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Regional Nodal Staging: Clinically Node Negative

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Practical Manual for Dermatologic and Surgical Melanoma Management

Abstract

First developed and introduced by Dr. Donald Morton and colleagues in the early 1990s, sentinel lymph node biopsy (SLNB) is a technique to evaluate the pathologic status of regional lymph nodes (LN) in patients who present with clinically node-negative melanoma. The evidence for performing SLNB is strongest for patients diagnosed with intermediate-thickness melanomas (>1.0–4.0 mm in Breslow thickness). Additionally, SLNB may be considered for patients with higher risk thin (<0.8 mm with high-risk features, or ≥0.8–1.0 mm) and thick (>4.0 mm) melanomas. Lymphoscintigraphy with radiolabeled colloid should be performed preoperatively in order to accurately identify the regional draining nodal basin. Intradermal injection of blue dye may be additionally used intraoperatively to assist with SLN identification. For thorough pathologic evaluation, SLNs should be bivalved and serially sectioned. A combination of hematoxylin-eosin staining and immunohistochemistry (S-100, HMB-45, and MART-1) is typically utilized to identify LN metastases. SLNB specimens should be evaluated for the location of the tumor deposit within the LN (subcapsular, trabecular or intraparenchymal), presence or absence of extracapsular invasion, and size of the tumor deposit.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30.

    Article  PubMed  Google Scholar 

  2. Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eight edition cancer staging manual. CA Cancer J Clin. 2017;67:472–92.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Morton DL, Wen D-R, Wong JH, Economou JS, Cagle LA, Storm FK, Foshag LJ, Cochran AJ. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127:392–9.

    Article  CAS  PubMed  Google Scholar 

  4. Balch CM, Soong S-J, 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;224:255–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cascinelli N, Morabito A, Santinami M, MacKie RM, Belli F, Melanoma Programme WHO. Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial. Lancet. 1998;351:793–6.

    Article  CAS  PubMed  Google Scholar 

  6. Morton DL, Thompson JF, Cochran AJ, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355:1307–17.

    Article  CAS  PubMed  Google Scholar 

  7. 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;370:599–609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Balch CM, Buzaid AC, Soong S-J, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001;19:3635–48.

    Article  CAS  PubMed  Google Scholar 

  9. Wong SL, Faries MB, Kennedy EB, et al. Sentinel lymph node biopsy and management of regional lymph nodes in melanoma: American Society of Clinical Oncology and Society of Surgical Oncology clinical practice guideline update. Ann Surg Oncol. 2018;25:356–77.

    Article  PubMed  Google Scholar 

  10. Coit DG, Thompson JF, Albertini MR, et al. NCCN clinical practice guidelines in oncology: cutaneous melanoma version 2.2019. 2019.

    Google Scholar 

  11. Bartlett EK, Gupta M, Datta J, Gimotty PA, Guerry D, Xu X, Elder DE, Czerniecki BJ, Fraker DL, Karakousis GC. Prognosis of patients with melanoma and microsatellitosis undergoing sentinel lymph node biopsy. Ann Surg Oncol. 2014;21:1016–23.

    Article  PubMed  Google Scholar 

  12. Kachare SD, Singla P, Vohra NA, Zervos EE, Wong JH, Fitzgerald TL. Sentinel lymph node biopsy is prognostic but not therapeutic for thick melanoma. Surgery. 2015;158:662–8.

    Article  PubMed  Google Scholar 

  13. van der Ploeg APT, Haydu LE, Spillane AJ, Quinn MJ, Saw RPM, Shannon KF, Stretch JR, Uren RF, Scolyer RA, Thompson JF. 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;260:149–57.

    Article  PubMed  Google Scholar 

  14. Sperry SM, Charlton ME, Pagedar NA. Association of sentinel lymph node biopsy with survival for head and neck melanoma: survival analysis using the SEER database. JAMA Otolaryngol Head Neck Surg. 2014;140:1101–9.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kachare SD, Brinkley J, Wong JH, Vohra NA, Zervos EE, Fitzgerald TL. The influence of sentinel lymph node biopsy on survival for intermediate-thickness melanoma. Ann Surg Oncol. 2014;21:3377–85.

    Article  PubMed  Google Scholar 

  16. Bartlett EK, Peters MG, Blair A, et al. Identification of patients with intermediate thickness melanoma at low risk for sentinel lymph node positivity. Ann Surg Oncol. 2016;23:250–6.

    Article  PubMed  Google Scholar 

  17. Chang JM, Kosiorek HE, Dueck AC, et al. Stratifying SLN incidence in intermediate thickness melanoma patients. Am J Surg. 2018;215:699–706.

    Article  PubMed  Google Scholar 

  18. Hanna AN, Sinnamon AJ, Roses RE, Kelz RR, Elder DE, Xu X, Pockaj BA, Zager JS, Fraker DL, Karakousis GC. Relationship between age and likelihood of lymph node metastases in patients with intermediate thickness melanoma (1.01–4.00 mm): a National Cancer Database study. J Am Acad Dermatol. 2019;80:433–40.

    Article  PubMed  Google Scholar 

  19. Ribero S, Osella-Abate S, Sanlorenzo M, Balagna E, Senetta R, FIerro MT, Macripo G, Macri L, Sapino A, Quaglino P. Sentinel lymph node biopsy in thick-melanoma patients (N=350): what is its prognostic role? Ann Surg Oncol. 2015;22:1967–73.

    Article  CAS  PubMed  Google Scholar 

  20. Boada A, Tejera-Vaquerizo A, Ribero S, et al. Sentinel lymph node biopsy versus observation in thick melanoma: a multicenter propensity score matching study. Int J Cancer. 2018;142:641–8.

    Article  CAS  PubMed  Google Scholar 

  21. de Oliveira Filho RS, da Silva AM, de Oliveira DA, Oliveira GG, Nahas FX. Sentinel node biopsy should not be recommended for patients with thick melanoma. Rev Col Bras Cir. 2013;40:127–9.

    Article  PubMed  Google Scholar 

  22. Gershenwald JE, Mansfield PF, Lee JE, Ross MI. Role for lymphatic mapping and sentinel lymph node biopsy in patients with thick (> or = 4 mm) primary melanoma. Ann Surg Oncol. 2000;7:160–5.

    Article  CAS  PubMed  Google Scholar 

  23. Ferrone CR, Panageas KS, Busam K, Brady MS, Coit DG. Multivariate prognostic model for patients with thick cutaneous melanoma: importance of sentinel lymph node status. Ann Surg Oncol. 2002;9:637–45.

    Article  PubMed  Google Scholar 

  24. Gajdos C, Griffith KA, Wong SL, Johnson TM, Chang AE, Cimmino VM, Lowe L, Bradford CR, Rees RS, Sabel MS. Is there a benefit to sentinel lymph node biopsy in patients with T4 melanoma? Cancer. 2009;115:5752–60.

    Article  PubMed  Google Scholar 

  25. 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;121:1628–36.

    Article  PubMed  Google Scholar 

  26. Mozillo N, Pennacchioli E, Gandini S, Caraco C, Crispo A, Botti C, Secondo L, Barberis M, Verrecchia F, Testori A. Sentinel node biopsy in thin and thick melanoma. Ann Surg Oncol. 2013;20:2780–6.

    Article  Google Scholar 

  27. Karakousis GC, Gimotty PA, Bartlett EK, Sim M-S, Neuwirth MG, Fraker DL, Czerniecki BJ, Faries MB. Thin melanoma with nodal involvement: analysis of demographic, pathologic, and treatment factors with regard to prognosis. Ann Surg Oncol. 2017;24:952–9.

    Article  PubMed  Google Scholar 

  28. Sinnamon AJ, Neuwirth MG, Yalamanchi P, et al. Association between patient age and lymph node positivity in thin melanoma. JAMA Dermatol. 2017;153:866–73.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Conic RRZ, Ko J, Damiani G, Funchain P, Knackstedt T, Vij A, Vidimos A, Gastman BR. Predictors of sentinel lymph node positivity in thin melanoma using the National Cancer Database. J Am Acad Dermatol. 2019;80:441–7.

    Article  PubMed  Google Scholar 

  30. Cordeiro E, Gervais M-K, Shah PS, Hong NJL, Wright FC. Sentinel lymph node biopsy in thin cutaneous melanoma: a systematic review and meta-analysis. Ann Surg Oncol. 2016;23:4178–88.

    Article  PubMed  Google Scholar 

  31. Piazzalunga D, Ceresoli M, Allievi N, et al. Can sentinel node biopsy be safely omitted in thin melanoma? Risk factor analysis of 1272 multicenter prospective cases. Eur J Surg Oncol. 2019;45:820–4. https://doi.org/10.1016/j.ejso.2018.11.022.

    Article  PubMed  Google Scholar 

  32. Karakousis GC, Gimotty PA, Botbyl JD, et al. Predictors of regional nodal disease in patients with thin melanomas. Ann Surg Oncol. 2006;13:533–41.

    Article  PubMed  Google Scholar 

  33. Balch CM, Soong S-J, Gershenwald JE, et al. Age as a prognostic factor in patients with localized melanoma and regional metastases. Ann Surg Oncol. 2013;20:3961.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Balch CM, Soong S-J, Thompson JF, et al. Age as a predictor of sentinel node metastasis among patients with localized melanoma: an inverse correlation of melanoma mortality and incidence of sentinel node metastasis among young and old patients. Ann Surg Oncol. 2014;21:1075–81.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Holmes EC, Moseley HS, Morton DL, Clark W, Robinson D, Urist MM. A rational approach to the surgical management of melanoma. Ann Surg. 1977;186:481–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. White DC, Schuler FR, Pruitt SK, Culhane DK, Seigler HF, Coleman RE, Tyler DS. Timing of sentinel lymph node mapping after lymphoscintigraphy. Surgery. 1999;126:156–61.

    Article  CAS  PubMed  Google Scholar 

  37. Rossi CR, De Salvo GL, Trifiro 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;47:234–41.

    PubMed  Google Scholar 

  38. Alazraki N, Glass EC, Castronovo F, Valdes Olmos RA, Podoloff D. Procedure guideline for lymphoscintigraphy and the use of intraoperative gamma probe for sentinel lymph node localization in melanoma of intermediate thickness 1.0. J Nucl Med. 2002;43:1414–8.

    PubMed  Google Scholar 

  39. Vermeeren L, Valdes Olmos RA, Klop MC, van der Ploeg IMC, Nieweg OE, Balm AJM, van den Brekel MWM. SPECT/CT for sentinel lymph node mapping in head and neck melanoma. Head Neck. 2011;33:1–6.

    Article  PubMed  Google Scholar 

  40. Bilde A, von Buchwald C, Mortensen J, Marving J, Hamilton Therkildsen M, Kirkegaard J, Charabi B, Specht L. The role of SPECT-CT in the lymphoscintigraphic identification of sentinel nodes in patients with oral cancer. Acta Otolaryngol. 2006;126:1096–103.

    Article  PubMed  Google Scholar 

  41. Stoffels I, Boy C, Poppel T, Kuhn J, Klotgen K, Dissemond J, Schadendorf D, Klode J. Association between sentinel lymph node excision with or without preoperative SPECT/CT and metastatic node detection and disease-free survival in melanoma. JAMA. 2012;308:1007–14.

    Article  CAS  PubMed  Google Scholar 

  42. Trinh BB, Chapman BC, Gleisner A, Kwak JJ, Morgan R, McCarter MD, Gajdos C, Kounalakis N. SPECT/CT adds distinct lymph node basins and influences radiologic findings and surgical approach for sentinel lymph node biopsy in head and neck melanoma. Ann Surg Oncol. 2018;25:1716–22.

    Article  PubMed  Google Scholar 

  43. Daley MD, Norman PH, Leak JA, et al. Adverse events associated with the intraoperative injection of isosulfan blue. J Clin Anesth. 2004;16:332–41.

    Article  CAS  PubMed  Google Scholar 

  44. Fujisawa Y, Nakamura Y, Kawachi Y, Otsuka F. Indocyanine green fluorescence-navigated sentinel node biopsy showed higher sensitivity than the radioisotope or blue dye method, which may help to reduce false-negative cases in skin cancer. J Surg Oncol. 2012;106:41–5.

    Article  PubMed  Google Scholar 

  45. Sondak VK, King DW, Zager JS, et al. Combined analysis of phase III trials evaluating [99mTc]tilmanocept and vital blue dye for identification of sentinel lymph nodes in clinically node-negative cutaneous melanoma. Ann Surg Oncol. 2013;20:680–8.

    Article  PubMed  Google Scholar 

  46. 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;30:2912–8.

    Article  PubMed  PubMed Central  Google Scholar 

  47. McMasters KM, Reintgen DS, Ross MI, Wong SL, Gershenwald JE, Krag DN, Noyes RD, Viar V, Cerrito PB, Edwards MJ. Sentinel lymph node biopsy for melanoma: how many radioactive nodes should be removed. Ann Surg Oncol. 2001;8:192–7.

    Article  CAS  PubMed  Google Scholar 

  48. Ariyan S, Ali-Salaam P, Cheng DW, Truini C. Reliability of lymphatic mapping after wide local excision of cutaneous melanoma. Ann Surg Oncol. 2007;14:2377–83.

    Article  PubMed  Google Scholar 

  49. Evans HL, Krag DN, Teates D, et al. Lymphoscintigraphy and sentinel node biopsy accurately stage melanoma in patients presenting after wide local excision. Ann Surg Oncol. 2003;10:416–25.

    Article  PubMed  Google Scholar 

  50. Gannon CJ, Rousseau DL, Ross MI, Johnson MM, Lee JE, Mansfield PF, Cormier JN, Prieto PA, Gershenwald JE. Accuracy of lymphatic mapping and sentinel lymph node biopsy after previous wide local excision in patients with primary melanoma. Cancer. 2006;107:2647–52.

    Article  PubMed  Google Scholar 

  51. Leong SPL, Thelmo MC, Kim RP, Gokhale R, Rhee JY, Achtem TA, Morita E, Allen RE, Kashani-Sabet M, Sagebiel RW. Delayed harvesting of sentinel lymph nodes after previous wide local excision of extremity melanoma. Ann Surg Oncol. 2003;10:196–200.

    Article  PubMed  Google Scholar 

  52. Hodges M, Jones E, Jones T, Pearlman N, Gajdos C, Kounalakis N, McCarter M. Analysis of melanoma recurrence following a negative sentinel lymph node biopsy. Melanoma Manag. 2015;2:285–94.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Lee DY, Huynh KT, Teng A, Lau BJ, Vitug S, Lee J-H, Stern SL, Foshag LJ, Faries MB. Predictors and survival impact of false-negative sentinel nodes in melanoma. Ann Surg Oncol. 2016;23:1012–8.

    Article  PubMed  Google Scholar 

  54. Scolyer RA, Murali R, McCarthy SW, Thompson JF. Pathologic examination of sentinel lymph nodes from melanoma patients. Semin Diagn Pathol. 2008;25:100–11.

    Article  PubMed  Google Scholar 

  55. Cochran AJ, Wen D-R, Morton DL. Occult tumor cells in lymph nodes of patients with pathological stage I malignant melanoma. An immunohistological study. Am J Surg Pathol. 1988;12:612–8.

    Article  CAS  PubMed  Google Scholar 

  56. Mitteldorf C, Bertsch HP, Zapf A, Neumann C, Kretschmer L. Cutting a sentinel lymph node into slices is the optimal first step for examination of sentinel lymph nodes in melanoma patients. Mod Pathol. 2009;22:1622–7.

    Article  PubMed  Google Scholar 

  57. Jannink I, Fan M, Nagy S, Rayudu G, Dowlatshahi K. Serial sectioning of sentinel nodes in patients with breast cancer: a pilot study. Ann Surg Oncol. 1998;5:310–4.

    Article  CAS  PubMed  Google Scholar 

  58. Association of Directors of Anatomic and Surgical Pathology (ADASP). ADASP recommendations for processing and reporting of lymph node specimens submitted for evaluation of metastatic disease. Am J Surg Pathol. 2001;25:961–3.

    Article  Google Scholar 

  59. Messina JL, Glass LF, Cruse CW, Berman C, Ku NK, Reintgen DS. Pathologic examination of sentinel lymph node in malignant melanoma. Am J Surg Pathol. 1999;23:686–90.

    Article  CAS  PubMed  Google Scholar 

  60. Prieto VG, Clark SH. Processing of sentinel lymph nodes for detection of metastatic melanoma. Ann Diagn Pathol. 2002;6:257–64.

    Article  PubMed  Google Scholar 

  61. Cibull M. Handling sentinel lymph node biopsy specimens. Arch Pathol Lab Med. 1999;123:620–1.

    Article  CAS  PubMed  Google Scholar 

  62. Shidham VB, Qi DY, Acker S, Kampalath B, Chang C-C, George V, Komorowski R. Evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma: higher diagnostic accuracy with Melan-A and MART-1 compared with S-100 protein and HMB-45. Am J Surg Pathol. 2001;25:1039–46.

    Article  CAS  PubMed  Google Scholar 

  63. Chakera AH, Hesse B, Burak Z, et al. EANM-EORTC general recommendations for sentinel node diagnostics in melanoma. Eur J Nucl Med Mol Imaging. 2009;36:1713–42.

    Article  CAS  PubMed  Google Scholar 

  64. Karimipour DJ, Lowe L, Su L, Hamilton T, Sondak VK, Johnson TM, Fullen D. Standard immunostains for melanoma in sentinel lymph node specimens: Which ones are most useful? J Am Acad Dermatol. 2004;50:759–64.

    Article  PubMed  Google Scholar 

  65. Cook MG, Green MA, Anderson B, Eggermont AM, Ruiter DJ, Spatz A, Kissin MW, BWEM P, EORTC Melanoma Group. The development of optimal assessment of sentinel lymph nodes for melanoma. J Pathol. 2003;200:314–9.

    Article  PubMed  Google Scholar 

  66. Murray CA, Leong WL, McCready DR, Ghazarian DM. Histopathological patterns of melanoma metastases in sentinel lymph nodes. J Clin Pathol. 2004;57:64–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Lobo AZC, Tanabe KK, Luo S, Muzikansky A, Sober AJ, Tsao H, Cosimi B, Duncan LM. The distribution of microscopic melanoma metastases in sentinel lymph nodes: implications for pathology protocols. Am J Surg Pathol. 2012;36:1841–8.

    Article  PubMed  Google Scholar 

  68. van der Ploeg APT, van Akkooi ACJ, 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;29:2206–14.

    Article  PubMed  Google Scholar 

  69. Scoggins CR, Ross MI, Reintgen DS, et al. Prospective multi-institutional study of reverse transcriptase polymerase chain reaction for molecular staging of melanoma. J Clin Oncol. 2006;24:2849–57.

    Article  CAS  PubMed  Google Scholar 

  70. Temple CL, Snell LJ, Power SM, et al. Clinical significance of the RT-PCR positive sentinel node in melanoma. J Surg Oncol. 2007;95:546–54.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Giorgos C. Karakousis .

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Song, Y., Bruce, A.N., Tieniber, A.D., Xu, X., Karakousis, G.C. (2021). Regional Nodal Staging: Clinically Node Negative. In: Lee, D., Faries, M. (eds) Practical Manual for Dermatologic and Surgical Melanoma Management. Springer, Cham. https://doi.org/10.1007/978-3-030-27400-9_7

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