Melanoma Epidemiology, Staging and Prognostic Factors



Melanoma is one of the most feared human malignancies because of its metastatic potential. However, most melanomas are fully cured by surgical removal and only a minority of patients diagnosed with melanoma will succumb to the disease. To care for our patients with this potentially deadly disease, it is essential to understand the metastatic and mortality risk of the disease. Staging has been developed to categorize patients and create groups who are expected to have similar clinical outcomes. Staging uses the best prognostic markers, but staging does not provide precise individual assessment of likely outcome. Numerous prognostic factors exist beyond the staging criteria, which may also help predict distant metastasis and mortality risk. In this chapter we will review the staging and prognostic factors of melanoma.


Melanoma Epidemiology Incidence Staging Ulceration Breslow depth Thickness Mitotic rate Sentinel lymph node Metastasis Prognostic factors Lactate dehydrogenase 


  1. 1.
    Surveillance E, End Results (SEER) Program. Cancer stat facts: melanoma of the skin. Surveillance, epidemiology, and end results (SEER) program. 2019.Google Scholar
  2. 2.
    Gershenwald JE, et al. Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67:472–92. Scholar
  3. 3.
    American Cancer Society. Cancer facts & figures 2019. 29 Apr 2019.Google Scholar
  4. 4.
    Gershenwald JE, Scolyer RA. Melanoma staging: American Joint Committee on Cancer (AJCC) 8th edition and beyond. Ann Surg Oncol. 2018;25:2105–10. Scholar
  5. 5.
    Gershenwald JE, Scolyer R, Hess KR, et al. Melanoma of the skin. In: Edge SB, Amin MB, Greene FL, et al., editors. AJCC cancer staging manual. 8th ed. New York: Springer International Publishing; 2017. p. 563–85.CrossRefGoogle Scholar
  6. 6.
    Balch CM, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27:6199–206. Scholar
  7. 7.
    Clark WH Jr, From L, Bernardino EA, Mihm MC. The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res. 1969;29:705–27.PubMedGoogle Scholar
  8. 8.
    Marghoob AA, Koenig K, Bittencourt FV, Kopf AW, Bart RS. Breslow thickness and Clark level in melanoma: support for including level in pathology reports and in American Joint Committee on Cancer Staging. Cancer. 2000;88:589–95.CrossRefGoogle Scholar
  9. 9.
    Balch CM, et al. A multifactorial analysis of melanoma: prognostic histopathological features comparing Clark’s and Breslow’s staging methods. Ann Surg. 1978;188:732–42. Scholar
  10. 10.
    Cherobin ACFP, Wainstein AJA, Colosimo EA, Goulart EMA, Bittencourt FV. Prognostic factors for metastasis in cutaneous melanoma. An Bras Dermatol. 2018;93:19–26. Scholar
  11. 11.
    Stucky CC, et al. Risk factors associated with local and in-transit recurrence of cutaneous melanoma. Am J Surg. 2010;200:770–4; discussion 774–775. Scholar
  12. 12.
    Faries MB, Wanek LA, Elashoff D, Wright BE, Morton DL. Predictors of occult nodal metastasis in patients with thin melanoma. Arch Surg. 2010;145:137–42. Scholar
  13. 13.
    Buttner P, et al. Primary cutaneous melanoma. Optimized cutoff points of tumor thickness and importance of Clark’s level for prognostic classification. Cancer. 1995;75:2499–506.CrossRefGoogle Scholar
  14. 14.
    Balch CM, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622–34. Scholar
  15. 15.
    Ellis R, et al. Epidermal AMBRA1 and Loricrin; a paradigm shift in the prognostication and stratification of AJCC stage I melanomas. Br J Dermatol. 2019.
  16. 16.
    Gimotty PA, et al. Thin primary cutaneous malignant melanoma: a prognostic tree for 10-year metastasis is more accurate than American Joint Committee on Cancer staging. J Clin Oncol. 2004;22:3668–76. Scholar
  17. 17.
    Baum C, et al. Sentinel node metastasis mitotic rate (SN-MMR) as a prognostic indicator of rapidly progressing disease in patients with sentinel node-positive melanomas. Int J Cancer. 2017;140:1907–17. Scholar
  18. 18.
    Barnhill RL, Fine JA, Roush GC, Berwick M. Predicting five-year outcome for patients with cutaneous melanoma in a population-based study. Cancer. 1996;78:427–32.<427::AID-CNCR8>3.0.CO;2-G.CrossRefPubMedGoogle Scholar
  19. 19.
    Kunte C, et al. Prognostic factors associated with sentinel lymph node positivity and effect of sentinel status on survival: an analysis of 1049 patients with cutaneous melanoma. Melanoma Res. 2010;20:330–7. Scholar
  20. 20.
    Lattanzi M, et al. Primary melanoma histologic subtype: impact on survival and response to therapy. J Natl Cancer Inst. 2019;111:180–8. Scholar
  21. 21.
    Chen LL, Jaimes N, Barker CA, Busam KJ, Marghoob AA. Desmoplastic melanoma: a review. J Am Acad Dermatol. 2013;68:825–33. Scholar
  22. 22.
    Moreau JF, Weissfeld JL, Ferris LK. Characteristics and survival of patients with invasive amelanotic melanoma in the USA. Melanoma Res. 2013;23:408–13. Scholar
  23. 23.
    Swetter SM, Ecker PM, Johnson DL, Harvell JD. Primary dermal melanoma: a distinct subtype of melanoma. Arch Dermatol. 2004;140:99–103. Scholar
  24. 24.
    Zettersten E, Shaikh L, Ramirez R, Kashani-Sabet M. Prognostic factors in primary cutaneous melanoma. Surg Clin North Am. 2003;83:61–75.CrossRefGoogle Scholar
  25. 25.
    Isaksson K, et al. Sentinel lymph node biopsy in patients with thin melanomas: Frequency and predictors of metastasis based on analysis of two large international cohorts. J Surg Oncol. 2018;118:599–605. Scholar
  26. 26.
    Clark WH Jr, et al. Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst. 1989;81:1893–904. Scholar
  27. 27.
    Crowson AN, Magro CM, Mihm MC. Prognosticators of melanoma, the melanoma report, and the sentinel lymph node. Mod Pathol. 2006;19(Suppl 2):S71–87. Scholar
  28. 28.
    Ladanyi A, et al. T-cell activation marker expression on tumor-infiltrating lymphocytes as prognostic factor in cutaneous malignant melanoma. Clin Cancer Res. 2004;10:521–30.CrossRefGoogle Scholar
  29. 29.
    Conroy JM, et al. Analytical validation of a next-generation sequencing assay to monitor immune responses in solid tumors. J Mol Diagn. 2018;20:95–109. Scholar
  30. 30.
    Xu X, et al. Lymphatic invasion is independently prognostic of metastasis in primary cutaneous melanoma. Clin Cancer Res. 2012;18:229–37. Scholar
  31. 31.
    Barnhill RL, Lugassy C. Angiotropic malignant melanoma and extravascular migratory metastasis: description of 36 cases with emphasis on a new mechanism of tumor spread. Pathology. 2004;36:485–90. Scholar
  32. 32.
    Baer SC, Schultz D, Synnestvedt M, Elder DE. Desmoplasia and neurotropism. Prognostic variables in patients with stage I melanoma. Cancer. 1995;76:2242–7.CrossRefGoogle Scholar
  33. 33.
    Cymerman RM, et al. De novo vs nevus-associated melanomas: differences in associations with prognostic indicators and survival. J Natl Cancer Inst. 2016;108:djw121. Scholar
  34. 34.
    Balch CM, et al. Age as a prognostic factor in patients with localized melanoma and regional metastases. Ann Surg Oncol. 2013;20:3961–8. Scholar
  35. 35.
    Kretschmer L, et al. Age as a key factor influencing metastasizing patterns and disease-specific survival after sentinel lymph node biopsy for cutaneous melanoma. Int J Cancer. 2011;129:1435–42. Scholar
  36. 36.
    Mervic L. Time course and pattern of metastasis of cutaneous melanoma differ between men and women. PLoS One. 2012;7:e32955. Scholar
  37. 37.
    Scoggins CR, et al. Gender-related differences in outcome for melanoma patients. Ann Surg. 2006;243:693–8; discussion 698–700. Scholar
  38. 38.
    Aizer AA, et al. Marital status and survival in patients with cancer. J Clin Oncol. 2013;31:3869–76. Scholar
  39. 39.
    McLaughlin JM, Fisher JL, Paskett ED. Marital status and stage at diagnosis of cutaneous melanoma: results from the Surveillance Epidemiology and End Results (SEER) program, 1973–2006. Cancer. 2011;117:1984–93. Scholar
  40. 40.
    Howard MD, et al. Anatomical location of primary melanoma: survival differences and sun exposure. J Am Acad Dermatol. 2019.
  41. 41.
    Garbe C, et al. Primary cutaneous melanoma. Prognostic classification of anatomic location. Cancer. 1995;75:2492–8.CrossRefGoogle Scholar
  42. 42.
    Bae JM, et al. Metastatic melanomas of unknown primary show better prognosis than those of known primary: a systematic review and meta-analysis of observational studies. J Am Acad Dermatol. 2015;72:59–70. Scholar
  43. 43.
    Weide B, et al. Serum markers lactate dehydrogenase and S100B predict independently disease outcome in melanoma patients with distant metastasis. Br J Cancer. 2012;107:422–8. Scholar
  44. 44.
    Diem S, et al. Serum lactate dehydrogenase as an early marker for outcome in patients treated with anti-PD-1 therapy in metastatic melanoma. Br J Cancer. 2016;114:256–61. Scholar
  45. 45.
    Sanmamed MF, et al. Relevance of MIA and S100 serum tumor markers to monitor BRAF inhibitor therapy in metastatic melanoma patients. Clin Chim Acta. 2014;429:168–74. Scholar
  46. 46.
    Huang SK, Hoon DS. Liquid biopsy utility for the surveillance of cutaneous malignant melanoma patients. Mol Oncol. 2016;10:450–63. Scholar
  47. 47.
    Alegre E, et al. Circulating melanoma exosomes as diagnostic and prognosis biomarkers. Clin Chim Acta. 2016;454:28–32. Scholar
  48. 48.
    Hyams DM, Cook RW, Buzaid AC. Identification of risk in cutaneous melanoma patients: prognostic and predictive markers. J Surg Oncol. 2019;119:175–86. Scholar
  49. 49.
    Gerami P, et al. Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. Clin Cancer Res. 2015;21:175–83. Scholar
  50. 50.
    Xing Y, et al. Conditional survival estimates improve over time for patients with advanced melanoma: results from a population-based analysis. Cancer. 2010;116:2234–41. Scholar
  51. 51.
    Soong SJ, et al. Predicting survival outcome of localized melanoma: an electronic prediction tool based on the AJCC Melanoma Database. Ann Surg Oncol. 2010;17:2006–14. Scholar

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© Springer Nature Switzerland AG 2021

Authors and Affiliations

  1. 1.Department of DermatologyRoswell Park Comprehensive Cancer CenterBuffaloUSA
  2. 2.Department of Cell Stress BiologyRoswell Park Comprehensive Cancer CenterBuffaloUSA
  3. 3.Department of DermatologyCollege of Medicine, Al Imam Mohammad Ibn Saud Islamic University (IMSIU)RiyadhSaudi Arabia
  4. 4.Institute of Cellular MedicineNewcastle UniversityNewcastle upon TyneUK
  5. 5.Department of DermatologyJames Cook University HospitalMiddlesbroughUK

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