Cutaneous Melanoma

  • Author: Susan M Swetter, MD; Chief Editor: Dirk M Elston, MD  more...
Updated: Mar 28, 2016


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 less than 5% 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. Malignant melanoma. Courtesy of Hon Pak, MD.
Cutaneous melanoma with characteristic asymmetry, Cutaneous melanoma with characteristic asymmetry, irregular borders, and color variation. Courtesy of Wendy Brick, MD.

See Can You Recognize Benign Skin Lesions From Cancerous Ones?, a Critical Images slideshow, to help identify various skin lesions.

Also see the Critical Images slideshow, Cutaneous Clues to Diagnosing Metastatic Cancer, to help identify skin lesions that are cause for concern.



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]




United States

The incidence of melanoma has more than doubled in the white population over the last 30 years, and melanoma currently is the sixth most common cancer in the United States. Approximately 76,380 Americans (46,870 men and 29,510 women) will develop invasive cutaneous melanoma in 2016, with an estimated additional 68,480 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 54 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 white women younger than 40 years; annual incidence of melanoma more than doubled in this group 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 white 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] Pilots and flight crews demonstrate melanoma risk double that of the general population.[12]


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 2012, demonstrated an age-standardized incidence of 34.9 cases per 100,000 men and women in Australia and 35.84 cases per 100,000 men and women in New Zealand, compared with 14.3 cases per 100,000 men and women in the United States.[13]


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.


In the United States, invasive melanoma has a higher female predilection from birth to age 49 years (1 in 206 women compared with 1 in 297 men). However, from age 50 years and older, melanoma in men predominates, occurring in 1 in 33 men compared with 1 in 52 women over a lifetime.[8]

Worldwide, of the 232,000 new cases estimated to have occurred in 2012, women were affected slightly more than men. Conversely, of the estimated 55,000 worldwide deaths in 2012, more occurred in men than in women.


The median age at melanoma diagnosis is 63 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.[14]

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]



While melanoma accounts for roughly 4% of all skin cancers, it is responsible for nearly 75% of skin cancer deaths. In the United States, one person each hour dies from metastatic disease. Treatment of melanoma in its early stages provides the best opportunity for cure.

US mortality/morbidity

An estimated 10,130 deaths will occur in 2016 (6,750 men and 3,380 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).[14] 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. Subsequent analyses continue to demonstrate the highest incidence and mortality rates in older white men in the United States.

Worldwide mortality/morbidity

Individuals with cutaneous melanoma have higher survival rates in developed countries (92% 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, 232,000 new cases of melanoma were estimated to occur in 2012, with over 55,000 deaths reported. Australia and New Zealand have the highest reported mortality.[13]

Contributor Information and Disclosures

Susan M Swetter, MD Director, Pigmented Lesion and Melanoma Program, Professor, Department of Dermatology, Stanford University Medical Center and Cancer Institute, Veterans Affairs Palo Alto Health Care System

Susan M Swetter, MD is a member of the following medical societies: American Academy of Dermatology, Women's Dermatologic Society, American Society of Clinical Oncology, Society for Melanoma Research, Eastern Cooperative Oncology Group, American Medical Association, Pacific Dermatologic Association, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

John G Albertini, MD Private Practice, The Skin Surgery Center; Clinical Associate Professor (Volunteer), Department of Plastic and Reconstructive Surgery, Wake Forest University School of Medicine; President-Elect, American College of Mohs Surgery

John G Albertini, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery

Disclosure: Received grant/research funds from Genentech for investigator.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.


Günter Burg, MD Professor and Chairman Emeritus, Department of Dermatology, University of Zürich School of Medicine; Delegate of The Foundation for Modern Teaching and Learning in Medicine Faculty of Medicine, University of Zürich, Switzerland

Günter Burg, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, International Society for Dermatologic Surgery, North American Clinical Dermatologic Society, and Pacific Dermatologic Association

Disclosure: Nothing to disclose.

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Superficial spreading melanoma, left breast, 1.3-mm Breslow depth.
Lentigo maligna melanoma, right lower cheek. Centrally located erythematous papule represents invasive melanoma with surrounding macular lentigo maligna (melanoma in situ).
Acral lentiginous melanoma (1-mm Breslow depth), left sole. Diagnostic punch biopsy site is located superiorly.
Malignant melanoma. Courtesy of Hon Pak, MD.
Cutaneous melanoma with characteristic asymmetry, irregular borders, and color variation. Courtesy of Wendy Brick, MD.
Table. AJCC 2002 Revised Melanoma Staging
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

IIA T2b N0 M0

T3a N0 M0

1.01-2 mm with ulceration

2.01-4 mm without ulceration

IIB T3b N0 M0

T4a N0 M0

2.01-4 mm with ulceration

4 mm without ulceration

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

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

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

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.
Medscape Consult
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