Melanoma and Other Skin Cancers

Overview

Skin cancer is the most common form of malignancy, accounting for more than 75% of all cancer diagnoses. More than 3 million cases of squamous cell carcinomas, basal cell carcinomas, and melanomas are diagnosed annually in the US, with one in five Americans developing skin cancer. The vast majority of skin cancers can be cured via localized therapies including topical therapy, radiation therapy, and simple surgical interventions. Resection with wide surgical margins remains the mainstay of therapy for melanoma.

The interaction of genes and the environment is responsible for most skin cancers. Exposure to ultraviolet radiation is the best-known and best-studied environmental risk factor for squamous cell and basal cell skin cancer, and is the only known environmental risk factor for melanoma. Genetic predisposition to skin cancer, which may be expressed by phenotypic traits such as red hair or the presence of many nevi, also plays a significant role. Genetic susceptibility to melanoma clearly varies across the population and correlates to a large degree with light skin, hair, and eye color. Melanoma contributes to 75% of deaths from skin cancer. An estimated 73,870 new cases of melanoma of the skin will be diagnosed in the United States in 2015, with approximately 9,940 deaths. The overall death rate from melanoma increased by 5.8% in the United States between 1990 and 2005; this increase was the result of a significant rise in melanoma deaths in men. The mortality rate in women over the same period of time actually showed a slight decrease. The lifetime risk of melanoma for Caucasians is 1 in 35 for men and 1 in 54 for women in the United States. The 5-year survival was 92% of patients diagnosed with melanoma in the United States between 1996 and 2004, an increase of 10% compared with the years 1975 through 1977. This is almost certainly due to an increase in early detection.

The knowledge that melanoma and other skin cancers begin their growth within the superficial layers of the skin supports campaigns to raise public awareness and healthcare provider expertise in detecting skin cancers at the earliest possible stage. High-risk groups, for whom screening efforts might make the largest impact, are older men, individuals with many nevi, those with a personal or family history of skin cancer, and families with numerous cases of melanoma, just to mention a few of the high-risk groups.

Melanoma

Epidemiology

The vast majority of melanomas arise from cutaneous sites. Most arise from intermittently sun-exposed skin. A small percentage arise on acral surfaces of the hands and feet. Melanoma can arise from melanocytes adjacent to the retina or within mucosal surfaces in the oropharynx, sinuses, rectum, or vulva. These noncutaneous melanomas have distinct clinical and biological features when compared to cutaneous melanoma.

The relationship between the incidence of melanoma and age is unusual in comparison to other common cancers. There is not an exponential increase in risk with age but rather a more even distribution across age groups. The median age at diagnosis of melanoma is 53 years, almost 10 years younger than the median age of diagnosis of most common cancers. Forty-two percent of cases present in people younger than age 55, contributing to the third highest number of years of life lost across all cancers. In contrast, the incidence of squamous cell and basal cell carcinomas increases exponentially with age.

Men are more likely than women to develop melanoma (67% higher incidence), and their prognosis is worse (136% higher risk of death from melanoma). The reasons for this are unclear.

Caucasians are by far the most susceptible race for all skin cancers. Hispanics have a lower incidence but represent the group at next-highest risk. Asians and African Americans have the lowest rates of skin cancer. For those populations, cutaneous melanomas arising from sun-exposed sites are uncommon but not unseen. The most common type of primary melanoma in low-risk groups is the acral subtype, occurring on the hands and feet.

The rates of melanoma and other skin cancers are highest in countries where fair-skinned Caucasians migrated to lower latitudes, with annual sun exposure that is substantially higher than their historically native climates. Australia, New Zealand, South Africa, and Israel bear a disproportionate burden of skin cancer. In Australia, melanoma is the third most common cancer. In the United States, Hawaii and the desert Southwest have the highest rates of skin cancer of all kinds, including melanoma.

Skin cancers that are confined to the skin at presentation and with adequate staging evaluation have a high rate of cure. The 10-year survival of patients with invasive melanomas that are 1 mm or less in thickness and that lack ulceration is 97%. Melanoma that is microscopically present in regional lymph nodes is associated with a 10-year survival of 50% to 60%; when macroscopic or clinically apparent lymph nodes are detected, the 10-year survival is only 30% to 40%. The presence of more distant metastatic disease is associated with only a 5% possibility of survival 10 years from initial recognition.

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