Melanoma: classification, pathophysiology and clinical characteristics

Melanoma

Malignant melanoma is the leading cause of death from skin cancer, despite only accounting for a fraction of all cutaneous cancers. The incidence of melanoma has doubled over the past 35 years in the United States. In 2002, there were 53,000 new cases in the U.S. The mean age of diagnosis was 45 years and the lifetime risk (in the U.S.) is 1 in 58 for men and 1 in 82 for women. The lowest rates occur in China and Japan (0.3/100,000) and the highest rates are in Australia and New Zealand (36/100,000).

In addition to geographic risk factors, there are several patient-related factors that are associated with an increased incidence of disease. Individuals with fair skin have a higher risk of developing melanoma. The incidence is 10 times higher in whites than blacks. People with red hair have a 3.6 times higher incidence of melanoma than those with black hair. Other risk factors include a history of severe sunburns in childhood, freckling after sun exposure, and people with more than 20 nevi on their body. Of patients with melanoma, 5-11% will have a family member with melanoma.

Classification

Histologic level of invasion (Clark's level) and tumor thickness (Breslow thickness or depth) are important indicators of metastatic risk and outcome. Lymph node status is the single most powerful predictor of survival. When lymph nodes are not involved, the most important factors for prognosis are Breslow depth and ulceration. Surgical margins and the need for sentinel node biopsy are based on tumor thickness.

Pathophysiology

The intermittent exposure hypothesis states that intermittent high energy exposure of melanocytes to sunlight is more damaging than the total cumulative dose. This is because continuous exposure can actually increase the amount of melanin (tanning) which protects the nucleus of the cell. People who have had three or more blistering sunburns before age 20 are at increased risk for disease.

Melanoma arises in epidermal melanocytes. Melanocytes produce melanin in response to sunlight and transport it to keratinocytes via dendrites. The keratinocytes regulate melanocyte growth, thus maintaining homeostasis. When these melanocytes escape from regulation, a dysplastic nevus arises. These lesions are premalignant and grow in a radial growth phase, parallel to the skin surface. A primary melanoma arises when a vertical growth phase begins with the capacity to invade deeper structures.

Clinical characteristics

There are four subtypes of melanoma, each with a different appearance and clinical behavior.

Superficial spreading melanoma is the most common subtype (70-75%). This type frequently arises from a pre-existing dysplastic nevus and always grows in a radial growth phase.

Nodular melanoma is the second most common type (15%). This subtype lacks a radial growth phase, making it very difficult to diagnose at an early stage as it does not arise from a pre-existing pigmented lesion. The appearance of these melanomas is shiny and smooth with a uniform color.

Acral lentiginous melanoma is a rare subtype with a poor prognosis. These lesions are notoriously difficult to diagnose as they are commonly masked by thick stratum corneum of the palms and soles of the feet or on difficult to find mucosal surfaces. They are flat, dark brown or black and have irregular borders. Subungal melanomas belong to this category. These lesions occur equally among all races and arise in the nail bed or matrix. Hyperpigmentation of the nail fold (Hutchinson's sign) or a dark band (~3 mm in width) along the nail are presenting signs.

Lentigo maligna melanoma is the rarest form (5%) and is the least aggressive type. They arise on chronically sun-exposed parts, commonly the face and neck. They are dark brown or black, larger than the other subtypes (1-3 cm diameter) and have highly irregular borders.

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