Organ transplant recipients (OTR) are at a significantly increased risk for developing a wide variety of skin cancers, particularly epithelial skin cancer, Merkel cell carcinoma and Kaposi's sarcoma. Melanoma, skin adnexal neoplasm and cutaneous lymphomas are also more common in OTR and may differ in their clinicopathologic presentation from tumors in immunocompetent patients. The accuracy of clinical diagnosis of suspected premalignant and malignant skin lesions in OTR is modest. Therefore, histopathological diagnosis is an essential element for the diagnostic workup of skin cancers and, in addition, provides important information on prognosis. Squamous cell carcinoma and intraepithelial neoplasias (actinic keratosis, squamous cell carcinoma in situ or Bowen's disease) are the most common forms of skin cancer in OTR. The risk of Merkel cell carcinoma and Kaposi's sarcoma is dramatically increased in OTR. Merkel cell carcinoma shows a highly aggressive course. Kaposi's sarcoma tends to spread to extracutaneous sites. Primary cutaneous lymphomas developing after organ transplantation are rare. The spectrum of cutaneous B cell lymphomas in OTR, in particular, differs significantly from that of the general population, with a predominance of Epstein-Barr virus-driven posttransplant lymphoproliferative disorder. This review discusses the clinical and histopathological aspects of skin cancers in OTR, the impact of dermatopathological analysis on prognosis and the understanding of the pathogenesis of these neoplasms.

1.
Euvrard S, Kanitakis J, Claudy A: Skin cancers after organ transplantation. N Engl J Med 2003;348:1681-1691.
2.
Cooper SM, Wojnarowska F: The accuracy of clinical diagnosis of suspected premalignant and malignant skin lesions in renal transplant recipients. Clin Exp Dermatol 2002;27:436-438.
3.
Lindelöf B, Sigurgeirsson B, Gabel H, Stern RS: Incidence of skin cancer in 5,356 patients following organ transplantation. Br J Dermatol 2000;143:513-519.
4.
Harwood CA, McGregor JM, Swale VJ, Proby CM, Leigh IM, Newton R, Khorshid SM, Cerio R: High frequency and diversity of cutaneous appendageal tumors in organ transplant recipients. J Am Acad Dermatol 2003;48:401-408.
5.
Hu B, Castillo E, Harewood L, Ostano P, Reymond A, Dummer R, Raffoul W, Hoetzenecker W, Hofbauer GF, Dotto GP: Multifocal epithelial tumors and field cancerization from loss of mesenchymal CSL signaling. Cell 2012;149:1207-1220.
6.
Hofbauer GF, Anliker M, Arnold A, Binet I, Hunger R, Kempf W, Laffitte E, Lapointe AC, Pascual M, Pelloni F, Serra A: Swiss clinical practice guidelines for skin cancer in organ transplant recipients. Swiss Med Wkly 2009;139:407-415.
7.
Smith KJ, Hamza S, Skelton H: Histologic features in primary cutaneous squamous cell carcinomas in immunocompromised patients focusing on organ transplant patients. Dermatol Surg 2004;30:634-641.
8.
Mühleisen B, Petrov I, Gachter T, Kurrer M, Scharer L, Dummer R, French LE, Hofbauer GF: Progression of cutaneous squamous cell carcinoma in immunosuppressed patients is associated with reduced CD123+ and FOXP3+ cells in the perineoplastic inflammatory infiltrate. Histopathology 2009;55:67-76.
9.
Kosmidis M, Dziunycz P, Suarez-Farinas M, Muhleisen B, Scharer L, Lauchli S, Hafner J, French LE, Schmidt-Weber C, Carucci JA, Hofbauer GF: Immunosuppression affects CD4+ mRNA expression and induces Th2 dominance in the microenvironment of cutaneous squamous cell carcinoma in organ transplant recipients. J Immunother 2010;33:538-546.
10.
Harwood CA, Proby CM, McGregor JM, Sheaff MT, Leigh IM, Cerio R: Clinicopathologic features of skin cancer in organ transplant recipients: a retrospective case-control series. J Am Acad Dermatol 2006;54:290-300.
11.
Farasat S, Yu SS, Neel VA, Nehal KS, Lardaro T, Mihm MC, Byrd DR, Balch CM, Califano JA, Chuang AY, Sharfman WH, Shah JP, Nghiem P, Otley CC, Tufaro AP, Johnson TM, Sober AJ, Liegeois NJ: A new American Joint Committee on Cancer staging system for cutaneous squamous cell carcinoma: creation and rationale for inclusion of tumor (T) characteristics. J Am Acad Dermatol 2011;64:1051-1059.
12.
O'Donovan P, Perrett CM, Zhang X, Montaner B, Xu YZ, Harwood CA, McGregor JM, Walker SL, Hanaoka F, Karran P: Azathioprine and UVA light generate mutagenic oxidative DNA damage. Science 2005;309:1871-1874.
13.
Hofbauer GF, Attard NR, Harwood CA, McGregor JM, Dziunycz P, Iotzova-Weiss G, Straub G, Meyer R, Kamenisch Y, Berneburg M, French LE, Wüthrich RP, Karran P, Serra AL: Reversal of UVA skin photosensitivity and DNA damage in kidney transplant recipients by replacing azathioprine. Am J Transplant 2011;12:218-225.
14.
Bouwes Bavinck JN, Neale RE, Abeni D, Euvrard S, Green AC, Harwood CA, de Koning MN, Naldi L, Nindl I, Pawlita M, Pfister H, Proby CM, Quint WG, ter Schegget J, Waterboer T, Weissenborn S, Feltkamp MC: Multicenter study of the association between betapapillomavirus infection and cutaneous squamous cell carcinoma. Cancer Res 2010;70:9777-9786.
15.
Gibson GE, O'Grady A, Kay EW, Leader M, Murphy GM: p53 Tumor suppressor gene protein expression in premalignant and malignant skin lesions of kidney transplant recipients. J Am Acad Dermatol 1997;36:924-931.
16.
Haider AS, Peters SB, Kaporis H, Cardinale I, Fei J, Ott J, Blumenberg M, Bowcock AM, Krueger JG, Carucci JA: 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;126:869-881.
17.
Mühleisen B, Petrov I, Frigerio S, Dziunycz P, French LE, Hofbauer GF: Pronounced allelic imbalance at D9S162 in skin squamous cell carcinoma of organ transplant recipients. Arch Dermatol 2012;148:697-703.
18.
Dziunycz P, Iotzova-Weiss G, Eloranta JJ, Lauchli S, Hafner J, French LE, Hofbauer GF: Squamous cell carcinoma of the skin shows a distinct microRNA profile modulated by UV radiation. J Invest Dermatol 2010;130:2686-2689.
19.
O'Reilly Zwald F, Brown M: Skin cancer in solid organ transplant recipients: advances in therapy and management. Part II. Management of skin cancer in solid organ transplant recipients. J Am Acad Dermatol 2011;65:263-279.
20.
Rival-Tringali AL, Euvrard S, Decullier E, Claudy A, Faure M, Kanitakis J: Conversion from calcineurin inhibitors to sirolimus reduces vascularization and thickness of post-transplant cutaneous squamous cell carcinomas. Anticancer Res 2009;29:1927-1932.
21.
Euvrard S, Morelon E, Rostaing L, Goffin E, Brocard A, Tromme I, Broeders N, del Marmol V, Chatelet V, Dompmartin A, Kessler M, Serra AL, Hofbauer GF, Pouteil-Noble C, Campistol JM, Kanitakis J, Roux AS, Decullier E, Dantal J: Sirolimus and secondary skin-cancer prevention in kidney transplantation. N Engl J Med 2012;367:329-339.
22.
Mertz KD, Proske D, Kettelhack N, Kegel C, Keusch G, Schwarz A, Ambuhl PM, Pfaltz M, Kempf W: Basal cell carcinoma in a series of renal transplant recipients: epidemiology and clinicopathologic features. Int J Dermatol 2010;49:385-389.
23.
Saldanha G, Fletcher A, Slater DN: Basal cell carcinoma: a dermatopathological and molecular biological update. Br J Dermatol 2003;148:195-202.
24.
Mougel F, Kanitakis J, Faure M, Euvrard S: Basosquamous cell carcinoma in organ transplant patients: a clinicopathologic study. J Am Acad Dermatol 2012;66:151-157.
25.
Kanitakis J, Alhaj-Ibrahim L, Euvrard S, Claudy A: Basal cell carcinomas developing in solid organ transplant recipients: clinicopathologic study of 176 cases. Arch Dermatol 2003;139:1133-1137.
26.
Buell JF, Trofe J, Hanaway MJ, Beebe TM, Gross TG, Alloway RR, First MR, Woodle ES: Immunosuppression and Merkel cell cancer. Transplant Proc 2002;34:1780-1781.
27.
Koljonen V, Kukko H, Tukiainen E, Bohling T, Sankila R, Pukkala E, Sihto H, Joensuu H, Kyllonen L, Makisalo H: Incidence of Merkel cell carcinoma in renal transplant recipients. Nephrol Dial Transplant 2009;24:3231-3235.
28.
Kanitakis J, Euvrard S, Chouvet B, Butnaru AC, Claudy A: Merkel cell carcinoma in organ-transplant recipients: report of two cases with unusual histological features and literature review. J Cutan Pathol 2006;33:686-694.
29.
Vazmitel M, Michal M, Kempf W, Mukensnabl P, Kazakov DV: Merkel cell carcinoma with a follicular lymphocytic infiltrate: report of 2 cases. Am J Dermatopathol 2008;30:389-391.
30.
Mitteldorf C, Mertz KD, Fernandez-Figueras MT, Schmid M, Tronnier M, Kempf W: Detection of Merkel cell polyomavirus and human papillomaviruses in Merkel cell carcinoma combined with squamous cell carcinoma in immunocompetent European patients. Am J Dermatopathol 2012;34:506-510.
31.
Hall BJ, Pincus LB, Yu SS, Oh DH, Wilson AR, McCalmont TH: Immunohistochemical prognostication of Merkel cell carcinoma: p63 expression but not polyomavirus status correlates with outcome. J Cutan Pathol 2012;39:911-917.
32.
Mertz KD, Pfaltz M, Junt T, Schmid M, Fernandez Figueras MT, Pfaltz K, Barghorn A, Kempf W: Merkel cell polyomavirus is present in common warts and carcinoma in situ of the skin. Hum Pathol 2010;41:1369-1379.
33.
Mertz KD, Junt T, Schmid M, Pfaltz M, Kempf W: Inflammatory monocytes are a reservoir for Merkel cell polyomavirus. J Invest Dermatol 2010;130:1146-1151.
34.
Duncavage EJ, Le BM, Wang D, Pfeifer JD: Merkel cell polyomavirus: a specific marker for Merkel cell carcinoma in histologically similar tumors. Am J Surg Pathol 2009;33:1771-1777.
35.
Penn I, First MR: Merkel's cell carcinoma in organ recipients: report of 41 cases. Transplantation 1999;68:1717-1721.
36.
Penn I: Cancers in renal transplant recipients. Adv Ren Replace Ther 2000;7:147-156.
37.
Frances C: Kaposi's sarcoma after renal transplantation. Nephrol Dial Transplant 1998;13:2768-2773.
38.
Kempf W, Cathomas G, Burg G, Trueb RM: Micronodular Kaposi's sarcoma - a new variant of classic-sporadic Kaposi's sarcoma. Dermatology 2004;208:255-258.
39.
Grayson W, Pantanowitz L: Histological variants of cutaneous Kaposi sarcoma. Diagn Pathol 2008;3:31.
40.
Robin YM, Guillou L, Michels JJ, Coindre JM: Human herpesvirus 8 immunostaining: a sensitive and specific method for diagnosing Kaposi sarcoma in paraffin-embedded sections. Am J Clin Pathol 2004;121:330-334.
41.
Woodle ES, Hanaway M, Buell J, Gross T, First MR, Trofe J, Beebe T: Kaposi sarcoma: an analysis of the US and international experiences from the Israel Penn International Transplant Tumor Registry. Transplant Proc 2001;33:3660-3661.
42.
Prinz BM, Hofbauer GF, Dummer R, French LE, Kempf W: Topical treatment of cutaneous Kaposi sarcoma with imiquimod 5% in renal transplant recipients - a clinico-pathological observation. Clin Exp Dermatol 2011;37:620-625.
43.
Hollenbeak CS, Todd MM, Billingsley EM, Harper G, Dyer AM, Lengerich EJ: Increased incidence of melanoma in renal transplantation recipients. Cancer 2005;104:1962-1967.
44.
Le Mire L, Hollowood K, Gray D, Bordea C, Wojnarowska F: Melanomas in renal transplant recipients. Br J Dermatol 2006;154:472-477.
45.
Penn I: Malignant melanoma in organ allograft recipients. Transplantation 1996;61:274-278.
46.
Brewer JD, Christenson LJ, Weaver AL, Dapprich DC, Weenig RH, Lim KK, Walsh JS, Otley CC, Cherikh W, Buell JF, Woodle ES, Arpey C, Patton PR: Malignant melanoma in solid transplant recipients: collection of database cases and comparison with surveillance, epidemiology, and end results data for outcome analysis. Arch Dermatol 2011;147:790-796.
47.
Matin RN, Mesher D, Proby CM, McGregor JM, Bouwes Bavinck JN, del Marmol V, Euvrard S, Ferrandiz C, Geusau A, Hackethal M, Ho WL, Hofbauer GF, Imko-Walczuk B, Kanitakis J, Lally A, Lear JT, Lebbe C, Murphy GM, Piaserico S, Seckin D, Stockfleth E, Ulrich C, Wojnarowska FT, Lin HY, Balch C, Harwood CA: Melanoma in organ transplant recipients: clinicopathological features and outcome in 100 cases. Am J Transplant 2008;8:1891-1900.
48.
Kanitakis J, Baldassini S, Lora V, Euvrard S: BRAF mutations in melanocytic tumors (nevi and melanomas) from organ transplant recipients. Eur J Dermatol 2010;20:167-171.
49.
Beynet DP, Wee SA, Horwitz SS, Kohler S, Horning S, Hoppe R, Kim YH: Clinical and pathological features of posttransplantation lymphoproliferative disorders presenting with skin involvement in 4 patients. Arch Dermatol 2004;140:1140-1146.
50.
Swerdlow SH, Webber SA, Chadburn A, Ferry JA: Post-transplant lymphoproliferative disorders; in Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, IARC, 2008, pp 343-349.
51.
Yurtsever H, Kempf W, Laeng RH: Posttransplant CD30+ anaplastic large cell lymphoma with skin and lymph node involvement. Dermatology 2003;207:107-110.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.