Objectives: This study was aimed at investigating the prognostic role of multiple lymph node basin drainage (MLBD) in patients with positive sentinel lymph node (SLN) biopsy. Background: MLBD is frequently observed in patients with trunk melanoma undergoing SLN. The prognostic value of MLBD in SLN-positive patients is still debated. Methods: Retrospective data from 312 trunk melanoma patients with positive SLN biopsy (1991-2012) at 6 Italian referral centres were gathered in a multicentre database. MLBD was defined at preoperative lymphoscintigraphy. Clinical and pathological data were analysed for their association with disease-free interval (DFI) and disease-specific (DSS) survival. Results: MLBD was identified in 34.6% of patients (108/312) and was significantly associated with >1 positive SLN (37 vs. 15.2%; p < 0.001) and with >1 positive lymph node (LN) after complete lymph node dissection (CLND) (50.9 vs. 34.8%; p = 0.033). No differences were observed according to drainage pattern in patients who had negative and positive non-SLN at CLND. MLBD was not associated with either DFI or DSS. Multivariate analyses showed that tumour thickness, ulceration, and number of metastatic LNs were associated with worse DFI and DSS, while regression confirmed its protective role in survival. Conclusion: In positive SLN patients, MLBD has no association with survival, which is mainly related to American Joint Committee on Cancer (AJCC) prognostic factors. Since the overall number of positive LNs drives the prognosis, the importance of a CLND in all the positive basins is confirmed.

1.
Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Nieweg OE, Roses DF, et al: Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med 2014;370:599-609.
2.
Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al: Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009;27:6199-6206.
3.
Fadaki N, Li R, Parrett B, Sanders G, Thummala S, Martineau L, et al: Is head and neck melanoma different from trunk and extremity melanomas with respect to sentinel lymph node status and clinical outcome? Ann Surg Oncol 2013;20:3089-3097.
4.
White RL Jr, Ayers GD, Stell VH, Ding S, Gershenwald JE, Salo JC, et al: Factors predictive of the status of sentinel lymph nodes in melanoma patients from a large multicenter database. Ann Surg Oncol 2011;18:3593-3600.
5.
Quaglino P, Ribero S, Osella-Abate S, Macrì L, Grassi M, Caliendo V, et al: Clinico-pathologic features of primary melanoma and sentinel lymph node predictive for non-sentinel lymph node involvement and overall survival in melanoma patients: a single centre observational cohort study. Surg Oncol 2011;20:259-264.
6.
Balch CM, Soong SJ, Bartolucci AA, Urist MM, Karakousis CP, Smith TJ, 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;224:255-266.
7.
Garbe C, Büttner P, Bertz J, Burg G, d'Hoedt B, Drepper H, et al: Primary cutaneous melanoma. Prognostic classification of anatomic location. Cancer 1995;75:2492-499.
8.
Schuchter L, Schultz DJ, Synnestvedt M, Trock BJ, Guerry D, Elder DE, et al: A prognostic model for predicting ten-year survival in patients with primary melanoma. The Pigmented Lesion Group. Ann Intern Med 1996;125:369-375.
9.
Bradford PT, Anderson WF, Purdue MP Goldstein AM, Tucker MA: Rising melanoma incidence rates of the trunk among younger women in the United States. Cancer Epidemiol Biomarkers Prev 2010;19:2401-2406.
10.
Dal H, Boldemann C, Lindelof B: Does relative melanoma distribution by body site 1960-2004 reflect changes in intermittent exposure and intentional tanning in the Swedish population? Eur J Dermatol 2007;17:428-434.
11.
Sanlorenzo M, Ribero S, Osella-Abate S, Zugna D, Marenco F, Macripò G, et al: Prognostic differences across sexes in melanoma patients: what has changed from the past? Melanoma Res 2014;24:568-576.
12.
Porter GA, Ross MI, Berman RS, Lee JE, Mansfield PF, Gershenwald JE: Significance of multiple nodal basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy. Ann Surg Oncol 2000;7:256-261.
13.
Jimenez RE, Panageas K, Busam KJ, Brady MS: Prognostic implications of multiple lymphatic basins drainage in patients with truncal melanoma. J Clin Oncol 2005;23:518-524.
14.
Jacobs IA, Chang CK, Salti GI: Significance of dual-basins drainage in patients with truncal melanoma undergoing sentinel lymph node biopsy. J Am Acad Dermatol 2003;49:615-619.
15.
McHugh JB, Su L, Griffith KA, Schwartz JL, Wong SL, Cimmino V, et al: Significance of multiple lymphatic basins drainage in truncal melanoma patients undergoing sentinel lymph node biopsy. Ann Surg Oncol 2006;13:1216-1223.
16.
Rossi CR, De Salvo GL, Trifirò G, Trifirò G, Mocellin S, Landi G, et al: The impact of lymphoscintigraphy technique on the outcome of sentinel node biopsy in 1,313 patients with cutaneous melanoma: an Italian multicentric study (SOLISM-IMI). J Nucl Med 2006;47:234-241.
17.
Sommariva A, Clemente C, Rossi CR: Standardization and quality control of surgical treatment of cutaneous melanoma: looking for consensus of the Italian melanoma intergroup. Eur J Surg Oncol 2015;41:148-156.
18.
Kang S, Barnhill RL, Mihm MC Jr, Sober AJ: Histologic regression in malignant melanoma: an interobserver concordance study. J Cutan Pathol 1993;20:126-129.
19.
Ribero S, Moscarella E, Ferrara G, Piana S, Argenziano G, Longo C: Regression in cutaneous melanoma: a comprehensive review from diagnosis to prognosis. J Eur Acad Dermatol Venereol 2016;30:2030-2037.
20.
Azzola MF, Shaw HM, Thompson JF, Soong SJ, Scolyer RA, Watson GF, et al: Tumor mitotic rate is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma: an analysis of 3661 patients from a single center. Cancer 2003;97:1488-1498.
21.
Gillgren P, Brattstrom G, Frisell J, Palmgren J, Ringborg U, Hansson J, et al: Effect of primary site on prognosis in patients with cutaneous malignant melanoma: a study using a new model to analyze anatomical locations. Melanoma Res 2005;15:125- 132.
22.
Kuller LH, Goldstein BD: Suggestions for STROBE recommendations. Epidemiology 2007;18:792-793.
23.
Ribero S, Osella-Abate S, Sanlorenzo M, Balagna E, Senetta R, Fierro MT, et al: Sentinel lymph node biopsy in thick-melanoma patients (n = 350): what is its prognostic role? Ann Surg Oncol 2015;22:1967-1973.
24.
Mandalà M, Galli F, Cattaneo L, Merelli B, Rulli E, Ribero S, et al: Mitotic rate correlates with sentinel lymph node status and outcome in cutaneous melanoma greater than 1 millimeter in thickness: a multi-institutional study of 1,524 cases. J Am Acad Dermatol 2017;76:264-273.e2.
25.
Thompson JF, Soong SJ, Balch CM, Gershenwald JE, Ding S, Coit DG, et al: Prognostic significance of mitotic rate in localized primary cutaneous melanoma: an analysis of patients in the multi-institutional American Joint Committee on Cancer melanoma staging database. J Clin Oncol 2011;29:2199-2205.
26.
Sondak VK, Taylor JM, Sabel MS, Wang Y, Lowe L, Grover AC, et al: Mitotic rate and younger age are predictors of sentinel lymph node positivity: lessons learned from the generation of a probabilistic model. Ann Surg Oncol 2004;11:247-258.
27.
Mocellin S, Ambrosi A, Montesco MC, Foletto M, Zavagno G, Nitti D, et al: Support vector machine learning model for the prediction of sentinel node status in patients with cutaneous melanoma. Ann Surg Oncol 2006;13:1113-1122.
28.
Mitra A, Conway C, Walker C, Cook M, Powell B, Lobo S, Chan M, et al: Melanoma sentinel node biopsy and prediction models for relapse and overall survival. Br J Cancer 2010;103:1229-1236.
29.
Roach BA, Burton AL, Mays MP, Ginter BA, Martin RC, Stromberg AJ, et al: Does mitotic rate predict sentinel lymph node metastasis or survival in patients with intermediate and thick melanoma? Am J Surg 2010;200:759-764.
30.
Speijers MJ, Bastiaannet E, Sloot S, Suurmeijer AJ, Hoekstra HJ: Tumor Mitotic Rate Added to the Equation: Melanoma Prognostic Factors Changed? : A single-institution database study on the prognostic value of tumor mitotic rate for sentinel lymph node status and survival of cutaneous melanoma patients. Ann Surg Oncol 2015;22:2978-2987.
31.
MacKie RM, Hauschild A, Eggermont AM: Epidemiology of invasive cutaneous melanoma. Ann Oncol 2009;20(supp 6):vi1-vi71.
32.
Pollack LA, Li J, Berkowitz Z, et al: Melanoma survival in the United States, 1992 to 2005. J Am Acad Dermatol 2011;65(5 suppl 1):S78-S86.
33.
Uren RF, Howman-Giles R, Thompson JF, et al: Interval nodes: the forgotten sentinel nodes in patients with melanoma. Arch Surg 2000;135:1168-1172.
34.
Joosse A, Collette S, Suciu S, Nijsten T, Patel PM, Keilholz U, et al: Sex is an independent prognostic indicator for survival and relapse/progression-free survival in metastasized stage III to IV melanoma: a pooled analysis of five European Organisation for Research and Treatment of Cancer randomized controlled trials. J Clin Oncol 2013;31:2337-2346.
35.
Ribero S, Osella-Abate S, Sanlorenzo M, Savoia P, Astrua C, Cavaliere G, et al: Favourable prognostic role of regression of primary melanoma in AJCC stage I-II patients. Br J Dermatol 2013;169:1240-1245.
36.
Caracò C, Marone U, Di Monta G, et al: Surgical management of sentinel lymph node biopsy outside major nodal basin in patients with cutaneous melanoma. Ann Surg Oncol 2014;21:300-305.
37.
Gualano MR, Osella-Abate S, Scaioli G, Marra E, Bert F, Faure E, Baduel ES, Balagna E, Quaglino P, Fierro MT, Siliquini R, Ribero S: Prognostic role of histologic regression in primary cutaneous melanoma: a systematic review and meta-analysis. Br J Dermatol 2017, Epub ahead of print.
38.
Ribero S, Gualano MR, Osella-Abate S, Scaioli G, Bert F, Sanlorenzo M, et al: Association of histologic regression in primary melanoma with sentinel lymph node status: a systematic review and meta-analysis. JAMA Dermatol 2015;151:1301-1307.
39.
Ma MW, Medicherla RC, Qian M, et al: Immune response in melanoma: an in-depth analysis of the primary tumor and corresponding sentinel lymph node. Mod Pathol 2012;25:1000-1010.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.