Annals of Surgical Oncology

, Volume 19, Issue 7, pp 2360–2366 | Cite as

Merkel Cell Carcinoma of Unknown Primary Origin

  • Jeremiah L. Deneve
  • Jane L. Messina
  • Suroosh S. Marzban
  • Ricardo J. Gonzalez
  • Brooke M. Walls
  • Kate J. Fisher
  • Y. Ann Chen
  • C. Wayne Cruse
  • Vernon K. Sondak
  • Jonathan S. Zager



Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. MCC from an unknown primary origin (MCCUP) can present a diagnostic and therapeutic challenge. We describe our single-institution experience with the diagnosis and management of MCCUP presenting as metastases to lymph nodes.


After institutional review board approval, our institutional database spanning the years 1998–2010 was queried for patients with MCCUP. Clinicopathologic variables and outcomes were assessed.


From a database of 321 patients with MCC, 38 (12%) were identified as having nodal MCCUP. Median age was 67 years, and 79% were men. Nodal basins involved at presentation were cervical (58%), axillary/epitrochlear (21%), or inguinal/iliac (21%). CK20 staining was positive in 93% of tumors tested, and all were negative for thyroid transcription factor-1. Twenty-nine patients (76%) underwent complete regional lymph node dissection (LND): 3 had LND alone, ten had LND and adjuvant radiotherapy, and 16 underwent LND followed by chemoradiotherapy. Definitive chemoradiotherapy without surgery was provided to six patients (16%), while radiotherapy alone was provided to three (8%). Recurrence was observed in 34% of patients. Median recurrence-free survival was 35 months. Ten patients (26%) died, five of disease and five of other causes. The median overall survival was 104 months.


Nodal MCCUP is a rare disease affecting primarily elderly white men. Recurrence is observed in approximately one-third of patients, with a 104 month median overall survival after a multimodal treatment approach consisting of surgery along with adjuvant chemotherapy and radiotherapy in the majority of patients.


  1. 1.
    Hodgson NC. Merkel cell carcinoma: changing incidence trends. J Surg Oncol. 2005;89:1–4.PubMedCrossRefGoogle Scholar
  2. 2.
    Pan D, Narayan D, Ariyan S. Merkel cell carcinoma: five case reports using sentinel lymph node biopsy and a review of 110 new cases. Plast Reconstr Surg. 2002;110:1259–65.PubMedCrossRefGoogle Scholar
  3. 3.
    Koljonen V. Merkel cell carcinoma. World J Surg Oncol. 2006;4:7.PubMedCrossRefGoogle Scholar
  4. 4.
    Lemos B, Nghiem P. Merkel cell carcinoma: more deaths but still no pathway to blame. J Invest Dermatol. 2007;127:2100–3.PubMedCrossRefGoogle Scholar
  5. 5.
    Merkel cell carcinoma. In: Edge SB, editor. AJCC cancer staging manual. 7th ed. New York: Springer; 2010. p. 315–23.Google Scholar
  6. 6.
    Toker C. Trabecular carcinoma of the skin. Arch Dermatol. 1972;105:107–10.PubMedCrossRefGoogle Scholar
  7. 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 1,024 cases. Ann Surg Oncol. 2001;8:204–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Veness MJ, Perera L, McCourt J, Shannon J, Hughes TM, Morgan GJ, et al. Merkel cell carcinoma: improved outcome with adjuvant radiotherapy. ANZ J Surg. 2005;75:275–81.PubMedCrossRefGoogle Scholar
  9. 9.
    Tai PT, Yu E, Winquist E, Hammond A, Stitt L, Tonita J, 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.PubMedGoogle Scholar
  10. 10.
    Heath M, Jaimes N, Lemos B, Mostaghimi A, Wang LC, Peñas PF, et al. Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. J Am Acad Dermatol. 2008;58:375–81.PubMedCrossRefGoogle Scholar
  11. 11.
    Albores-Saavedra J, Batich K, Chable-Montero F, Sagy N, Schwartz AM, Henson DE, et al. Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study. J Cutan Pathol. 2010;37:20–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Richetta AG, Mancini M, Torroni A, Lorè B, Iannetti G, Sardella B, et al. Total spontaneous regression of advanced Merkel cell carcinoma after biopsy: review and a new case. Dermatol Surg. 2008;34:815–22.PubMedCrossRefGoogle Scholar
  13. 13.
    Val-Bernal JF, Garcia-Castano A, Garcia-Barredo R, Landeras R, De Juan A, Garijo MF, et al. Spontaneous complete regression in Merkel cell carcinoma after biopsy. Adv Anat Pathol. 2011;18:174–7.PubMedCrossRefGoogle Scholar
  14. 14.
    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;19:96.CrossRefGoogle Scholar
  15. 15.
    Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008;319:1096–100.PubMedCrossRefGoogle Scholar
  16. 16.
    Mir R, Sciubba JJ, Bhuiya TA, Blomquist K, Zelig D, Friedman E. Merkel cell carcinoma arising in the oral mucosa. Oral Surg Oral Med Oral Pathol. 1988;65:71–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Snow SN, Larson PO, Hardy S, Bentz M, Madjar D, Landeck A, et al. Merkel cell carcinoma of the skin and mucosa: report of 12 cutaneous cases with 2 cases arising from the nasal mucosa. Dermatol Surg. 2001;27:165–70.PubMedCrossRefGoogle Scholar
  18. 18.
    McCardle TW, Sondak VK, Zager J, Messina JL. Merkel cell carcinoma: pathologic findings and prognostic factors. Curr Probl Cancer. 2010;34:47–64.PubMedCrossRefGoogle Scholar
  19. 19.
    Linjawi A, Jamison WB, Meterissian S. Merkel cell carcinoma: important aspects of diagnosis and management. Am Surg. 2001;67:943–7.PubMedGoogle Scholar
  20. 20.
    Iacocca MV, Abernethy JL, Stefanato CM, Allan AE, Bhawan J. Mixed Merkel cell carcinoma and squamous cell carcinoma of the skin. J Am Acad Dermatol. 1998;39:882–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Ordonez NG. Thyroid transcription factor-1 is a marker of lung and thyroid carcinomas. Adv Anat Pathol. 2000;7:123–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Hitchcock CL, Bland KI, Laney RG 3rd, Franzini D, Harris B, Copeland EM 3rd. Neuroendocrine (Merkel cell) carcinoma of the skin. Its natural history, diagnosis, and treatment. Ann Surg. 1988;207:201–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Messina JL, Reintgen DS, Cruse CW, Rappaport DP, Berman C, Fenske NA, et al. Selective lymphadenectomy in patients with Merkel cell (cutaneous neuroendocrine) carcinoma. Ann Surg Oncol. 1997;4:389–95.PubMedCrossRefGoogle Scholar
  24. 24.
    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.PubMedCrossRefGoogle Scholar
  25. 25.
    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.PubMedCrossRefGoogle Scholar
  26. 26.
    Rao NG. Review of the role of radiation therapy in the management of Merkel cell carcinoma. Curr Probl Cancer. 2010;34:108–17.PubMedCrossRefGoogle Scholar
  27. 27.
    Howle JR, Hughes TM, Gebski V, Veness MJ. Merkel cell carcinoma: an Australian perspective and the importance of addressing the regional lymph nodes in clinically node-negative patients. J Am Acad Dermatol. Epub ahead of print 2011.Google Scholar
  28. 28.
    Gonzalez RJ, Padhya TA, Cherpelis BS, Prince MD, Aya-Ay ML, Sondak VK, et al. The surgical management of primary and metastatic Merkel cell carcinoma. Curr Probl Cancer. 2010; 34:77–96.PubMedCrossRefGoogle Scholar
  29. 29.
    Poulsen MG, Rischin D, Porter I, Walpole E, Harvey J, Hamilton C, 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.PubMedCrossRefGoogle Scholar
  30. 30.
    Kudchadkar R, Deconti R. Systemic treatments for Merkel cell carcinoma. Curr Probl Cancer. 2010;34:97–107.PubMedCrossRefGoogle Scholar
  31. 31.
    Fields RC, Busam KJ, Chou JF, Panageas KS, Pulitzer MP, Allen PJ, et al. Recurrence after complete resection and selective use of adjuvant therapy for stage I through III Merkel cell carcinoma. Cancer. Epub ahead of print 2011.Google Scholar
  32. 32.
    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.PubMedCrossRefGoogle Scholar
  33. 33.
    Fields RC, Busam KJ, Chou JF, Panageas KS, Pulitzer MP, Allen PJ, et al. Five hundred patients with Merkel cell carcinoma evaluated at a single institution. Ann Surg. 2011;254:465–473.PubMedCrossRefGoogle Scholar
  34. 34.
    Foote M, Veness M, Zarate D, Poulsen M. Merkel cell carcinoma: the prognostic implications of an occult primary in stage IIIB (nodal) disease. J Am Acad Dermatol. Epub ahead of print 2011.Google Scholar

Copyright information

© Society of Surgical Oncology 2012

Authors and Affiliations

  • Jeremiah L. Deneve
    • 1
  • Jane L. Messina
    • 1
    • 2
  • Suroosh S. Marzban
    • 1
  • Ricardo J. Gonzalez
    • 1
    • 4
  • Brooke M. Walls
    • 1
  • Kate J. Fisher
    • 3
  • Y. Ann Chen
    • 3
  • C. Wayne Cruse
    • 1
    • 4
  • Vernon K. Sondak
    • 1
    • 4
  • Jonathan S. Zager
    • 1
    • 4
  1. 1.Department of Cutaneous OncologyMoffitt Cancer CenterTampaUSA
  2. 2.Departments of Anatomic Pathology and Cell Biology and DermatologyUniversity of South FloridaTampaUSA
  3. 3.Department of BiostatisticsMoffitt Cancer CenterTampaUSA
  4. 4.Departments of Oncologic Sciences and SurgeryUniversity of South FloridaTampaUSA

Personalised recommendations