International Journal of Clinical Oncology

, Volume 20, Issue 1, pp 188–193

Role of sentinel lymph node biopsy in patients with Merkel cell carcinoma: statistical analysis of 403 reported cases

  • Yoshitsugu Shibayama
  • Shinichi Imafuku
  • Akira Takahashi
  • Juichiro Nakayama
Original Article



Merkel cell carcinoma (MCC) is a rare cutaneous malignancy with a high rate of nodal metastasis. Sentinel lymph node biopsy (SLNB) is used in MCC and other cancers to identify regional node micrometastases in patients with clinically negative nodes; however, whether SLN status is associated with recurrence or prognosis in MCC is unclear.


A statistical analysis was performed of 397 published cases of MCC with SLNB results from 22 reports and 6 new cases, in order to elucidate any correlation between SLN status and recurrence, and to determine false-negative rates for SLNB.


Of these 403 cases, 128 (31.8 %) had positive SLNs; 16 of these 128 (12.5 %) developed recurrence (6 nodal, 10 distant). Of 275 patients with negative SLNs, 27 (9.8 %) developed recurrence (19 nodal, 8 distant). Patients with positive SLNs had a greater risk of distant metastasis (OR 2.82; P = 0.037; 95 % CI 1.089–7.347). The false-negative rate for SLNB in all 403 patients was 12.9 %. Use of the immunohistochemical approach to diagnosis of micrometastasis with anti-CK20 antibody did not affect the false-negative rate.


Patients with positive SLNs had a greater risk of distant metastasis in MCC; positive SLN was an important prognostic factor in MCC. Further studies using standardized, more-sensitive techniques to examine entire SLNs may decrease the false-negative rate, and improve the significance of SLNB in MCC.


Merkel cell carcinoma Sentinel lymph node False negative Recurrence Meta-analysis 


  1. 1.
    Gupta SG, Wang LC, Penas PF et al (2006) 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 142:685–690PubMedCrossRefGoogle Scholar
  2. 2.
    Morton DL, Wanek L, Nizze JA et al (1991) Improved long-term survival after lymphadenectomy of melanoma metastatic to regional nodes. Analysis of prognostic factors in 1134 patients from the John Wayne Cancer Clinic. Ann Surg 214:491–499 (discussion 9–501)PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Messina JL, Reintgen DS, Cruse CW et al (1997) Selective lymphadenectomy in patients with Merkel cell (cutaneous neuroendocrine) carcinoma. Ann Surg Oncol 4:389–395PubMedCrossRefGoogle Scholar
  4. 4.
    Pfeifer T, Weinberg H, Brady MS (1997) Lymphatic mapping for Merkel cell carcinoma. J Am Acad Dermatol 37:650–651PubMedCrossRefGoogle Scholar
  5. 5.
    Ames SE, Krag DN, Brady MS (1998) Radiolocalization of the sentinel lymph node in Merkel cell carcinoma: a clinical analysis of seven cases. J Surg Oncol 67:251–254PubMedCrossRefGoogle Scholar
  6. 6.
    Hill AD, Brady MS, Coit DG (1999) Intraoperative lymphatic mapping and sentinel lymph node biopsy for Merkel cell carcinoma. Br J Surg 86:518–521PubMedCrossRefGoogle Scholar
  7. 7.
    Sian KU, Wagner JD, Sood R et al (1999) Lymphoscintigraphy with sentinel lymph node biopsy in cutaneous Merkel cell carcinoma. Ann Plast Surg 42:679–682PubMedCrossRefGoogle Scholar
  8. 8.
    Kurul S, Mudun A, Aksakal N et al (2000) Lymphatic mapping for Merkel cell carcinoma. Plast Reconstr Surg 105:680–683PubMedCrossRefGoogle Scholar
  9. 9.
    Wasserberg N, Schachter J, Fenig E et al (2000) Applicability of the sentinel node technique to Merkel cell carcinoma. Dermatol Surg 26:138–141PubMedCrossRefGoogle Scholar
  10. 10.
    Zeitouni NC, Cheney RT, Delacure MD (2000) Lymphoscintigraphy, sentinel lymph node biopsy, and Mohs micrographic surgery in the treatment of Merkel cell carcinoma. Dermatol Surg 26:12–18PubMedCrossRefGoogle Scholar
  11. 11.
    Allen PJ, Busam K, Hill AD et al (2001) Immunohistochemical analysis of sentinel lymph nodes from patients with Merkel cell carcinoma. Cancer 92:1650–1655PubMedCrossRefGoogle Scholar
  12. 12.
    Duker I, Starz H, Bachter D et al (2001) Prognostic and therapeutic implications of sentinel lymphonodectomy and S-staging in Merkel cell carcinoma. Dermatology 202:225–229PubMedCrossRefGoogle Scholar
  13. 13.
    Rodrigues LK, Leong SP, Kashani-Sabet M et al (2001) Early experience with sentinel lymph node mapping for Merkel cell carcinoma. J Am Acad Dermatol 45:303–308PubMedCrossRefGoogle Scholar
  14. 14.
    Mehrany K, Otley CC, Weenig RH et al (2002) A meta-analysis of the prognostic significance of sentinel lymph node status in Merkel cell carcinoma. Dermatol Surg 28:113–117 discussion 7PubMedGoogle Scholar
  15. 15.
    Su LD, Lowe L, Bradford CR et al (2002) Immunostaining for cytokeratin 20 improves detection of micrometastatic Merkel cell carcinoma in sentinel lymph nodes. J Am Acad Dermatol 46:661–666PubMedCrossRefGoogle Scholar
  16. 16.
    Michl C, Starz H, Bachter D et al (2003) Sentinel lymphonodectomy in nonmelanoma skin malignancies. Br J Dermatol 149:763–769PubMedCrossRefGoogle Scholar
  17. 17.
    Pan D, Narayan D, Ariyan S (2002) Merkel cell carcinoma: five case reports using sentinel lymph node biopsy and a review of 110 new cases. Plast Reconstr Surg 110:1259–1265PubMedCrossRefGoogle Scholar
  18. 18.
    Blom A, Kolb F, Lumbroso J et al (2003) Significance of sentinel lymph node biopsy in Merkel cell carcinoma. Analysis of 11 cases. Ann Dermatol Venereol 130:417–422PubMedGoogle Scholar
  19. 19.
    Schmalbach CE, Lowe L, Teknos TN et al (2005) Reliability of sentinel lymph node biopsy for regional staging of head and neck Merkel cell carcinoma. Arch Otolaryngol Head Neck Surg 131:610–614PubMedCrossRefGoogle Scholar
  20. 20.
    Maza S, Trefzer U, Hofmann M et al (2006) Impact of sentinel lymph node biopsy in patients with Merkel cell carcinoma: results of a prospective study and review of the literature. Eur J Nucl Med Mol Imaging 33:433–440PubMedCrossRefGoogle Scholar
  21. 21.
    Ortin-Perez J, van Rijk MC, Valdes-Olmos RA et al (2007) Lymphatic mapping and sentinel node biopsy in Merkel’s cell carcinoma. Eur J Surg Oncol 33:119–122PubMedCrossRefGoogle Scholar
  22. 22.
    Warner RE, Quinn MJ, Hruby G et al (2008) Management of merkel cell carcinoma: the roles of lymphoscintigraphy, sentinel lymph node biopsy and adjuvant radiotherapy. Ann Surg Oncol 15:2509–2518PubMedCrossRefGoogle Scholar
  23. 23.
    Fields RC, Busam KJ, Chou JF et al (2011) 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 18:2529–2537PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Howle J, Veness M (2012) Sentinel lymph node biopsy in patients with Merkel cell carcinoma: an emerging role and the Westmead hospital experience. Australas J Dermatol 53:26–31PubMedCrossRefGoogle Scholar
  25. 25.
    Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17:1471–1474PubMedCrossRefGoogle Scholar
  26. 26.
    Allen PJ, Bowne WB, Jaques DP et al (2005) Merkel cell carcinoma: prognosis and treatment of patients from a single institution. J Clin Oncol 23:2300–2309PubMedCrossRefGoogle Scholar
  27. 27.
    Lemos BD, Storer BE, Iyer JG et al (2010) 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 63:751–761PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Chao C, Wong SL, Ross MI et al (2002) Patterns of early recurrence after sentinel lymph node biopsy for melanoma. Am J Surg 184:520–524 (discussion 5)PubMedCrossRefGoogle Scholar
  29. 29.
    Morton DL, Thompson JF, Cochran AJ et al (2006) Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med 355:1307–1317PubMedCrossRefGoogle Scholar
  30. 30.
    Testori A, De Salvo GL, Montesco MC et al (2009) Clinical considerations on sentinel node biopsy in melanoma from an Italian multicentric study on 1,313 patients (SOLISM-IMI). Ann Surg Oncol 16:2018–2027PubMedCrossRefGoogle Scholar
  31. 31.
    Nowecki ZI, Rutkowski P, Nasierowska-Guttmejer A et al (2006) Survival analysis and clinicopathological factors associated with false-negative sentinel lymph node biopsy findings in patients with cutaneous melanoma. Ann Surg Oncol 13:1655–1663PubMedCrossRefGoogle Scholar
  32. 32.
    Jones EL, Jones TS, Pearlman NW et al (2013) Long-term follow-up and survival of patients following a recurrence of melanoma after a negative sentinel lymph node biopsy result. JAMA Surg 16:1–6Google Scholar
  33. 33.
    Namikawa K, Yamazaki N (2011) Sentinel lymph node biopsy guided by indocyanine green fluorescence for cutaneous melanoma. Eur J Dermatol 21:184–190PubMedGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2014

Authors and Affiliations

  • Yoshitsugu Shibayama
    • 1
  • Shinichi Imafuku
    • 1
  • Akira Takahashi
    • 1
  • Juichiro Nakayama
    • 1
  1. 1.Department of Dermatology, Faculty of MedicineFukuoka UniversityFukuokaJapan

Personalised recommendations