The etiology and pathogenesis of cutaneous melanoma are unknown. Epidemiologic studies demonstrate a role for genetic predisposition and sun exposure in melanoma development. The major genes involved in melanoma development reside on chromosome 9p21. Twenty-five percent to 40% of members of melanoma-prone families have mutations in cyclin-dependent kinase inhibitor 2A (CDKN2A) and a few families in the cyclin-dependent kinase 4 (CDK4). These are tumor-suppressor genes that provide a rational basis for the link to susceptibility to melanoma. Sixty-six percent of melanomas have a mutation of the BRAF gene, others of MC1R.

There is convincing evidence from epidemiologic studies that exposure to solar radiation is the major cause of cutaneous melanoma. Cutaneous melanoma is a greater problem in people with lighter skin. Sunburns during childhood and intermittent burning exposure in fair skin also seem to have a higher impact than cumulative UV exposure over time. Other predisposing and risk factors are the presence of precursor lesions (dysplastic nevi and congenital nevi) and a family history of melanoma in parents, children, or siblings. Risk factors for melanoma are listed in Table 12-2.

Melanoma Growth Patterns

Almost all melanomas show an initial radial growth phase followed by a subsequent vertical growth phase. Radial growth phase refers to a mostly intraepidermal, preinvasive, or minimally invasive growth pattern; vertical growth refers to growth into the dermis and thus into the vicinity of vessels that serve as avenues for metastasis. Since most melanomas produce melanin pigment, even preinvasive melanomas in their radial growth phase are clinically detectable by their color patterns. The prognostic difference among the clinical types of melanoma relates mainly to the duration of the radial growth phase, which may last from years to decades in LMM, from months to 2 years in SSM, and 6 months or less in NM.

Melanoma Recognition

Six Signs of Malignant Melanoma (ABCDE Rule)

Note: This does not apply to nodular melanoma.

• Asymmetry in shape—one-half unlike the other half.
• Border is irregular—edges irregularly scalloped, notched, or sharply defined.
• Color is not uniform; mottled—haphazard display of colors; all shades of brown, black, gray, blue, red, and white.
• Diameter is usually large—greater than the tip of a pencil eraser (6.0 mm). "D" is also used for the "ugly duckling" sign. These lesions are different from other pigmented lesions (nevi) on the body with respect to change in size, shape, and color.
• Elevation is almost always present and is irregular—surface distortion is assessed by side lighting. MIS and acral lentiginous lesions initially macular; "E" is also used for Evolving or Enlargement. A history of an increase in the size of lesion is one of the most important signs of malignant melanoma.

Clinical Presentations of Melanoma

The clinical characteristics of the four major types of melanoma are summarized in Table 12-3.Frequency of melanoma by type of tumor: SSM, 70%; NM, 15%; LMM, 5%; and acral and unclassified melanoma, 10%. MIS and DM are also discussed in this section.