Regional Therapies: Clinically-Apparent Nodal Disease



Although the majority of newly diagnosed melanomas are early stage, a significant proportion present with clinically-apparent nodal disease. This particular subset is managed quite differently from those with clinically node negative microscopic disease identified on sentinel lymph node biopsy. The focus of this chapter will be on multi-modality management of clinical apparent nodal disease as a synchronous presentation in patients with a newly diagnosed cutaneous malignant melanoma. Review of the state of the art, current controversies and future directions are all discussed in the context of a typical clinical presentation.


Melanoma Lymph nodes Palpable Lymphadenectomy 


  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.CrossRefGoogle Scholar
  2. 2.
    Jemal A, Saraiya M, Patel P, Cherala SS, Barnholtz-Sloan J, Kim J, et al. Recent trends in cutaneous melanoma incidence and death rates in the United States, 1992–2006. J Am Acad Dermatol. 2011;65(5 Suppl 1):S17–25.e1–3.PubMedGoogle Scholar
  3. 3.
    Faries MB, Thompson JF, Cochran AJ, Andtbacka RH, Mozzillo N, Zager JS, et al. Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med. 2017;376(23):2211–22.CrossRefGoogle Scholar
  4. 4.
    Basler GC, Fader DJ, Yahanda A, Sondak VK, Johnson TM. The utility of fine needle aspiration in the diagnosis of melanoma metastatic to lymph nodes. J Am Acad Dermatol. 1997;36(3 Pt 1):403–8.CrossRefGoogle Scholar
  5. 5.
    Hall BJ, Schmidt RL, Sharma RR, Layfield LJ. Fine-needle aspiration cytology for the diagnosis of metastatic melanoma: systematic review and meta-analysis. Am J Clin Pathol. 2013;140(5):635–42.CrossRefGoogle Scholar
  6. 6.
    Buzaid AC, Tinoco L, Ross MI, Legha SS, Benjamin RS. Role of computed tomography in the staging of patients with local-regional metastases of melanoma. J Clin Oncol. 1995;13(8):2104–8.CrossRefGoogle Scholar
  7. 7.
    Johnson TM, Fader DJ, Chang AE, Yahanda A, Smith JW 2nd, Hamlet KR, et al. Computed tomography in staging of patients with melanoma metastatic to the regional nodes. Ann Surg Oncol. 1997;4(5):396–402.CrossRefGoogle Scholar
  8. 8.
    Kuvshinoff BW, Kurtz C, Coit DG. Computed tomography in evaluation of patients with stage III melanoma. Ann Surg Oncol. 1997;4(3):252–8.CrossRefGoogle Scholar
  9. 9.
    Schroer-Gunther MA, Wolff RF, Westwood ME, Scheibler FJ, Schurmann C, Baumert BG, et al. F-18-fluoro-2-deoxyglucose positron emission tomography (PET) and PET/computed tomography imaging in primary staging of patients with malignant melanoma: a systematic review. Syst Rev. 2012;1:62.CrossRefGoogle Scholar
  10. 10.
    Schule SC, Eigentler TK, Garbe C, la Fougere C, Nikolaou K, Pfannenberg C. Influence of (18)F-FDG PET/CT on therapy management in patients with stage III/IV malignant melanoma. Eur J Nucl Med Mol Imaging. 2016;43(3):482–8.CrossRefGoogle Scholar
  11. 11.
    Rodriguez Rivera AM, Alabbas H, Ramjaun A, Meguerditchian AN. Value of positron emission tomography scan in stage III cutaneous melanoma: a systematic review and meta-analysis. Surg Oncol. 2014;23(1):11–6.CrossRefGoogle Scholar
  12. 12.
    Romano E, Scordo M, Dusza SW, Coit DG, Chapman PB. Site and timing of first relapse in stage III melanoma patients: implications for follow-up guidelines. J Clin Oncol. 2010;28(18):3042–7.CrossRefGoogle Scholar
  13. 13.
    Matthey-Gie ML, Gie O, Deretti S, Demartines N, Matter M. Prospective randomized study to compare lymphocele and lymphorrhea control following inguinal and axillary therapeutic lymph node dissection with or without the use of an ultrasonic scalpel. Ann Surg Oncol. 2016;23(5):1716–20.CrossRefGoogle Scholar
  14. 14.
    Gyorki DE, Boyle JO, Ganly I, Morris L, Shaha AR, Singh B, et al. Incidence and location of positive nonsentinel lymph nodes in head and neck melanoma. Eur J Surg Oncol. 2014;40(3):305–10.CrossRefGoogle Scholar
  15. 15.
    Nessim C, Law C, McConnell Y, Shachar S, McKinnon G, Wright F. How often do level III nodes bear melanoma metastases and does it affect patient outcomes? Ann Surg Oncol. 2013;20(6):2056–64.CrossRefGoogle Scholar
  16. 16.
    Jakub JW, Terando AM, Sarnaik A, Ariyan CE, Faries MB, Zani S Jr, et al. Safety and feasibility of minimally invasive inguinal lymph node dissection in patients with melanoma (SAFE-MILND): report of a prospective multi-institutional trial. Ann Surg. 2017;265(1):192–6.CrossRefGoogle Scholar
  17. 17.
    Morton DL, Cochran AJ, Thompson JF, Elashoff R, Essner R, Glass EC, et al. Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-I, an international multicenter trial. Ann Surg. 2005;242(3):302–11; discussion 11–3.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Wrightson WR, Wong SL, Edwards MJ, Chao C, Reintgen DS, Ross MI, et al. Complications associated with sentinel lymph node biopsy for melanoma. Ann Surg Oncol. 2003;10(6):676–80.CrossRefGoogle Scholar
  19. 19.
    Delman KA, Kooby DA, Ogan K, Hsiao W, Master V. Feasibility of a novel approach to inguinal lymphadenectomy: minimally invasive groin dissection for melanoma. Ann Surg Oncol. 2010;17(3):731–7.CrossRefGoogle Scholar
  20. 20.
    Eggermont AM, Suciu S, Santinami M, Testori A, Kruit WH, Marsden J, et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet. 2008;372(9633):117–26.CrossRefGoogle Scholar
  21. 21.
    Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med. 2016;375(19):1845–55.CrossRefGoogle Scholar
  22. 22.
    Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM, Cowey CL, et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med. 2017;377(19):1824–35.CrossRefGoogle Scholar
  23. 23.
    Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson V, Dalle S, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med. 2018;378(19):1789–801.CrossRefGoogle Scholar
  24. 24.
    Henderson MA, Burmeister BH, Ainslie J, Fisher R, Di Iulio J, Smithers BM, et al. Adjuvant lymph-node field radiotherapy versus observation only in patients with melanoma at high risk of further lymph-node field relapse after lymphadenectomy (ANZMTG 01.02/TROG 02.01): 6-year follow-up of a phase 3, randomised controlled trial. Lancet Oncol. 2015;16(9):1049–60.CrossRefGoogle Scholar
  25. 25.
    Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Ding S, Byrd DR, et al. Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases. J Clin Oncol. 2010;28(14):2452–9.CrossRefGoogle Scholar
  26. 26.
    Khosrotehrani K, van der Ploeg AP, Siskind V, Hughes MC, Wright A, Thomas J, et al. Nomograms to predict recurrence and survival in stage IIIB and IIIC melanoma after therapeutic lymphadenectomy. Eur J Cancer. 2014;50(7):1301–9.CrossRefGoogle Scholar
  27. 27.
    Spillane AJ, Pasquali S, Haydu LE, Thompson JF. Patterns of recurrence and survival after lymphadenectomy in melanoma patients: clarifying the effects of timing of surgery and lymph node tumor burden. Ann Surg Oncol. 2014;21(1):292–9.CrossRefGoogle Scholar
  28. 28.
    Wevers KP, Bastiaannet E, Poos HP, van Ginkel RJ, Plukker JT, Hoekstra HJ. Therapeutic lymph node dissection in melanoma: different prognosis for different macrometastasis sites? Ann Surg Oncol. 2012;19(12):3913–8.CrossRefGoogle Scholar
  29. 29.
    Coit DG, Thompson JA, Albertini MR, Barker C, Carson WE, Contreras C, et al. Cutaneous melanoma, version 2.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2019;17(4):367–402.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2021

Authors and Affiliations

  1. 1.Division of Surgical Oncology, Department of SurgeryMayo Clinic ArizonaPhoenixUSA

Personalised recommendations