Skip to main content

Advertisement

SpringerLink
Log in

Merkel Cell Carcinoma: 30-Year Experience from a Single Institution

  • Melanomas
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy. Few single-institution series have been reported.

Methods

Review of MCC patients treated at our institution between 1980 and 2010. Patient, tumor, and treatment variables were analyzed to determine MCC-specific outcomes.

Results

We identified 161 patients with MCC. There was a 2.5-fold increase in cases over the last decade. Median length of follow-up was 36 months. Stage at diagnosis was I in 35 %, II in 21 %, IIIa in 12 %, IIIb in 23 %, and IV in 9 %. The 5-year MCC-specific survival rates were 87, 63, 42, and 0 % for stages I, II, III, and IV, respectively. Death from the disease occurred in 10 % of patients with T1 and in 50 % with larger lesions. One-third of patients presented with nodal disease. Sentinel lymph node biopsy (SLNB) identified micrometastases in 9 out of 27 (33 %) early-stage patients. Recurrence developed in 56 % of SLNB-positive and 39 % of SLNB-negative patients. Half of patients recurred after a median time of 9 months. Proportions of first recurrence location were distant (52 %), nodal (27 %), and local (21 %). Adjuvant treatments did not improve recurrence or survival rates. One-third of patients died of the disease.

Conclusions

SLNB identifies micrometastasis in one-third of early-stage patients. Negative SLNB may predict for improved but not necessarily favorable outcome. Initial tumor size and clinical nodal disease predict for poor outcome. High recurrence rates warrant the development of more effective adjuvant therapies, and better markers of recurrence and treatment response for MCC are needed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Albores-Saavedra J, Batich K, Chable-Montero F, Sagy N, Schwartz AM, Henson DE. Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study. J Cutan Pathol. 2010;37:20–7.

    Article  PubMed  Google Scholar 

  2. Agelli M, Clegg LX, Becker JC, Rollison DE. The etiology and epidemiology of Merkel cell carcinoma. Curr Probl Cancer. 2010;34:14–37.

    Article  PubMed  Google Scholar 

  3. Agelli M, Clegg LX. Epidemiology of primary Merkel cell carcinoma in the United States. J Am Acad Dermatol. 2003;49:832–41.

    Article  PubMed  Google Scholar 

  4. Hodgson NC. Merkel cell carcinoma: changing incidence trends. J Surg Oncol. 2005;89:1–4.

    Article  PubMed  Google Scholar 

  5. Ramahi E, Choi J, Fuller CD, Eng TY. Merkel cell carcinoma. Am J Clin Oncol. 2011 (in press).

  6. Ott MJ, Tanabe KK, Gadd MA, et al. Multimodality management of Merkel cell carcinoma. Arch Surg. 1999; 134:388–92; discussion 92–3

    Article  PubMed  CAS  Google Scholar 

  7. Medina-Franco H, Urist MM, Fiveash J, Heslin MJ, Bland KI, Beenken SW. Multimodality treatment of Merkel cell carcinoma: case series and literature review of 1024 cases. Ann Surg Oncol. 2001;8:204-8.

    Article  PubMed  CAS  Google Scholar 

  8. Warner RE, Quinn MJ, Hruby G, Scolyer RA, Uren RF, Thompson JF. Management of merkel cell carcinoma: the roles of lymphoscintigraphy, sentinel lymph node biopsy and adjuvant radiotherapy. Ann Surg Oncol. 2008;15:2509–18.

    Article  PubMed  Google Scholar 

  9. Muller A, Keus R, Neumann N, Lammering G, Schnabel T. Management of Merkel cell carcinoma: case series of 36 patients. Oncol Rep. 2003;10:577–85.

    PubMed  Google Scholar 

  10. Allen PJ, Zhang ZF, Coit DG. Surgical management of Merkel cell carcinoma. Ann Surg. 1999;229:97–105.

    Article  PubMed  CAS  Google Scholar 

  11. 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;47:885–92.

    Article  PubMed  Google Scholar 

  12. 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;127:149–54.

    PubMed  CAS  Google Scholar 

  13. 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;31:325–31.

    Article  PubMed  CAS  Google Scholar 

  14. Morrison WH, Peters LJ, Silva EG, Wendt CD, Ang KK, Goepfert H. The essential role of radiation therapy in securing locoregional control of Merkel cell carcinoma. Int J Radiat Oncol Biol Phys. 1990;19:583–91.

    Article  PubMed  CAS  Google Scholar 

  15. Bajetta E, Celio L, Platania M, et al. Single-institution series of early-stage Merkel cell carcinoma: long-term outcomes in 95 patients managed with surgery alone. Ann Surg Oncol. 2009;16:2985–93.

    Article  PubMed  Google Scholar 

  16. Lewis KG, Weinstock MA, Weaver AL, Otley CC. Adjuvant local irradiation for Merkel cell carcinoma. Arch Dermatol. 2006;142:693–700.

    Article  PubMed  Google Scholar 

  17. 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;25:1043–7.

    Article  PubMed  Google Scholar 

  18. Edge SB BD, Compton CC, et al. american joint committee on cancer: AJCC cancer staging manual. 7th ed. pp 315–23. New York, NY: Springer; 2010.

    Google Scholar 

  19. Allen PJ, Bowne WB, Jaques DP, Brennan MF, Busam K, Coit DG. Merkel cell carcinoma: prognosis and treatment of patients from a single institution. J Clin Oncol. 2005;23:2300–9.

    Article  PubMed  Google Scholar 

  20. Hui AC, Stillie AL, Seel M, Ainslie J. Merkel cell carcinoma: 27-year experience at the Peter MacCallum cancer centre. Int J Radiat Oncol Biol Phys. 2010;80(5):1430–5.

    Google Scholar 

  21. Fields RC, Busam KJ, Chou JF, et al. Five hundred patients with Merkel cell carcinoma evaluated at a single institution. Ann Surg.254:465–73; discussion 73–5.

  22. Toker C. Trabecular carcinoma of the skin. Arch Dermatol. 1972;105:107–10.

    Article  PubMed  CAS  Google Scholar 

  23. Tang CK, Toker C. Trabecular carcinoma of the skin: further clinicopathologic and ultrastructural study. Mt Sinai J Med. 1979;46:516–23.

    PubMed  CAS  Google Scholar 

  24. Toker C. Trabecular carcinoma of the skin. A question of title. Am J Dermatopathol. 1982;4:497–500.

    Article  PubMed  CAS  Google Scholar 

  25. 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;140:427–47.

    PubMed  CAS  Google Scholar 

  26. Scott MP, Helm KF. Cytokeratin 20: a marker for diagnosing Merkel cell carcinoma. Am J Dermatopathol. 1999;21:16–20.

    Article  PubMed  CAS  Google Scholar 

  27. Hanly AJ, Elgart GW, Jorda M, Smith J, Nadji M. Analysis of thyroid transcription factor-1 and cytokeratin 20 separates merkel cell carcinoma from small cell carcinoma of lung. J Cutan Pathol. 2000;27:118–20.

    Article  PubMed  CAS  Google Scholar 

  28. Allen PJ, Busam K, Hill AD, Stojadinovic A, Coit DG. Immunohistochemical analysis of sentinel lymph nodes from patients with Merkel cell carcinoma. Cancer. 2001;92:1650–5.

    Article  PubMed  CAS  Google Scholar 

  29. Andea AA, Coit DG, Amin B, Busam KJ. Merkel cell carcinoma: histologic features and prognosis. Cancer. 2008;113:2549–58.

    Article  PubMed  Google Scholar 

  30. 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;58:375–81.

    Article  PubMed  Google Scholar 

  31. Guler-Nizam E, Leiter U, Metzler G, Breuninger H, Garbe C, Eigentler TK. Clinical course and prognostic factors of Merkel cell carcinoma of the skin. Br J Dermatol. 2009;161:90–4.

    Article  PubMed  CAS  Google Scholar 

  32. 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;63:751–61.

    Article  PubMed  Google Scholar 

  33. Pfeifer T, Weinberg H, Brady MS. Lymphatic mapping for Merkel cell carcinoma. J Am Acad Dermatol. 1997;37:650–1.

    Article  PubMed  CAS  Google Scholar 

  34. Ames SE, Krag DN, Brady MS. Radiolocalization of the sentinel lymph node in Merkel cell carcinoma: a clinical analysis of seven cases. J Surg Oncol. 1998;67:251–4.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  36. Gupta SG, Wang LC, Penas PF, Gellenthin M, Lee SJ, Nghiem P. 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;142:685–90.

    Article  PubMed  Google Scholar 

  37. Stokes JB, Graw KS, Dengel LT, et al. Patients with Merkel cell carcinoma tumors < or = 1.0 cm in diameter are unlikely to harbor regional lymph node metastasis. J Clin Oncol. 2009;27:3772–7.

    Article  PubMed  Google Scholar 

  38. Fields RC, Busam KJ, Chou JF, et al. Recurrence and survival in patients undergoing sentinel lymph node biopsy for Merkel cell carcinoma: analysis of 153 patients from a single institution. Ann Surg Oncol. 2011.

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

    Article  PubMed  Google Scholar 

  40. Veness MJ. Merkel cell carcinoma: improved outcome with the addition of adjuvant therapy. J Clin Oncol. 2005;23:7235-6; author reply 7–8.

    Google Scholar 

  41. Clark JR, Veness MJ, Gilbert R, O’Brien CJ, Gullane PJ. Merkel cell carcinoma of the head and neck: is adjuvant radiotherapy necessary? Head Neck. 2007;29:249–57.

    Article  PubMed  Google Scholar 

  42. Foote M, Harvey J, Porceddu S, et al. Effect of radiotherapy dose and volume on relapse in Merkel cell cancer of the skin. Int J Radiat Oncol Biol Phys. 2010;77:677–84.

    Article  PubMed  Google Scholar 

  43. Poulsen M, Round C, Keller J, Tripcony L, Veness M. 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;76:393–7.

    Article  PubMed  Google Scholar 

  44. Veness M, Foote M, Gebski V, Poulsen M. The role of radiotherapy alone in patients with Merkel cell carcinoma: reporting the Australian experience of 43 patients. Int J Radiat Oncol Biol Phys. 2010;78:703–9.

    Article  PubMed  Google Scholar 

  45. Merkel cell carcinoma. NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 4/23/2011.

  46. 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;118(13):3311–20. doi:10.1002/cncr.26626.

  47. Voog E, Biron P, Martin JP, Blay JY. Chemotherapy for patients with locally advanced or metastatic Merkel cell carcinoma. Cancer. 1999;85:2589–95.

    Article  PubMed  CAS  Google Scholar 

  48. 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;18:2493–9.

    PubMed  CAS  Google Scholar 

  49. Poulsen M, Rischin D, Walpole E, et al. Analysis of toxicity of Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group study. Int J Radiat Oncol Biol Phys. 2001;51:156–63.

    Article  PubMed  CAS  Google Scholar 

  50. 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;21:4371–6.

    Article  PubMed  CAS  Google Scholar 

  51. 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;64:114–9.

    Article  PubMed  Google Scholar 

  52. 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;72:1070–4.

    Article  PubMed  CAS  Google Scholar 

  53. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008;319:1096–100.

    Article  PubMed  CAS  Google Scholar 

  54. Kassem A, Schopflin 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;68:5009–13.

    Article  PubMed  CAS  Google Scholar 

  55. Becker JC, Houben R, Ugurel S, Trefzer U, Pfohler C, Schrama D. MC polyomavirus is frequently present in Merkel cell carcinoma of European patients. J Invest Dermatol. 2009;129:248–50.

    Article  PubMed  CAS  Google Scholar 

  56. Varga E, Kiss M, Szabo K, Kemeny L. Detection of Merkel cell polyomavirus DNA in Merkel cell carcinomas. Br J Dermatol. 2009;161:930–2.

    Article  PubMed  CAS  Google Scholar 

  57. Duncavage EJ, Zehnbauer BA, Pfeifer JD. Prevalence of Merkel cell polyomavirus in Merkel cell carcinoma. Mod Pathol. 2009;22:516–21.

    Article  PubMed  CAS  Google Scholar 

  58. Busam KJ, Jungbluth AA, Rekthman N, et al. Merkel cell polyomavirus expression in merkel cell carcinomas and its absence in combined tumors and pulmonary neuroendocrine carcinomas. Am J Surg Pathol. 2009;33:1378–85.

    Article  PubMed  Google Scholar 

  59. Nardi V, Song Y, Santamaria-Barria JA, et al. Activation of PI3K signaling in merkel cell carcinoma. Clin Cancer Res. 18:1227–36. doi:1078-0432.CCR-11-2308.

  60. Hafner C, Houben R, Baeurle A, et al. Activation of the PI3 K/AKT Pathway in Merkel Cell Carcinoma. PLoS One. 2012;7(2):e31255.

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosures

The authors have no potential conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, YAW 7B, 55 Fruit Street, Boston, MA, 02114, USA

    Juan A. Santamaria-Barria MD, Genevieve M. Boland MD, PhD & James C. Cusack Jr. MD

  2. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Beow Y. Yeap ScD

  3. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Valentina Nardi MD & Dora Dias-Santagata PhD

Authors
  1. Juan A. Santamaria-Barria MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Genevieve M. Boland MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Beow Y. Yeap ScD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Valentina Nardi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dora Dias-Santagata PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. James C. Cusack Jr. MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James C. Cusack Jr. MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Santamaria-Barria, J.A., Boland, G.M., Yeap, B.Y. et al. Merkel Cell Carcinoma: 30-Year Experience from a Single Institution. Ann Surg Oncol 20, 1365–1373 (2013). https://doi.org/10.1245/s10434-012-2779-3

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-012-2779-3

Keywords

Search

Navigation