Evaluation and treatment of regional lymph nodes in melanoma
- Michael Stone, MD
Michael Stone, MD
- Chairman of Surgery
- Stamford Hospital
- Section Editors
- Michael B Atkins, MD
Michael B Atkins, MD
- Section Editor — Malignant Melanoma and Other Cutaneous Neoplasms; Cancer of the Kidney
- Deputy Director
- Georgetown Lombardi Comprehensive Cancer Center
- Russell S Berman, MD
Russell S Berman, MD
- Section Editor — Skin and Soft Tissue Surgery
- Chief of Surgical Oncology
- New York University Langone Medical Center
Surgical excision is the appropriate treatment for melanoma. Although resection usually controls the primary lesion, melanoma often metastasizes through lymphatic channels to regional lymph nodes. Accurate staging at diagnosis is important to assess the prognosis and determine whether the patient is eligible for clinical trials of adjuvant therapies (table 1A-B and table 2A-B). (See "Tumor node metastasis (TNM) staging system and other prognostic factors in cutaneous melanoma".)
The physical examination of regional lymph nodes is often inaccurate, since approximately 20 percent of clinically node-negative patients have metastatic involvement, and 20 percent of those with clinically positive nodes are pathologically negative. More definitive information about the status of the regional nodes can be obtained from sentinel lymph node biopsy (SLNB), elective lymph node dissection, or fine needle aspiration [1,2].
Both the staging of subclinical disease using lymphatic mapping followed by SLNB and the management of clinically apparent regional lymph nodes will be reviewed here. The surgical management of the primary lesion and adjuvant therapy are discussed separately. (See "Initial surgical management of melanoma of the skin and unusual sites" and "Adjuvant immunotherapy for melanoma".)
CLINICALLY NEGATIVE REGIONAL LYMPH NODES
Sentinel lymph node biopsy — Lymphatic mapping and sentinel lymph node biopsy (SLNB) is the standard approach for the management of patients with melanoma in whom there is a substantial risk of regional node metastasis. This approach permits the identification of patients with positive nodes and avoids elective lymph node dissection in those without nodal involvement. Proper application of this technique requires sufficient experience to identify the sentinel lymph nodes and ensure a low false negative rate.
The impact of lymphatic mapping with SLNB (with completion lymphadenectomy when positive nodes are identified) on survival remains uncertain [3-8].
- Rodrigues LK, Leong SP, Ljung BM, et al. Fine needle aspiration in the diagnosis of metastatic melanoma. J Am Acad Dermatol 2000; 42:735.
- Voit CA, van Akkooi AC, Schäfer-Hesterberg G, et al. Rotterdam Criteria for sentinel node (SN) tumor burden and the accuracy of ultrasound (US)-guided fine-needle aspiration cytology (FNAC): can US-guided FNAC replace SN staging in patients with melanoma? J Clin Oncol 2009; 27:4994.
- Morton DL, Thompson JF, Cochran AJ, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med 2006; 355:1307.
- Kretschmer L, Hilgers R, Möhrle M, et al. Patients with lymphatic metastasis of cutaneous malignant melanoma benefit from sentinel lymphonodectomy and early excision of their nodal disease. Eur J Cancer 2004; 40:212.
- Roka F, Kittler H, Cauzig P, et al. Sentinel node status in melanoma patients is not predictive for overall survival upon multivariate analysis. Br J Cancer 2005; 92:662.
- Cascinelli N, Belli F, Santinami M, et al. Sentinel lymph node biopsy in cutaneous melanoma: the WHO Melanoma Program experience. Ann Surg Oncol 2000; 7:469.
- Nowecki ZI, Rutkowski P, Nasierowska-Guttmejer A, Ruka W. Sentinel lymph node biopsy in melanoma patients with clinically negative regional lymph nodes--one institution's experience. Melanoma Res 2003; 13:35.
- Leiter U, Buettner PG, Bohnenberger K, et al. Sentinel lymph node dissection in primary melanoma reduces subsequent regional lymph node metastasis as well as distant metastasis after nodal involvement. Ann Surg Oncol 2010; 17:129.
- Krag DN, Meijer SJ, Weaver DL, et al. Minimal-access surgery for staging of malignant melanoma. Arch Surg 1995; 130:654.
- Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992; 127:392.
- Reintgen D, Cruse CW, Wells K, et al. The orderly progression of melanoma nodal metastases. Ann Surg 1994; 220:759.
- Wong SL, Balch CM, Hurley P, et al. Sentinel lymph node biopsy for melanoma: American Society of Clinical Oncology and Society of Surgical Oncology joint clinical practice guideline. J Clin Oncol 2012; 30:2912.
- Wong SL, Balch CM, Hurley P, et al. Sentinel lymph node biopsy for melanoma: American Society of Clinical Oncology and Society of Surgical Oncology joint clinical practice guideline. Ann Surg Oncol 2012; 19:3313.
- Morton DL, Thompson JF, Cochran AJ, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med 2014; 370:599.
- Mudun A, Murray DR, Herda SC, et al. Early stage melanoma: lymphoscintigraphy, reproducibility of sentinel node detection, and effectiveness of the intraoperative gamma probe. Radiology 1996; 199:171.
- Norman J, Cruse CW, Espinosa C, et al. Redefinition of cutaneous lymphatic drainage with the use of lymphoscintigraphy for malignant melanoma. Am J Surg 1991; 162:432.
- Thompson JF, Uren RF, Shaw HM, et al. Location of sentinel lymph nodes in patients with cutaneous melanoma: new insights into lymphatic anatomy. J Am Coll Surg 1999; 189:195.
- de Rosa N, Lyman GH, Silbermins D, et al. Sentinel node biopsy for head and neck melanoma: a systematic review. Otolaryngol Head Neck Surg 2011; 145:375.
- Valsecchi ME, Silbermins D, de Rosa N, et al. Lymphatic mapping and sentinel lymph node biopsy in patients with melanoma: a meta-analysis. J Clin Oncol 2011; 29:1479.
- Scoggins CR, Martin RC, Ross MI, et al. Factors associated with false-negative sentinel lymph node biopsy in melanoma patients. Ann Surg Oncol 2010; 17:709.
- van der Ploeg AP, Haydu LE, Spillane AJ, et al. Outcome following sentinel node biopsy plus wide local excision versus wide local excision only for primary cutaneous melanoma: analysis of 5840 patients treated at a single institution. Ann Surg 2014; 260:149.
- Morton DL, Hoon DS, Cochran AJ, et al. Lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: therapeutic utility and implications of nodal microanatomy and molecular staging for improving the accuracy of detection of nodal micrometastases. Ann Surg 2003; 238:538.
- Wrightson WR, Wong SL, Edwards MJ, et al. Complications associated with sentinel lymph node biopsy for melanoma. Ann Surg Oncol 2003; 10:676.
- Reintgen DS, Rapaport DP, Tanabe KK, Ross MI. Lymphatic mapping and sentinel lymphadenectomy. In: Cutaneous Melanoma, 3rd, Balch CM, Houghton AN, Sober AJ, Soong SJ (Eds), Quality Medical Publishing, St. Louis 1997.
- van der Ploeg AP, van Akkooi AC, Rutkowski P, et al. Prognosis in patients with sentinel node-positive melanoma is accurately defined by the combined Rotterdam tumor load and Dewar topography criteria. J Clin Oncol 2011; 29:2206.
- Gershenwald JE, Colome MI, Lee JE, et al. Patterns of recurrence following a negative sentinel lymph node biopsy in 243 patients with stage I or II melanoma. J Clin Oncol 1998; 16:2253.
- Rousseau DL Jr, Ross MI, Johnson MM, et al. Revised American Joint Committee on Cancer staging criteria accurately predict sentinel lymph node positivity in clinically node-negative melanoma patients. Ann Surg Oncol 2003; 10:569.
- Yamamoto M, Fisher KJ, Wong JY, et al. Sentinel lymph node biopsy is indicated for patients with thick clinically lymph node-negative melanoma. Cancer 2015; 121:1628.
- Han D, Zager JS, Shyr Y, et al. Clinicopathologic Predictors of Sentinel Lymph Node Metastasis in Thin Melanoma. J Clin Oncol 2013.
- Andtbacka RH, Gershenwald JE. Role of sentinel lymph node biopsy in patients with thin melanoma. J Natl Compr Canc Netw 2009; 7:308.
- Wong SL, Morton DL, Thompson JF, et al. Melanoma patients with positive sentinel nodes who did not undergo completion lymphadenectomy: a multi-institutional study. Ann Surg Oncol 2006; 13:809.
- Sondak VK. Nonsentinel node metastases in melanoma: do they reflect the biology of the tumor, the lymph node or the surgeon? : Editorial to Accompany Ghaferi et al., ASO-2009-03-0312.R1. Ann Surg Oncol 2009; 16:2965.
- Gershenwald JE, Andtbacka RH, Prieto VG, et al. Microscopic tumor burden in sentinel lymph nodes predicts synchronous nonsentinel lymph node involvement in patients with melanoma. J Clin Oncol 2008; 26:4296.
- van Akkooi AC, Nowecki ZI, Voit C, et al. Sentinel node tumor burden according to the Rotterdam criteria is the most important prognostic factor for survival in melanoma patients: a multicenter study in 388 patients with positive sentinel nodes. Ann Surg 2008; 248:949.
- Kingham TP, Panageas KS, Ariyan CE, et al. Outcome of patients with a positive sentinel lymph node who do not undergo completion lymphadenectomy. Ann Surg Oncol 2010; 17:514.
- Leiter U, Stadler F, Mauch C, et al. Complete lymph node dissection versus node dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial. Lancet Oncol 2016.
- National Institutes of Health clinical trials database. http://www.clinicaltrials.gov/ (Accessed on November 19, 2010).
- Veronesi U, Adamus J, Bandiera DC, et al. Delayed regional lymph node dissection in stage I melanoma of the skin of the lower extremities. Cancer 1982; 49:2420.
- Balch CM. Randomized surgical trials involving elective node dissection for melanoma. Adv Surg 1999; 32:255.
- Cascinelli N, Morabito A, Santinami M, et al. Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial. WHO Melanoma Programme. Lancet 1998; 351:793.
- Sim FH, Taylor WF, Pritchard DJ, Soule EH. Lymphadenectomy in the management of stage I malignant melanoma: a prospective randomized study. Mayo Clin Proc 1986; 61:697.
- Balch CM, Soong S, Ross MI, et al. Long-term results of a multi-institutional randomized trial comparing prognostic factors and surgical results for intermediate thickness melanomas (1.0 to 4.0 mm). Intergroup Melanoma Surgical Trial. Ann Surg Oncol 2000; 7:87.
- Balch CM, Soong SJ, Bartolucci AA, et al. Efficacy of an elective regional lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger. Ann Surg 1996; 224:255.
- Stadelmann WK, Rapaport DP, Soong SJ, et al. Prognostic clinical and pathologic features. In: Cutaneous Melanoma, 3rd, Balch CM, Houghton AN, Sober AJ, Soong SJ (Eds), Quality Medical Publishing, St. Louis 1997. p.12.
- Stadelmann WK, Rapaport DP, Soong SJ, et al. Stadelmann, WK, Rapaport, DP, Soong, SJ, et al. In: Cutaneous Melanoma, 3rd, Balch CM, Houghton AN, Sober AJ, Soon SJ (Eds), Quality Medical Publishing, St. Louis 1997. p.26.
- Shaw JH, Rumball EM. Complications and local recurrence following lymphadenectomy. Br J Surg 1990; 77:760.
- Coit DG, Brennan MF. Extent of lymph node dissection in melanoma of the trunk or lower extremity. Arch Surg 1989; 124:162.
- Badgwell B, Xing Y, Gershenwald JE, et al. Pelvic lymph node dissection is beneficial in subsets of patients with node-positive melanoma. Ann Surg Oncol 2007; 14:2867.
- CLINICALLY NEGATIVE REGIONAL LYMPH NODES
- Sentinel lymph node biopsy
- - Rationale
- - Sensitivity and specificity
- - Multicenter Selective Lymphadenectomy Trial-I
- Prognostic significance of the sentinel node
- Intermediate thickness melanomas
- - Incidence of nodal metastases
- - Melanoma-specific survival
- Thick melanomas
- Thin melanomas
- - Complications of SLNB
- - Minimal metastases
- - Patient selection
- Management of a positive SLNB
- Elective lymph node dissection
- CLINICALLY APPARENT REGIONAL LYMPH NODES
- Therapeutic lymphadenectomy
- Extent of dissection and morbidity
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS