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Melanoma: Clinical features and diagnosis

Susan Swetter, MD
Alan C Geller, RN, MPH
Section Editor
Hensin Tsao, MD, PhD
Deputy Editor
Rosamaria Corona, MD, DSc


Melanoma is the most serious form of skin cancer and the sixth most common cancer in North America [1]; its incidence increases with age. Five-year survival rates for people with melanoma depend on the stage of the disease at the time of diagnosis. There are five stages: stage 0 is in situ (intraepithelial) melanoma, stages I and II are localized invasive cutaneous disease, stage III is regional nodal disease, and stage IV is distant metastatic disease (table 1A-B). Most people with thin stage I melanoma can expect prolonged disease-free survival and likely cure following treatment, whereas those with more advanced stage II to IV lesions are more likely to develop metastatic disease [2,3].

This topic will discuss the clinical features and diagnosis of cutaneous melanoma. The principles and rationale of screening and early detection of melanoma are discussed separately, as are histopathologic features, initial management, and staging of melanoma. The clinical features, diagnosis, and management of melanoma in children are also discussed separately.

(See "Screening and early detection of melanoma".)

(See "Pathologic characteristics of melanoma".)

(See "Initial surgical management of melanoma of the skin and unusual sites".)


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Literature review current through: Apr 2017. | This topic last updated: May 08, 2017.
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  1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014; 64:9.
  2. Balch CM, Soong SJ, Gershenwald JE, 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.
  3. Geller AC, Miller DR, Annas GD, et al. Melanoma incidence and mortality among US whites, 1969-1999. JAMA 2002; 288:1719.
  4. Breslow A. Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 1970; 172:902.
  5. Paek SC, Sober AJ, Tsao H, et al. Cutaneous melanoma. In: Fitzpatrick's Dermatology in General Medicine, 7th, Wolff K, Goldsmith LA, Katz SI, et al. (Eds), McGraw Hill Medical, New York 2008. Vol I, p.1134.
  6. Lasithiotakis KG, Leiter U, Gorkievicz R, et al. The incidence and mortality of cutaneous melanoma in Southern Germany: trends by anatomic site and pathologic characteristics, 1976 to 2003. Cancer 2006; 107:1331.
  7. American Academy of Dermatology Ad Hoc Task Force for the ABCDEs of Melanoma, Tsao H, Olazagasti JM, et al. Early detection of melanoma: reviewing the ABCDEs. J Am Acad Dermatol 2015; 72:717.
  8. Geller AC, Elwood M, Swetter SM, et al. Factors related to the presentation of thin and thick nodular melanoma from a population-based cancer registry in Queensland Australia. Cancer 2009; 115:1318.
  9. Warycha MA, Christos PJ, Mazumdar M, et al. Changes in the presentation of nodular and superficial spreading melanomas over 35 years. Cancer 2008; 113:3341.
  10. Demierre MF, Chung C, Miller DR, Geller AC. Early detection of thick melanomas in the United States: beware of the nodular subtype. Arch Dermatol 2005; 141:745.
  11. Clark WH Jr, Mihm MC Jr. Lentigo maligna and lentigo-maligna melanoma. Am J Pathol 1969; 55:39.
  12. Swetter SM, Boldrick JC, Jung SY, et al. Increasing incidence of lentigo maligna melanoma subtypes: northern California and national trends 1990-2000. J Invest Dermatol 2005; 125:685.
  13. Coleman WP 3rd, Loria PR, Reed RJ, Krementz ET. Acral lentiginous melanoma. Arch Dermatol 1980; 116:773.
  14. Buka R, Friedman KA, Phelps RG, et al. Childhood longitudinal melanonychia: case reports and review of the literature. Mt Sinai J Med 2001; 68:331.
  15. Ruben BS. Pigmented lesions of the nail unit: clinical and histopathologic features. Semin Cutan Med Surg 2010; 29:148.
  16. Jaimes N, Braun RP, Thomas L, Marghoob AA. Clinical and dermoscopic characteristics of amelanotic melanomas that are not of the nodular subtype. J Eur Acad Dermatol Venereol 2012; 26:591.
  17. Pizzichetta MA, Talamini R, Stanganelli I, et al. Amelanotic/hypomelanotic melanoma: clinical and dermoscopic features. Br J Dermatol 2004; 150:1117.
  18. Gualandri L, Betti R, Crosti C. Clinical features of 36 cases of amelanotic melanomas and considerations about the relationship between histologic subtypes and diagnostic delay. J Eur Acad Dermatol Venereol 2009; 23:283.
  19. Chen LL, Jaimes N, Barker CA, et al. Desmoplastic melanoma: a review. J Am Acad Dermatol 2013; 68:825.
  20. Kottschade LA, Grotz TE, Dronca RS, et al. Rare presentations of primary melanoma and special populations: a systematic review. Am J Clin Oncol 2014; 37:635.
  21. Vyas R, Keller JJ, Honda K, et al. A systematic review and meta-analysis of animal-type melanoma. J Am Acad Dermatol 2015; 73:1031.
  22. Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009; 27:6199.
  23. Brady MS, Oliveria SA, Christos PJ, et al. Patterns of detection in patients with cutaneous melanoma. Cancer 2000; 89:342.
  24. Carli P, De Giorgi V, Palli D, et al. Self-detected cutaneous melanomas in Italian patients. Clin Exp Dermatol 2004; 29:593.
  25. Carli P, De Giorgi V, Palli D, et al. Dermatologist detection and skin self-examination are associated with thinner melanomas: results from a survey of the Italian Multidisciplinary Group on Melanoma. Arch Dermatol 2003; 139:607.
  26. Epstein DS, Lange JR, Gruber SB, et al. Is physician detection associated with thinner melanomas? JAMA 1999; 281:640.
  27. Schwartz JL, Wang TS, Hamilton TA, et al. Thin primary cutaneous melanomas: associated detection patterns, lesion characteristics, and patient characteristics. Cancer 2002; 95:1562.
  28. Swetter SM, Johnson TM, Miller DR, et al. Melanoma in middle-aged and older men: a multi-institutional survey study of factors related to tumor thickness. Arch Dermatol 2009; 145:397.
  29. Gachon J, Beaulieu P, Sei JF, et al. First prospective study of the recognition process of melanoma in dermatological practice. Arch Dermatol 2005; 141:434.
  30. Vestergaard ME, Macaskill P, Holt PE, Menzies SW. Dermoscopy compared with naked eye examination for the diagnosis of primary melanoma: a meta-analysis of studies performed in a clinical setting. Br J Dermatol 2008; 159:669.
  31. Grob JJ, Gaudy-Marqueste C, Cha KB, et al. Melanoma. In: Rook's Textbook of Dermatology, Ninth Edition, Griffiths C, Barker J, Bleiker T, et al. (Eds), Wiley, 2016.
  32. Abbasi NR, Shaw HM, Rigel DS, et al. Early diagnosis of cutaneous melanoma: revisiting the ABCD criteria. JAMA 2004; 292:2771.
  33. Grob JJ, Bonerandi JJ. The 'ugly duckling' sign: identification of the common characteristics of nevi in an individual as a basis for melanoma screening. Arch Dermatol 1998; 134:103.
  34. Friedman RJ, Rigel DS, Kopf AW. Early detection of malignant melanoma: the role of physician examination and self-examination of the skin. CA Cancer J Clin 1985; 35:130.
  35. Whited JD, Grichnik JM. The rational clinical examination. Does this patient have a mole or a melanoma? JAMA 1998; 279:696.
  36. Harrington E, Clyne B, Wesseling N, et al. Diagnosing malignant melanoma in ambulatory care: a systematic review of clinical prediction rules. BMJ Open 2017; 7:e014096.
  37. Thomas L, Tranchand P, Berard F, et al. Semiological value of ABCDE criteria in the diagnosis of cutaneous pigmented tumors. Dermatology 1998; 197:11.
  38. Carli P, De Giorgi V, Crocetti E, et al. Diagnostic and referral accuracy of family doctors in melanoma screening: effect of a short formal training. Eur J Cancer Prev 2005; 14:51.
  39. Peuvrel L, Quereux G, Jumbou O, et al. Impact of a campaign to train general practitioners in screening for melanoma. Eur J Cancer Prev 2009; 18:225.
  40. National Collaborating Centre for Cancer (UK). Melanoma: Assessment and Management. London: National Institute for Health and Care Excellence (UK); 2015. www.ncbi.nlm.nih.gov/pubmedhealth/PMH0079031/pdf/PubMedHealth_PMH0079031.pdf (Accessed on March 28, 2017).
  41. Scottish Intercollegiate Guidelines Network. Cutaneous Melanoma. A national clinical guideline. January 2017. www.sign.ac.uk/pdf/SIGN146.pdf (Accessed on March 28, 2017).
  42. MacKie RM. Clinical recognition of early invasive malignant melanoma. BMJ 1990; 301:1005.
  43. Healsmith MF, Bourke JF, Osborne JE, Graham-Brown RA. An evaluation of the revised seven-point checklist for the early diagnosis of cutaneous malignant melanoma. Br J Dermatol 1994; 130:48.
  44. Walter FM, Prevost AT, Vasconcelos J, et al. Using the 7-point checklist as a diagnostic aid for pigmented skin lesions in general practice: a diagnostic validation study. Br J Gen Pract 2013; 63:e345.
  45. Gaudy-Marqueste C, Wazaefi Y, Bruneu Y, et al. Ugly Duckling Sign as a Major Factor of Efficiency in Melanoma Detection. JAMA Dermatol 2017; 153:279.
  46. Scope A, Dusza SW, Halpern AC, et al. The "ugly duckling" sign: agreement between observers. Arch Dermatol 2008; 144:58.
  47. Chamberlain AJ, Fritschi L, Kelly JW. Nodular melanoma: patients' perceptions of presenting features and implications for earlier detection. J Am Acad Dermatol 2003; 48:694.
  48. Tan KB, Moncrieff M, Thompson JF, et al. Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting. Am J Surg Pathol 2007; 31:1902.
  49. Levit EK, Kagen MH, Scher RK, et al. The ABC rule for clinical detection of subungual melanoma. J Am Acad Dermatol 2000; 42:269.
  50. Forsea AM, Tschandl P, Del Marmol V, et al. Factors driving the use of dermoscopy in Europe: a pan-European survey. Br J Dermatol 2016; 175:1329.
  51. Murzaku EC, Hayan S, Rao BK. Methods and rates of dermoscopy usage: a cross-sectional survey of US dermatologists stratified by years in practice. J Am Acad Dermatol 2014; 71:393.
  52. Engasser HC, Warshaw EM. Dermatoscopy use by US dermatologists: a cross-sectional survey. J Am Acad Dermatol 2010; 63:412.
  53. March J, Hand M, Grossman D. Practical application of new technologies for melanoma diagnosis: Part I. Noninvasive approaches. J Am Acad Dermatol 2015; 72:929.
  54. Ferris LK, Harris RJ. New diagnostic aids for melanoma. Dermatol Clin 2012; 30:535.
  55. Que SK, Fraga-Braghiroli N, Grant-Kels JM, et al. Through the looking glass: Basics and principles of reflectance confocal microscopy. J Am Acad Dermatol 2015; 73:276.
  56. Losi A, Longo C, Cesinaro AM, et al. Hyporeflective pagetoid cells: a new clue for amelanotic melanoma diagnosis by reflectance confocal microscopy. Br J Dermatol 2014; 171:48.
  57. Maier T, Sattler EC, Braun-Falco M, et al. Reflectance confocal microscopy in the diagnosis of partially and completely amelanotic melanoma: report on seven cases. J Eur Acad Dermatol Venereol 2013; 27:e42.
  58. Braga JC, Scope A, Klaz I, et al. The significance of reflectance confocal microscopy in the assessment of solitary pink skin lesions. J Am Acad Dermatol 2009; 61:230.
  59. Guitera P, Moloney FJ, Menzies SW, et al. Improving management and patient care in lentigo maligna by mapping with in vivo confocal microscopy. JAMA Dermatol 2013; 149:692.
  60. Pellacani G, Pepe P, Casari A, Longo C. Reflectance confocal microscopy as a second-level examination in skin oncology improves diagnostic accuracy and saves unnecessary excisions: a longitudinal prospective study. Br J Dermatol 2014; 171:1044.
  61. Farnetani F, Scope A, Braun RP, et al. Skin Cancer Diagnosis With Reflectance Confocal Microscopy: Reproducibility of Feature Recognition and Accuracy of Diagnosis. JAMA Dermatol 2015; 151:1075.
  62. Monheit G, Cognetta AB, Ferris L, et al. The performance of MelaFind: a prospective multicenter study. Arch Dermatol 2011; 147:188.
  63. Fink C, Jaeger C, Jaeger K, Haenssle HA. Diagnostic performance of the MelaFind device in a real-life clinical setting. J Dtsch Dermatol Ges 2017; 15:414.
  64. Haniffa MA, Lloyd JJ, Lawrence CM. The use of a spectrophotometric intracutaneous analysis device in the real-time diagnosis of melanoma in the setting of a melanoma screening clinic. Br J Dermatol 2007; 156:1350.
  65. Walter FM, Morris HC, Humphrys E, et al. Effect of adding a diagnostic aid to best practice to manage suspicious pigmented lesions in primary care: randomised controlled trial. BMJ 2012; 345:e4110.
  66. Kassianos AP, Emery JD, Murchie P, Walter FM. Smartphone applications for melanoma detection by community, patient and generalist clinician users: a review. Br J Dermatol 2015; 172:1507.
  67. Wolf JA, Moreau JF, Akilov O, et al. Diagnostic inaccuracy of smartphone applications for melanoma detection. JAMA Dermatol 2013; 149:422.
  68. Dreiseitl S, Binder M, Hable K, Kittler H. Computer versus human diagnosis of melanoma: evaluation of the feasibility of an automated diagnostic system in a prospective clinical trial. Melanoma Res 2009; 19:180.
  69. Burroni M, Corona R, Dell'Eva G, et al. Melanoma computer-aided diagnosis: reliability and feasibility study. Clin Cancer Res 2004; 10:1881.
  70. Esteva A, Kuprel B, Novoa RA, et al. Dermatologist-level classification of skin cancer with deep neural networks. Nature 2017; 542:115.
  71. Marsden JR, Newton-Bishop JA, Burrows L, et al. Revised U.K. guidelines for the management of cutaneous melanoma 2010. Br J Dermatol 2010; 163:238.
  72. Sober AJ, Chuang TY, Duvic M, et al. Guidelines of care for primary cutaneous melanoma. J Am Acad Dermatol 2001; 45:579.
  73. Coit DG, Andtbacka R, Anker CJ, et al. Melanoma, version 2.2013: featured updates to the NCCN guidelines. J Natl Compr Canc Netw 2013; 11:395.
  74. Bichakjian CK, Halpern AC, Johnson TM, et al. Guidelines of care for the management of primary cutaneous melanoma. American Academy of Dermatology. J Am Acad Dermatol 2011; 65:1032.
  75. Coit DG, Andtbacka R, Bichakjian CK, et al. Melanoma. J Natl Compr Canc Netw 2009; 7:250.
  76. www.aad.org/education-and-quality-care/clinical-guidelines/current-and-upcoming-guidelines/current-guidelines-and-guidelines-in-development (Accessed on April 25, 2011).
  77. Marghoob AA, Terushkin V, Dusza SW, et al. Dermatologists, general practitioners, and the best method to biopsy suspect melanocytic neoplasms. Arch Dermatol 2010; 146:325.
  78. Eriksson H, Frohm-Nilsson M, Hedblad MA, et al. Interobserver variability of histopathological prognostic parameters in cutaneous malignant melanoma: impact on patient management. Acta Derm Venereol 2013; 93:411.
  79. Ji AL, Bichakjian CK, Swetter SM. Molecular Profiling in Cutaneous Melanoma. J Natl Compr Canc Netw 2016; 14:475.
  80. Minca EC, Al-Rohil RN, Wang M, et al. Comparison between melanoma gene expression score and fluorescence in situ hybridization for the classification of melanocytic lesions. Mod Pathol 2016; 29:832.
  81. Gerami P, Alsobrook JP 2nd, Palmer TJ, Robin HS. Development of a novel noninvasive adhesive patch test for the evaluation of pigmented lesions of the skin. J Am Acad Dermatol 2014; 71:237.
  82. Gerami P, Wass A, Mafee M, et al. Fluorescence in situ hybridization for distinguishing nevoid melanomas from mitotically active nevi. Am J Surg Pathol 2009; 33:1783.
  83. Ponti G, Ruini C, Massi D, et al. Fluorescence in-situ hybridization and dermoscopy in the assessment of controversial melanocytic tumors. Melanoma Res 2013; 23:474.
  84. Weissinger SE, Frick M, Möller P, et al. Performance Testing of RREB1, MYB, and CCND1 Fluorescence In Situ Hybridization in Spindle-Cell and Desmoplastic Melanoma Argues for a Two-Step Test Algorithm. Int J Surg Pathol 2017; 25:148.
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