Background
Melanoma is a malignancy of pigment-producing cells (melanocytes) located predominantly in the skin, but also found in the eyes, ears, GI tract, leptomeninges, and oral and genital mucous membranes. Melanoma accounts for only 4% of all skin cancers; however, it causes the greatest number of skin cancer–related deaths worldwide. Early detection of thin cutaneous melanoma is the best means of reducing mortality. Characteristic images are shown below.
Malignant melanoma. Courtesy of Hon Pak, MD. 
Cutaneous melanoma with characteristic asymmetry, irregular borders, and color variation. Courtesy of Wendy Brick, MD. Pathophysiology
The sequence of events in which normal melanocytes transform into melanoma cells, referred to as melanomagenesis, is poorly understood. It likely involves a multistep process of progressive genetic mutations that (1) alter cell proliferation, differentiation, and death and (2) impact susceptibility to the carcinogenic effects of ultraviolet radiation.[1] Recent data suggest multiple pathways of melanoma pathogenesis, with melanomas in sun-protected skin (trunk) developing in association with a high nevus count and intermittent ultraviolet radiation as opposed to those developing on sun-exposed skin in patients with low nevus counts and chronic sun exposure.[2, 3]
Differences in frequency of BRAF or NRAS mutations are also related to patterns of sun exposure, with BRAF mutations more common in intermittently UV-exposed skin compared with chronically sun exposed skin or relatively unexposed skin (eg, acral sites, mucosal sites), which more frequently demonstrate KIT mutations.[3]
A meta-analysis by Lee et al demonstrated that the prevalence of these mutations may also depend on melanoma histologic subtype.[4]
Primary cutaneous melanoma may develop in precursor melanocytic nevi (ie, common, congenital, and atypical/dysplastic types), although more than 70% of cases are believed to arise de novo (ie, not from a preexisting pigmented lesion).
The development of melanoma is multifactorial and appears to be related to multiple risk factors, including fair complexion/sun sensitivity, excessive childhood sun exposure and blistering childhood sunburns, an increased number of common or atypical/dysplastic nevi (moles), a family history of melanoma, the presence of a changing mole or evolving lesion on the skin, and, importantly, older age.[5, 6, 7]
Epidemiology
Frequency
United States
The incidence of melanoma has more than tripled in the white population during the last 20 years, and melanoma currently is the sixth most common cancer in the United States. Approximately 70,230 Americans (40,010 men and 30.220 women) will develop invasive cutaneous melanoma in 2011, with an estimated additional 46,770 or more cases of melanoma in situ.[8] The incidence may be higher due to melanoma underreporting to cancer registries, particularly for tumors that are diagnosed and managed in the outpatient setting.[9] The current lifetime risk for developing invasive melanoma is 1 case per 57 Americans, a 2000% increase since 1930. This risk rises to 1 case per 33 Americans if noninvasive melanoma in situ is included.
Encouragingly, a stable-to-reduced melanoma incidence rate has been noted in younger age groups in the United States, which may be a result of primary prevention campaigns aimed at reducing excessive sun exposure over the past 30 or more years; however, the full impact of primary prevention strategies on melanoma incidence and mortality will not be apparent for several decades.
Of recent concern, however, is the rising melanoma incidence in Caucasian women younger than 40 years; this group has demonstrated a 50% increase in the annual incidence of melanoma from 1980-2004. Increased UV radiation exposure through tanning bed use, a World Health Organization (WHO)–classified carcinogen, has been proposed as a potential explanation for this alarming trend.[10] In addition, a study assessing melanoma incidence among young Caucasian girls and women (15-39 y) in California showed significantly higher incidence in those living in higher socioeconomic areas with the highest UV radiation exposure compared with those from lower socioeconomic neighborhoods, suggesting that affluence (and associated lifestyle behaviors) may have a bigger impact on melanoma risk than UV exposure alone.[11]
International
Melanoma incidence has continued to increase worldwide, with the highest incidence in Australia and New Zealand. The most recent analysis of global cancer statistics for melanoma, from 2002, demonstrated a prevalence of 37.7 cases per 100,000 men and 29.4 cases per 100,000 women in Australia and New Zealand, compared with 6.4 cases per 100,000 men and 11.7 cases per 100,000 women in North America.[12]
Mortality/Morbidity
While melanoma accounts for roughly 4% of all skin cancers, it is responsible for more than 73% of skin cancer deaths. In the United States, one person each hour dies from metastatic melanoma. Treatment of melanoma in its early stages provides the best opportunity for cure.
United States: An estimated 8790 deaths will occur in 2011 (5750 men and 3040 women).[8] Analysis of US Surveillance, Epidemiology, and End Results (SEER) data from 1969-1999 has demonstrated a disproportionate burden of melanoma deaths among middle-aged and older white men. While melanoma mortality rates have fallen 39% in women and 29% in men aged 20-44 years over this period, they have increased 66% in men aged 45-64 years and 157% in older men (≥65 y).[13] Incidence data generally parallel mortality data and have shown a 3-fold increase in middle-aged men and a 5-fold increase in older men over a similar period.
Worldwide: Individuals with cutaneous melanoma have higher survival rates in developed countries (91% in US SEER registries and 81% in Europe) than in developing countries (approximately 40%). Increased educational efforts in developed areas result in earlier diagnosis, treatment, and potential cure of thinner lesions. Worldwide, 160,000 new cases of melanoma were estimated to occur in 2002, with 41,000 deaths reported.[12]
Race
Melanoma is primarily a malignancy of white individuals. African American persons develop melanoma approximately one twentieth as frequently as white persons, and the prevalence in Hispanic persons is approximately one sixth of that in white persons. However, mortality rates are higher in African Americans and Hispanics, who are more likely to have acral melanoma and advanced disease at presentation.
Sex
In the United States, invasive melanoma has a higher female predilection from birth to age 39 years (1 in 370 women compared with 1 in 645 men). However, from age 40 years and older, melanoma in men predominates, occurring in 1 in 39 men compared with 1 in 58 women over a lifetime.[14] Worldwide, of the 160,000 new cases estimated to have occurred in 2002, women were affected slightly more than men (male-to-female ratio, 0.97:1). Conversely, of the estimated 41,000 worldwide deaths in 2002, more occurred in men than in women (male-to-female ratio 1.2:1).
Age
The median age at melanoma diagnosis is 59 years; however, it is the most common cancer in women aged 25-29 years and is second only to breast cancer in women aged 30-34 years. The most striking differences in melanoma incidence and mortality occur in individuals older than 65 years, although modest differences in age-specific incidence and mortality are notable in persons older than 50 years.[13]
Older individuals are both more likely to acquire and to die from melanoma; thus, elderly persons should be a primary target for secondary melanoma prevention, including early detection and screening.[15] Treatment options in elderly persons may also be limited because of comorbid medical conditions, an inability to tolerate adverse medication effects or toxicity, the increased likelihood of drug interactions, and potential exclusion from clinical trials based on age criteria.[15]
Demierre MF, Nathanson L. Chemoprevention of melanoma: an unexplored strategy. J Clin Oncol. Jan 1 2003;21(1):158-65. [Medline].
Whiteman DC, Watt P, Purdie DM, Hughes MC, Hayward NK, Green AC. Melanocytic nevi, solar keratoses, and divergent pathways to cutaneous melanoma. J Natl Cancer Inst. Jun 4 2003;95(11):806-12. [Medline].
Maldonado JL, Fridlyand J, Patel H, et al. Determinants of BRAF mutations in primary melanomas. J Natl Cancer Inst. Dec 17 2003;95(24):1878-90. [Medline].
Lee JH, Choi JW, Kim YS. Frequencies of BRAF and NRAS mutations are different in histologic types and sites of origin of cutaneous melanoma: a meta-analysis. Br J Dermatol. Dec 16 2010;[Medline].
Sober AJ, Fitzpatrick TB, Mihm MC, et al. Early recognition of cutaneous melanoma. JAMA. Dec 21 1979;242(25):2795-9. [Medline].
Rhodes AR, Weinstock MA, Fitzpatrick TB, Mihm MC Jr, Sober AJ. Risk factors for cutaneous melanoma. A practical method of recognizing predisposed individuals. JAMA. Dec 4 1987;258(21):3146-54. [Medline].
Williams ML, Sagebiel RW. Melanoma risk factors and atypical moles. West J Med. Apr 1994;160(4):343-50. [Medline].
ACS. 2011 Cancer Facts and Figures. Cancer.org. Available at http://89. http://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/cancer-facts-figures-2011. Accessed September 2, 2011.
Cockburn M, Swetter SM, Peng D, Keegan TH, Deapen D, Clarke CA. Melanoma underreporting: why does it happen, how big is the problem, and how do we fix it?. J Am Acad Dermatol. Dec 2008;59(6):1081-5. [Medline].
Purdue MP, Freeman LE, Anderson WF, Tucker MA. Recent trends in incidence of cutaneous melanoma among US Caucasian young adults. J Invest Dermatol. Dec 2008;128(12):2905-8. [Medline]. [Full Text].
Hausauer AK, Swetter SM, Cockburn MG, Clarke CA. Increases in melanoma among adolescent girls and young women in California: trends by socioeconomic status and UV radiation exposure. Arch Dermatol. Jul 2011;147(7):783-9. [Medline].
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. Mar-Apr 2005;55(2):74-108. [Medline].
Geller AC, Miller DR, Annas GD, Demierre MF, Gilchrest BA, Koh HK. Melanoma incidence and mortality among US whites, 1969-1999. JAMA. Oct 9 2002;288(14):1719-20. [Medline].
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. Jul-Aug 2009;59(4):225-49. [Medline].
Swetter SM, Geller AC, Kirkwood JM. Melanoma in the older person. Oncology (Williston Park). Aug 2004;18(9):1187-96; discussion 1196-7. [Medline].
Terushkin V, Halpern AC. Melanoma early detection. Hematol Oncol Clin North Am. Jun 2009;23(3):481-500, viii. [Medline].
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. May-Jun 1985;35(3):130-51. [Medline].
Abbasi NR, Shaw HM, Rigel DS, et al. Early diagnosis of cutaneous melanoma: revisiting the ABCD criteria. JAMA. Dec 8 2004;292(22):2771-6. [Medline].
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. Jan 1998;134(1):103-4. [Medline].
Gachon J, Beaulieu P, Sei JF, et al. First prospective study of the recognition process of melanoma in dermatological practice. Arch Dermatol. Apr 2005;141(4):434-8. [Medline].
Miracco C, Santopietro R, Biagioli M, et al. Different patterns of cell proliferation and death and oncogene expression in cutaneous malignant melanoma. J Cutan Pathol. May 1998;25(5):244-51. [Medline].
Bastian BC, Kashani-Sabet M, Hamm H, et al. Gene amplifications characterize acral melanoma and permit the detection of occult tumor cells in the surrounding skin. Cancer Res. Apr 1 2000;60(7):1968-73. [Medline].
Sasaki Y, Niu C, Makino R, et al. BRAF point mutations in primary melanoma show different prevalences by subtype. J Invest Dermatol. Jul 2004;123(1):177-83. [Medline].
Richard MA, Grob JJ, Avril MF, et al. Melanoma and tumor thickness: challenges of early diagnosis. Arch Dermatol. Mar 1999;135(3):269-74. [Medline].
Demierre MF, Chung C, Miller DR, Geller AC. Early detection of thick melanomas in the United States: beware of the nodular subtype. Arch Dermatol. Jun 2005;141(6):745-50. [Medline].
Swetter SM, Boldrick JC, Jung SY, Egbert BM, Harvell JD. Increasing incidence of lentigo maligna melanoma subtypes: northern California and national trends 1990-2000. J Invest Dermatol. Oct 2005;125(4):685-91. [Medline].
Farrahi F, Egbert BM, Swetter SM. Histologic similarities between lentigo maligna and dysplastic nevus: importance of clinicopathologic distinction. J Cutan Pathol. Jul 2005;32(6):405-12. [Medline].
Cress RD, Holly EA. Incidence of cutaneous melanoma among non-Hispanic whites, Hispanics, Asians, and blacks: an analysis of california cancer registry data, 1988-93. Cancer Causes Control. Mar 1997;8(2):246-52. [Medline].
Byrd KM, Wilson DC, Hoyler SS, Peck GL. Advanced presentation of melanoma in African Americans. J Am Acad Dermatol. Jan 2004;50(1):21-4; discussion 142-3. [Medline].
Rogers RS 3rd, Gibson LE. Mucosal, genital, and unusual clinical variants of melanoma. Mayo Clin Proc. Apr 1997;72(4):362-6. [Medline].
Jain S, Allen PW. Desmoplastic malignant melanoma and its variants. A study of 45 cases. Am J Surg Pathol. May 1989;13(5):358-73. [Medline].
Elwood JM, Jopson J. Melanoma and sun exposure: an overview of published studies. Int J Cancer. Oct 9 1997;73(2):198-203. [Medline].
Gilchrest BA, Eller MS, Geller AC, Yaar M. The pathogenesis of melanoma induced by ultraviolet radiation. N Engl J Med. Apr 29 1999;340(17):1341-8. [Medline].
Cust AE, Armstrong BK, Goumas C, et al. Sunbed use during adolescence and early adulthood is associated with increased risk of early-onset melanoma. Int J Cancer. May 1 2011;128(10):2425-35. [Medline]. [Full Text].
Lederman JS, Lew RA, Koh HK, Sober AJ. Influence of estrogen administration on tumor characteristics and survival in women with cutaneous melanoma. J Natl Cancer Inst. May 1985;74(5):981-5. [Medline].
Hannaford PC, Villard-Mackintosh L, Vessey MP, Kay CR. Oral contraceptives and malignant melanoma. Br J Cancer. Mar 1991;63(3):430-3. [Medline].
Driscoll MS, Grin-Jorgensen CM, Grant-Kels JM. Does pregnancy influence the prognosis of malignant melanoma?. J Am Acad Dermatol. Oct 1993;29(4):619-30. [Medline].
Smith MA, Fine JA, Barnhill RL, Berwick M. Hormonal and reproductive influences and risk of melanoma in women. Int J Epidemiol. Oct 1998;27(5):751-7. [Medline].
Schwartz JL, Mozurkewich EL, Johnson TM. Current management of patients with melanoma who are pregnant, want to get pregnant, or do not want to get pregnant. Cancer. May 1 2003;97(9):2130-3. [Medline].
Weiss M, Loprinzi CL, Creagan ET, Dalton RJ, Novotny P, O'Fallon JR. Utility of follow-up tests for detecting recurrent disease in patients with malignant melanomas. JAMA. Dec 6 1995;274(21):1703-5. [Medline].
Johnson TM, Bradford CR, Gruber SB, Sondak VK, Schwartz JL. Staging workup, sentinel node biopsy, and follow-up tests for melanoma: update of current concepts. Arch Dermatol. Jan 2004;140(1):107-13. [Medline].
Wang TS, Johnson TM, Cascade PN, Redman BG, Sondak VK, Schwartz JL. Evaluation of staging chest radiographs and serum lactate dehydrogenase for localized melanoma. J Am Acad Dermatol. Sep 2004;51(3):399-405. [Medline].
Hafner J, Schmid MH, Kempf W, et al. Baseline staging in cutaneous malignant melanoma. Br J Dermatol. Apr 2004;150(4):677-86. [Medline].
Miranda EP, Gertner M, Wall J, Grace E, Kashani-Sabet M, Allen R. Routine imaging of asymptomatic melanoma patients with metastasis to sentinel lymph nodes rarely identifies systemic disease. Arch Surg. Aug 2004;139(8):831-6; discussion 836-7. [Medline].
Bichakjian CK, Halpern AC, Johnson TM, et al. Guidelines of Care for the Management of Primary Cutaneous Melanoma. American Academy of Dermatology. Available at http://www.aad.org/education-and-quality-care/clinical-guidelines/current-and-upcoming-guidelines. Accessed June 9, 2011.
National Comprehensive Cancer Care Network. Clinical Practice Guidelines in Oncology - v.1.2011: Melanoma. Accessed January 4, 2011. Available at http://www.nccn.org/professionals/physician_gls/PDF/melanoma.pdf.
Kaskel P, Berking C, Sander S, Volkenandt M, Peter RU, Krahn G. S-100 protein in peripheral blood: a marker for melanoma metastases: a prospective 2-center study of 570 patients with melanoma. J Am Acad Dermatol. Dec 1999;41(6):962-9. [Medline].
Morris KT, Busam KJ, Bero S, Patel A, Brady MS. Primary cutaneous melanoma with regression does not require a lower threshold for sentinel lymph node biopsy. Ann Surg Oncol. Jan 2008;15(1):316-22. [Medline].
Elder DE, Guerry D 4th, Epstein MN, et al. Invasive malignant melanomas lacking competence for metastasis. Am J Dermatopathol. 1984;6 Suppl:55-61. [Medline].
Guerry D 4th, Synnestvedt M, Elder DE, Schultz D. Lessons from tumor progression: the invasive radial growth phase of melanoma is common, incapable of metastasis, and indolent. J Invest Dermatol. Mar 1993;100(3):342S-345S. [Medline].
Clark WH Jr, Elder DE, Guerry D 4th, et al. Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst. Dec 20 1989;81(24):1893-904. [Medline].
Balch CM. Cutaneous melanoma: prognosis and treatment results worldwide. Semin Surg Oncol. Nov-Dec 1992;8(6):400-14. [Medline].
Buzaid AC, Ross MI, Balch CM, et al. Critical analysis of the current American Joint Committee on Cancer staging system for cutaneous melanoma and proposal of a new staging system. J Clin Oncol. Mar 1997;15(3):1039-51. [Medline].
Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, et al. Melanoma of the Skin. In: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2009:325-40.
Balch CM, Buzaid AC, Atkins MB, et al. A new American Joint Committee on Cancer staging system for cutaneous melanoma. Cancer. Mar 15 2000;88(6):1484-91. [Medline].
Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. Aug 15 2001;19(16):3635-48. [Medline].
Balch CM, Soong SJ, Atkins MB, et al. An evidence-based staging system for cutaneous melanoma. CA Cancer J Clin. May-Jun 2004;54(3):131-49; quiz 182-4. [Medline].
Agarwala SS, Glaspy J, O'Day SJ, et al. Results from a randomized phase III study comparing combined treatment with histamine dihydrochloride plus interleukin-2 versus interleukin-2 alone in patients with metastatic melanoma. J Clin Oncol. Jan 1 2002;20(1):125-33. [Medline].
Veronesi U, Adamus J, Aubert C, et al. A randomized trial of adjuvant chemotherapy and immunotherapy in cutaneous melanoma. N Engl J Med. Oct 7 1982;307(15):913-6. [Medline].
Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol. Jan 1996;14(1):7-17. [Medline].
Kirkwood JM, Ibrahim JG, Sondak VK, et al. High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol. Jun 2000;18(12):2444-58. [Medline].
Kirkwood JM, Ibrahim JG, Sosman JA, et al. High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. J Clin Oncol. May 1 2001;19(9):2370-80. [Medline].
Kirkwood JM, Manola J, Ibrahim J, et al. A pooled analysis of eastern cooperative oncology group and intergroup trials of adjuvant high-dose interferon for melanoma. Clin Cancer Res. Mar 1 2004;10(5):1670-7. [Medline].
Eggermont AM, Suciu S, Santinami M, et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet. Jul 12 2008;372(9633):117-26. [Medline].
Gogas H, Ioannovich J, Dafni U, et al. Prognostic significance of autoimmunity during treatment of melanoma with interferon. N Engl J Med. Feb 16 2006;354(7):709-18. [Medline].
Demierre MF, Swetter SM, Sondak VK. Vaccine therapy of melanoma: an update. Curr Canc Ther Rev. 2005;1:115-25.
Schwartzentruber DJ, Lawson D, Richards J, et al. A phase III multi-institutional randomized study of immunization with the gp100:209-217(210M) peptide followed by high-dose IL-2 compared with high-dose IL-2 alone in patients with metastatic melanoma. J Clin Oncol. 2009;27:18 s (suppl; abstr CRA9011).
Schwartzentruber DJ, Lawson DH, Richards JM, et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. Jun 2 2011;364(22):2119-27. [Medline].
Long GV, Menzies AM, Nagrial AM, et al. Prognostic and Clinicopathologic Associations of Oncogenic BRAF in Metastatic Melanoma. J Clin Oncol. Apr 1 2011;29(10):1239-46. [Medline].
Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. Jun 30 2011;364(26):2507-16. [Medline].
National Institutes of Health. NIH Consensus conference. Diagnosis and treatment of early melanoma. JAMA. Sep 9 1992;268(10):1314-9. [Medline].
Kunishige JH, Brodland DG, Zitelli JA. Surgical margins for melanoma in situ. J Am Acad Dermatol. Mar 2012;66(3):438-44. [Medline].
Balch CM, Urist MM, Karakousis CP, et al. Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 mm). Results of a multi-institutional randomized surgical trial. Ann Surg. Sep 1993;218(3):262-7; discussion 267-9. [Medline].
Veronesi U, Cascinelli N, Adamus J, et al. Thin stage I primary cutaneous malignant melanoma. Comparison of excision with margins of 1 or 3 cm. N Engl J Med. May 5 1988;318(18):1159-62. [Medline].
Thomas JM, Newton-Bishop J, A'Hern R, et al. Excision margins in high-risk malignant melanoma. N Engl J Med. Feb 19 2004;350(8):757-66. [Medline].
Heaton KM, Sussman JJ, Gershenwald JE, et al. Surgical margins and prognostic factors in patients with thick (>4mm) primary melanoma. Ann Surg Oncol. Jun 1998;5(4):322-8. [Medline].
Gillgren P, Drzewiecki KT, Niin M, et al. 2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial. Lancet. Nov 5 2011;378(9803):1635-42. [Medline].
Zitelli JA, Brown C, Hanusa BH. Mohs micrographic surgery for the treatment of primary cutaneous melanoma. J Am Acad Dermatol. Aug 1997;37(2 Pt 1):236-45. [Medline].
Balch CM. Randomized surgical trials involving elective node dissection for melanoma. Adv Surg. 1999;32:255-70. [Medline].
Balch CM, Soong SJ, 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. Sep 1996;224(3):255-63; discussion 263-6. [Medline].
Cascinelli N, Morabito A, Santinami M, MacKie RM, Belli F. Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial. WHO Melanoma Programme. Lancet. Mar 14 1998;351(9105):793-6. [Medline].
Morton DL, Thompson JF, Essner R, et al. Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: a multicenter trial. Multicenter Selective Lymphadenectomy Trial Group. Ann Surg. Oct 1999;230(4):453-63; discussion 463-5. [Medline].
Gershenwald JE, Thompson W, Mansfield PF, et al. Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. J Clin Oncol. Mar 1999;17(3):976-83. [Medline].
McMasters KM, Reintgen DS, Ross MI, et al. Sentinel lymph node biopsy for melanoma: controversy despite widespread agreement. J Clin Oncol. Jun 1 2001;19(11):2851-5. [Medline].
[Best Evidence] Morton DL, Thompson JF, Cochran AJ, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. Sep 28 2006;355(13):1307-17. [Medline].
Hancock BW, Wheatley K, Harris S, et al. Adjuvant interferon in high-risk melanoma: the AIM HIGH Study--United Kingdom Coordinating Committee on Cancer Research randomized study of adjuvant low-dose extended-duration interferon Alfa-2a in high-risk resected malignant melanoma. J Clin Oncol. Jan 1 2004;22(1):53-61. [Medline].
Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. Aug 19 2010;363(8):711-23. [Medline].
Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. Jun 30 2011;364(26):2517-26. [Medline].
Levi F, Randimbison L, Te VC, La Vecchia C. High constant incidence rates of second cutaneous melanomas. Int J Cancer. Jun 14 2005;[Medline].
Francis DM, Busmanis I, Becker G. Peritoneal calcification in a peritoneal dialysis patient: a case report. Perit Dial Int. 1990;10(3):237-40. [Medline].
Atkins MB, Hsu J, Lee S, et al. Phase III trial comparing concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b with cisplatin, vinblastine, and dacarbazine alone in patients with metastatic malignant melanoma (E3695): a trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. Dec 10 2008;26(35):5748-54. [Medline]. [Full Text].
Leachman SA, Carucci J, Kohlmann W, et al. Selection criteria for genetic assessment of patients with familial melanoma. J Am Acad Dermatol. Oct 2009;61(4):677.e1-14. [Medline].
American Joint Committee on Cancer. Manual for Staging of Cancer. 6th ed. Philadelphia, Pa: Lippincott; 2002:209-20.
| Stage | TNM Classification | Histologic/Clinical Features | 5-Year Survival Rate, % |
| 0 | Tis N0 M0 | Intraepithelial/in situ melanoma | 100 |
| IA | T1a N0 M0 | ≤1 mm without ulceration and mitotic rate < 1/mm2 | 97 |
| IB | T1b N0 M0 T2a N0 M0 | ≤1 mm with ulceration or mitotic rate ≥1/mm2 1.01-2 mm without ulceration | 91-94 |
| IIA | T2b N0 M0 T3a N0 M0 | 1.01-2 mm with ulceration 2.01-4 mm without ulceration | 79-82 |
| IIB | T3b N0 M0 T4a N0 M0 | 2.01-4 mm with ulceration 4 mm without ulceration | 68-71 |
| IIC | T4b N0 M0 | >4 mm with ulceration | 53 |
| IIIA | T1-4a N1a M0 T1-4a N2a M0 | Single regional nodal micrometastasis, nonulcerated primary 2-3 microscopic positive regional nodes, nonulcerated primary | 78 |
| IIIB | T1-4b N1a M0 T1-4b N2a M0 T1-4a N1b M0 T1-4a N2b M0 T1-4a/b N2c M0 | Single regional nodal micrometastasis, ulcerated primary 2-3 microscopic regional nodes, nonulcerated primary Single regional nodal macrometastasis, nonulcerated primary 2-3 macroscopic regional nodes, no ulceration of primary In-transit met(s)* and/or satellite lesion(s) without metastatic lymph nodes | 54-59 |
| IIIC | T1-4b N2a M0 T1-4b N2b M0 Any T N3 M0 | Single macroscopic regional node, ulcerated primary 2-3 macroscopic metastatic regional nodes, ulcerated primary 4 or more metastatic nodes, matted nodes/gross extracapsular extension, or in-transit met(s)/satellite lesion(s) and metastatic nodes | 40 |
| IV | Any T any N M1a Any T any N M1b Any T any N M1c | Distant skin, subcutaneous, or nodal mets with normal LDH levels Lung mets with normal LDH All other visceral mets with normal LDH or any distant mets with elevated LDH | < 20 |
| *Met is metastasis. | |||
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