- Email: [email protected]
Skin Cancer Following Kidney Transplantation: A Single-Center Experience
Skin Cancer Following Kidney Transplantation: A Single-Center Experience M. Karczewski, M. Stronka, J. Karczewski, and K. Wiktorowicz ABSTRACT One of the major problems associated with prolonged immunosuppression is a high occurrence of skin malignancies among kidney recipients. Studies have shown that nonmelanoma skin cancer is the most frequently occurring tumor after organ transplantation. The aim of this study was to determine the incidence of and identify possible risk factors for skin malignancies among a population of kidney recipients. This retrospective, single-center cohort comprised 1672 patients transplanted from 1994 to 2011. Only patients with a confirmed diagnosis of skin cancer were selected for medical records review. Among 836 kidney transplant recipients remaining under our care since 1994, skin malignancies were diagnosed in 16 patients (1.9%). The histological diagnoses included squamous cell carcinoma (n ⫽ 8; 50.0%); basal cell carcinoma (n ⫽ 6; 37.5%) or malignant melanoma (n ⫽ 2; 12.5%). The slightly lower incidence of skin malignancies noted in our study compared with other reports might result from differences in the length of follow-up. Some patients diagnosed with skin cancer were treated in local dermatology clinics. Also, a lower exposure to the sun characteristic for the latitude and differences in immunosuppressive therapies could be partially responsible for the lower skin cancer incidence. We also did not observe any association between other reported risk factors, such as age, human leukocyte antigen mismatch, duration of pretransplant hemodialysis, particular immunosuppressive therapies and the skin cancer occurrence among our kidney recipients. IDNEY TRANSPLANTATION is the preferred treatment for end-stage renal disease. The development of new, potent immunosuppressants has prolonged graft survival; however, their side effects may result in various complications. Kidney transplant patients are known to be at a higher risk for cancer than the normal, immunocompetent population.1 Cancers in transplanted patients are frequently more aggressive. They have become the second cause of death.2,3 The most common neoplasm observed among kidney recipients is skin cancer, comprising 40% to 50% of all malignancies.4,5 Various studies have shown that nonmelanoma skin cancer is the most frequent tumor after organ transplantation.6 – 8 Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are believed to account for more than 90% of all skin cancers in transplant recipients.9 Various factors contribute to the development of skin cancer in transplanted patients, including age, gender, sun exposure, human papillomavirus infections, genetic susceptibility as well as type, duration, and level of immunosuppression.10 The aim of this study was to determine the incidence of and identify the possible risk factors for skin
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malignancies among a population of Polish kidney recipients.
PATIENTS AND METHODS This retrospective, single-center cohort comprised 1672 patients transplanted during 1994 to 2011. Skin cancer data were reviewed in 836 patients who remained under our care. The medical records of patients with a confirmed diagnosis of skin cancer were selected (n ⫽ 16) for review. Demographic and clinical characteristics of skin cancer versus cancer-free patients, including age, gender, time on dialysis, cold and warm ischemia time, human leukocyte antigen (HLA) match, percent panel-reaction antibody value, and type of From the Department of Transplantology and General Surgery, District Hospital in Poznan (M.K.), Solumed, Research Unit (M.S.); Poznan University of Medical Sciences in Poznan (J.K., K.W.), Poznan, Poland. Address reprint requests to Marek Karczewski, MD, PhD, Department of Transplantology and General Surgery, District Hospital in Poznan, Juraszow 7/19, 60-479 Poznan, Poland. E-mail: [email protected]
0041-1345/11/$–see front matter doi:10.1016/j.transproceed.2011.08.080
© 2011 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
3760
Transplantation Proceedings, 43, 3760 –3761 (2011)
SKIN CANCER POST–KIDNEY TRANSPLANTATION immunosuppressive therapy, were examined values considered to be significant when P ⬍ .05.
RESULTS
Among our 836 kidney transplant recipients since 1994, skin malignancies were diagnosed in 16 patients (1.9%), all of whom where Caucasians. The analysis did not show significant differences in demographic and clinical characteristics, except for gender (P ⬍ .05); the majority of patients with skin cancer were men (n ⫽ 13), comprising 81.2%. The overall mean age at transplantation was 49.86 ⫾ 7.4 years and the skin malignancies were diagnosed at an average of 48.6 months after the surgery. The histological diagnosis included SCC (n ⫽ 8; 50.0%), BCC (n ⫽ 6; 37.5%), and malignant melanoma (MM; n ⫽ 2; 12.5%). No other types of skin malignancies were observed among the investigated group. In the group of patients with SCC diagnosis, 5 (62.5%) developed multiple lesions located on the head and extremities. The majority of lesions were found on the head (n ⫽ 7; 87.5%), on the upper extremities (n ⫽ 5; 62.5%), and on the thorax (n ⫽ 1; 12.5%). All patients with diagnosed BCC had isolated lesions located on the head (n ⫽ 3; 50%) and the thorax (n ⫽ 3; 50%). Both patients with malignant melanoma (superficial spreading melanoma) had isolated lesions on the back (n ⫽ 2; 100%). DISCUSSION
Livelong immunosuppression following transplantation results in long-term graft survival but also in some complications. One of the major problems associated with prolonged immunosuppression in kidney recipients is a high occurrence of various skin diseases, up to 98% as reported by some authors.11 Skin cancers, undoubtedly the most common malignant conditions in transplanted patients, can show aggressive and even life-threatening course. Our study revealed 1.9% of kidney recipients to have developed skin malignancies after transplantation. The histological diagnoses included SCC (50.0%), BCC (37.5%), and MM (12.5%). SCC and BCC are the most common invasive skin cancers after transplantation. Our data are consistent with these observations. Compared with the normal population, the incidence of SCC shows a 65 to 250-fold increase among transplanted patients, while the incidence of BCC is increased about 10-fold.10 It is believed that the SCC:BCC ratio is reversed in transplanted patients from normal subjects; SCC being 2 to 4 times more frequent than BSS.12 The incidence of these malignancies increases with the level and duration of immunosuppressive therapy, ultimately affecting more than 50% of transplant recipients.9
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MM, in turn, is a highly malignant tumor responsible for more deaths than any other skin cancer. Superficial spreading melanoma diagnosed in two patients is the most common type of melanoma associated with white skin. Various reports show different rates of MM incidence, probably due to differences in the level of immunosuppression, the skin type, sun habits, and so on. The reported risk is increased by a factor of 1.6 to 3.4 in Europe and 2 to 4 in Australia.10,12 The slightly lower incidence of skin malignancies observed in our study compared with other reports might result from differences in the length of follow-up.13 Some of the patients may have been diagnosed for skin cancer and treated in local dermatology clinics. Also, a lower exposure to the sun characteristic for the latitude and differences in immunosuppressive therapies could be partially responsible for the lower skin cancer incidence. We also did not observe any association with reported risk factors, such as age, HLA mismatch, duration of pretransplant hemodialysis, particular immunosuppressive therapies,9,10 possibly due to the limited sample size and the already mentioned reasons. REFERENCES 1. Arichi N, Kishikawa H, Nishimua K, et al: Malignancy following kidney transplantation. Transplant Proc 40:2400, 2008 2. Barrett W, First M, Aron B, et al: Clinical course of malignancies in renal transplant recipients. Cancer 72:2186, 1993 3. Bichari W, Bartiromo M, Mohey H, et al: Significant risk factors for occurence of cancer renal transplantation: a single center cohort study of 1265 cases. Transplant Proc 41:672, 2009 4. Falsarella PM, Alves-Filho G, Mazzali M: Skin malignancies in renal transplant recipients: a Brazilian Center Registry. Transplant Proc 40:767, 2008 5. Penn I: Cancers in renal transplant recipients. Adv Ren Replace Ther 7:147, 2000 6. Webb MC, Compton F, Andrews PA, et al: Skin tumours posttransplantation: a retrospective analysis of 28 years’ experience at a single centre. Transplant Proc 29:828, 1997 7. Hiesse C, Rieu P, Kriaa F, et al: Malignancy after renal transplantation: analysis of incidence and risk factors in 1700 patients followed during a 25-year period. Transplant Proc 29:831, 1997 8. Winkelhorst JT, Brokleman WJ, Tiggeler RG, et al: Incidence and clinical course of de-novo malignancies in renal allograft recipients. Euro J Dermatol 27:409, 2001 9. Euvrard S, Kanitakis J, Claudy A: Skin cancers after organ transplantation. N Engl J Med 348:1681, 2003 10. Stockfleth E, Ulrich C, Euvrard S, et al: Skin cancer after organ transplantation. New York: Springer 2009 11. Strumia R, Perini L, Tarroni G, et al: Skin lesions in kidney transplant recipients. Nephron 62:137, 1992 12. Stockfleth E, Rosen T, Schumaak S: Managing Skin Cancer. 1st ed. Heidelberg: Springer-Verlag; 2010 13. Bordea C, Wojnarowska F, Millard PR, et al: Skin cancers in renal-transplant recipients occur more frequently than previously recognized in a temperate climate. Transplantation 77:574, 2004
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malignancies among a population of Polish kidney recipients.
PATIENTS AND METHODS This retrospective, single-center cohort comprised 1672 patients transplanted during 1994 to 2011. Skin cancer data were reviewed in 836 patients who remained under our care. The medical records of patients with a confirmed diagnosis of skin cancer were selected (n ⫽ 16) for review. Demographic and clinical characteristics of skin cancer versus cancer-free patients, including age, gender, time on dialysis, cold and warm ischemia time, human leukocyte antigen (HLA) match, percent panel-reaction antibody value, and type of From the Department of Transplantology and General Surgery, District Hospital in Poznan (M.K.), Solumed, Research Unit (M.S.); Poznan University of Medical Sciences in Poznan (J.K., K.W.), Poznan, Poland. Address reprint requests to Marek Karczewski, MD, PhD, Department of Transplantology and General Surgery, District Hospital in Poznan, Juraszow 7/19, 60-479 Poznan, Poland. E-mail: [email protected]
0041-1345/11/$–see front matter doi:10.1016/j.transproceed.2011.08.080
© 2011 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
3760
Transplantation Proceedings, 43, 3760 –3761 (2011)
SKIN CANCER POST–KIDNEY TRANSPLANTATION immunosuppressive therapy, were examined values considered to be significant when P ⬍ .05.
RESULTS
Among our 836 kidney transplant recipients since 1994, skin malignancies were diagnosed in 16 patients (1.9%), all of whom where Caucasians. The analysis did not show significant differences in demographic and clinical characteristics, except for gender (P ⬍ .05); the majority of patients with skin cancer were men (n ⫽ 13), comprising 81.2%. The overall mean age at transplantation was 49.86 ⫾ 7.4 years and the skin malignancies were diagnosed at an average of 48.6 months after the surgery. The histological diagnosis included SCC (n ⫽ 8; 50.0%), BCC (n ⫽ 6; 37.5%), and malignant melanoma (MM; n ⫽ 2; 12.5%). No other types of skin malignancies were observed among the investigated group. In the group of patients with SCC diagnosis, 5 (62.5%) developed multiple lesions located on the head and extremities. The majority of lesions were found on the head (n ⫽ 7; 87.5%), on the upper extremities (n ⫽ 5; 62.5%), and on the thorax (n ⫽ 1; 12.5%). All patients with diagnosed BCC had isolated lesions located on the head (n ⫽ 3; 50%) and the thorax (n ⫽ 3; 50%). Both patients with malignant melanoma (superficial spreading melanoma) had isolated lesions on the back (n ⫽ 2; 100%). DISCUSSION
Livelong immunosuppression following transplantation results in long-term graft survival but also in some complications. One of the major problems associated with prolonged immunosuppression in kidney recipients is a high occurrence of various skin diseases, up to 98% as reported by some authors.11 Skin cancers, undoubtedly the most common malignant conditions in transplanted patients, can show aggressive and even life-threatening course. Our study revealed 1.9% of kidney recipients to have developed skin malignancies after transplantation. The histological diagnoses included SCC (50.0%), BCC (37.5%), and MM (12.5%). SCC and BCC are the most common invasive skin cancers after transplantation. Our data are consistent with these observations. Compared with the normal population, the incidence of SCC shows a 65 to 250-fold increase among transplanted patients, while the incidence of BCC is increased about 10-fold.10 It is believed that the SCC:BCC ratio is reversed in transplanted patients from normal subjects; SCC being 2 to 4 times more frequent than BSS.12 The incidence of these malignancies increases with the level and duration of immunosuppressive therapy, ultimately affecting more than 50% of transplant recipients.9
3761
MM, in turn, is a highly malignant tumor responsible for more deaths than any other skin cancer. Superficial spreading melanoma diagnosed in two patients is the most common type of melanoma associated with white skin. Various reports show different rates of MM incidence, probably due to differences in the level of immunosuppression, the skin type, sun habits, and so on. The reported risk is increased by a factor of 1.6 to 3.4 in Europe and 2 to 4 in Australia.10,12 The slightly lower incidence of skin malignancies observed in our study compared with other reports might result from differences in the length of follow-up.13 Some of the patients may have been diagnosed for skin cancer and treated in local dermatology clinics. Also, a lower exposure to the sun characteristic for the latitude and differences in immunosuppressive therapies could be partially responsible for the lower skin cancer incidence. We also did not observe any association with reported risk factors, such as age, HLA mismatch, duration of pretransplant hemodialysis, particular immunosuppressive therapies,9,10 possibly due to the limited sample size and the already mentioned reasons. REFERENCES 1. Arichi N, Kishikawa H, Nishimua K, et al: Malignancy following kidney transplantation. Transplant Proc 40:2400, 2008 2. Barrett W, First M, Aron B, et al: Clinical course of malignancies in renal transplant recipients. Cancer 72:2186, 1993 3. Bichari W, Bartiromo M, Mohey H, et al: Significant risk factors for occurence of cancer renal transplantation: a single center cohort study of 1265 cases. Transplant Proc 41:672, 2009 4. Falsarella PM, Alves-Filho G, Mazzali M: Skin malignancies in renal transplant recipients: a Brazilian Center Registry. Transplant Proc 40:767, 2008 5. Penn I: Cancers in renal transplant recipients. Adv Ren Replace Ther 7:147, 2000 6. Webb MC, Compton F, Andrews PA, et al: Skin tumours posttransplantation: a retrospective analysis of 28 years’ experience at a single centre. Transplant Proc 29:828, 1997 7. Hiesse C, Rieu P, Kriaa F, et al: Malignancy after renal transplantation: analysis of incidence and risk factors in 1700 patients followed during a 25-year period. Transplant Proc 29:831, 1997 8. Winkelhorst JT, Brokleman WJ, Tiggeler RG, et al: Incidence and clinical course of de-novo malignancies in renal allograft recipients. Euro J Dermatol 27:409, 2001 9. Euvrard S, Kanitakis J, Claudy A: Skin cancers after organ transplantation. N Engl J Med 348:1681, 2003 10. Stockfleth E, Ulrich C, Euvrard S, et al: Skin cancer after organ transplantation. New York: Springer 2009 11. Strumia R, Perini L, Tarroni G, et al: Skin lesions in kidney transplant recipients. Nephron 62:137, 1992 12. Stockfleth E, Rosen T, Schumaak S: Managing Skin Cancer. 1st ed. Heidelberg: Springer-Verlag; 2010 13. Bordea C, Wojnarowska F, Millard PR, et al: Skin cancers in renal-transplant recipients occur more frequently than previously recognized in a temperate climate. Transplantation 77:574, 2004