cyclosporine a in carcinogenesis. Laryngoscope 2006; 116(5):762–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Euvrard S, Ulrich C, Lefrancois N. Immunosuppressants and skin cancer in transplant patients: focus on rapamycin. Dermatol Surg 2004; 30(4 pt 2):628–33.PubMedCrossRefGoogle Scholar
  25. 25.
    Stracke S, Ramudo L, Keller F, Henne-Bruns D, Mayer JM. Antiproliferative and overadditive effects of everolimus and mycophenolate mofetil in pancreas and lung cancer cells in vitro. Transplant Proc 2006; 38(3):766–70.PubMedCrossRefGoogle Scholar
  26. 26.
    Guba M, Von Breitenbuch P, Steinbauer M, et al. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med 2002; 8(2):128–35.PubMedCrossRefGoogle Scholar
  27. 27.
    Mathew T, Kreis H, Friend P. Two-year incidence of malignancy in sirolimus-treated renal transplant recipients: results from five multicenter studies. Clin Transplant 2004; 18(4):446–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Campistol JM, Eris J, Oberbauer R, et al. Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation. J Am Soc Nephrol 2006; 17(2):581–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Stallone G, Schena A, Infante B, et al. Sirolimus for Kaposi’s sarcoma in renal-transplant recipients. N Engl J Med 2005; 352(13):1317–23.PubMedCrossRefGoogle Scholar
  30. 30.
    Augustine JJ, Bodziak KA, Hricik DE. Use of sirolimus in solid organ transplantation. Drugs 2007; 67(3):369–91.PubMedCrossRefGoogle Scholar
  31. 31.
    Dunn C, Croom KF. Everolimus: a review of its use in renal and cardiac transplantation. Drugs 2006; 66(4):547–70.PubMedCrossRefGoogle Scholar
  32. 32.
    Flechner SM, Goldfarb D, Modlin C, et al. Kidney transplantation without calcineurin inhibitor drugs: a prospective, randomized trial of sirolimus versus cyclosporine. Transplantation 2002; 74(8):1070–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Flechner SM, Kurian SM, Solez K, et al. De novo kidney transplantation without use of calcineurin inhibitors preserves renal structure and function at two years. Am J Transplant 2004; 4(11):1776–85.PubMedCrossRefGoogle Scholar
  34. 34.
    Kreis H, Cisterne JM, Land W, et al. Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation 2000; 69(7):1252–60.PubMedCrossRefGoogle Scholar
  35. 35.
    Larson TS, Dean PG, Stegall MD, et al. Complete avoidance of calcineurin inhibitors in renal transplantation: a randomized trial comparing sirolimus and tacrolimus. Am J Transplant 2006; 6(3):514–22.PubMedCrossRefGoogle Scholar
  36. 36.
    Mahe E, Morelon E, Lechaton S, et al. Cutaneous adverse events in renal transplant recipients receiving sirolimus-based therapy. Transplantation 2005; 79(4):476–82.PubMedCrossRefGoogle Scholar
  37. 37.
    Champion L, Stern M, Israel-Biet D, et al. Brief communication: Sirolimus-associated pneumonitis: 24 cases in renal transplant recipients. Ann Intern Med 2006; 144(7):505–9.PubMedGoogle Scholar
  38. 38.
    Weiner SM, Sellin L, Vonend O, et al. Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome. A single-centre experience and review of the literature. Nephrol Dial Transplant 2007; 22:3631.PubMedCrossRefGoogle Scholar
  39. 39.
    Thaunat O, Beaumont C, Chatenoud L, et al. Anemia after late introduction of sirolimus may correlate with biochemical evidence of a chronic inflammatory state. Transplantation 2005; 80(9):1212–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Letavernier E, Pe’raldi MN, Pariente A, Morelon E, Legendre C. Proteinuria following a switch from calcineurin inhibitors to sirolimus. Transplantation 2005; 80(9):1198–203.PubMedCrossRefGoogle Scholar
  41. 41.
    Morelon E, Kreis H. Sirolimus therapy without calcineurin inhibitors: Necker Hospital 8-year experience. Transplant Proc 2003; 35(3 Suppl):52S–7S.PubMedCrossRefGoogle Scholar
  42. 42.
    Ruiz JC, Campistol JM, Sanchez-Fructuoso A, et al. Increase of proteinuria after conversion from calcineurin inhibitor to sirolimus-based treatment in kidney transplant patients with chronic allograft dysfunction. Nephrol Dial Transplant 2006; 21(11):3252–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Mulay AV, Cockfield S, Stryker R, Fergusson D, Knoll GA. Conversion from calcineurin inhibitors to sirolimus for chronic renal allograft dysfunction: a systematic review of the evidence. Transplantation 2006; 82(9):1153–62.PubMedCrossRefGoogle Scholar
  44. 44.
    Schena F, Vitko S, Wali R, et al. Efficacy and safety of conversion from calcineurin inhibitors to sirolimus versus continued use of calcineurin inhibitors in renal allograft recipients: 18-months results from a randomized, open-label comparative trial abstract. In: World Transplant Congress, Boston, 2006 p.412.Google Scholar
  45. 45.
    Buell JF, Gross TG, Woodle ES. Malignancy after transplantation. Transplantation 2005; 80(2 Suppl):S254–64.PubMedCrossRefGoogle Scholar
  46. 46.
    Diekmann F, Budde K, Oppenheimer F, Fritsche L, Neumayer HH, Campistol JM. Predictors of success in conversion from calcineurin inhibitor to sirolimus in chronic allograft dysfunction. Am J Transplant 2004; 4(11):1869–75.PubMedCrossRefGoogle Scholar
  47. 47.
    Kreis H, Oberbauer R, Campistol JM, et al. Long-term benefits with sirolimus-based therapy after early cyclosporine withdrawal. J Am Soc Nephrol 2004; 15(3):809–17.PubMedCrossRefGoogle Scholar
  48. 48.
    Segoloni GP, Giraudi R, Messina M, et al. No recurrence of Kaposi’s sarcoma in a case of renal retransplantation under a calcineurin inhibitor free immunosuppressive regimen: first report. Transplant Int 2007; 20(4):395–6.CrossRefGoogle Scholar
  49. 49.
    Lebbe C, Euvrard S, Barrou B, et al. Sirolimus conversion for patients with posttransplant Kaposi’s sarcoma. Am J Transplant 2006; 6(9):2164–8.PubMedCrossRefGoogle Scholar
  50. 50.
    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(8):1093–100.PubMedCrossRefGoogle Scholar
  51. 51.
    Picard N, Premaud A, Rousseau A, Le Meur Y, Marquet P. A comparison of the effect of ciclosporin and sirolimus on the pharmokinetics of mycophenolate in renal transplant patients. Br J Clin Pharmacol 2006; 62(4):477–84.PubMedCrossRefGoogle Scholar
  52. 52.
    Chuang P, Langone AJ. Clobetasol ameliorates aphthous ulceration in renal transplant patients on sirolimus. Am J Transplant 2007; 7(3):714–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Levi Z, Hazazi R, Kedar-Barnes I, et al. Switching from tacrolimus to sirolimus halts the appearance of new sebaceous neoplasms in Muir–Torre syndrome. Am J Transplant 2007; 7(2):476–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Frimat L, Cassuto-Viquier E, Charpentier B, et al. Impact of cyclosporine reduction with MMF: a randomized trial in chronic allograft dysfunction. The reference study. Am J Transplant 2006; 6(11):2725–34.PubMedCrossRefGoogle Scholar
  55. 55.
    Solez K, Colvin R, Racusen L, et al. Banff ‘05 Meeting Report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy (‘CAN’). Am J Transplant 2007; 7(3):518–26.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Emmanuel Morelon
    • 1
  • Emmanuel Mahe
    • 2
  • Jean-Louis Touraine
    • 1
  1. 1.Département de TransplantationUniversité Claude-Bernard Lyon 1, Hôpital Edouard HerriotLyonFrance
  2. 2.Department of DermatologyAmbroise Paré University Hospital, Assistance Publique- Hôpitaux de ParisFrance

Personalised recommendations