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Pathologic evaluation of regional lymph nodes in melanoma

April W Armstrong, MD, MPH
Vincent Liu, MD
Martin C Mihm, Jr, MD
Section Editors
Michael B Atkins, MD
Hensin Tsao, MD, PhD
Deputy Editor
Michael E Ross, MD


Cutaneous melanoma characteristically spreads via the lymphatic system from its primary site to the locoregional lymph nodes. Knowledge of lymph node status is important for prognosis and to determine the appropriateness of adjuvant systemic therapy.

The identification of patients with subclinical nodal metastases has undergone significant evolution over the past two decades. For patients for whom there is a reasonable risk of regional lymph node metastasis (melanomas >1 mm in thickness and certain thinner melanomas, especially those with ulceration or >1 mitosis/mm2), lymphatic mapping with sentinel lymph node (SLN) biopsy has become the standard staging approach [1]. If melanoma metastasis is present in the SLN biopsy, completion lymphadenectomy is usually recommended and adjuvant therapy considered. (See "Evaluation and treatment of regional lymph nodes in melanoma", section on 'Sentinel lymph node biopsy'.)

The pathologic evaluation of regional lymph nodes is discussed in this topic. The role of SLN biopsy and the management of patients with a positive SLN biopsy are discussed separately, as is the pathology of the primary lesion. (See "Evaluation and treatment of regional lymph nodes in melanoma" and "Pathologic characteristics of melanoma".)


Specimen preparation with hematoxylin and eosin (H&E) staining remains the gold standard for histologic interpretation of nodal material (picture 1) [2].

However, both serial sectioning and immunohistochemical staining for melanoma-associated tumor markers (eg, the highly sensitive S100 and the highly specific melanoma antigen recognized by T cells 1 [MART-1]) facilitate the detection of metastatic melanoma cells (picture 2). In one retrospective study of 235 histologically negative sentinel lymph nodes (SLNs) from 94 patients with cutaneous melanoma, deeper serial sections and immunohistochemical stains detected microscopic metastases in approximately 12 percent of cases that would otherwise have been reported as negative for metastasis [3].

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Literature review current through: Nov 2017. | This topic last updated: Nov 28, 2017.
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  1. Stebbins WG, Garibyan L, Sober AJ. Sentinel lymph node biopsy and melanoma: 2010 update Part I. J Am Acad Dermatol 2010; 62:723.
  2. http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2012/SkinMelanoma_12protocol.pdf (Accessed on November 06, 2014).
  3. Yu LL, Flotte TJ, Tanabe KK, et al. Detection of microscopic melanoma metastases in sentinel lymph nodes. Cancer 1999; 86:617.
  4. Gershenwalk JE, Scolyer RA, Hess KR, et al. Melanoma of the skin. In: AJCC Cancer Staging Manual, Eighth, Amin MB (Ed), Springer, Chicago 2017. p.563.
  5. Lino-Silva LS, Castillo-Medina AL, Salcedo-Hernández RA, García-Pérez L. Exhaustive pathologic work-up in sentinel lymph node biopsy for melanoma: is it necessary? Melanoma Res 2017; 27:116.
  6. Stowman AM, Hickman AW, Gru AA, Slingluff CL Jr. Histopathologic review of negative sentinel lymph node biopsies in thin melanomas: an argument for the routine use of immunohistochemistry. Melanoma Res 2017; 27:369.
  7. Carson KF, Wen DR, Li PX, et al. Nodal nevi and cutaneous melanomas. Am J Surg Pathol 1996; 20:834.
  8. Siroy AE, Aung PP, Torres-Cabala CA, et al. Clinical significance of BRAF V600E mutational status in capsular nevi of sentinel lymph nodes in patients with primary cutaneous melanoma. Hum Pathol 2017; 59:48.
  9. Scolyer RA, Thompson JF, McCarthy SW, et al. Intraoperative frozen-section evaluation can reduce accuracy of pathologic assessment of sentinel nodes in melanoma patients. J Am Coll Surg 2005; 201:821.
  10. Murray CA, Leong WL, McCready DR, Ghazarian DM. Histopathological patterns of melanoma metastases in sentinel lymph nodes. J Clin Pathol 2004; 57:64.
  11. Dewar DJ, Newell B, Green MA, et al. The microanatomic location of metastatic melanoma in sentinel lymph nodes predicts nonsentinel lymph node involvement. J Clin Oncol 2004; 22:3345.
  12. van Akkooi AC, Spatz A, Eggermont AM, et al. Expert opinion in melanoma: the sentinel node; EORTC Melanoma Group recommendations on practical methodology of the measurement of the microanatomic location of metastases and metastatic tumour burden. Eur J Cancer 2009; 45:2736.
  13. van der Ploeg AP, van Akkooi AC, Haydu LE, et al. The prognostic significance of sentinel node tumour burden in melanoma patients: an international, multicenter study of 1539 sentinel node-positive melanoma patients. Eur J Cancer 2014; 50:111.
  14. Debarbieux S, Duru G, Dalle S, et al. Sentinel lymph node biopsy in melanoma: a micromorphometric study relating to prognosis and completion lymph node dissection. Br J Dermatol 2007; 157:58.
  15. Kakavand H, Vilain RE, Wilmott JS, et al. Tumor PD-L1 expression, immune cell correlates and PD-1+ lymphocytes in sentinel lymph node melanoma metastases. Mod Pathol 2015; 28:1535.
  16. Alessi C, Scapulatempo Neto C, Viana CR, Vazquez VL. PD-1/PD-L1 and VEGF-A/VEGF-C expression in lymph node microenvironment and association with melanoma metastasis and survival. Melanoma Res 2017; 27:565.
  17. Gibbs JF, Huang PP, Zhang PJ, et al. Accuracy of pathologic techniques for the diagnosis of metastatic melanoma in sentinel lymph nodes. Ann Surg Oncol 1999; 6:699.
  18. Messina JL, Glass LF, Cruse CW, et al. Pathologic examination of the sentinel lymph node in malignant melanoma. Am J Surg Pathol 1999; 23:686.
  19. Prieto VG. Sentinel lymph nodes in cutaneous melanoma: handling, examination, and clinical repercussion. Arch Pathol Lab Med 2010; 134:1764.
  20. Blessing K, Sanders DS, Grant JJ. Comparison of immunohistochemical staining of the novel antibody melan-A with S100 protein and HMB-45 in malignant melanoma and melanoma variants. Histopathology 1998; 32:139.
  21. Donato R. Functional roles of S100 proteins, calcium-binding proteins of the EF-hand type. Biochim Biophys Acta 1999; 1450:191.
  22. Coulie PG, Brichard V, Van Pel A, et al. A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 1994; 180:35.
  23. Busam KJ, Chen YT, Old LJ, et al. Expression of melan-A (MART1) in benign melanocytic nevi and primary cutaneous malignant melanoma. Am J Surg Pathol 1998; 22:976.
  24. Hochberg M, Lotem M, Gimon Z, et al. Expression of tyrosinase, MIA and MART-1 in sentinel lymph nodes of patients with malignant melanoma. Br J Dermatol 2002; 146:244.
  25. King R, Googe PB, Weilbaecher KN, et al. Microphthalmia transcription factor expression in cutaneous benign, malignant melanocytic, and nonmelanocytic tumors. Am J Surg Pathol 2001; 25:51.
  26. Busam KJ, Iversen K, Coplan KC, Jungbluth AA. Analysis of microphthalmia transcription factor expression in normal tissues and tumors, and comparison of its expression with S-100 protein, gp100, and tyrosinase in desmoplastic malignant melanoma. Am J Surg Pathol 2001; 25:197.
  27. King R, Weilbaecher KN, McGill G, et al. Microphthalmia transcription factor. A sensitive and specific melanocyte marker for MelanomaDiagnosis. Am J Pathol 1999; 155:731.
  28. Sheffield MV, Yee H, Dorvault CC, et al. Comparison of five antibodies as markers in the diagnosis of melanoma in cytologic preparations. Am J Clin Pathol 2002; 118:930.
  29. Hofbauer GF, Kamarashev J, Geertsen R, et al. Tyrosinase immunoreactivity in formalin-fixed, paraffin-embedded primary and metastatic melanoma: frequency and distribution. J Cutan Pathol 1998; 25:204.
  30. Willis BC, Johnson G, Wang J, Cohen C. SOX10: a useful marker for identifying metastatic melanoma in sentinel lymph nodes. Appl Immunohistochem Mol Morphol 2015; 23:109.
  31. Tacha D, Qi W, Ra S, et al. A newly developed mouse monoclonal SOX10 antibody is a highly sensitive and specific marker for malignant melanoma, including spindle cell and desmoplastic melanomas. Arch Pathol Lab Med 2015; 139:530.
  32. Ordóñez NG. Value of SOX10 immunostaining in tumor diagnosis. Adv Anat Pathol 2013; 20:275.
  33. Chen PL, Chen WS, Li J, et al. Diagnostic utility of neural stem and progenitor cell markers nestin and SOX2 in distinguishing nodal melanocytic nevi from metastatic melanomas. Mod Pathol 2013; 26:44.
  34. Reintgen, DS, Rapaport, et al. Lymphatic mapping and sentinel lymphadenectomy. In: Cutaneous Melanoma, 3rd, Balch, CM, Houghton, AN, Sober, AJ, Soong, SJ (Eds), Quality Medical Publishing, St. Louis 1997.
  35. Bostick PJ, Morton DL, Turner RR, et al. Prognostic significance of occult metastases detected by sentinel lymphadenectomy and reverse transcriptase-polymerase chain reaction in early-stage melanoma patients. J Clin Oncol 1999; 17:3238.
  36. Shivers SC, Wang X, Li W, et al. Molecular staging of malignant melanoma: correlation with clinical outcome. JAMA 1998; 280:1410.
  37. Goydos JS, Ravikumar TS, Germino FJ, et al. Minimally invasive staging of patients with melanoma: sentinel lymphadenectomy and detection of the melanoma-specific proteins MART-1 and tyrosinase by reverse transcriptase polymerase chain reaction. J Am Coll Surg 1998; 187:182.
  38. Li W, Stall A, Shivers SC, et al. Clinical relevance of molecular staging for melanoma: comparison of RT-PCR and immunohistochemistry staining in sentinel lymph nodes of patients with melanoma. Ann Surg 2000; 231:795.
  39. Blaheta HJ, Ellwanger U, Schittek B, et al. Examination of regional lymph nodes by sentinel node biopsy and molecular analysis provides new staging facilities in primary cutaneous melanoma. J Invest Dermatol 2000; 114:637.
  40. 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.
  41. Hao H, Xiao D, Pan J, et al. Sentinel Lymph Node Genes to Predict Prognosis in Node-Positive Melanoma Patients. Ann Surg Oncol 2017; 24:108.