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Malignant
melanoma arises from melanocytes in a pigmented area: skin, mucous
membranes, eyes, and CNS. Metastasis is correlated with depth of
dermal invasion. With spread, prognosis is poor. Diagnosis is by
biopsy. Wide surgical excision is the rule for operable tumors. Metastatic
disease requires chemotherapy but is difficult to cure.
About 50,000 new cases of melanoma occur yearly in the US, causing about 8000 deaths. The incidence is increasing at a faster rate than any other malignant tumor. Sun exposure is a risk, as is family history, increased numbers of melanocytic nevi, and the occurrence of lentigo maligna, large congenital melanocytic nevus, and the dysplastic nevus syndrome. Melanoma is rare in blacks.
People who have one or more 1st-degree relatives with a history of melanoma have an increased risk (up to 6 or 8 times) over those without a family history.
About 40 to 50% of melanomas develop from pigmented moles (see also Benign Tumors: Moles); almost all the rest arise from melanocytes in normal skin. Precancerous lesions include atypical moles (dysplastic nevi—see Benign Tumors: Atypical Moles). The very rare melanomas of childhood almost always arise from large pigmented moles (giant congenital nevi) present at birth. Although melanomas occur during pregnancy, pregnancy does not increase the likelihood that a mole will become a melanoma; nevi frequently change in size and darken uniformly during pregnancy. However, signs of malignant transformation should be carefully sought: change in size; irregular change in color, especially spread of red, white, and blue pigmentation to surrounding normal skin; change in surface characteristics, consistency, or shape; and especially signs of inflammation in surrounding skin, with possible bleeding, ulceration, itching, or tenderness.
Melanomas also occur on the mucosa of the oral and genital regions and conjunctiva. Mucosal melanomas (especially anorectal melanomas), which are more common in nonwhites, have an unfavorable prognosis.
Melanomas vary in size, shape, and color (usually pigmented) and in their propensity to invade and metastasize. The tumor may spread rapidly, causing death within months of its recognition, yet the 5-yr cure rate of early, very superficial lesions is nearly 100%. Thus, cure depends on early diagnosis and early treatment. Four major types of melanoma are described here.
Lentigo
maligna melanoma accounts for up to 15% of melanomas. It tends to arise in older patients. It arises from lentigo maligna (Hutchinson's freckle or malignant melanoma in situ). It appears on the face or other sun-exposed areas as an asymptomatic, 2- to 6-cm, flat, tan or brown, irregularly shaped macule or patch with darker brown or black spots scattered irregularly on its surface. In lentigo maligna, both normal and malignant melanocytes are confined to the epidermis; when malignant melanocytes invade the dermis, the lesion is called lentigo maligna melanoma, and the cancer may metastasize.
Superficial spreading
melanoma accounts for 2⁄3 of melanomas. Typically asymptomatic, it is usually diagnosed when smaller than lentigo maligna melanoma and occurs most commonly on women's legs and men's torsos. The lesion is usually a plaque with irregular raised, indurated tan or brown areas, which often show red, white, black, and blue spots or small, sometimes protuberant, blue-black nodules. Small notchlike indentations of the margins may be noted, along with enlargement or color change. Histologically, atypical melanocytes characteristically invade dermis and epidermis.
Nodular melanoma accounts for 10 to 15% of melanomas. It may occur anywhere on the body as a dark, protuberant papule or a plaque that varies from pearl to gray to black. Occasionally, a lesion contains little if any pigment or may look like a vascular tumor. Unless it ulcerates, nodular melanoma is asymptomatic, but the patient usually seeks advice because the lesion enlarges rapidly.
Acral-lentiginous
melanoma, although uncommon, is the most common form of melanoma in blacks. It arises on palmar, plantar, and subungual skin and has a characteristic histologic picture similar to lentigo maligna melanoma.
Metastasis of melanoma occurs via lymphatics and blood vessels. Local metastasis results in the formation of nearby satellite papules or nodules that may or may not be pigmented. Direct metastasis to skin or internal organs may occur, and occasionally metastatic nodules or enlarged lymph nodes are discovered before the primary lesion is identified.
Diagnosis
The differential diagnosis includes basal cell and squamous cell carcinomas, seborrheic keratoses, dysplastic nevi, blue nevi, dermatofibromas, moles, hematomas (especially on the hands or feet), venous lakes, pyogenic granulomas, and warts with focal thromboses. If doubt exists, biopsy should include the full depth of the dermis and extend slightly beyond the edges of the lesion. Biopsy should be excisional for small lesions and incisional for larger lesions. By doing step sections, the pathologist can determine the maximal thickness of the melanoma. Definitive radical surgery should not precede histologic diagnosis.
Guidelines for selecting pigmented lesions for excision or biopsy include recent enlargement, darkening, bleeding, or ulceration. However, these features usually indicate that the melanoma has already invaded the skin deeply. Earlier diagnosis is possible if biopsy specimens can be obtained from lesions having variegated colors (eg, brown or black with shades of red, white, or blue), irregular elevations that are visible or palpable, and borders with angular indentations or notches. The dermatoscope, a modified ophthalmoscope used with immersion oil to examine pigmented lesions, may be useful in distinguishing melanomas from benign lesions.
The 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.
The staging of melanoma is based on clinical and pathologic criteria and is categorized into local, regional, or distant disease; the stage strongly correlates with survival. A minimally invasive microstaging technique, the so-called sentinel node biopsy, is a major advance in the ability to stage patients more accurately. Staging studies are usually performed by a coordinated team that includes dermatologists, general surgeons, plastic surgeons, and dermatopathologists.
Prognosis
and Treatment
For tumors of cutaneous origin (not CNS and subungual melanomas), survival rate varies depending on the thickness of the tumor at the time of diagnosis (see
Table 1: Cancers of the Skin: 5-Year Survival for Malignant Melanoma, Relative to Thickness ). Melanomas arising from mucous membranes have a poor prognosis, although they often seem quite limited when discovered. Once melanoma has metastasized, 5-yr survival is about 10%.
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Table 1
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5-Year Survival for Malignant
Melanoma,
Relative to Thickness
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Tumor Thickness (mm)*
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5-Yr Survival (%)
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< 0.76
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98–100
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0.76–1.5
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90–94
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1.51–2.25
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83–84
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2.26–3.0
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72–77
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> 3.0
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46
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*Tumor thickness is very difficult to assess if histologic signs of regression are present.
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Treatment is by surgical excision. Although the width of margins is debated, most experts agree that a 1-cm lateral tumor-free margin is adequate for lesions < 1 mm thick. Thicker lesions may deserve more radical surgery and sentinel node biopsy.
Metastatic disease is generally inoperable. Adjuvant therapy, the active suppression of clinically inapparent micrometastasis using recombinant biological response modifiers, particularly the intensely studied interferon-α, is being evaluated. For advanced stages, studies involve infusing lymphokine-activated killer cells, or antibodies. Vaccine therapy is also being investigated. Brain metastases may be treated with radiation, but the response is poor.
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. Early excision of lentigo maligna—before the lesion is very large—is recommended; most other treatment methods except controlled cryosurgery usually do not reach deep enough into involved follicles, which must be removed.
Spreading or nodular melanomas are usually treated by wide local excision extending down to the fascia. Lymph node dissection may be recommended when nodes are involved.
Last full review/revision November 2005
Content last modified January 2008
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