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Skin Cancers Associated with Lymphoid Malignancies

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Skin Diseases in the Immunosuppressed

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Abstract

Lymphoid malignancies, in particular chronic lymphocytic leukemia/small cell lymphoma, are associated with an increased rate of secondary malignancy development. Skin cancers can occur eightfold more often in the setting of chronic lymphocytic leukemia/small cell lymphoma. Not only does cutaneous malignancy occur more often in the setting of lymphoid malignancies, these skin cancers have a tendency toward a more aggressive nature, with higher recurrence rates and increased metastatic potential, especially with squamous cell carcinoma and malignant melanoma. In fact, melanoma is found to occur anywhere from two to six times more often in patients with lymphoma, and in patients with a prior history of chronic lymphocytic leukemia, there is a 2.8 times higher chance of death due to metastatic melanoma. Merkel cell carcinoma also occurs more often in patients with lymphoid malignancies and is associated with a 3.8 times higher chance of death due to metastatic Merkel cell carcinoma in patients with a prior history of chronic lymphocytic leukemia.

Other rare forms of skin cancer have also been observed to have a higher chance of bad outcomes. In particular, malignant fibrous histiocytoma has a higher chance of metastasizing in patients with chronic lymphocytic leukemia.

Patients with lymphoid malignancies should sun protect on a regular basis, see a dermatologist for regular skin examinations, perform self-skin examinations, and receive education regarding skin cancer. When skin cancers occur in patients with lymphoid malignancies, a prompt treatment strategy in a multi-collaborative nature when necessary should be undertaken to provide the lowest chance of recurrence and bad outcomes.

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Abbreviations

AFX:

Atypical fibroxanthoma

BCC:

Basal cell carcinoma

B-CLL:

B-cell chronic lymphocytic leukemia

CLL:

Chronic lymphocytic leukemia

IL:

Interleukin

MCC:

Merkel cell carcinoma

MCPyV:

Merkel cell polyomavirus

MFH:

Malignant fibrous histiocytoma

MM:

Malignant melanoma

NHL:

Non-Hodgkin lymphoma

NMSC:

Nonmelanoma skin cancer

SCC:

Squamous cell carcinoma

SLL:

Small lymphocytic lymphoma

References

  1. Mehrany K, Weenig RH, Pittelkow MR, Roenigk RK, Otley CC. High recurrence rates of basal cell carcinoma after Mohs surgery in patients with chronic lymphocytic leukemia. Arch Dermatol. 2004;140(8):985–8.

    Article  PubMed  Google Scholar 

  2. Adami J, Frisch M, Yuen J, Glimelius B, Melbye M. Evidence of an association between non-Hodgkin’s lymphoma and skin cancer. BMJ. 1995;310(6993):1491–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5):277–300. Epub 2010 Jul 7. Erratum in: CA Cancer J Clin. 2011 Mar-Apr;61(2):133–4.

    Article  PubMed  Google Scholar 

  4. Otley CC. Non-Hodgkin lymphoma and skin cancer: a dangerous combination. Australas J Dermatol. 2006;47(4):231–6.

    Article  PubMed  Google Scholar 

  5. Rozman C, Montserrat E. Chronic lymphocytic leukemia. N Engl J Med. 1995;333(16):1052–7. Erratum in: N Engl J Med 1995 Nov 30;333(22):1515.

    Article  CAS  PubMed  Google Scholar 

  6. Ghia P, Ferreri AM, Caligaris-Cappio F. Chronic lymphocytic leukemia. Crit Rev Oncol Hematol. 2007;64(3):234–46. Epub 2007 Jun 1.

    Article  PubMed  Google Scholar 

  7. Kubica AW, Rose PS, Weaver AL, Brewer JD. Increased metastasis of malignant fibrous histiocytoma in patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma. Mayo Clin Proc. 2011;86(8):738–43.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Montserrat E, Moreno C. Chronic lymphocytic leukaemia: a short overview. Ann Oncol. 2008;19(Suppl 7):vii320–5.

    PubMed  Google Scholar 

  9. Plaza JA, Comfere NI, Gibson LE, Colgan M, Davis DM, Pittelkow MR, et al. Unusual cutaneous manifestations of B-cell chronic lymphocytic leukemia. J Am Acad Dermatol. 2009;60(5):772–80.

    Article  PubMed  Google Scholar 

  10. Cerroni L, Zenahlik P, Hofler G, Kaddu S, Smolle J, Kerl H. Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia: a clinicopathologic and prognostic study of 42 patients. Am J Surg Pathol. 1996;20(8):1000–10.

    Article  CAS  PubMed  Google Scholar 

  11. Padgett JK, Parlette HL III, English JC III. A diagnosis of chronic lymphocytic leukemia prompted by cutaneous lymphocytic infiltrates present in Mohs micrographic surgery frozen sections. Dermatol Surg. 2003;29(7):769–71.

    PubMed  Google Scholar 

  12. Khandelwal A, Seilstad KH, Magro CM. Subclinical chronic lymphocytic leukaemia associated with a 13q deletion presenting initially in the skin: apropos of a case. J Cutan Pathol. 2006;33(3):256–9.

    Article  PubMed  Google Scholar 

  13. Hallek M. New concepts in the pathogenesis, diagnosis, prognostic factors and clinical presentation of chronic lymphocytic leukemia. Rev Clin Exp Hematol. 2000;4(2):103–17.

    Article  Google Scholar 

  14. Giles FJ, O’Brien SM, Keating MJ. Chronic lymphocytic leukemia in (Richter’s) transformation. Semin Oncol. 1998;25(1):117–25.

    CAS  PubMed  Google Scholar 

  15. Hoyer JD, Ross CW, Li CY, Witzig TE, Gascoyne RD, Dewald GW, et al. True T-cell chronic lymphocytic leukemia: a morphologic and immunophenotypic study of 25 cases. Blood. 1995;86(3):1163–9.

    CAS  PubMed  Google Scholar 

  16. Robak E, Robak T. Skin lesions in chronic lymphocytic leukemia. Leuk Lymphoma. 2007;48(5):855–65.

    Article  PubMed  Google Scholar 

  17. Agnew KL, Ruchlemer R, Catovsky D, Matutes E, Bunker CB. Cutaneous findings in chronic lymphocytic leukaemia. Br J Dermatol. 2004;150(6):1129–35.

    Article  CAS  PubMed  Google Scholar 

  18. Landgren O, Pfeiffer RM, Stewart L, Gridley G, Mellemkjaer L, Hemminki K, et al. Risk of second malignant neoplasms among lymphoma patients with a family history of cancer. Int J Cancer. 2007;120(5):1099–102.

    Article  CAS  PubMed  Google Scholar 

  19. Kyasa MJ, Hazlett L, Parrish RS, Schichman SA, Zent CS. Veterans with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have a markedly increased rate of second malignancy, which is the most common cause of death. Leuk Lymphoma. 2004;45(3):507–13.

    Article  PubMed  Google Scholar 

  20. Mellemgaard A, Geisler CH, Storm HH. Risk of kidney cancer and other second solid malignancies in patients with chronic lymphocytic leukemia. Eur J Haematol. 1994;53(4):218–22.

    Article  CAS  PubMed  Google Scholar 

  21. Travis LB, Curtis RE, Hankey BF, Fraumeni JF Jr. Second cancers in patients with chronic lymphocytic leukemia. J Natl Cancer Inst. 1992;84(18):1422–7.

    Article  CAS  PubMed  Google Scholar 

  22. Manusow D, Weinerman BH. Subsequent neoplasia in chronic lymphocytic leukemia. JAMA. 1975;232(3):267–9.

    Article  CAS  PubMed  Google Scholar 

  23. Royle JA, Baade PD, Joske D, Girschik J, Fritschi L. Second cancer incidence and cancer mortality among chronic lymphocytic leukaemia patients: a population-based study. Br J Cancer. 2011;105(7):1076–81. https://doi.org/10.1038/bjc.2011.313. Epub 2011 Aug 16.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Tsimberidou AM, Wen S, McLaughlin P, O’Brien S, Wierda WG, Lerner S, et al. Other malignancies in chronic lymphocytic leukemia/small lymphocytic lymphoma. J Clin Oncol. 2009;27(6):904–10. Epub 2008 Dec 29.

    Article  PubMed  Google Scholar 

  25. Mehrany K, Weenig RH, Pittelkow MR, Roenigk RK, Otley CC. High recurrence rates of squamous cell carcinoma after Mohs’ surgery in patients with chronic lymphocytic leukemia. Dermatol Surg. 2005;31(1):38–42.

    Article  CAS  PubMed  Google Scholar 

  26. Cottoni F, Masia IM, Cossu S, Montesu MA, Pardini S, Massarelli G. Classical Kaposi’s sarcoma and chronic lymphocytic leukaemia in the same skin biopsy: report of two cases. Br J Dermatol. 1998;139(4):753–4.

    Article  CAS  PubMed  Google Scholar 

  27. Kemp JD, Stenn KS, Arons M, Fischer J. Metastasizing atypical fibroxanthoma: coexistence with chronic lymphocytic leukemia. Arch Dermatol. 1978;114(10):1533–5.

    Article  CAS  PubMed  Google Scholar 

  28. Carroll P, Goldstein GD, Brown CW Jr. Metastatic microcystic adnexal carcinoma in an immunocompromised patient. Dermatol Surg. 2000;26(6):531–4.

    Article  CAS  PubMed  Google Scholar 

  29. Warakaulle DR, Rytina E, Burrows NP. Merkel cell tumour associated with chronic lymphocytic leukaemia. Br J Dermatol. 2001;144(1):216–7.

    Article  CAS  PubMed  Google Scholar 

  30. Vlad R, Woodlock TJ. Merkel cell carcinoma after chronic lymphocytic leukemia: case report and literature review. Am J Clin Oncol. 2003;26(6):531–4.

    Article  PubMed  Google Scholar 

  31. Liegl B, Leibl S, Okcu M, Beham-Schmid C, Regauer S. Malignant transformation within benign adnexal skin tumours. Histopathology. 2004;45(2):162–70.

    Article  CAS  PubMed  Google Scholar 

  32. Levi F, Randimbison L, Te VC, La Vecchia C. Non-Hodgkin’s lymphomas, chronic lymphocytic leukaemias and skin cancers. Br J Cancer. 1996;74(11):1847–50.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Greene MH, Hoover RN, Fraumeni JF Jr. Subsequent cancer in patients with chronic lymphocytic leukemia: a possible immunologic mechanism. J Natl Cancer Inst. 1978;61(2):337–40.

    CAS  PubMed  Google Scholar 

  34. Brewer JD, Shanafelt TD, Otley CC, Roenigk RK, Cerhan JR, Kay NE, et al. Chronic lymphocytic leukemia is associated with decreased survival of patients with malignant melanoma and Merkel cell carcinoma in a SEER population-based study. J Clin Oncol. 2012;30(8):843–9. Epub 2012 Feb 13.

    Article  PubMed  Google Scholar 

  35. Levine PH, Hoover R. The emerging epidemic of non-Hodgkin’s lymphoma: current knowledge regarding etiological factors. Cancer Epidemiol Biomark Prev. 1992;1(6):515–7.

    CAS  Google Scholar 

  36. Aslakson CJ, Lee G, Boomer JS, Gilman-Sachs A, Kucuk O, Beaman KD. Expression of regeneration and tolerance factor on B cell chronic lymphocytic leukemias: a possible mechanism for escaping immune surveillance. Am J Hematol. 1999;61(1):46–52.

    Article  CAS  PubMed  Google Scholar 

  37. Cantwell M, Hua T, Pappas J, Kipps TJ. Acquired CD40-ligand deficiency in chronic lymphocytic leukemia. Nat Med. 1997;3(9):984–9.

    Article  CAS  PubMed  Google Scholar 

  38. Lacombe C, Gombert J, Dreyfus B, Brizard A, Preud’Homme JL. Heterogeneity of serum IgG subclass deficiencies in B chronic lymphocytic leukemia. Clin Immunol. 1999;90(1):128–32.

    Article  CAS  PubMed  Google Scholar 

  39. Kipps TJ. Chronic lymphocytic leukemia. Curr Opin Hematol. 2000;7(4):223–34.

    Article  CAS  PubMed  Google Scholar 

  40. Brewer JD, Christenson LJ, Weenig RH, Weaver AL. Effects of chronic lymphocytic leukemia on the development and progression of malignant melanoma. Dermatol Surg. 2010;36(3):368–76. Epub 2010 Jan 19.

    Article  CAS  PubMed  Google Scholar 

  41. Molica S. Second neoplasms in chronic lymphocytic leukemia: incidence and pathogenesis with emphasis on the role of different therapies. Leuk Lymphoma. 2005;46(1):49–54.

    Article  PubMed  Google Scholar 

  42. Hampton T. Skin cancer’s ranks rise: immunosuppression to blame. JAMA. 2005;294(12):1476–80.

    Article  CAS  PubMed  Google Scholar 

  43. Jensen P, Hansen S, Moller B, Leivestad T, Pfeffer P, Geiran O, 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):177–86.

    Article  CAS  PubMed  Google Scholar 

  44. Wiernik PH. Second neoplasms in patients with chronic lymphocytic leukemia. Curr Treat Options in Oncol. 2004;5(3):215–23.

    Article  Google Scholar 

  45. Hamblin AD, Hamblin TJ. The immunodeficiency of chronic lymphocytic leukaemia. Br Med Bull. 2008;87:49–62. Epub 2008 Aug 27.

    Article  CAS  PubMed  Google Scholar 

  46. Hu S, Federman DG, Ma F, Kirsner RS. Skin cancer and non-Hodgkin’s lymphoma: examining the link. Dermatol Surg. 2005;31(1):76–82.

    Article  CAS  PubMed  Google Scholar 

  47. McIntosh BC, Ariyan S, Esche G, Zelterman D, Narayan D. Metachronous primary melanoma and lymphoma. Ann Plast Surg. 2010;64(2):229–32.

    Article  CAS  PubMed  Google Scholar 

  48. Tsao H, Atkins MB, Sober AJ. Management of cutaneous melanoma. N Engl J Med. 2004;351(10):998–1012. Erratum in: N Engl J Med. 2004 Dec 2;351(23):2461.

    Article  CAS  PubMed  Google Scholar 

  49. Boffetta P, van der Hel O, Kricker A, Nieters A, de Sanjose S, Maynadie M, et al. Exposure to ultraviolet radiation and risk of malignant lymphoma and multiple myeloma: a multicentre European case-control study. Int J Epidemiol. 2008;37(5):1080–94. Epub 2008 May 29.

    Article  PubMed  Google Scholar 

  50. Kricker A, Armstrong BK, Hughes AM, Goumas C, Smedby KE, Zheng T, et al; Interlymph Consortium. Personal sun exposure and risk of non Hodgkin lymphoma: a pooled analysis from the Interlymph Consortium. Int J Cancer. 2008;122(1):144–54.

    Google Scholar 

  51. Hughes AM, Armstrong BK, Vajdic CM, Turner J, Grulich AE, Fritschi L, et al. Sun exposure may protect against non-Hodgkin lymphoma: a case-control study. Int J Cancer. 2004;112(5):865–71.

    Article  CAS  PubMed  Google Scholar 

  52. McMichael AJ, Giles GG. Have increases in solar ultraviolet exposure contributed to the rise in incidence of non-Hodgkin’s lymphoma? Br J Cancer. 1996;73(7):945–50.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Girschik J, Fritschi L, Threlfall T, Slevin T. Deaths from non-melanoma skin cancer in Western Australia. Cancer Causes Control. 2008;19(8):879–85. Epub 2008 Apr 2.

    Article  CAS  PubMed  Google Scholar 

  54. Mehrany K, Byrd DR, Roenigk RK, Weenig RH, Phillips PK, Nguyen TH, et al. Lymphocytic infiltrates and subclinical epithelial tumor extension in patients with chronic leukemia and solid-organ transplantation. Dermatol Surg. 2003;29(2):129–34.

    PubMed  Google Scholar 

  55. Martinez JC, Otley CC, Stasko T, Euvrard S, Brown C, Schanbacher CF, et al; Transplant-Skin Cancer Collaborative. Defining the clinical course of metastatic skin cancer in organ transplant recipients: a multicenter collaborative study. Arch Dermatol. 2003;139(3):301–6.

    Google Scholar 

  56. Kim J, Modlin RL, Moy RL, Dubinett SM, McHugh T, Nickoloff BJ, et al. IL-10 production in cutaneous basal and squamous cell carcinomas: a mechanism for evading the local T cell immune response. J Immunol. 1995;155(4):2240–7.

    CAS  PubMed  Google Scholar 

  57. Wong DA, Bishop GA, Lowes MA, Cooke B, Barnetson RS, Halliday GM. Cytokine profiles in spontaneously regressing basal cell carcinomas. Br J Dermatol. 2000;143(1):91–8.

    Article  CAS  PubMed  Google Scholar 

  58. Berhane T, Halliday GM, Cooke B, Barnetson RS. Inflammation is associated with progression of actinic keratoses to squamous cell carcinomas in humans. Br J Dermatol. 2002;146(5):810–5.

    Article  CAS  PubMed  Google Scholar 

  59. Byrne SN, Halliday GM. High levels of Fas ligand and MHC class II in the absence of CD80 or CD86 expression and a decreased CD4+ T cell infiltration, enables murine skin tumours to progress. Cancer Immunol Immunother. 2003;52(6):396–402. Epub 2003 Mar 5.

    CAS  PubMed  Google Scholar 

  60. Daniel D, Meyer-Morse N, Bergsland EK, Dehne K, Coussens LM, Hanahan D. Immune enhancement of skin carcinogenesis by CD4+ T cells. J Exp Med. 2003;197(8):1017–28. Epub 2003 Apr 14.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Martinez JC, Otley CC. The management of melanoma and nonmelanoma skin cancer: a review for the primary care physician. Mayo Clin Proc. 2001;76(12):1253–65.

    Article  CAS  PubMed  Google Scholar 

  62. Swanson NA. Mohs surgery: technique, indications, applications, and the future. Arch Dermatol. 1983;119(9):761–73.

    Article  CAS  PubMed  Google Scholar 

  63. Mehrany K, Weenig RH, Lee KK, Pittelkow MR, Otley CC. Increased metastasis and mortality from cutaneous squamous cell carcinoma in patients with chronic lymphocytic leukemia. J Am Acad Dermatol. 2005;53(6):1067–71.

    Article  PubMed  Google Scholar 

  64. Rohr LR, Layfield LJ, Wallin D, Hardy D. A comparison of routine and rapid microwave tissue processing in a surgical pathology laboratory: quality of histologic sections and advantages of microwave processing. Am J Clin Pathol. 2001;115(5):703–8.

    Article  CAS  PubMed  Google Scholar 

  65. Zachary CB, Rest EB, Furlong SM, Arcedo PN, McGeorge BC, Kist DA. Rapid cytokeratin stains enhance the sensitivity of Mohs micrographic surgery for squamous cell carcinoma. J Dermatol Surg Oncol. 1994;20(8):530–5.

    Article  CAS  PubMed  Google Scholar 

  66. Shimm DS, Wilder RB. Radiation therapy for squamous cell carcinoma of the skin. Am J Clin Oncol. 1991;14(5):383–6.

    Article  CAS  PubMed  Google Scholar 

  67. Wagner JD, Evdokimow DZ, Weisberger E, Moore D, Chuang TY, Wenck S, et al. Sentinel node biopsy for high-risk nonmelanoma cutaneous malignancy. Arch Dermatol. 2004;140(1):75–9.

    Article  PubMed  Google Scholar 

  68. Belloni-Fortina A, Piaserico S, Tonin E, Alaibac M. Melanoma and immunosuppression. Dermatology. 2009;218(1):88. Epub 2008 Oct 2.

    Article  PubMed  Google Scholar 

  69. Clemente CG, Mihm MC Jr, Bufalino R, Zurrida S, Collini P, Cascinelli N. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 1996;77(7):1303–1310.

    Google Scholar 

  70. Marshall JA, Forster TH, Purdie DM, Lanagan CM, O’Connor LE, O’Rourke MG, et al. Immunological characteristics correlating with clinical response to immunotherapy in patients with advanced metastatic melanoma. Immunol Cell Biol. 2006;84(3):295–302.

    Article  CAS  PubMed  Google Scholar 

  71. Menzies SW, McCarthy WH. Complete regression of primary cutaneous malignant melanoma. Arch Surg. 1997;132(5):553–6.

    Article  CAS  PubMed  Google Scholar 

  72. Kubica AW, Brewer JD. Melanoma in immunosuppressed patients. Mayo Clin Proc. 2012;87(10):991–1003.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Zhang QJ, Seipp RP, Chen SS, Vitalis TZ, Li XL, Choi KB, et al. TAP expression reduces IL-10 expressing tumor infiltrating lymphocytes and restores immunosurveillance against melanoma. Int J Cancer. 2007;120(9):1935–41.

    Article  CAS  PubMed  Google Scholar 

  74. Zwald FO, Christenson LJ, Billingsley EM, Zeitouni NC, Ratner D, Bordeaux J, et al; Melanoma Working Group of The International Transplant Skin Cancer Collaborative and Skin Care in Organ Transplant Patients, Europe. Melanoma in solid organ transplant recipients. Am J Transplant. 2010;10(5):1297–304. Epub 2010 Mar 26.

    Google Scholar 

  75. Koh HK. Cutaneous melanoma. N Engl J Med. 1991;325(3):171–82.

    Article  CAS  PubMed  Google Scholar 

  76. Brewer JD, Habermann TM, Shanafelt TD. Lymphoma-associated skin cancer: incidence, natural history, and clinical management. Int J Dermatol. 2014;53(3):267–74. https://doi.org/10.1111/ijd.12208. Epub 2013 Dec 10.

    Article  PubMed  Google Scholar 

  77. McKenna DB, Stockton D, Brewster DH, Doherty VR. Evidence for an association between cutaneous malignant melanoma and lymphoid malignancy: a population-based retrospective cohort study in Scotland. Br J Cancer. 2003;88(1):74–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Baumgartner J, Wilson C, Palmer B, Richter D, Banerjee A, McCarter M. Melanoma induces immunosuppression by up-regulating FOXP3(+) regulatory T cells. J Surg Res. 2007;141(1):72–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Javia LR, Rosenberg SA. CD4+CD25+ suppressor lymphocytes in the circulation of patients immunized against melanoma antigens. J Immunother. 2003;26(1):85–93.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Viguier M, Lemaitre F, Verola O, Cho MS, Gorochov G, Dubertret L, et al. Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J Immunol. 2004;173(2):1444–53.

    Article  CAS  PubMed  Google Scholar 

  81. Wolchok JD, Saenger Y. The mechanism of anti-CTLA-4 activity and the negative regulation of T-cell activation. Oncologist. 2008;13(Suppl 4):2–9.

    Article  CAS  PubMed  Google Scholar 

  82. McCarter MD, Baumgartner J, Escobar GA, Richter D, Lewis K, Robinson W, et al. Immunosuppressive dendritic and regulatory T cells are upregulated in melanoma patients. Ann Surg Oncol. 2007;14(10):2854–60. Epub 2007 Jun 26.

    Article  PubMed  Google Scholar 

  83. Boon T, Coulie PG, Van den Eynde B. Tumor antigens recognized by T cells. Immunol Today. 1997;18(6):267–8.

    Article  CAS  PubMed  Google Scholar 

  84. Romero P, Dunbar PR, Valmori D, Pittet M, Ogg GS, Rimoldi D, et al. Ex vivo staining of metastatic lymph nodes by class I major histocompatibility complex tetramers reveals high numbers of antigen-experienced tumor-specific cytolytic T lymphocytes. J Exp Med. 1998;188(9):1641–50.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  85. Grover R, Wilson GD. Bcl-2 expression in malignant melanoma and its prognostic significance. Eur J Surg Oncol. 1996;22(4):347–9.

    Article  CAS  PubMed  Google Scholar 

  86. Lones MA, Pinkus GS, Shintaku IP, Said JW. Bcl-2 oncogene protein is preferentially expressed in Reed-Sternberg cells in Hodgkin’s disease of the nodular sclerosis subtype. Am J Clin Pathol. 1994;102(4):464–7.

    Article  CAS  PubMed  Google Scholar 

  87. Said JW, Pinkus GS, Lones MA, et al. Expression of bcl-2 oncogene protein in malignant lymphomas, including Hodgkin’s disease and non-Hodgkin’s lymphomas of T-cell phenotype. Appl Immunohistochem. 1993;1:108–14.

    CAS  Google Scholar 

  88. Thomadaki H, Scorilas A. BCL2 family of apoptosis-related genes: functions and clinical implications in cancer. Crit Rev Clin Lab Sci. 2006;43(1):1–67.

    Article  CAS  PubMed  Google Scholar 

  89. Efeyan A, Serrano M. p53: guardian of the genome and policeman of the oncogenes. Cell Cycle. 2007;6(9):1006–10. Epub 2007 May 28.

    Article  CAS  PubMed  Google Scholar 

  90. Coll-Mulet L, Gil J. Genetic alterations in chronic lymphocytic leukaemia. Clin Transl Oncol. 2009;11(4):194–8.

    Article  CAS  PubMed  Google Scholar 

  91. Paulson KG, Iyer JG, Blom A, Warton EM, Sokil M, Yelistratova L, et al. Systemic immune suppression predicts diminished Merkel cell carcinoma-specific survival independent of stage. J Invest Dermatol. 2013;133(3):642–6. Epub 2012 Nov 29.

    Article  CAS  PubMed  Google Scholar 

  92. Penn I, First MR. Merkel’s cell carcinoma in organ recipients: report of 41 cases. Transplantation. 1999;68(11):1717–21.

    Article  CAS  PubMed  Google Scholar 

  93. Frankenthaler A, Sullivan RJ, Wang W, Renzi S, Seery V, Lee MY, et al. Impact of concomitant immunosuppression on the presentation and prognosis of patients with melanoma. Melanoma Res. 2010;20(6):496–500.

    Article  CAS  PubMed  Google Scholar 

  94. Matin RN, Mesher D, Proby CM, McGregor JM, Bouwes Bavinck JN, del Marmol V, et al; Skin Care in Organ Transplant Patients, Europe (SCOPE) group. Melanoma in organ transplant recipients: clinicopathological features and outcome in 100 cases. Am J Transplant. 2008;8(9):1891–900.

    Google Scholar 

  95. Heath M, Jaimes N, Lemos B, Mostaghimi A, Wang LC, Penas PF, et al. Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. J Am Acad Dermatol. 2008;58(3):375–81.

    Article  PubMed Central  PubMed  Google Scholar 

  96. Szeder V, Grim M, Halata Z, Sieber-Blum M. Neural crest origin of mammalian Merkel cells. Dev Biol. 2003;253(2):258–63.

    Article  CAS  PubMed  Google Scholar 

  97. Morrison KM, Miesegaes GR, Lumpkin EA, Maricich SM. Mammalian Merkel cells are descended from the epidermal lineage. Dev Biol. 2009;336(1):76–83. Epub 2009 Sep 25.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  98. Bichakjian CK, Lowe L, Lao CD, Sandler HM, Bradford CR, Johnson TM, et al. Merkel cell carcinoma: critical review with guidelines for multidisciplinary management. Cancer. 2007;110(1):1):1–12.

    Article  PubMed  Google Scholar 

  99. Poulsen M. Merkel-cell carcinoma of the skin. Lancet Oncol. 2004;5(10):593–9.

    Article  PubMed  Google Scholar 

  100. Moll R, Lowe A, Laufer J, Franke WW. Cytokeratin 20 in human carcinomas: a new histodiagnostic marker detected by monoclonal antibodies. Am J Pathol. 1992;140(2):427–47.

    CAS  PubMed Central  PubMed  Google Scholar 

  101. Halata Z, Grim M, Bauman KI. Friedrich Sigmund Merkel and his “Merkel cell”, morphology, development, and physiology: review and new results. Anat Rec A Discov Mol Cell Evol Biol. 2003;271(1):225–39.

    Article  PubMed  Google Scholar 

  102. Erovic I, Erovic BM. Merkel cell carcinoma: the past, the present, and the future. J Skin Cancer. 2013;2013:929364. Epub 2013 Apr 16.

    Article  PubMed Central  PubMed  Google Scholar 

  103. An KP, Ratner D. Merkel cell carcinoma in the setting of HIV infection. J Am Acad Dermatol. 2001;45(2):309–12.

    Article  CAS  PubMed  Google Scholar 

  104. Engels EA, Frisch M, Goedert JJ, Biggar RJ, Miller RW. Merkel cell carcinoma and HIV infection. Lancet. 2002;359(9305):497–8.

    Article  PubMed  Google Scholar 

  105. Lanoy E, May M, Mocroft A, Phillip A, Justice A, Chene G, et al; Antiretroviral Therapy Cohort Collaboration (ART-CC). Prognosis of patients treated with cART from 36 months after initiation, according to current and previous CD4 cell count and plasma HIV-1 RNA measurements. AIDS. 2009;23(16):2199–208.

    Google Scholar 

  106. Lanoy E, Dores GM, Madeleine MM, Toro JR, Fraumeni JF Jr, Engels EA. Epidemiology of nonkeratinocytic skin cancers among persons with AIDS in the United States. AIDS. 2009;23(3):385–93.

    Article  PubMed Central  PubMed  Google Scholar 

  107. Muirhead R, Ritchie DM. Partial regression of Merkel cell carcinoma in response to withdrawal of azathioprine in an immunosuppression-induced case of metastatic Merkel cell carcinoma. Clin Oncol (R Coll Radiol). 2007;19(1):96.

    Article  CAS  Google Scholar 

  108. Urbatsch A, Sams WM Jr, Urist MM, Sturdivant R. Merkel cell carcinoma occurring in renal transplant patients. J Am Acad Dermatol. 1999;41(2 Pt 2):289–91.

    Article  CAS  PubMed  Google Scholar 

  109. Veness MJ. Aggressive skin cancers in a cardiac transplant recipient. Australas Radiol. 1997;41(4):363–6.

    Article  CAS  PubMed  Google Scholar 

  110. Kempf W, Mertz KD, Hofbauer GF, Tinguely M. Skin cancer in organ transplant recipients. Pathobiology. 2013;80(6):302–9. Epub 2013 Aug 30.

    Article  PubMed  Google Scholar 

  111. Ben-David A, Lazarov A, Lev S, Nussbaum B. Merkel cell tumor and chronic lymphocytic leukemia: coincidence or a possible association? Dermatol Online J. 2005;11(3):16.

    PubMed  Google Scholar 

  112. Koljonen V, Kukko H, Pukkala E, Sankila R, Bohling T, Tukiainen E, et al. Chronic lymphocytic leukaemia patients have a high risk of Merkel-cell polyomavirus DNA-positive Merkel-cell carcinoma. Br J Cancer. 2009;101(8):1444–7. Epub 2009 Sep 15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  113. Papageorgiou KI, Kaniorou-Larai MG. A case report of Merkel cell carcinoma on chronic lymphocytic leukemia: differential diagnosis of coexisting lymphadenopathy and indications for early aggressive treatment. BMC Cancer. 2005;5:106.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  114. Quaglino D, Di Leonardo G, Lalli G, Pasqualoni E, Di Simone S, Vecchio L, et al. Association between chronic lymphocytic leukaemia and secondary tumours: unusual occurrence of a neuroendocrine (Merkell cell) carcinoma. Eur Rev Med Pharmacol Sci. 1997;1(1–3):11–6.

    CAS  PubMed  Google Scholar 

  115. Tadmor T, Aviv A, Polliack A. Merkel cell carcinoma, chronic lymphocytic leukemia and other lymphoproliferative disorders: an old bond with possible new viral ties. Ann Oncol. 2011;22(2):250–6. Epub 2010 Jun 29.

    Article  CAS  PubMed  Google Scholar 

  116. Nakamura T, Sato Y, Watanabe D, Ito H, Shimonohara N, Tsuji T, et al. Nuclear localization of Merkel cell polyomavirus large T antigen in Merkel cell carcinoma. Virology. 2010;398(2):273–9. Epub 2010 Jan 13.

    Article  CAS  PubMed  Google Scholar 

  117. Gandhi RK, Rosenberg AS, Somach SC. Merkel cell polyomavirus: an update. J Cutan Pathol. 2009;36(12):1327–9.

    Article  PubMed  Google Scholar 

  118. Bergstrom KG. A polyomavirus may cause Merkel cell carcinoma: implications for immunosuppressed states and viral reactivation. J Drugs Dermatol. 2008;7(11):1104–5.

    PubMed  Google Scholar 

  119. Pantulu ND, Pallasch CP, Kurz AK, Kassem A, Frenzel L, Sodenkamp S, et al. Detection of a novel truncating Merkel cell polyomavirus large T antigen deletion in chronic lymphocytic leukemia cells. Blood. 2010;116(24):5280–4. Epub 2010 Sep 3.

    Article  CAS  PubMed  Google Scholar 

  120. Andres C, Puchta U, Sander CA, Ruzicka T, Flaig MJ. Prevalence of Merkel cell polyomavirus DNA in cutaneous lymphomas, pseudolymphomas, and inflammatory skin diseases. Am J Dermatopathol. 2010;32(6):593–8.

    Article  PubMed  Google Scholar 

  121. Dreno B. Skin cancers after transplantation. Nephrol Dial Transplant. 2003;18(6):1052–8.

    Article  PubMed  Google Scholar 

  122. Bichakjian CK, Alam M, Andersen J, Berg D, Bowen G, Cheney RT, et al. NCCN clinical practice guidelines in oncology: Merkel cell carcinoma [Internet]. Version 2.2013, 26 Jul 2013. National Comprehensive Cancer Network; c2013 [cited 9 Sept 2013]. http://www.nccn.org/.

  123. Boyer JD, Zitelli JA, Brodland DG, D’Angelo G. Local control of primary Merkel cell carcinoma: review of 45 cases treated with Mohs micrographic surgery with and without adjuvant radiation. J Am Acad Dermatol. 2002;47(6):885–92.

    Article  PubMed  Google Scholar 

  124. Gollard R, Weber R, Kosty MP, Greenway HT, Massullo V, Humberson C. Merkel cell carcinoma: review of 22 cases with surgical, pathologic, and therapeutic considerations. Cancer. 2000;88(8):1842–51.

    Article  CAS  PubMed  Google Scholar 

  125. Catalano O, Catalano G, Nunziata A. [The echographic and computed radiographic findings in 2 cases of Merkel-cell carcinoma]. Radiol Med. 1997;94(5):529–30. Italian.

    Google Scholar 

  126. Peloschek P, Novotny C, Mueller-Mang C, Weber M, Sailer J, Dawid M, et al. Diagnostic imaging in Merkel cell carcinoma: lessons to learn from 16 cases with correlation of sonography, CT, MRI and PET. Eur J Radiol. 2010;73(2):317–23. Epub 2008 Dec 23.

    Article  PubMed  Google Scholar 

  127. Tarantola TI, Vallow LA, Halyard MY, Weenig RH, Warschaw KE, Grotz TE, et al. Prognostic factors in Merkel cell carcinoma: analysis of 240 cases. J Am Acad Dermatol. 2013;68(3):425–32. Epub 2012 Nov 27.

    Article  PubMed  Google Scholar 

  128. Loyo M, Schussel J, Colantuoni E, Califano J, Brait M, Kang S, et al. Detection of Merkel cell virus and correlation with histologic presence of Merkel cell carcinoma in sentinel lymph nodes. Br J Cancer. 2012;106(7):1314–9. Epub 2012 Mar 13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  129. Kumar RV, Mukherjee G, Bhargava MK. Malignant fibrous histiocytoma of bone. J Surg Oncol. 1990;44(3):166–70.

    Article  CAS  PubMed  Google Scholar 

  130. Rooser B, Willen H, Gustafson P, Alvegard TA, Rydholm A. Malignant fibrous histiocytoma of soft tissue: a population-based epidemiologic and prognostic study of 137 patients. Cancer. 1991;67(2):499–505.

    Article  CAS  PubMed  Google Scholar 

  131. Stein A, Hackert I, Sebastian G, Meurer M. Cutaneous malignant fibrous histiocytoma of the scalp in a renal transplant recipient. Br J Dermatol. 2006;154(1):183–5.

    Article  CAS  PubMed  Google Scholar 

  132. Shinjo K. Analysis of prognostic factors and chemotherapy of malignant fibrous histiocytoma of soft tissue: a preliminary report. Jpn J Clin Oncol. 1994;24(3):154–9.

    CAS  PubMed  Google Scholar 

  133. Pezzi CM, Rawlings MS Jr, Esgro JJ, Pollock RE, Romsdahl MM. Prognostic factors in 227 patients with malignant fibrous histiocytoma. Cancer. 1992;69(8):2098–103.

    Article  CAS  PubMed  Google Scholar 

  134. Nascimento AF, Raut CP. Diagnosis and management of pleomorphic sarcomas (so-called “MFH”) in adults. J Surg Oncol. 2008;97(4):330–9.

    Article  PubMed  Google Scholar 

  135. Zagars GK, Mullen JR, Pollack A. Malignant fibrous histiocytoma: outcome and prognostic factors following conservation surgery and radiotherapy. Int J Radiat Oncol Biol Phys. 1996;34(5):983–94.

    Article  CAS  PubMed  Google Scholar 

  136. Fangman WL, Cook JL. Postradiation sarcoma: case report and review of the potential complications of therapeutic ionizing radiation. Dermatol Surg. 2005;31(8 Pt 1):966–72.

    Article  CAS  PubMed  Google Scholar 

  137. Patel SR. Radiation-induced sarcoma. Curr Treat Options in Oncol. 2000;1(3):258–61.

    Article  CAS  Google Scholar 

  138. Weiss SW, Enzinger FM. Malignant fibrous histiocytoma: an analysis of 200 cases. Cancer. 1978;41(6):2250–66.

    Article  CAS  PubMed  Google Scholar 

  139. Oddou S, Vey N, Viens P, Bardou VJ, Faucher C, Stoppa AM, et al. Second neoplasms following high-dose chemotherapy and autologous stem cell transplantation for malignant lymphomas: a report of six cases in a cohort of 171 patients from a single institution. Leuk Lymphoma. 1998;31(1–2):187–94.

    Article  CAS  PubMed  Google Scholar 

  140. Skubitz KM, D’Adamo DR. Sarcoma. Mayo Clin Proc. 2007;82(11):1409–32.

    Article  CAS  PubMed  Google Scholar 

  141. Spanier SS, Enneking WF, Enriquez P. Primary malignant fibrous histiocytoma of bone. Cancer. 1975;36(6):2084–98.

    Article  CAS  PubMed  Google Scholar 

  142. Pisters PW, Harrison LB, Leung DH, Woodruff JM, Casper ES, Brennan MF. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol. 1996;14(3):859–68.

    Article  CAS  PubMed  Google Scholar 

  143. Rosenberg SA, Tepper J, Glatstein E, Costa J, Baker A, Brennan M, et al. The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg. 1982;196(3):305–15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  144. Yang JC, Chang AE, Baker AR, Sindelar WF, Danforth DN, Topalian SL, et al. Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol. 1998;16(1):197–203.

    Article  CAS  PubMed  Google Scholar 

  145. Colgan MB, Brewer JD, Weaver AL, Roenigk RK, Otley CC. Atypical fibroxanthoma in the setting of chronic lymphocytic leukemia and other non-Hodgkin lymphomas. Dermatol Surg. 2011;37(5):671–6. Epub 2011 Mar 29.

    Article  CAS  PubMed  Google Scholar 

  146. Helwig EB, May D. Atypical fibroxanthoma of the skin with metastasis. Cancer. 1986;57(2):368–76.

    Article  CAS  PubMed  Google Scholar 

  147. Wang YH, Zou ZJ, Liu L, Zhang LN, Fang C, Zhu DX, et al. Quantification of ZAP-70 mRNA by real-time PCR is a prognostic factor in chronic lymphocytic leukemia. J Cancer Res Clin Oncol. 2012;138(6):1011–7. Epub 2012 Feb 24.

    Article  CAS  PubMed  Google Scholar 

  148. Colombo M, Cutrona G, Reverberi D, Fabris S, Neri A, Fabbi M, et al. Intraclonal cell expansion and selection driven by B cell receptor in chronic lymphocytic leukemia. Mol Med. 2011;17(7–8):834–9. Epub 2011 Apr 28.

    CAS  PubMed Central  PubMed  Google Scholar 

  149. Nelson BP, Gupta R, Dewald GW, Paternoster SF, Rosen ST, Peterson LC. Chronic lymphocytic leukemia FISH panel: impact on diagnosis. Am J Clin Pathol. 2007;128(2):323–32.

    Article  PubMed  Google Scholar 

  150. Ooi T, Barnetson RS, Zhuang L, McKane S, Lee JH, Slade HB, et al. Imiquimod-induced regression of actinic keratosis is associated with infiltration by T lymphocytes and dendritic cells: a randomized controlled trial. Br J Dermatol. 2006;154(1):72–8.

    Article  CAS  PubMed  Google Scholar 

  151. Black HS. Influence of dietary factors on actinically-induced skin cancer. Mutat Res. 1998;422(1):185–90.

    Article  CAS  PubMed  Google Scholar 

  152. De Graaf YG, Euvrard S, Bouwes Bavinck JN. Systemic and topical retinoids in the management of skin cancer in organ transplant recipients. Dermatol Surg. 2004;30(4 Pt 2):656–61.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA

    Stanislav N. Tolkachjov M.D. & Jerry D. Brewer M.D.

  2. Mayo Clinic College of Medicine, Rochester, MN, USA

    Jerry D. Brewer M.D.

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  1. Stanislav N. Tolkachjov M.D.
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Correspondence to Jerry D. Brewer M.D. .

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  1. Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA

    Oscar R. Colegio

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Tolkachjov, S.N., Brewer, J.D. (2018). Skin Cancers Associated with Lymphoid Malignancies. In: Colegio, O. (eds) Skin Diseases in the Immunosuppressed. Springer, Cham. https://doi.org/10.1007/978-3-319-68790-2_7

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