Management of Skin Cancers in Solid Organ Transplant Recipients

  • John Carucci
  • Dariush Moussai


The number of organ transplant recipients continues to rise in the United States, with nearly 30,000 organ transplant procedures performed in 2007 and 225,000 organ transplant recipients currently living in the United States.1 While long-term survival after organ transplantation has also increased, with the 3-year survival rate for kidney and heart transplants approaching 90%,2 as many as 70% of organ transplant recipients will ultimately develop skin cancer.


Squamous Cell Carcinoma Transplant Recipient Skin Cancer Human Papilloma Virus Basal Cell Carcinoma 
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.


  1. 1.
    United Network for Organ Sharing (UNOS) Last accessed January 19, 2009.
  2. 2.
    Berg D, Otley CC. Skin cancer in organ transplant recipients: epidemiology, pathogenesis, and management. J Am Acad Dermatol. 2002;47(1):1–17.CrossRefPubMedGoogle Scholar
  3. 3.
    Harwood CA, Proby CM. Human papillomaviruses and non-melanoma skin cancer. Curr Opin Infect Dis. 2002;15(2):101–114.PubMedGoogle Scholar
  4. 4.
    Jensen P, Hansen S, Moller B, et al. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol. 1999;40(2 Pt 1):177–186.CrossRefPubMedGoogle Scholar
  5. 5.
    Lindelof B, Sigurgeirsson B, Gabel H, Stern RS. Incidence of skin cancer in 5356 patients following organ transplantation. Br J Dermatol. 2000;143(3):513–519.PubMedGoogle Scholar
  6. 6.
    Boyd S, Tolvanen K, Virolainen S, Kuivanen T, Kyllonen L, Saarialho-Kere U. Differential expression of stromal MMP-1, MMP-9 and TIMP-1 in basal cell carcinomas of immunosuppressed patients and controls. Virchows Arch. 2008;452(1):83–90.CrossRefPubMedGoogle Scholar
  7. 7.
    Penn I. Malignancies associated with renal transplantation. Urology. 1977;10(Suppl 1):57–63.CrossRefPubMedGoogle Scholar
  8. 8.
    Hollenbeak CS, Todd MM, Billingsley EM, Harper G, Dyer AM, Lengerich EJ. Increased incidence of melanoma in renal transplantation recipients. Cancer. 2005;104(9):1962–1967.CrossRefPubMedGoogle Scholar
  9. 9.
    Le Mire L, Hollowood K, Gray D, Bordea C, Wojnarowska F. Melanomas in renal transplant recipients. Br J Dermatol. 2006;154(3):472–477.CrossRefPubMedGoogle Scholar
  10. 10.
    Dapprich DC, Weenig RH, Rohlinger AL, et al. Outcomes of melanoma in recipients of solid organ transplant. J Am Acad Dermatol. 2008;59(3):405–417.CrossRefPubMedGoogle Scholar
  11. 11.
    Ramsay HM, Reece SM, Fryer AA, et al. Seven-year prospective study of nonmelanoma skin cancer incidence in U.K. renal transplant recipients. Transplantation. 2007;84(3):437–439.CrossRefPubMedGoogle Scholar
  12. 12.
    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(6):735–741.CrossRefPubMedGoogle Scholar
  13. 13.
    Lampros TD, Cobanoglu A, Parker F, Ratkovec R, Norman DJ, Hershberger R. Squamous and basal cell carcinoma in heart transplant recipients. J Heart Lung Transplant. 1998;17(6):586–591.PubMedGoogle Scholar
  14. 14.
    Ong CS, Keogh AM, Kossard S, Macdonald PS, Spratt PM. Skin cancer in Australian heart transplant recipients. J Am Acad Dermatol. 1999;40(1):27–34.CrossRefPubMedGoogle Scholar
  15. 15.
    Adamson R, Obispo E, Dychter S, et al. High incidence and clinical course of aggressive skin cancer in heart transplant patients: a single-center study. Transplant Proc. 1998;30(4):1124–1126.CrossRefPubMedGoogle Scholar
  16. 16.
    Perera GK, Child FJ, Heaton N, O’Grady J, Higgins EM. Skin lesions in adult liver transplant recipients: a study of 100 consecutive patients. Br J Dermatol. 2006;154(5):868–872.CrossRefPubMedGoogle Scholar
  17. 17.
    Levy M, Backman L, Husberg B, et al. De novo malignancy following liver transplantation: a single-center study. Transplant Proc. 1993;25(1 Pt 2):1397–1399.PubMedGoogle Scholar
  18. 18.
    Frezza EE, Fung JJ, van Thiel DH. Non-lymphoid cancer after liver transplantation. Hepatogastroenterology. 1997;44(16):1172–1181.PubMedGoogle Scholar
  19. 19.
    Leisenring W, Friedman DL, Flowers ME, et al. Nonmelanoma skin and mucosal cancers after hematopoietic cell transplantation. J Clin Oncol. 2006;24(7):1119–1126.CrossRefPubMedGoogle Scholar
  20. 20.
    Goldman GD. Squamous cell cancer: a practical approach. Semin Cutan Med Surg. 1998;17(2):80–95.CrossRefPubMedGoogle Scholar
  21. 21.
    Brash DE, Ziegler A, Jonason AS, et al. Sunlight and sunburn in human skin cancer: p53, apoptosis, and tumor promotion. J Investig Dermatol Symp Proc. 1996;1(2):136–142.PubMedGoogle Scholar
  22. 22.
    Leffell DJ, Brash DE. Sunlight and skin cancer. Sci Am. 1996;275(1):52–53, 56–59.CrossRefGoogle Scholar
  23. 23.
    Alam M, Caldwell JB, Eliezri YD. Human papillomavirus-associated digital squamous cell carcinoma: literature review and report of 21 new cases. J Am Acad Dermatol. 2003;48(3):385–393.Google Scholar
  24. 24.
    Bouwes Bavinck JN, Feltkamp M, Struijk L, Schegget J. Human papillomavirus infection and skin cancer risk in organ transplant recipients. J Investig Dermatol Symp Proc. 2001;6(3):207–211.CrossRefPubMedGoogle Scholar
  25. 25.
    Khavari TA, Rinn J. Ras/Erk MAPK signaling in epidermal homeostasis and neoplasia. Cell Cycle. 2007;6(23):2928–2931.CrossRefPubMedGoogle Scholar
  26. 26.
    Dajee M, Lazarov M, Zhang JY, et al. NF-kappaB blockade and oncogenic Ras trigger invasive human epidermal neoplasia. Nature. 2003;421(6923):639–643.CrossRefPubMedGoogle Scholar
  27. 27.
    Haider AS, Peters SB, Kaporis H, et al. Genomic analysis defines a cancer-specific gene expression signature for human squamous cell carcinoma and distinguishes malignant hyperproliferation from benign hyperplasia. J Invest Dermatol. 2006;126(4):869–881.CrossRefPubMedGoogle Scholar
  28. 28.
    Lai EC. Notch signaling: control of cell communication and cell fate. Development (Cambridge, England ). 2004;131(5):965–973.Google Scholar
  29. 29.
    Nicolas M, Wolfer A, Raj K, et al. Notch1 functions as a tumor suppressor in mouse skin. Nat Genet. 2003;33(3):416–421.CrossRefPubMedGoogle Scholar
  30. 30.
    Proweller A, Tu L, Lepore JJ, et al. Impaired notch signaling promotes de novo squamous cell carcinoma formation. Cancer Res. 2006;66(15):7438–7444.CrossRefPubMedGoogle Scholar
  31. 31.
    Chan GL, Erdmann GR, Gruber SA, Matas AJ, Canafax DM. Azathioprine metabolism: pharmacokinetics of 6-mercaptopurine, 6-thiouric acid and 6-thioguanine nucleotides in renal transplant patients. J Clin Pharmacol. 1990;30(4):358–363.PubMedGoogle Scholar
  32. 32.
    Lennard L, Maddocks JL. Assay of 6-thioguanine nucleotide, a major metabolite of azathioprine, 6-mercaptopurine and 6-thioguanine, in human red blood cells. J Pharm Pharmacol. 1983;35(1):15–18.PubMedGoogle Scholar
  33. 33.
    O’Donovan P, Perrett CM, Zhang X, et al. Azathioprine and UVA light generate mutagenic oxidative DNA damage. Science. 2005;309(5742):1871–1874.CrossRefPubMedGoogle Scholar
  34. 34.
    Borel JF, Di Padova F, Mason J, Quesniaux V, Ryffel B, Wenger R. Pharmacology of cyclosporine (sandimmune). I. Introduction. Pharmacol Rev. 1990;41(3):239–242.PubMedGoogle Scholar
  35. 35.
    Hojo M, Morimoto T, Maluccio M, et al. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature. 1999;397(6719):530–534.CrossRefPubMedGoogle Scholar
  36. 36.
    Servilla KS, Burnham DK, Daynes RA. Ability of cyclosporine to promote the growth of transplanted ultraviolet radiation-induced tumors in mice. Transplantation. 1987;44(2):291–295.CrossRefPubMedGoogle Scholar
  37. 37.
    Morath C, Arns W, Schwenger V, et al. Sirolimus in renal transplantation. Nephrol Dial Transplant. 2007;22(Suppl 8):viii61–viii5.Google Scholar
  38. 38.
    Euvrard S, Ulrich C, Lefrancois N. Immunosuppressants and skin cancer in transplant patients: focus on rapamycin. Dermatol Surg. 2004;30(4 Pt 2):628–633.CrossRefPubMedGoogle Scholar
  39. 39.
    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):581–589.CrossRefPubMedGoogle Scholar
  40. 40.
    Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip: implications for treatment modality selection. J Am Acad Dermatol. 1992;26(6):976–990.CrossRefPubMedGoogle Scholar
  41. 41.
    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):642–650.CrossRefPubMedGoogle Scholar
  42. 42.
    Glover MT, Niranjan N, Kwan JT, Leigh IM. Non-melanoma skin cancer in renal transplant recipients: the extent of the problem and a strategy for management. Br J Plast Surg. 1994;47(2):86–89.CrossRefPubMedGoogle Scholar
  43. 43.
    Carucci JA, Martinez JC, Zeitouni NC, et al. In-transit metastasis from primary cutaneous squamous cell carcinoma in organ transplant recipients and nonimmunosuppressed patients: clinical characteristics, management, and outcome in a series of 21 patients. Dermatol Surg. 2004;30(4 Pt 2):651–655.CrossRefPubMedGoogle Scholar
  44. 44.
    Martinez JC, Otley CC. Megasession: excision of numerous skin cancers in a single session. Dermatol Surg. 2005;31(7 Pt 1):757–761; discussion 61–62.Google Scholar
  45. 45.
    Wollina U, Hansel G, Koch A, Kostler E. Oral capecitabine plus subcutaneous interferon alpha in advanced squamous cell carcinoma of the skin. J Cancer Res Clin Oncol. 2005;131(5):300–304.CrossRefPubMedGoogle Scholar
  46. 46.
    Petersen JE. The use of oral capecitabine chemotherapy for radioresistant and large recurrent squamous cell carcinomas of the scalp. American College of Mohs Surgery Annual Meeting 2008.Google Scholar
  47. 47.
    Smith KJ, Hamza S, Skelton H. Topical imidazoquinoline therapy of cutaneous squamous cell carcinoma polarizes lymphoid and monocyte/macrophage populations to a Th1 and M1 cytokine pattern. Clin Exp Dermatol. 2004;29(5):505–512.CrossRefPubMedGoogle Scholar
  48. 48.
    Ulrich C, Busch JO, Meyer T, et al. Successful treatment of multiple actinic keratoses in organ transplant patients with topical 5% imiquimod: a report of six cases. Br J Dermatol. 2006;155(2):451–454.Google Scholar
  49. 49.
    Ulrich C, Bichel J, Euvrard S, et al. Topical immunomodulation under systemic immunosuppression: results of a multicentre, randomized, placebo-controlled safety and efficacy study of imiquimod 5% cream for the treatment of actinic keratoses in kidney, heart, and liver transplant patients. Br J Dermatol. 2007;157(Suppl 2):25–31.CrossRefPubMedGoogle Scholar
  50. 50.
    Ulrich C, Hackethal M, Ulrich M, et al. Treatment of multiple actinic keratoses with topical diclofenac 3% gel in organ transplant recipients: a series of six cases. Br J Dermatol. 2007;156(Suppl 3):40–42.CrossRefPubMedGoogle Scholar
  51. 51.
    Perrett CM, McGregor JM, Warwick J, et al. Treatment of post-transplant premalignant skin disease: a randomized intrapatient comparative study of 5-fluorouracil cream and topical photodynamic therapy. Br J Dermatol. 2007;156(2):320–328.CrossRefPubMedGoogle Scholar
  52. 52.
    Piaserico S, Belloni Fortina A, Rigotti P, et al. Topical photodynamic therapy of actinic keratosis in renal transplant recipients. Transplant Proc. 2007;39(6):1847–1850.CrossRefPubMedGoogle Scholar
  53. 53.
    Harwood CA, Leedham-Green M, Leigh IM, Proby CM. Low-dose retinoids in the prevention of cutaneous squamous cell carcinomas in organ transplant recipients: a 16-year retrospective study. Arch Dermatol. 2005;141(4):456–464.CrossRefPubMedGoogle Scholar
  54. 54.
    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):623–628.CrossRefPubMedGoogle Scholar
  55. 55.
    Otley CC, Coldiron BM, Stasko T, Goldman GD. Decreased skin cancer after cessation of therapy with transplant-associated immunosuppressants. Arch Dermatol. 2001;137(4):459–463.PubMedGoogle Scholar
  56. 56.
    Otley CC, Maragh SL. Reduction of immunosuppression for transplant-associated skin cancer: rationale and evidence of efficacy. Dermatol Surg. 2005;31(2):163–168.CrossRefPubMedGoogle Scholar
  57. 57.
    Van Cutsem E, Van de Velde C, Roth A, et al. Expert opinion on management of gastric and gastro-oesophageal junction adenocarcinoma on behalf of the European Organisation for Research and Treatment of Cancer (EORTC)-gastrointestinal cancer group. Eur J Cancer. 2008;44(2):182–194.CrossRefPubMedGoogle Scholar
  58. 58.
    Christenson LJ, Geusau A, Ferrandiz C, et al. Specialty clinics for the dermatologic care of solid-organ transplant recipients. Dermatol Surg. 2004;30(4 Pt 2):598–603.CrossRefPubMedGoogle Scholar
  59. 59.
    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):712–718.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • John Carucci
    • 1
  • Dariush Moussai
    • 2
  1. 1.Department of DermatologyMohs Micrographic and Dermatologic Surgery, Weill Medical College of CornellNew YorkUSA
  2. 2.Department of DermatologyWeill Medical College of CornellNew YorkUSA

Personalised recommendations