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Merkel Cell Carcinoma

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Abstract

Merkel cell carcinoma (MCC), also referred to as primary cutaneous neuroendocrine carcinoma , is a rare but potentially aggressive cutaneous malignancy. First described in 1972 as trabecular carcinoma, MCC is believed to arise from Merkel cells which function as mechanoreceptors in the skin (Tang and Toker, Cancer 42(5):2311–2321, 1978; Toker, Arch Dermatol 105(1):107–110, 1972).

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References

  1. Tang CK, Toker C. Trabecular carcinoma of the skin: an ultrastructural study. Cancer. 1978;42(5):2311–21.

    Article  CAS  PubMed  Google Scholar 

  2. Toker C. Trabecular carcinoma of the skin. Arch Dermatol. 1972;105(1):107–10.

    Article  CAS  PubMed  Google Scholar 

  3. NCCN. National Comprehensive Cancer Network Clinical practice guidelines in oncology. Merkel cell carcinoma (Version 1.2016). Available: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 24 Sept 2017.

  4. Heath M, Jaimes N, Lemos B, 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  PubMed Central  Google Scholar 

  5. Schwartz JL, Bichakjian CK, Lowe L, et al. Clinicopathologic features of primary Merkel cell carcinoma: a detailed descriptive analysis of a large contemporary cohort. Dermatol Surg. 2013;39(7):1009–16.

    Article  CAS  PubMed  Google Scholar 

  6. 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):204–8.

    Article  CAS  PubMed  Google Scholar 

  7. Harms KL, Healy MA, Nghiem P, et al. Analysis of prognostic factors from 9387 Merkel cell carcinoma cases forms the basis for the new 8th edition AJCC staging system. Ann Surg Oncol. 2016;23(11):3564–71.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Fitzgerald TL, Dennis S, Kachare SD, et al. Dramatic increase in the incidence and mortality from Merkel cell carcinoma in the United States. Am Surg. 2015;81(8):802–6.

    Article  PubMed  Google Scholar 

  9. Clarke CA, Robbins HA, Tatalovich Z, et al. Risk of Merkel cell carcinoma after solid organ transplantation. J Natl Cancer Inst. 2015;107(2):dju382.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Buell JF, Trofe J, Hanaway MJ, et al. Immunosuppression and Merkel cell cancer. Transplant Proc. 2002;34(5):1780–1.

    Article  CAS  PubMed  Google Scholar 

  11. Engels EA, Frisch M, Goedert JJ, et al. Merkel cell carcinoma and HIV infection. Lancet. 2002;359(9305):497–8.

    Article  PubMed  Google Scholar 

  12. 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 

  13. 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 

  14. Miller RW, Rabkin CS. Merkel cell carcinoma and melanoma: etiological similarities and differences. Cancer Epidemiol Biomark Prev. 1999;8(2):153–8.

    CAS  Google Scholar 

  15. Harms PW, Vats P, Verhaegen ME, et al. The distinctive mutational spectra of polyomavirus-negative Merkel cell carcinoma. Cancer Res. 2015;75(18):3720–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wong SQ, Waldeck K, Vergara IA, et al. UV-associated mutations underlie the etiology of MCV-negative Merkel cell carcinomas. Cancer Res. 2015;75(24):5228–34.

    Article  CAS  PubMed  Google Scholar 

  17. Feng H, Shuda M, Chang Y, et al. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008;319(5866):1096–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Martel-Jantin C, Pedergnana V, Nicol JT, et al. Merkel cell polyomavirus infection occurs during early childhood and is transmitted between siblings. J Clin Virol. 2013;58(1):288–91.

    Article  CAS  PubMed  Google Scholar 

  19. Carter JJ, Paulson KG, Wipf GC, et al. Association of Merkel cell polyomavirus-specific antibodies with Merkel cell carcinoma. J Natl Cancer Inst. 2009;101(21):1510–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Moshiri AS, Doumani R, Yelistratova L, et al. Polyomavirus-negative Merkel cell carcinoma: a more aggressive subtype based on analysis of 282 cases using multimodal tumor virus detection. J Invest Dermatol. 2017;137(4):819–27.

    Article  CAS  PubMed  Google Scholar 

  21. Hanly AJ, Elgart GW, Jorda M, et al. Analysis of thyroid transcription factor-1 and cytokeratin 20 separates Merkel cell carcinoma from small cell carcinoma of lung. J Cutan Pathol. 2000;27(3):118–20.

    Article  CAS  PubMed  Google Scholar 

  22. Cheuk W, Kwan MY, Suster S, et al. Immunostaining for thyroid transcription factor 1 and cytokeratin 20 aids the distinction of small cell carcinoma from Merkel cell carcinoma, but not pulmonary from extrapulmonary small cell carcinomas. Arch Pathol Lab Med. 2001;125(2):228–31.

    Article  CAS  PubMed  Google Scholar 

  23. Gruber SB, Wilson LD. Merkel cell carcinoma. In: Cutaneous oncology: pathophysiology, diagnosis, and management. Malden: Blackwell Science; 1998.

    Google Scholar 

  24. Gupta SG, Wang LC, Penas PF, et al. Sentinel lymph node biopsy for evaluation and treatment of patients with Merkel cell carcinoma: the Dana-Farber experience and meta-analysis of the literature. Arch Dermatol. 2006;142(6):685–90.

    Article  PubMed  Google Scholar 

  25. Gunaratne DA, Howle JR, Veness MJ. Sentinel lymph node biopsy in Merkel cell carcinoma: a 15-year institutional experience and statistical analysis of 721 reported cases. Br J Dermatol. 2016;174(2):273–81.

    Article  CAS  PubMed  Google Scholar 

  26. 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):2300–9.

    Article  PubMed  Google Scholar 

  27. Schwartz JL, Griffith KA, Lowe L, et al. Features predicting sentinel lymph node positivity in Merkel cell carcinoma. J Clin Oncol. 2011;29(8):1036–41.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Su LD, Lowe L, Bradford CR, et al. Immunostaining for cytokeratin 20 improves detection of micrometastatic Merkel cell carcinoma in sentinel lymph nodes. J Am Acad Dermatol. 2002;46(5):661–6.

    Article  PubMed  Google Scholar 

  29. Schmalbach CE, Lowe L, Teknos TN, et al. Reliability of sentinel lymph node biopsy for regional staging of head and neck Merkel cell carcinoma. Arch Otolaryngol Head Neck Surg. 2005;131(7):610–4.

    Article  PubMed  Google Scholar 

  30. Lemos BD, Storer BE, Iyer JG, et al. Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: analysis of 5823 cases as the basis of the first consensus staging system. J Am Acad Dermatol. 2010;63(5):751–61.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Fields RC, Busam KJ, Chou JF, et al. Recurrence after complete resection and selective use of adjuvant therapy for stage I through III Merkel cell carcinoma. Cancer. 2012;118(13):3311–20.

    Article  PubMed  Google Scholar 

  32. Bichakjian CK, Johnson T, Wright CL, Sober AJ. Merkel cell carcinoma. In: Amin MB, Edge SB, Greene FL, et al., editors. AJCC cancer staging manual. New York: Springer; 2017. p. 549–62.

    Chapter  Google Scholar 

  33. Voog E, Biron P, Martin JP, et al. Chemotherapy for patients with locally advanced or metastatic Merkel cell carcinoma. Cancer. 1999;85(12):2589–95.

    Article  CAS  PubMed  Google Scholar 

  34. Treglia G, Kakhki VR, Giovanella L, et al. Diagnostic performance of fluorine-18-fluorodeoxyglucose positron emission tomography in patients with Merkel cell carcinoma: a systematic review and meta-analysis. Am J Clin Dermatol. 2013;14(6):437–47.

    Article  PubMed  Google Scholar 

  35. Hawryluk EB, O’Regan KN, Sheehy N, et al. Positron emission tomography/computed tomography imaging in Merkel cell carcinoma: a study of 270 scans in 97 patients at the Dana-Farber/Brigham and Women’s Cancer Center. J Am Acad Dermatol. 2013;68(4):592–9.

    Article  PubMed  Google Scholar 

  36. Boyer JD, Zitelli JA, Brodland DG, et al. 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 

  37. Leonard JH, Ramsay JR, Kearsley JH, et al. Radiation sensitivity of Merkel cell carcinoma cell lines. Int J Radiat Oncol Biol Phys. 1995;32(5):1401–7.

    Article  CAS  PubMed  Google Scholar 

  38. Eng TY, Boersma MG, Fuller CD, et al. Treatment of Merkel cell carcinoma. Am J Clin Oncol. 2004;27(5):510–5.

    Article  PubMed  Google Scholar 

  39. Frohm ML, Griffith KA, Harms KL, et al. Recurrence and survival in patients with Merkel cell carcinoma undergoing surgery without adjuvant radiation therapy to the primary site. JAMA Dermatol. 2016;152(9):1001–7.

    Article  PubMed  Google Scholar 

  40. Jabbour J, Cumming R, Scolyer RA, et al. Merkel cell carcinoma: assessing the effect of wide local excision, lymph node dissection, and radiotherapy on recurrence and survival in early-stage disease--results from a review of 82 consecutive cases diagnosed between 1992 and 2004. Ann Surg Oncol. 2007;14(6):1943–52.

    Article  PubMed  Google Scholar 

  41. Lewis KG, Weinstock MA, Weaver AL, et al. Adjuvant local irradiation for Merkel cell carcinoma. Arch Dermatol. 2006;142(6):693–700.

    Article  PubMed  Google Scholar 

  42. Meeuwissen JA, Bourne RG, Kearsley JH. The importance of postoperative radiation therapy in the treatment of Merkel cell carcinoma. Int J Radiat Oncol Biol Phys. 1995;31(2):325–31.

    Article  CAS  PubMed  Google Scholar 

  43. Mojica P, Smith D, Ellenhorn JD. Adjuvant radiation therapy is associated with improved survival in Merkel cell carcinoma of the skin. J Clin Oncol. 2007;25(9):1043–7.

    Article  PubMed  Google Scholar 

  44. Poulsen M, Round C, Keller J, et al. Factors influencing relapse-free survival in Merkel cell carcinoma of the lower limb--a review of 60 cases. Int J Radiat Oncol Biol Phys. 2010;76(2):393–7.

    Article  PubMed  Google Scholar 

  45. Veness MJ, Perera L, McCourt J, et al. Merkel cell carcinoma: improved outcome with adjuvant radiotherapy. ANZ J Surg. 2005;75(5):275–81.

    Article  PubMed  Google Scholar 

  46. Harrington C, Kwan W. Radiotherapy and conservative surgery in the locoregional management of Merkel cell carcinoma: the British Columbia Cancer Agency experience. Ann Surg Oncol. 2016;23(2):573–8.

    Article  PubMed  Google Scholar 

  47. Lok B, Khan S, Mutter R, et al. Selective radiotherapy for the treatment of head and neck Merkel cell carcinoma. Cancer. 2012;118(16):3937–44.

    Article  PubMed  Google Scholar 

  48. Mortier L, Mirabel X, Fournier C, et al. Radiotherapy alone for primary Merkel cell carcinoma. Arch Dermatol. 2003;139(12):1587–90.

    Article  PubMed  Google Scholar 

  49. Koh CS, Veness MJ. Role of definitive radiotherapy in treating patients with inoperable Merkel cell carcinoma: the Westmead Hospital experience and a review of the literature. Australas J Dermatol. 2009;50(4):249–56.

    Article  PubMed  Google Scholar 

  50. Gunaratne DA, Howle JR, Veness MJ. Definitive radiotherapy for Merkel cell carcinoma confers clinically meaningful in-field locoregional control: a review and analysis of the literature. J Am Acad Dermatol. 2017;77(1):142–148 e141.

    Article  PubMed  Google Scholar 

  51. Erman AB, Collar RM, Griffith KA, et al. Sentinel lymph node biopsy is accurate and prognostic in head and neck melanoma. Cancer. 2012;118(4):1040–7.

    Article  PubMed  Google Scholar 

  52. Mehrany K, Otley CC, Weenig RH, et al. A meta-analysis of the prognostic significance of sentinel lymph node status in Merkel cell carcinoma. Dermatol Surg. 2002;28(2):113–117; discussion 117.

    PubMed  Google Scholar 

  53. Veness M, Howle J. Patients with clinically node negative extremity Merkel cell carcinoma: the importance of identifying and treating patients with microscopic nodal metastases. Australas J Dermatol. 2010;51(4):274–8.

    Article  PubMed  Google Scholar 

  54. Hill AD, Brady MS, Coit DG. Intraoperative lymphatic mapping and sentinel lymph node biopsy for Merkel cell carcinoma. Br J Surg. 1999;86(4):518–21.

    Article  CAS  PubMed  Google Scholar 

  55. Messina JL, Reintgen DS, Cruse CW, et al. Selective lymphadenectomy in patients with Merkel cell (cutaneous neuroendocrine) carcinoma. Ann Surg Oncol. 1997;4(5):389–95.

    Article  CAS  PubMed  Google Scholar 

  56. Fang LC, Lemos B, Douglas J, et al. Radiation monotherapy as regional treatment for lymph node-positive Merkel cell carcinoma. Cancer. 2010;116(7):1783–90.

    Article  PubMed  Google Scholar 

  57. Grotz TE, Joseph RW, Pockaj BA, et al. Negative sentinel lymph node biopsy in Merkel cell carcinoma is associated with a low risk of same-nodal-basin recurrences. Ann Surg Oncol. 2015;22(12):4060–6.

    Article  PubMed  Google Scholar 

  58. 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):4371–6.

    Article  CAS  PubMed  Google Scholar 

  59. Garneski KM, Nghiem P. Merkel cell carcinoma adjuvant therapy: current data support radiation but not chemotherapy. J Am Acad Dermatol. 2007;57(1):166–9.

    Article  PubMed  PubMed Central  Google Scholar 

  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):114–9.

    Article  PubMed  Google Scholar 

  61. Gupta AS, Heinzman S, Levine EA. Successful treatment of in-transit metastases from Merkel’s cell carcinoma with isolated hyperthermic limb perfusion. South Med J. 1998;91(3):289–92.

    Article  CAS  PubMed  Google Scholar 

  62. Olieman AF, Lienard D, Eggermont AM, et al. Hyperthermic isolated limb perfusion with tumor necrosis factor alpha, interferon gamma, and melphalan for locally advanced nonmelanoma skin tumors of the extremities: a multicenter study. Arch Surg. 1999;134(3):303–7.

    Article  CAS  PubMed  Google Scholar 

  63. 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):2493–9.

    Article  CAS  PubMed  Google Scholar 

  64. Iyer JG, Blom A, Doumani R, et al. Response rates and durability of chemotherapy among 62 patients with metastatic Merkel cell carcinoma. Cancer Med. 2016;5(9):2294–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Desch L, Kunstfeld R. Merkel cell carcinoma: chemotherapy and emerging new therapeutic options. J Skin Cancer. 2013;2013:327150.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Hersh EM, O’Day SJ, Powderly J, et al. A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-naive patients with advanced melanoma. Investig New Drugs. 2011;29(3):489–98.

    Article  CAS  Google Scholar 

  67. Nghiem PT, Bhatia S, Lipson EJ, et al. PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N Engl J Med. 2016;374(26):2542–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kaufman HL, Russell J, Hamid O, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016;17(10):1374–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Gillenwater AM, Hessel AC, Morrison WH, et al. Merkel cell carcinoma of the head and neck: effect of surgical excision and radiation on recurrence and survival. Arch Otolaryngol Head Neck Surg. 2001;127(2):149–54.

    Article  CAS  PubMed  Google Scholar 

  70. Paulson KG, Carter JJ, Johnson LG, et al. Antibodies to Merkel cell polyomavirus T antigen oncoproteins reflect tumor burden in Merkel cell carcinoma patients. Cancer Res. 2010;70(21):8388–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Christopher K. Bichakjian .

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Noh, I.K., Bichakjian, C.K. (2019). Merkel Cell Carcinoma. In: Alam, M. (eds) Evidence-Based Procedural Dermatology. Springer, Cham. https://doi.org/10.1007/978-3-030-02023-1_45

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  • DOI: https://doi.org/10.1007/978-3-030-02023-1_45

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