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Malignant melanoma arises from melanocytes in a pigmented area (eg, skin, mucous membranes, eyes, or 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 60,000 new cases of melanoma occur yearly in the US, causing about 8400 deaths. Incidence has remained steady over the last 8 yr (it had previously been increasing at a faster rate than any other malignant tumor).
Melanomas occur mainly on the skin but also on the mucosa of the oral and genital regions and conjunctiva. Melanomas vary in size, shape, and color (usually pigmented) and in their propensity to invade and metastasize. Metastasis 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.
Etiology
Risk factors include
Patients with a personal history of melanoma have an increased risk of additional melanomas. 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. Melanoma is rare in blacks.
About 40 to 50% of melanomas develop from pigmented moles (see also Benign Skin Tumors: Moles); almost all the rest arise from melanocytes in normal skin. Atypical moles (dysplastic nevi) may be precursors to melanoma (see Benign Skin 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; moles frequently change in size and darken uniformly during pregnancy. However, the following signs of malignant transformation should be carefully sought:
Classification
There are 4 main types of melanoma.
Lentigo maligna melanoma:
This type accounts for 5 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, 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:
This type accounts for two thirds of melanomas. Typically asymptomatic, it 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 have 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 the dermis and epidermis.
Nodular melanoma:
This type 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 patients usually seek advice because the lesion enlarges rapidly.
Acral-lentiginous melanoma:
This type accounts for only 5 to 10% of melanomas, but it 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 that of lentigo maligna melanoma.
Diagnosis
The differential diagnosis includes basal cell and squamous cell carcinomas, seborrheic keratoses, atypical moles, 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.
Pigmented lesions with the following features should be excised or biopsied:
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. Polarized light and immersion contact dermoscopy, which is used to examine pigmented lesions, may be useful for distinguishing melanomas from benign lesions.
Staging:
The staging of melanoma is based on clinical and pathologic criteria and closely corresponds to the traditional tumor-node-metastasis (TNM) classification system. The staging system classifies melanomas based on local, regional, or distant disease.
Stage strongly correlates with survival. A minimally invasive microstaging technique, the so-called sentinel lymph node biopsy (SLNB), is a major advance in the ability to stage cancers more accurately. Recommended staging studies depend on the Breslow depth (how deeply tumor cells have invaded) and histologic characteristics of the melanoma. Staging studies may include SLNB, laboratory tests (CBC, LDH, liver function tests), chest x-ray, CT, and PET and are done by a coordinated team that includes dermatologists, oncologists, general surgeons, plastic surgeons, and dermatopathologists.
Prognosis
Melanoma 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. For tumors of cutaneous origin (not CNS and subungual melanomas) that have not metastasized, the survival rate varies depending on the thickness of the tumor at the time of diagnosis (see Table 1: Cancers of the Skin: 5–Yr Survival* for Malignant Melanoma Relative to Thickness and Ulceration ). Mucosal melanomas (especially anorectal melanomas), which are more common in nonwhites, have a poor prognosis, although they often seem quite limited when discovered. Once melanoma has metastasized to the lymph nodes, 5-yr survival ranges from 25 to 70% depending on the degree of ulceration and number of nodes involved. Once melanoma has metastasized to distant sites, 5-yr survival is about 10%.
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Table 1
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PrintOpen table  |
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| 5–Yr Survival* for Malignant Melanoma Relative to Thickness and Ulceration |
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Stage
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Description
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5–Yr Survival (%)
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0
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Intraepithelial or in situ melanoma
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100
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IA
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≤ 1 mm with no ulceration
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≥ 95
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IB
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≤ 1 mm with ulceration
1.01–2 mm with no ulceration
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89–91
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IIA
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1.01–2 mm with ulceration
2.01–4 mm with no ulceration
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77–79
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IIB
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2.01–4 mm with ulceration
≥ 4 mm with no ulceration
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63–67
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IIC
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> 4 mm with ulceration
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45
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*Survival rates change with stage, degree of ulceration, and, for stages III and IV, presence and number of nodal and distant metastases.
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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.
Treatment
Treatment is primarily 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 larger margins, more radical surgery, and SLNB.
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. Treatment of lentigo maligna includes early excision (before the lesion is very large), imiquimod, and controlled cryotherapy. Most other treatment methods usually do not penetrate deeply enough into involved follicles, which must be removed.
Spreading or nodular melanomas are usually treated with wide local excision extending down to the fascia. Lymph node dissection may be recommended when nodes are involved. (See also the American Academy of Dermatology Association's Guidelines of Care for Primary Cutaneous Melanoma.)
Metastatic disease:
Metastatic disease is generally inoperable, but in certain cases, localized and regional metastases can be excised. Chemotherapy with dacarbazine or temozolamide (oral dacarbazine analog) and aldesleukin can be used for the treatment of metastatic melanoma. Adjuvant therapy with recombinant biologic response modifiers (particularly interferon alfa) to suppress clinically inapparent micrometastases may also be used for inoperable metastatic melanoma. Brain metastases may be treated with palliative radiation, but the response is poor.
The following are under study:
Last full review/revision October 2008 by Gregory L. Wells, MD
Content last modified February 2012
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