• Dimitrios Papakostas
  • Alexander J. StratigosEmail author


Melanoma is a malignant melanocytic tumor developing in most cases from epidermal melanocytes. A steady incidence increase (3–7 %) in fair-skinned Caucasian populations in the past four to five decades has utterly transformed the epidemiology and the socioeconomic impact of this formerly infrequent skin malignancy. Early recognition and diagnosis of thinner melanomas has led to stabilization of mortality with improved 5-year survival rates. Phenotype, sun exposure, and genetic predisposition are considered key risk factors. The identification of molecular signatures or mutations based on anatomic location and sun exposure has shed light on the molecular basis of melanoma; 40–50 % of all melanomas are positive for the BRAF mutation. Novel treatments targeting this specific mutation are in clinical use for disseminated disease, e.g., vemurafenib and dabrafenib, which together with novel immunotherapies such as the CTLA-4 blocking autoantibody ipilimumab hold promise to revolutionize the treatment of metastatic melanoma. Surgical excision is the primary treatment of melanoma and of locoregional metastasis and has an increasing role in the treatment of localized metastatic disease.


Melanoma Diagnosis Prognosis Surgical excision Immunotherapy Targeted treatments Sentinel lymph node biopsy Radiotherapy Adjuvant therapy Interferon Chemotherapy 

Further Reading

  1. Ascierto PA, Simeone E, Giannarelli D, Grimaldi AM, Romano A, Mozzillo N. Sequencing of BRAF inhibitors and ipilimumab in patients with metastatic melanoma: a possible algorithm for clinical use. J Transl Med. 2012;10:107.CrossRefGoogle Scholar
  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(36):6199–206.CrossRefGoogle Scholar
  3. Bichakjian CK, Halpern AC, Johnson TM, Foote Hood A, Grichnik JM, Swetter SM, et al. Guidelines of care for the management of primary cutaneous melanoma. American Academy of Dermatology. J Am Acad Dermatol. 2011;65(5):1032–47.CrossRefGoogle Scholar
  4. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455–65.CrossRefGoogle Scholar
  5. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16.CrossRefGoogle Scholar
  6. Chatzinasiou F, Lill CM, Kypreou K, Stefanaki I, Nicolaou V, Spyrou G, et al. Comprehensive field synopsis and systematic meta-analyses of genetic association studies in cutaneous melanoma. J Natl Cancer Inst. 2011;103(16):1227–35.CrossRefGoogle Scholar
  7. Coit DG, Andtbacka R, Anker CJ, Bichakjian CK, Carson 3rd WE, Daud A, et al. Melanoma, version 2.2013: featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2013;11(4):395–407.CrossRefGoogle Scholar
  8. Dessinioti C, Gogas H, Stratigos AJ. Advances and trends in dermato-oncology. Expert Rev Anticancer Ther. 2010;10(11):1691–6.CrossRefGoogle Scholar
  9. Eggermont AM, Robert C. New drugs in melanoma: it’s a whole new world. Eur J Cancer. 2011;47(14):2150–7.CrossRefGoogle Scholar
  10. Finn L, Markovic SN, Joseph RW. Therapy for metastatic melanoma: the past, present, and future. BMC Med. 2012;10:23.CrossRefGoogle Scholar
  11. Fong ZV, Tanabe KK. Comparison of melanoma guidelines in the United States, Canada, Europe, Australia and New Zealand. A critical appraisal and comprehensive review. Br J Dermatol. 2014;170:20–30.CrossRefGoogle Scholar
  12. Greger JG, Eastman SD, Zhang V, Bleam MR, Hughes AM, Smitheman KN, et al. Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations. Mol Cancer Ther. 2012;11(4):909–20.CrossRefGoogle Scholar
  13. Guo J, Si L, Kong Y, Flaherty KT, Xu X, Zhu Y, et al. Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification. J Clin Oncol. 2011;29(21):2904–9.CrossRefGoogle Scholar
  14. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.CrossRefGoogle Scholar
  15. Jang S, Atkins MB. Which drug, and when, for patients with BRAF-mutant melanoma? Lancet Oncol. 2013;14(2):e60–9.CrossRefGoogle Scholar
  16. Johnson TM. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2013;69(6):1049–50.CrossRefGoogle Scholar
  17. Marsden JR, Newton-Bishop JA, Burrows L, Cook M, Corrie PG, Cox NH, et al. Revised U.K. guidelines for the management of cutaneous melanoma 2010. Br J Dermatol. 2010;163(2):238–56.CrossRefGoogle Scholar
  18. McArthur GA, Ribas A. Targeting oncogenic drivers and the immune system in melanoma. J Clin Oncol. 2013;31(4):499–506.CrossRefGoogle Scholar
  19. Nagaraja V, Eslick GD. Is complete lymph node dissection after a positive sentinel lymph node biopsy for cutaneous melanoma always necessary? A meta analysis. Eur J Surg Oncol. 2013;39(7):669–80.CrossRefGoogle Scholar
  20. Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, et al. Melanomas acquire resistance to B-RAF (V600E) inhibition by RTK or N-RAS upregulation. Nature. 2010;468(7326):973–7.CrossRefGoogle Scholar
  21. Nikolaou V, Stratigos AJ. Emerging trends in the epidemiology of melanoma. Br J Dermatol. 2014;170:11–9.CrossRefGoogle Scholar
  22. Nikolaou VA, Stratigos AJ, Flaherty KT, Tsao H. Melanoma: new insights and new therapies. J Invest Dermatol. 2012;132(3 Pt 2):854–63.CrossRefGoogle Scholar
  23. Pflugfelder A, Kochs C, Blum A, Capellaro M, Czeschik C, Dettenborn T, et al. Malignant melanoma S3-guideline “diagnosis, therapy and follow-up of melanoma”. J Dtsch Dermatol Ges. 2013;11 Suppl 6:1–116, 1–126.PubMedGoogle Scholar
  24. Ribas A. Tumor immunotherapy directed at PD-1. N Engl J Med. 2012;366(26):2517–9.CrossRefGoogle Scholar
  25. Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–26.CrossRefGoogle Scholar
  26. Stratigos AJ, Dimisianos G, Nikolaou V, Poulou M, Sypsa V, Stefanaki I, et al. Melanocortin receptor-1 gene polymorphisms and the risk of cutaneous melanoma in a low-risk southern European population. J Invest Dermatol. 2006a;126(8):1842–9. Epub 2006 Apr 6.CrossRefGoogle Scholar
  27. Stratigos AJ, Yang G, Dimisianos R, Nicolaou V, Stefanaki I, Katsambas AD, Tsao H. Germline CDKN2A mutations among Greek patients with early-onset and multiple primary cutaneous melanoma. J Invest Dermatol. 2006b;126(2):399–401.CrossRefGoogle Scholar
  28. Wasif N, Bagaria SP, Ray P, Morton DL. Does metastasectomy improve survival in patients with Stage IV melanoma? A cancer registry analysis of outcomes. J Surg Oncol. 2011;104(2):111–5.CrossRefGoogle Scholar
  29. Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122–33.CrossRefGoogle Scholar
  30. Wong SL, Balch CM, Hurley P, Agarwala SS, Akhurst TJ, Cochran A, 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(23):2912–8.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.1st Department of DermatologyUniversity of Athens Medical School, Andreas Sygros HospitalAthensGreece

Personalised recommendations