Melanomas

ALSO KNOWN AS: Skin cancer

RELATED CONDITIONS: Basal cell cancer, squamous cell cancer

DEFINITION: Melanomas are malignant tumors of the skin that occur in the melanocytes, the cells that produce melanin (skin pigment).

Risk factors: Melanomas occur most commonly in fair-skinned people, particularly natural blonds and redheads, especially those with a history of sun exposure or multiple severe sunburns. A history of serious sunburns in childhood is a particular risk. Risk for the disease is strongly related to family history, which is characteristic of about 1 in 10 patients with melanoma. Additional risk factors include large or multiple moles and a history of melanoma or less serious skin cancers, known as basal cell or squamous cell cancers. People with diseases that suppress the immune system are at added risk for melanoma. Occupational exposure to coal tar, pitch, creosote, arsenic compounds, or radium increases a person’s disease risk. Celtic descent, male gender, and older age are also risk factors.

Etiology and the disease process: Repeat exposure to harmful ultraviolet rays from the sun or artificial sources such as sunlamps or tanning booths appears to be the most significant factor contributing to melanoma development. This is borne out by melanoma increasing in the world’s lower latitudes where the sun is strongest. Additionally, the incidence is higher in parts of the world where the ozone layer is thin. In Queensland, Australia, between 1979 and 1987, the rate of melanoma doubled to 55.8 per 100,000 men and rose to 42.9 per 100,000 women because of a thinning of the ozone layer. Melanomas can occur on body parts not usually exposed to the sun, including the soles of the feet and the genitals. Melanoma starts with abnormal skin growth, which is generally quite small. When discovered early, melanomas can be easily removed and the cancer cured. If the growth is not removed, it thickens and invades surrounding tissue and nearby lymph nodes. The cancer can then spread through the lymph nodes to sites distant from the original growth, including vital organs, soft tissues, and other lymph nodes.

Incidence: Skin cancer is consistently the most common form of cancer in the United States. In the 1970s, the incidence rate of melanoma rose dramatically to about 6 percent a year. Incidence continues to increase but at a slower rate. From 1981 to 2001, the growth rate was about 3 percent a year. By 2011, the rate of new cases had doubled from 1982. From 2003 to 2012, the increase in incidence was 1.7 among men and 1.4 among women, with White Americans seeing this increase while other ethnicities mostly remained level. Around 2.2 percent of Americans will receive a skin cancer diagnosis at some point.

Melanoma affects adults of all ages, as well as teenagers. Rates for White Americans are over twenty times higher than for Black Americans. However, one type of melanoma, which develops on the palms of the hands, soles of the feet, and nail beds, occurs more frequently in Black and Asian Americans.

Symptoms: Melanoma generally first appears as a new mole or a change in an existing mole's shape, size, or color. The American Cancer Society describes the warning signals regarding the mnemonic ABCD. "A" for asymmetry, meaning that the mole is not uniformly round; “B” for border, in that the edges of the mole are irregular; “C” for color, referring to the varied colors (generally in tones of tan, brown, and black) throughout the mole; and “D” for diameter, meaning that the mole is larger than 6 millimeters (mm).

Screening and diagnosis: People with serious risk factors or symptoms should have regular full-body exams by a dermatologist to identify any skin abnormalities. Baseline photographs should be taken so that any changes can be tracked. Suspect moles or skin abnormalities should be removed and analyzed for cancer cells.

The stages of melanoma are defined as follows:

• Localized, Stage 0: These melanomas involve only the top layer of skin, the epidermis.
• Localized, Stages I and II: These melanomas involve the underlying layer of skin, the dermis, and are rated according to the depth they penetrate the skin (known as the Breslow depth) and their degree of ulceration (how much the epidermis is eroded and exposes the dermis below). Ulceration is determined by a pathologist using a microscope.
• Regional, Stage III: These melanomas include those in which the cancer has spread to nearby lymph nodes.
• Advanced, Stage IV: These melanomas include those where cancer has spread beyond the region of the skin growth to distant sites in the body, including internal organs and distant lymph nodes.

Treatment and therapy: Significant advances have been made in the early detection of melanoma. All suspect moles or skin growths should be removed and tested for cancerous cells. Removal of localized growths (Stages 0-II) can be done one of three ways—surgically, cutting out the suspect tissue; by electrodesiccation and curettage, using an electric current to destroy the tissue and then scraping the area with a special tool to remove any possible remaining cancer cells; or by cryosurgery, which freezes the tissue. About 80 percent of melanomas are diagnosed in these early stages, while the cancer is still confined to the primary skin growth. Surgery successfully removes the cancer for the majority of patients with early-stage melanoma. Instead of surgery, some patients' tumors are injected with injections of the T-VEC vaccine (Imlygic). In some cases, radiation therapy may be directed at the area following surgery to kill any cancer cells that may remain. Other patients may use imiquimod cream (Zyclara) following surgery. Patients with Stages 0 to II melanoma have an excellent prognosis.

If the growth is extensive, the surgeon will remove lymph nodes in a sentinel lymph node biopsy (SLNB) to determine if the cancer has spread. After their removal, Stage III and IV melanomas may be treated with radiation or immunotherapy (agents that attempt to harness the human body’s disease-fighting properties to kill cancer cells) or chemotherapy (toxic agents targeted to kill cancer cells). Two therapeutic agents approved by the US Food and Drug Administration (FDA) for the treatment of Stage III and IV melanoma are dacarbazine (DTIC, chemotherapy) and interleukin-2 (IL-2, immunotherapy, also called aldesleukin). Some patients with Stage III and IV disease experience a full recovery with chemotherapy. However, positive responses to the drug therapy, when they occur, are most often partial and brief. Much research is being done to explore other possible treatments for melanoma, including combinations of different chemotherapies and new immunotherapies. The FDA does not explicitly approve some of these agents for treating melanoma. Patients with melanoma may be eligible to become subjects in clinical trials where these experimental agents or combinations of agents are tested.

Prognosis, prevention, and outcomes: The five-year survival rate for all skin cancer patients is 94.1 percent. A patient’s tumor's thickness is the best indicator of the prognosis. After removing melanomas of less than 0.76 mm, about 96 to 99 percent of patients are cured. About 1 in 10 patients with melanoma is diagnosed after the cancer has spread to nearby lymph nodes. For these patients in the regional stage (Stage III), the prognosis is not as good, but survival rates for patients with Stage III disease range widely, depending on how many lymph nodes are affected by the cancer. About 3 of 10 patients with melanoma are diagnosed in an advanced stage (Stage IV) after the cancer has already spread (metastasized) to distant sites. Those with metastases to the skin, soft tissue, or distant lymph nodes appear to fare better than those with lung or other vital organ metastases. The death rate for all skin cancer types is 2 per 100,000 people.

Recommended measures to prevent melanoma include avoiding excessive direct sunlight, especially from midmorning to midafternoon; using sunscreen and protective clothing to prevent sunburn; and avoiding sunlamps, tanning booths, or other artificial sources of ultraviolet light. People should also become familiar with the moles and spots on their bodies and report any changes that could indicate melanoma to their doctors.

Bibliography

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"Melanoma." Mayo Clinic, Mayo Foundation for Medical Education and Research, 30 Dec. 2023, www.mayoclinic.org/diseases-conditions/melanoma/symptoms-causes/syc-20374884. Accessed 20 June 2024.

"Melanoma Skin Cancer." American Cancer Society, www.cancer.org/cancer/melanoma-skin-cancer.html. Accessed 20 June 2024.

"Melanoma of the Skin Statistics." Centers for Disease Control and Prevention, US Department of Health & Human Services, 13 June 2024, www.cdc.gov/skin-cancer/statistics/index.html. Accessed 20 June 2023.

"Melanoma Treatment (PDQ®)–Patient Version." National Cancer Institute, National Institutes of Health, 30 June 2023, www.cancer.gov/types/skin/patient/melanoma-treatment-pdq. Accessed 20 June 2024.

Poole, Catherine M., and I. V. DuPont Guerry. Melanoma: Prevention, Detection, and Treatment. 2nd ed. Yale UP, 2005.

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