Melanoma

Risk factors for melanoma include

Patients with a personal history of melanoma have an increased risk of additional melanomas. People who have one or more first-degree relatives with a history of melanoma have an increased risk (up to 6 or 8 times) over those without a family history.

Atypical mole syndrome is the presence of large numbers of moles (eg,> 50), at least one of which is atypical and at least one of which is > 8 mm in diameter.

Familial atypical mole–melanoma syndrome is the presence of multiple atypical moles and melanoma in 2 or more first-degree relatives; such people are at markedly increased risk (25 times) of melanoma.

Melanoma is less common among people with darker pigmentation; when it occurs, the nail beds, palms, and soles are more often affected.

About 30% of melanomas develop from pigmented moles Diagnosis Malignant melanoma arises from melanocytes in a pigmented area (eg, skin, mucous membranes, eyes, or central nervous system). Metastasis is correlated with depth of dermal invasion. With spread... read more (about half each from typical and atypical moles); almost all the rest arise from melanocytes in normal skin. Atypical moles Atypical Moles Atypical moles are benign melanocytic nevi with irregular and ill-defined borders, variegated colors usually of brown and tan tones, and macular or papular components. Patients with atypical... read more (dysplastic nevi) may be precursors to melanoma. The very rare melanomas of childhood almost always arise in the leptomeninges or from giant congenital nevi. Although melanomas occur during pregnancy, pregnancy does not increase the likelihood that a mole will become a melanoma; moles frequently change in size and darken uniformly during pregnancy. In all people, lesions that have certain characteristics of concern, such as size, irregular borders, recent enlargement, darkening, ulceration, or bleeding, should be evaluated (see diagnosis of melanoma Diagnosis Malignant melanoma arises from melanocytes in a pigmented area (eg, skin, mucous membranes, eyes, or central nervous system). Metastasis is correlated with depth of dermal invasion. With spread... read more ).

There are 4 main types of melanoma and a few minor subtypes.

Polarized light and immersion contact dermoscopy may be useful for distinguishing melanomas from benign lesions. However, biopsy and histologic evaluation should be considered if moles have certain characteristics of concern (known as the ABCDEs of melanoma):

Patients at risk can be taught self-examination to detect changes in existing moles and to recognize features suggesting melanoma.

Other red flags include

However, recent enlargement, darkening, ulceration, or bleeding usually indicates that the melanoma has already invaded the skin deeply.

If doubt exists, biopsy should include the full depth of the dermis and extend slightly beyond the edges of the lesion. Because earlier diagnosis can be lifesaving and features of melanoma can be variable, even slightly suspect lesions should be biopsied. Earlier diagnosis of melanoma is possible if biopsy specimens can be obtained from lesions having variegated colors (eg, brown or black with shades of red, gray, or blue), irregular elevations that are visible or palpable, and borders with angular indentations or notches.

Biopsy should be excisional for most lesions except those on anatomically sensitive or cosmetically important areas; in these cases, a broad shave biopsy can be done. For broader lesions such as lentigo maligna, representative shave biopsies from several areas can increase the diagnostic yield. By doing step sections, the pathologist can determine the maximal thickness of the melanoma. Definitive radical surgery should not precede histologic diagnosis.

Tumors, particularly if metastatic, are sometimes tested genetically for mutations, eg, to suggest treatment with vemurafenib, a BRAF inhibitor, for metastatic melanomas bearing a V600 mutation in the BRAF gene.

Differential diagnosis includes basal cell carcinomas Basal Cell Carcinoma Basal cell carcinoma is a superficial, slowly growing papule or nodule that derives from certain epidermal cells. Basal cell carcinomas arise from keratinocytes near the basal layer, which are... read more and squamous cell carcinomas Squamous Cell Carcinoma Squamous cell carcinoma is a malignant tumor of epidermal keratinocytes that invades the dermis; this cancer usually occurs in sun-exposed areas. Local destruction may be extensive, and metastases... read more , seborrheic keratoses Seborrheic Keratoses Seborrheic keratoses are superficial, often pigmented, epithelial lesions that are usually warty but may occur as smooth papules. The cause of seborrheic keratosis is unknown, but genetic mutations... read more , atypical moles Atypical Moles Atypical moles are benign melanocytic nevi with irregular and ill-defined borders, variegated colors usually of brown and tan tones, and macular or papular components. Patients with atypical... read more , blue nevi, dermatofibromas Dermatofibromas Dermatofibromas are firm, red-to-brown, small papules or nodules composed of fibroblastic tissue. They usually occur on the thighs or legs but can occur anywhere. This photo shows a small hyperpigmented... read more , moles Moles Moles are flesh- to brown-colored macules, papules, or nodules composed of nests of melanocytes or nevus cells. Their main significance (other than cosmetic) is their resemblance to melanoma... read more , hematomas (especially on the hands or feet), venous lakes, pyogenic granulomas Pyogenic Granulomas Pyogenic granulomas are fleshy, moist or crusty, usually scarlet vascular nodules composed of proliferating capillaries in an edematous stroma. The lesion, composed of vascular tissue, is neither... read more , and warts with focal thromboses.

Melanoma may spread rapidly, causing death within months of its recognition, yet the 5-year cure rate of early, very superficial lesions is very high. Thus, cure depends on early diagnosis and early treatment.

For tumors of cutaneous origin (not central nervous system and subungual melanomas) that have not metastasized, the survival rate varies depending on the thickness of the tumor at the time of diagnosis. The 5-year survival rates range from 99.5% for patients with stage IA melanomas to 70.6% for patients with stage IIC melanomas (1 Prognosis reference Malignant melanoma arises from melanocytes in a pigmented area (eg, skin, mucous membranes, eyes, or central nervous system). Metastasis is correlated with depth of dermal invasion. With spread... read more ); 10-year survival rates range from 93% for patients with stage IA melanomas to 39% for patients with stage IIC melanomas.

Mucosal melanomas (especially anorectal melanomas) have a poor prognosis, although they often seem quite limited when discovered. They account for a higher proportion of melanomas in Black, Hispanic, and Asian people compared with White people.

Once melanoma has metastasized to the lymph nodes, 5-year survival ranges from 31.9 to 70.6% depending on the degree of ulceration and number of nodes involved (1 Prognosis reference Malignant melanoma arises from melanocytes in a pigmented area (eg, skin, mucous membranes, eyes, or central nervous system). Metastasis is correlated with depth of dermal invasion. With spread... read more ). Once melanoma has metastasized to distant sites, 5-year survival is 31.9%.

Degree of lymphocytic infiltration, which represents reaction by the patient’s immunologic defense system, may correlate with the level of invasion and prognosis. Chances of cure are maximal when lymphocytic infiltration is limited to the most superficial lesions and decrease with deeper levels of tumor cell invasion, ulceration, and vascular or lymphatic invasion.

A commercially available test of gene expression can help determine whether patients who have stage I or II melanomas are at high or low risk of metastases. This test has not yet been added to consensus guidelines; using it to determine whether patients should receive immunotherapy is not recommended at this time.

(See also the American Academy of Dermatology Association’s 2019 guidelines of care for the management of primary cutaneous melanoma.)

Treatment of melanoma is primarily by surgical excision (wide local excision). Although the width of margins is debated, most experts agree that a 1-cm lateral tumor-free margin is adequate for lesions < 0.8 mm thick. In tumors < 0.8 mm thick but with ulceration, sentinel lymph node biopsy can be considered. Thicker lesions may deserve larger margins, more radical surgery, and sentinel lymph node biopsy.

Lentigo maligna melanoma and lentigo maligna are usually treated with wide local excision and, if necessary, skin grafting. Intensive radiation therapy is much less effective. The ideal treatment of melanoma in situ is surgical excision. Sometimes this can be accomplished with staged excisions or Mohs micrographic surgery, in which tissue borders are progressively excised until specimens are tumor-free (as determined by microscopic examination during surgery). If patients decline or are not candidates for surgical therapy (eg, because of comorbidities or involvement of cosmetically important areas), imiquimod and cryotherapy can be considered. Most other treatment methods usually do not penetrate deeply enough into involved follicles, which must be removed.

Spreading or nodular melanomas have usually been treated with wide local excision. Lymph node dissection is recommended when nodes are involved clinically or on histologic evaluation of sentinel lymph node biopsy.

Because melanoma seems to be related to ultraviolet (UV) exposure, a number of measures are recommended to limit exposure.

However, current evidence is inadequate to determine whether these measures reduce incidence or mortality of melanoma.

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