Merkel Cell Skin Carcinoma
Authors:
K. Krejčí 1; J. Zadražil 1; T. Tichý 2; P. Horák 1; H. Ciferská 1; M. Hodulová 1; M. Zezulová 3; M. Zlevorová 3
Authors‘ workplace:
III. interní nefrologická, revmatologická a endokrinologická klinika FN a LF UP, Olomouc
1; Ústav patologie FN a LF UP, Olomouc
2; Onkologická klinika FN a LF UP, Olomouc
3
Published in:
Klin Onkol 2010; 23(4): 210-217
Category:
Reviews
Overview
Merkel cell carcinoma is a rare tumour of the skin. It affects predominantly elderly Caucasian males on sun‑ exposed areas of the skin. Distinctively more frequent and at significantly lower age, its incidence is higher in immunocompromised patients. In these patients we often observe the highly aggressive course of Merkel cell carcinoma and a fatal outcome. The incidence of Merkel cell carcinoma has been rising in recent years and is more dramatic than the increased incidence of cutaneous melanoma. More than one‑ third of Merkel cell carcinoma patients will die from this cancer, making it twice as lethal as melanoma. The malignant transformation of Merkel cells is currently thought to be related to an infection with Merkel cell polyomavirus. In the early stage the discreet clinical picture may be contrary to extensive microscopic invasion and this seemingly benign appearance can delay diagnosis or increase the risk of insufficient tumour excision. The diagnosis is definitely confirmed by histological evaluation and immunohistochemical tests. A typical feature is the tendency of Merkel cell carcinoma to frequent local recurrence and early metastasizing into regional lymph nodes with subsequent tumour generalization. The mainstay of therapy is radical excision of the tumour and adjuvant radiotherapy targeted at the site of primary incidence and local draining lymph nodes. The efficacy of different chemotherapy protocols in Merkel cell carcinoma is limited and the median survival rate is measured in months. In the future, prophylaxis with vaccination against Merkel cell polyomavirus will hopefully be possible in high‑risk patients, as well as therapeutic usage of antisense oligonucleotides or microRNAs, eventually complete Merkel cell carcinoma elimination by affecting the tumour suppressor gene Atonal homolog 1 expression. The staging of the tumour at time of diagnosis is the most important prognostic factor. In this respect, the importance of preventative skin inspection in high‑risk immunocompromised patients must be stressed and suitable therapy must be indicated in suspected lesions.
Key words:
Merkel cell carcinoma – diagnostic imaging – etiology – cancer staging – cell cycle – Merkel cell polyomavirus – therapy – prognosis
Sources
1. Toker C. Trabecular carcinoma of the skin. Arch Dermatol 1972; 105(1): 107– 110.
2. Van Keymeulen A, Mascre G, Youseff KK et al. Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis. J Cell Biol 2009; 187(1): 91– 100.
3. Mottl H, Abrahamová J. Nádor z Merkelových buněk u dvouleté dívky – kazuistika. Klin Onkol 1990; 3(1): 19– 21.
4. Schmid C, Beham A, Feichtinger J et al. Recurrent and subsequently metastasizing Merkel cell carcinoma in a 7‑year‑ old girl. Histopathology 1992; 20(5): 437– 439.
5. Hodgson NC. Merkel cell carcinoma: changing incidence trends. J Surg Oncol 2005; 89(1): 1– 4.
6. Becker JC, Schrama D, Houben R. Merkel cell carcinoma. Cell Mol Life Sci 2009; 66(1): 1– 8.
7. Weller K, Vetter‑ Kauzcok C, Kahler K et al. Guideline implementation in Merkel cell carcinoma: an example of a rare disease. Dtsch Arztebl 2006; 103(42): 2791– 2796.
8. Girschik J, Fritschi L, Threlfall T et al. Deaths from non‑melanoma skin cancer in Western Australia. Cancer Causes Control 2008; 19(8): 879– 885.
9. Pectasides D, Pectasides M, Economopoulos T. Merkel cell cancer of the skin. Ann Oncol 2006; 17(10): 1489– 1495.
10. Feng H, Shuda M, Chang Y et al. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008; 319(5866): 1096– 1100.
11. Medina‑ Franco H, Urist MM, Fiveash J et al. Multimodality treatment of Merkel cell carcinoma: case series and literature review of 1024 cases. Ann Surg Oncol 2001; 8(3): 204–20 8.
12. Tai PT, Yu E, Tonita J et al. Merkel Cell Carcinoma of the Skin. J Cutan Med Surg 2000; 4(4): 186– 196.
13. Helmbold P, Schröter S, Holzhausen HJ et al. Merkel cell carcinoma: a diagnostic and therapeutic challenge. Chirurg 2001; 72(4): 396– 401.
14. Warner TF, Uno H, Hafez GR et al. Merkel cells and Merkel cell tumors. Ultrastructure, immunocytochemistry and review of the literature. Cancer 1983; 52(2): 238– 245.
15. Smith DF, Messina JL, Perrott R et al. Clinical approach to neuroendocrine carcinoma of the skin (Merkel cell carcinoma). Cancer Control 2000; 7(1): 72– 83.
16. Brenner B, Sulkes A, Rakowsky E et al. Second neoplasms in patients with Merkel cell carcinoma. Cancer 2001; 91(7): 1358– 1362.
17. Boyle F, Pendlebury S, Bell D. Further insights into the natural history and management of primary cutaneous neuroendocrine (Merkel cell) carcinoma. Int J Radiat Oncol Biol Phys 1995; 31(2): 315– 323.
18. Iagaru A, Quon A, McDougall IR et al. Merkel cell carcinoma: Is there a role for 2- deoxy- 2- [f- 18]fluoro‑D‑ glucose‑positron emission tomography/ computed tomography? Mol Imaging Biol 2006; 8(4): 212– 217.
19. Concannon R, Larcos GS, Genese M. The impact of 18F‑ FDG PET‑ CT scanning for staging and management of Merkel cell carcinoma: Results from Westmead Hospital, Sydney, Australia. J Am Acad Dermatol 2010; 62(1): 76– 84.
20. Swick BL, Ravdel L, Fitzpatrick JE et al. Platelet‑ derived growth factor receptor alpha mutational status and immunohistochemical expression in Merkel cell carcinoma: implications for treatment with imatinib mesylate. J Cutan Pathol 2008; 35(2): 197– 202.
21. Swick BL, Ravdel L, Fitzpatrick JE et al. Merkel cell carcinoma: evaluation of KIT (CD117) expression and failure to demonstrate activating mutations in the C‑ KIT proto‑ oncogene – implications for treatment with imatinib mesylate. J Cutan Pathol 2007; 34(4): 324– 329.
22. Feinmesser M, Halpern M, Kaganovsky E et al. c‑ kit expression in primary and metastatic merkel cell carcinoma. Am J Dermatopathol 2004; 26(6): 458– 462.
23. Strong S, Shalders K, Carr R et al. KIT receptor (CD117) expression in Merkel cell carcinoma. Br J Dermatol 2004; 150(2): 384– 385.
24. Brunner M, Thurnher D, Pammer J et al. Expression of VEGF‑ A/ C, VEGF‑ R2, PDGF‑alpha/ beta, c‑ kit, EGFR, Her‑ 2/ Neu, Mcl‑ 1 and Bmi‑ 1 in Merkel cell carcinoma. Mod Pathol 2008; 21(7): 876– 884.
25. Feinmesser M, Halpern M, Fenig E et al. Expression of the apoptosis‑related oncogenes bcl‑ 2, bax, and p53 in Merkel cell carcinoma: Can they predict treatment response and clinical outcome? Hum Pathol 1999; 30(11): 1367– 1372.
26. Kennedy MM, Blessing K, King G et al. Expression of bcl‑ 2 and p53 in Merkel cell carcinoma. An immunohistochemical study. Am J Dermatopathol 1996; 18(3): 273– 277.
27. Kim J, McNiff JM. Nuclear expression of survivin portends a poor prognosis in Merkel cell carcinoma. Mod Pathol 2008; 21(6): 764– 769.
28. Horn HF, Vousden KH. Coping with stress: multiple ways to activate p53. Oncogene 2007; 26(9): 1306– 1316.
29. Popp S, Waltering S, Herbst C et al. UV‑ B‑type mutations and chromosomal imbalances indicate common pathways for the development of Merkel and skin squamous cell carcinomas. Int J Cancer 2002; 99(3): 352– 360.
30. Van Gele M, Kaghad M, Leonard JH et al. Mutation analysis of P73 and TP53 in Merkel cell carcinoma. Br J Cancer 2000; 82(4): 823– 826.
31. Asioli S, Righi A, Volante M et al. p63 expression as a new prognostic marker in Merkel cell carcinoma. Cancer 2007; 110(3): 640– 647.
32. Becker JC, Houben R, Ugurel S et al. MC polyomavirus is frequently present in Merkel cell carcinoma of European patients. J Invest Dermatol 2009; 129(1): 248– 250.
33. Garneski KM, Warcola AH, Feng Q et al. Merkel cell polyomavirus is more frequently present in North American than Australian Merkel cell carcinoma tumors. J Invest Dermatol 2009; 129(1): 246– 248.
34. Kassem A, Schöpflin A, Diaz C et al. Frequent Detection of Merkel Cell Polyomavirus in Human Merkel Cell Carcinomas and Identification of a Unique Deletion in the VP1 Gene. Cancer Res 2008; 68(13): 5009– 5013.
35. Krejčí K, Tichý T, Horák P et al. Merkel cell carcinoma of gluteal region with ipsilateral metastasis into the pancreatic graft in patient after combined kidney‑ pancreas transplantation. Odesláno k publikaci do časopisu Onkologie.
36. zur Hausen H. Novel human polyomaviruses – re‑emergence of a well known virus family as possible human carcinogens. Int J Cancer 2008; 123(2): 247– 250.
37. Moens U, Van Ghelue M, Johannessen M. Oncogenic potentials of the human polyomavirus regulatory proteins. Cell Mol Life Sci 2007; 64(13): 1656– 1678.
38. Caracciolo V, Reiss K, Khalili K et al. Role of the interaction between large T antigen and Rb family members in the oncogenicity of JC virus. Oncogene 2006; 25(38): 5294– 5301.
39. Kean JM, Rao S, Wang M et al. Seroepidemiology of human polyomaviruses. PLoS Pathos 2009; 5(3): Dostupné z: http:/ / www.plospathogens.org/ article/ info:doi%2F10.1371%2Fjournal.ppat.1000363.
40. Tolstov YL, Pastrana DV, Feng H et al. Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays. Int J Cancer 2009; 125(6): 1250– 1256.
41. Sihto H, Kukko H, Koljonen V et al. Clinical Factors Associated With Merkel Cell Polyomavirus Infection in Merkel Cell Carcinoma. J Natl Cancer Inst 2009; 101(23): 938– 945.
42. Lawenda BD, Thiringer JK, Foss RD et al. Merkel Cell Carcinoma Arising in the Head and Neck: Optimizing Therapy. Am J Clin Oncol 2001; 24(1): 35– 42.
43. Ullrich SE. Mechanisms underlying UV‑induced immune suppression. Mutat Res 2005; 571(1– 2): 185– 205.
44. Ullrich SE. Sunlight and Skin Cancer: Lessons from the Immune Systém. Mol Carcinog 2007; 46(8): 629– 633.
45. Buell JF, Trofe J, Hanaway MJ et al. Immunosuppression and Merkel cell cancer. Transplant Proc 2002; 34(5): 1780– 1781.
46. Koljonen V, Kukko H, Tukiainen E et al. Incidence of Merkel cell carcinoma in renal transplant recipients. Nephrol Dial Transplant 2009; 24(10): 3231– 3235.
47. Busse PM, Clark JR, Muse VV et al. Case records of the Massachusetts General Hospital. Case 19– 2008. A 63‑year‑ old HIV‑ positive man with cutaneous Merkel‑ cell carcinoma. N Engl J Med 2008; 358(25): 2717– 2723.
48. Veness MJ, Harris D. Role of radiotherapy in the management of organ transplant recipients diagnosed with non‑melanoma skin cancers. Australas Radiol 2007; 51(1): 12– 20.
49. Engels EA, Frisch M, Goedert JJ et al. Merkel cell carcinoma and HIV infection. Lancet 2002; 9305(359): 497– 498.
50. Engels EA, Biggar RJ, Hall HI et al. Cancer risk in people infected with human immunodeficiency virus in the United States. Int J Cancer 2008; 123(1): 187– 194.
51. Friedlaender MM, Rubinger D, Rosenbaum E et al. Temporary regression of Merkel cell carcinoma metastases after cessation of cyclosporine. Transplantation 2002; 73(11): 1849– 1850.
52. Kessler M, Jay N, Molle R et al. Excess risk of cancer in renal transplant patients. Transpl Int 2006; 19(11): 908– 914.
53. Fortina AB, Piaserico S, Caforio AL et al. Immunosuppressive level and other risk factors for basal cell carcinoma and squamous cell carcinoma in heart transplant recipients. Arch Dermatol 2004; 140(9): 1079– 1085.
54. 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.
55. Boratyńska M, Watorek E, Smolska D et al. Anticancer effect of sirolimus in renal allograft recipients with de novo malignancies. Transplant Proc 2007; 39(9): 2736– 2739.
56. National Cancer Institute (NCI) guidelines for Merkel Cell Carcinoma treatment available online at http:/ / www.cancer.gov/ cancertopics/ pdq/ treatment/ merkelcell/ HealthProfessional/ page5 (Accessed May 15, 2010).
57. Goepfert H, Remmler D, Silva E et al. Merkel cell carcinoma (endocrine carcinoma of the skin) of the head and neck. Arch Otolaryngol 1984; 110(11): 707– 712.
58. Veness MJ, Morgan GJ, Gebski V. Adjuvant locoregional radiotherapy as best practice in patients with Merkel cell carcinoma of the head and neck. Head Neck 2005; 27(3): 208– 216.
59. Poulsen M, Rischin D, Walpole E et al. High‑risk Merkel cell carcinoma of the skin treated with synchronous carboplatin/ etoposide and radiation: a Trans‑Tasman Radiation Oncology Group Study – TROG 96:07. J Clin Oncol 2003; 21(23): 4371– 4376.
60. Poulsen MG, Rischin D, Porter I et al. Does chemotherapy improve survival in high‑risk stage I and II Merkel cell carcinoma of the skin? Int J Radiat Oncol Biol Phys 2006; 64(1): 114– 119.
61. National Comprehensive Cancer Network (NCCN) guidelines for cancer treatment available online at http:/ / www.nccn.org/ professionals/ physician_gls/ f_guidelines.asp (Accessed August 2, 2009).
62. Eng TY, Naguib M, Fuller CD et al. Treatment of recurrent Merkel cell carcinoma: an analysis of 46 cases. Am J Clin Oncol 2004; 27(6): 576– 583.
63. Poulsen M, Walpole E, Harvey J et al. Weekly Carboplatin Reduces Toxicity During Synchronous Chemoradiotherapy for Merkel Cell Carcinoma of Skin. Int J Radiat Oncol Biol Phys 2008; 72(4): 1070– 1074.
64. Tai PT, Yu E, Winquist E et al. Chemotherapy in neuroendocrine/ Merkel cell carcinoma of the skin: case series and review of 204 cases. J Clin Oncol 2000; 18(12): 2493– 2499.
65. Rečková M, Lawrence HE. Nezvyčajný prípad dlhodobého prežívania pacientky s chemorefraktérnym Merkelovym karcinómom. Klin Onkol 2007; 20(5): 354– 356.
66. Becker J, Mauch C, Kortmann RD et al. Short German guidelines: Merkel cell carcinoma. J Dtsch Dermatol Ges 2008; 6(Suppl 1): 15– 16.
67. Maubec E, Duvillard P, Velasco V et al. Immunohistochemical analysis of EGFR and HER‑ 2 in patients with metastatic squamous cell carcinoma of the skin. Anticancer Res 2005; 25(2B): 1205– 1210.
68. Dean NM, Bennett CF. Antisense oligonucleotide‑based therapeutics for cancer. Oncogene 2003; 22(56): 9087– 9096.
69. Krasagakis K, Krüger‑ Krasagakis S, Tzanakakis GN et al. Interferon‑alpha inhibits proliferation and induces apoptosis of merkel cell carcinoma in vitro. Cancer Invest 2008; 26(6): 562– 568.
70. Bossuyt W, Kazanjian A, De Geest N et al. Atonal homolog 1 is a tumor suppressor gene. PLoS Biol 2009; 7(2): Dostupné z: http:/ / www.plosbiology.org/ article/ info:doi/ 10.1371/ journal.pbio.1000039.
71. Pastrana DV, Tolstov YL, Becker JC et al. Quantitation of Human Seroresponsiveness to Merkel Cell Polyomavirus. PLoS Pathog 2009; 5(9): Dostupné z: http:/ / www.plospathogens.org/ article/ info:doi%2F10.1371%2Fjournal.ppat.1000578.
72. Allen PJ, Bowne WB, Jaques DP et al. Merkel cell carcinoma: prognosis and treatment of patients from a single institution. J Clin Oncol 2005; 23(10): 2300– 2309.
73. Shaw JH, Rumball E. Merkel cell tumour: clinical behaviour and treatment. Br J Surg 1991; 78(2): 138– 142.
74. Yiengpruksawan A, Coit DG, Thaler HT et al. Merkel cell carcinoma. Prognosis and management. Arch Surg 1991; 126(12): 1514– 1519.
75. Bielamowizc S, Smith D, Abemayor E. Merkel cell carcinoma: an aggressive skin neoplasm. Laryngoscope 1994; 104(5 Pt 1): 528– 532.
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