Melanoma and other skin cancers
Highlights
Risk factors
According to a report in the Archives of Dermatology, marathon runners are more likely than the general population to develop skin changes that increase the risk for melanoma.
Prevention
A study published in The Lancet indicates that the best ways to avoid sun damage are to reduce the time you spend in the sun and to wear a hat and clothing to protect as much of your skin as possible. Fabrics that are thick and tightly woven offer the best protection.
The U.S. Food and Drug Administration has approved a new type of sunscreen that may more effectively block UVA than products currently available in the United States. UVA light penetrates the skin deeper than other forms of sunlight. Exposure to UVA is believed to contribute to skin cancers. The new sunscreen, called Anthelios SX, is available over the counter.
Screening
A study published in CANCER has shown that older men are more likely to undergo a whole body skin exam if they understand their personal risk factors for melanoma and know where to go to have such an exam. The study emphasizes the importance of skin cancer awareness and education.
One-time melanoma screening for adults over age 50 seems to be as cost-effective as other nationally recommended cancer screening programs, according to a report in the Archives of Dermatology. The study authors also found that screening brothers and sisters of someone with melanoma every 2 years may also be cost-effective.
Diagnosis
Dermatologists detect melanoma earlier than other health care providers, according to an article in the Archives of Dermatology. The earlier melanoma is diagnosed and treated, the greater your chances of survival.
Introduction
Skin cancer is cancer that starts in the skin. Skin cancers are divided into two major groups:
- Nonmelanoma, which includes basal cell cancer and squamous cell cancer
- Melanoma, the deadliest form of skin cancer
Different skin cancers start in different layers or cells of the skin. To understand how skin cancer develops, it is useful to know something about the skin.
The Skin. The skin is the largest organ in the body and consists of layers.
- The outermost layer of the skin is called the epidermis. It is only about 20 cells deep, roughly as thick as a sheet of paper.
- The dermis ranges in thickness from 1 - 4 millimeters (about 1/32 - 1/8 inch). The dermis contains tiny blood and lymph vessels, which increase in number deeper in the skin.
Melanocytes. A layer of cells between the epidermis and the dermis, called melanocytes, produces a brown-black skin pigment ( melanin) that determines skin and hair color. Melanin also helps protect against the damaging rays of the sun.
As a person ages, melanocytes often proliferate, forming concentrated clusters that appear on the surface as small, dark, flat, or dome-shaped spots, which are usually harmless moles or liver spots.
- When cell proliferation occurs in a controlled and contained manner, the resulting lesion is benign and is commonly referred to as a mole or nevus.
- Sometimes, however, pigment cells grow out of control and become a cancerous and life-threatening melanoma.
Click the icon to see an image of melanin.
Melanoma
At first, melanoma cells are found in the epidermis and top layers of the dermis. However, once they grow downward into the dermis, the cancer can come into contact with lymph and blood vessels. The thicker the melanoma, the greater the likelihood that it could spread to distant sites.
Removal of the lesion before it reaches the deeper layers of the skin is important for achieving a cure.
Specific Melanomas
Superficial Spreading Melanoma. Superficial spreading melanoma is the most common and most curable. It is flat, asymmetrical, unevenly colored, and usually grows outward across the surface of the skin.
Nodular Melanoma. Nodular melanoma appears as a fast-growing brown or black lump, and its characteristics do not always fit the definitions described above. It is important to check for this type of melanoma because it is associated with an outbreak of other tumors.
Lentigo Maligna. Lentigo maligna (sometimes called Hutchinson's freckle) usually occurs in elderly people and is marked by flat, mottled, tan-to-brown freckle-like spots with irregular borders. These lesions often appear on the face or other sun-exposed areas and typically enlarge slowly for 5 - 15 years before cancer appears.
Acral Lentiginous Melanoma. Although rare, acral lentiginous melanoma is the most common melanoma among African and Asian populations. It commonly appears as a dark patch on the palms, soles, fingers, toes, under fingernails or toenails, or in mucous membranes.
Growth Pattern
Melanoma cells usually spread first through the lymph vessels or glands. Melanoma cells can also spread by way of blood vessels to various organs, spreading cancer to the liver, lungs, brain, or other sites.
Melanomas tend to grow in stages:
- Most melanomas tend to be flat initially and spread laterally across the skin surface as they grow. At this early stage, which can last 1 - 5 years or longer, removal of the growth has an excellent chance of curing the melanoma. Still, there is a chance that some of these melanomas are invasive, and they should be treated aggressively.
- Lesions that become raised or dome-shaped over at least part of their surface indicate that downward growth has occurred. In some cases, this growth is very rapid, occurring over a period of weeks to months.
Any suspicious lesion should be checked immediately, particularly if it has grown quickly or is partially flat and partially raised.
Location
Common sites of melanoma in men include:
- Head
- Middle of the body (trunk)
- Neck
Common sites of melanoma in women include:
- Arms
- Legs
However, any area of the skin may be affected. You may not notice melanomas if they appear on areas that are difficult to examine, such as the scalp or the back.
Less common sites for melanoma include:
- Fingers
- Palms
- Soles of the feet
- Genitals
- Lips
- Under the fingernails or toenails
The presence of a dark lesion under the nail that runs into the adjoining skin and doesn't heal may signal melanoma.
Rarely, melanomas appear in the mouth, in the iris of the eye, or in the retina at the back of the eye, where they may be detected during dental or eye examinations.
Click the icon to see an image of melanoma.
Nonmelanoma Skin Cancer
The two other types of skin cancers are called basal cell cancer and squamous cell cancer. These are nonmelanoma skin cancers.
Basal Cell Cancer
Basal cell cancer starts in the lowest part of the epidermis in round cells called basal cells. Basal cell is the most common form of skin cancer. It occurs in about 800,000 - 900,000 people every year.
Basal cell cancer usually develops later in life in areas that have received the most sun exposure, such as the head, neck, back, and especially the nose. However, some basal cell cancers appear in areas not exposed to the sun.
Basal cell cancers have many different appearances:
- They usually appear as a round area of thickened skin that does not change color or cause pain or itching.
- Very slowly, the lesion spreads out and develops a slightly raised edge, which may be translucent and smooth. Infrequently, basal cell cancers resemble malignant melanomas in color.
- Eventually, the center becomes hollowed and covered with a thin skin, which can become sore and open.
- A form known as aggressive-growth basal cell cancer resembles a scar with a hard base. This type is more likely to spread and must be treated very aggressively.
Basal cell cancers are sometimes hard to tell from benign skin conditions. For instance, occasionally they arise in unexposed skin, where they may mimic an ordinary mole, cyst, or pimple. They may be particularly difficult to distinguish from benign cysts when they occur near the eyes.
Usually, basal cells grow slowly. They are rarely deadly. Most basal cell cancers need not be treated as an emergency, although late treatment can cause disfigurement, so they should be removed as early as possible.
Basal cell cancers that are most likely to spread include those that are larger than 1 centimeter, scar-like, and those located on the cheek, nose, neck, earlobe, eyelid, or temple.
Some studies have shown that people with basal cell cancer may be at higher risk for second cancers, including melanoma, cancer of the lip, salivary glands, larynx, lung, breast, and kidney, and non-Hodgkin's lymphoma. Those at higher risk for such cancers appear to be men and anyone diagnosed before 60 with basal cell cancer.
Squamous Cell Cancer and Bowen's Disease
Squamous cell cancer develops from flat, scale-like skin cells called keratinocytes, which lie under the top layer of the epidermis. Most squamous cell cancers occur on sun-exposed areas, especially the forehead, temple, ears, neck, and back of the hands. People who have spent considerable time sunbathing may develop them on their lower legs.
Types of squamous cell cancer:
- Squamous cell carcinoma in situ (also called Bowen's disease) is the earliest form of this type of cancer. The cancer has not spread. Cancer areas appear as large reddish patches (often over 1 inch) that are scaly and crusted.
- Invasive squamous cell carcinoma is highly likely to spread (metastasize). The skin cancer lesions can grown rapidly (over months) or slowly (over years). Eventually they become ulcerated.
Click the icon to see an image of squamous cell cancer.
Prompt treatment is desirable because squamous cell cancers are more likely to spread to local lymph nodes than basal cell cancer. Squamous cell cancers most likely to spread include:
- Deep lesions, those larger than 2 cm in diameter, or patches with poorly defined margins
- Recurrent lesions
- Squamous cell cancer on neck, earlobe, eyelid, lips, or temple
- Squamous cell cancer that develops in ulcers
- Squamous cell cancer that develops on skin areas that have been previously treated with radiation or exposed to cancer-killing chemicals
People with squamous cell cancers seem to be at higher risk for other cancers, including melanoma, lung cancer, non-Hodgkin's lymphoma, bladder cancer, leukemia, testicular and prostate cancer in men, and breast cancer in women.
Precancerous Skin Conditions
Actinic (Solar) Keratosis. Actinic keratosis (also called solar keratosis) is a precancerous skin lesion caused by too much sun exposure. Such lesions can turn into cancer, but not always.
Actinic keratoses occur after years of sun exposure. They appear predominantly on sun-exposed skin, such as the face, neck, back of the hands and forearms, upper chest, and upper back. Men may develop keratoses along the rim of the ear.
Actinic keratoses have the following characteristics:
- Lesions typically occur on the surface of the skin and have a sandpaper-like feel. In fact, they are sometimes more easily felt than seen.
- Most lesions are pink and even flesh-colored. Some are red or brown, scaly, and tender. At times, they can resemble melanomas; even dermatologists may have trouble telling the two apart.
- They can range in size from microscopic to several inches in diameter.
Keratoacanthomas. Keratoacanthomas closely resemble squamous cell cancers, but they are not malignant. The majority occur in sun-exposed skin, usually on the hands or face. They are typically skin colored or slightly red when they first develop, but their appearance typically changes:
- In the early stages, keratoacanthomas are smooth, red, and dome shaped.
- Within a few weeks, they can grow rapidly, usually to 1 or 2 centimeters. Some reach the size of a quarter in less than a month and can be rather disfiguring.
- They eventually stop growing and become crater-like with a surrounding outer rim of tissue and sometimes have a crusty interior.
Most will spontaneously get better within 1 year, but they almost always scar after healing. Also about 25% develop into squamous cell cancers, most frequently in older people and in sun-exposed areas. Removal by surgery (sometimes by radiation) is recommended. They may also be treated with 5-fluorouracil, either as a cream or injections.
Causes
You cannot overestimate the role of the sun as the most important cause of prematurely aging skin (called photoaging ) and skin cancers.
Long-term repetitive and cumulative exposure to sunlight appears to be responsible for the vast majority of undesirable consequences of aging skin, including basal cell and squamous cell cancers.
Melanoma is more likely to be caused by intense exposure to sunlight in early life.
UVA and UVB Radiation. When sunlight penetrates the top layers of the skin, ultraviolet (UVA or UVB) radiation strikes the DNA inside the skin cells and damages it.
- UVB is the main type of radiation responsible for sunburns. It primarily affects the outer skin layers. This type of ultraviolet light is most intense at midday when sunlight is brightest.
- UVA penetrates more deeply and efficiently. Unlike UVB, window glass does not filter out UVA rays.
Damaging Effects of UV Radiation. Both UVA and UVB rays cause damage, including genetic injury, wrinkles, lower immunity against infection, aging skin disorders, and cancer, although the mechanisms are not yet fully clear. The following are some ways in which cancer may develop and some defensive actions that the skin uses to defend itself against DNA damage.
- Oxidation and Antioxidants. The effects of UV radiation are implicated in the production of oxidants, also called free radicals. Free radicals are unstable molecules produced by normal chemical processes in the body that, in excess, can damage the body's cells and even alter the DNA. This contributes to the aging process and sometimes to cancer.
- Defective DNA Repair and Protective Enzymes. Some skin cancers are caused by a breakdown in the body's mechanisms that help repair DNA damage. For example, xeroderma pigmentosum (XP) is a rare genetic disease in which the body cannot repair damage caused by ultraviolet light. Normally, a number of enzymes in the skin help protect against this damage.
- Breakdown of Immune Protection. Specific immune factors protect the skin, including white blood cells called T lymphocytes and specialized skin cells called Langerhans cells. These immune system cells attack developing cancer cells at the very earliest stages. However, certain substances in the skin, particularly a chemical called urocanic acid, can suppress such immune factors when exposed to sunlight.
Defective Cell Death (Apoptosis). Apoptosis is the last defense of the immune system. It is a natural process of cell-suicide, which occurs when cells are very severely damaged. Apoptosis in the skin kills off cells harmed by UVA so that they do not turn cancerous. The peeling after sunburn is the result of these dead skin cells. However, some gene defects or other factors interfere with apoptosis. If this occurs, damaged cells can continue to spread, resulting in skin cancer.
Genetic Factors
A number of genetic factors are being investigated for their role in melanomas, including inherited genes and genetic defects that are acquired from environmental assaults (particularly sunlight).
Mutations in Genes that Regulate Cell Growth. Noninherited mutations in a number of genes that block tumor growth or other cell-protecting properties may account for cancerous changes in moles and for aggressive melanomas. The following are some examples.
- Important studies have now identified a mutation in the BRAF gene that appears to be the most common event in the process that leads to melanoma. Some researchers have observed mutations in 66% of malignant melanomas. Researchers hope that agents that block this gene may be a viable treatment path.
- P16 is a tumor suppressive gene that may be abnormal in some melanoma cases.
- Genetic mutations that regulate Ku70 and Ku80 proteins may disrupt processes that repair strands of DNA.
- Researchers are also studying mutations in a gene that encodes for a substance called epidermal growth factor (EGF). EGF plays a role in skin cell growth and wound healing, and may account for many sporadic (non-inherited) cases of melanoma.
- Of further interest are mutations in genes that regulate Fas proteins, which are involved in apoptosis, a natural process of cell self-destruction. When apoptosis goes awry in melanoma cells, proliferation can become rampant.
CDKN2A Mutations. Mutations in a gene regulator called CDKN2A are the most common causes of inherited melanoma, which is still very uncommon. Mutations in this gene also appear in non-inherited cases of melanoma. Genetic tests are being developed for CDKN2A, although it is not clear if knowing the results of the test would benefit people carrying the gene.
Variations in the Melanocortin-1 Receptor Gene. One study found that the greater the number of variations from normal in a gene called the melanocortin-1 receptor gene, the greater the risk for melanoma. The gene plays an important role in determining if a person has red hair, fair skin, and sensitivity to UV radiation. Interestingly, people who had olive and darker skin and who carried one or more variations of the gene had a higher than average risk for melanoma.
Aging
Aging may weaken the body's ability to fend off impending cancers, including melanomas. As a person ages, they lose Langerhans cells that help fight off early skin cancers. The number of these immune cells decreases with age, possibly setting the stage for skin cancers in later life.
Risk Factors
In the United States, the rate of melanoma is rising more rapidly than any other cancer. According to the American Cancer Society, about 59,940 persons will be diagnosed with melanoma in 2007. More than 8,000 people will die from the cancer.
Survival rates have been improving, however, and the increase in melanomas has occurred principally with thin, less aggressive forms of the disease. Some experts believe this is due to the increased awareness from effective public programs and earlier diagnosis.
A risk factor is anything that increases your chance of getting a disease. The following factors increase your risk for skin cancer:
- Age over 40
- Being male
- Fair skin
- Too much exposure to sunlight and ultraviolet radiation
- Personal history of skin cancer
- Family history of skin cancer
- Smoking
- Certain chronic or severe skin problems
- Certain medical conditions or treatments that affect your immune system
- Exposure to chemicals or radiation
Age and Gender
Melanoma in Adults. Melanoma is most common in people over 40, and the incidence increases significantly as people get older. Before age 40, melanomas are slightly more common in women than men, but after age 40 men are more often affected. Men are also more likely to have invasive and fatal melanoma than are women, although some research suggests that the higher rates are only because men fail to seek a diagnosis of suspicious skin changes before they become dangerous. The rate in women levels off somewhat between age 45 and 60; researchers speculate that menopause could have some sort of protective effect during those years.
Melanoma in Children. Melanoma is rare in children under age 10. Among children ages 10 - 14 the incidence is only 0.3 per 100,000. Between ages 14 - 19, it is still very rare, 1.3 per 100,000. Parents, then, should not be unduly alarmed by every minor skin imperfection in their children. Nevertheless, melanoma is as serious in children as in adults, and early detection is still critical.
Intense Exposure to Sunlight and Ultraviolet Radiation
Skin cancer is associated with both duration and intensity of sun exposure. Risk of melanoma increases with excessive sun exposure during the first 10 - 18 years of life. Sunburns are also dangerous, with five or more sunburns doubling the risk of developing cancer. Cancer typically arises many years later.
Marathon runners are more likely than the general population to develop skin changes that increase your risk for melanoma. That's because marathon runners spend a lot of time outdoors. The study findings are published in the Archives of Dermatology.
Tanning Devices. Tanning beds and sunlamps increase the risk for developing melanoma, according to a 2005 review of epidemiologic studies. Previous findings have suggested that women who use tanning devices more than once a month significantly increase their melanoma risk. Women in their 20s, as well as blondes and redheads, are especially at risk.
Ethnic Groups and Complexion. People with light skin, blue, gray, or green eyes, red or blond hair, and lots of freckles are at highest risk for developing melanoma. The risk increases for those who are easily sunburned and rarely tan, particularly if they live close to the equator where sunlight is most intense. Darker ethnic groups or those with swarthy complexions are not immune, however.
Experts have devised a classification system for skin phototypes (SPTs) based on the sensitivity to sunlight. It ranges from SPT I (lightest skin plus other factors) to IV (darkest skin). Tanning and Sunburn Risk People with skin types I and II are at highest risk for photoaging skin diseases, including cancer. It should be noted, however, that premature aging from sunlight can affect people of all skin shades.
Tanning and Sunburn Risk | |
Skin Type | Tanning and Burning Risk |
I | Always burns, never tans, sensitive to sun exposure. |
II | Burns easily, tans minimally. |
III | Burns moderately, tans gradually to light brown. |
IV | Burns minimally, always tans well to moderately brown. |
V | Rarely burns, tans profusely to dark. |
VI | Never burns, deeply pigmented, least sensitive. |
Geographic Location
Australia has the highest melanoma rate in the world. In the United States the rate is highest in California, Florida, and Texas. The disease is by no means limited to such sunny states and countries, however. In general, the risks are highest in regions where the population tends to be blonde and fair-skinned. Norway, for example, has had the highest rate of melanoma in Europe, and rates are soaring in the UK, particularly among men, perhaps because Britons are increasingly vacationing in sunny climates.
Personal or Family History of Skin Cancer
Melanoma. Individuals who have been diagnosed with melanoma are at increased risk for a second primary melanoma. According to one 2003 study, the risk over time for developing a second melanoma is 1% in the first year after diagnosis, 2.1% at 5 years, 3.2% at 10 years, and 5.3% at 20 years. The risk is especially higher in older men and in those with first melanomas on the upper body and face.
People with family members who have or had melanoma should also be considered at high risk and examined on a regular basis.
Nonmelanoma Skin Cancers. Nonmelanoma skin cancers, including basal and squamous cell carcinomas, increase the risk of dying from other cancers, including melanoma itself, lung cancer, non-Hodgkin's lymphoma, bladder cancer, and leukemia as well as testicular and prostate cancers (in men) and breast cancer (in women).
Skin Conditions that Increase Skin Cancer Risk
Psoriasis. Psoriasis increases the risk for squamous cell carcinoma, but studies conflict on whether it has any effect on melanoma. One study, in fact, reported a lower risk. Nevertheless, there is some evidence that long-term treatment for psoriasis using UVA radiation (PUVA) may increase the risk for melanoma. In one study, there was a significantly higher risk even with relatively few treatments. In one study, invasive melanoma had occurred in 2.8% of patients 15 or more years after the initial treatment.
Moles (Nevi) and Other Dark Blemishes. Certain moles and dark blemishes increase the risk for skin cancer. Any mole ( nevus) or other blemish that seems new, changing, or unusual in any way should be evaluated by a health care professional.
Some specific moles or dark blemishes that are risk factors for melanoma include:
- Freckles. Freckles typically appear in children on sun-exposed areas and are usually evenly brown or tan. The more freckles a person develops as a child, the greater the risk for melanoma in adulthood.
- Dysplastic (or Atypical) Nevi. About 30% of the population has moles called dysplastic nevi, or atypical moles. They are larger than ordinary moles (most are 5 mm across, about the size of a pencil eraser, or larger), have irregular borders, and are various shades or colors. Individuals who have dysplastic nevi plus a family history of melanoma (a syndrome known as FAMM) are at a high risk for developing melanoma at an early age (younger than 40). The risk for those with atypical moles and no family history of melanoma is less clear.
- Large birthmarks (giant congenital nevi). Very large birthmarks more than 8 inches across are major risk factors for melanoma. In such cases, cancer usually appears by age 10. Medium-sized congenital nevi do not appear to increase the risk for melanoma. Whenever possible, very large birthmarks should be removed during infancy. Experts disagree, however, about whether small birthmarks need to be removed. Parents should watch any birthmark for changes.
The more moles one has the higher the risk that one of them will become cancerous, although the danger is still very small. A 2003 study estimated that the risk for a single mole to develop into melanoma by age 80 is 1 in 3,164 in men and 1 in 10,800 for women.
The risk is higher, however, with atypical moles. One study of people with melanoma indicated that the presence of even one atypical mole doubled the normal risk.
Some skin blemishes can look like -- but are not -- melanoma. Noncancerous moles typically have the following characteristics:
- They generally remain small with clearly defined, regular borders, and uniform coloration. Some have a regular stippled or net-like pattern of pigmentation, however, and may even resemble early melanoma.
- They typically first appear during childhood, puberty, or young adulthood. They may naturally grow, darken, or increase in number at certain times of life, such as adolescence or pregnancy.
Examples of moles or blemishes that may resemble skin cancer include:
Blue nevus. A benign mole that may easily be mistaken for melanoma. It is a blue-black, smooth, raised nodule and commonly occurs on the buttocks, hands, or feet.
Liver Spots. Liver spots are usually evenly brown or tan sun-induced lesions that are universal signs of aging. Occurring most noticeably on the hands and face, these harmless blemishes tend to enlarge and darken over time.
Spindle Cell (Spitz) Nevus. Children may develop a benign lesion called a spindle cell (or Spitz) nevus. The mole is firm, raised, and pink or reddish-brown. It may be smooth or scaly and usually appears on the face, particularly the cheeks. It is not harmful, but it may be difficult to differentiate from a melanoma, even for experts.
Diseases and Treatments that Increase Skin Cancer Risk
Non-Hodgkin's Lymphoma. Survivors of either non-Hodgkin's lymphoma or melanoma face a higher risk for the other malignancy. These may have common causes, such as exposure to UV radiation or shared genetic factors.
Human papillomavirus (HPV). Genital warts (human papillomavirus, or HPV) may also increase the risk of squamous cell cancer in the genital and anal areas and around fingernails.
Immunosuppression. Skin cancer risk is increased in persons whose immune systems are suppressed because of certain medications, organ transplantation, or medical conditions such as AIDS. Melanoma has also developed in patients who received heart transplants from donors who had the disease. Immune-suppressing drugs used to treat autoimmune disorders may also increase the risk of skin cancer. Potential skin cancer risks have been associated with the eczema drugs pimecrolimus (Elidel) and tacrolimus (Protopic).
Rheumatoid arthritis. Despite previous concerns, the rheumatoid arthritis drug etanercept (Enbrel) does not raise the risk for developing squamous cell skin cancer. The findings are reported in the Archives of Dermatology. Etanercept works by blocking tumor necrosis factor (TNF), an immune system chemical messenger that is involved in inflammatory processes and diseases.
Other Forms of Radiation Exposure
Occupational exposure to radiation, such as in health care or industrial settings, may increase the risk for melanoma. Airline pilots, too, are at increased risk for melanoma. It is uncertain, however, whether this higher risk is from excessive exposure to ionizing radiation at high altitudes or because they have more opportunity to spend time in sunny regions. Experts disagree over whether frequent flyers are also at increased jeopardy.
Prevention
The best way to lower the risk your risk of skin cancer is to protect your skin from the sun and UV light.
Wear sunscreen. The use of sunscreens is complex, and everyone should understand how and when to use them. Follow instructions closely and reapply as directed after swimming or sweating. The bottom line is not that people should avoid sunscreens or sunblocks, but that they should always use them in combination with other sun-protective measures.
Many parents are now taking effective steps to protect their children, although experts worry that they are relying too much on sunscreen and less on other protective measures. Adolescents are at special risk for sun-related cancers because, according to a 2002 study, most of them do not take protective measures when out in the sun. According to the study, boys are less likely to use sunscreen than girls, but girls are more likely to get sunburn and use tanning salons more often.
General Guidelines for Avoiding the Sun and UV Radiation
The best way to prevent skin damage in any case is to avoid episodes of excessive sun exposure. The following are some specific guidelines:
- Use sunscreens that block out both UVA and UVB radiation. Do not rely on sunscreen alone for sun protection. Also wear protective clothing and sunglasses.
- Avoid exposure particularly during the hours of 10 a.m. to 4 p.m., when UV rays are the strongest.
- Clouds and haze do not protect you from the sun and in some cases may intensify UVB rays.
- Avoid reflective surfaces such as water, sand, concrete, and white-painted areas.
- UV intensity depends on the angle of the sun, not heat or brightness. The dangers are greater the closer to the start of summer.
- Skin burns faster at higher altitudes. One study suggested that an average complexioned person burns in 6 minutes at 11,000 feet at noon compared to 25 minutes at sea level.
- Avoid sun lamps, tanning beds, and tanning salons. The machines use mostly high-output UVA rays. Some experts believe that 15 - 30 minutes at a tanning salon are as dangerous as a day spent in the sun. People should not be misled by advertising claims of "safe" tanning.
Sun-Protective Clothing
Wear protective clothing, sunglasses, and a hat to shield your face from the sun's rays. Special clothing can block out UV rays and is rated using sun protection factor (SPF) ratings or a system called the UPF (ultraviolet protection factor) index, with 50 UPF being the highest. (According to one study, this is a very reliable indicator of protection.) The clothing is expensive, however.
- Everyone, including children, should wear hats with wide brims. (Even wearing a hat, however, may not be fully protective against skin cancers on the head and neck.)
- People should look for loosely fitted, unbleached, tightly woven fabrics. The tighter the weave the more protective the garment.
- Washing clothes over and over improves UPF by drawing fabrics together during shrinkage. An easy way to assess protection is simply to hold the garment up to a window or lamp and see how much light comes through. The less the better.
- Everyone over age 1 should wear sunglasses that block all UVA and UVB rays when in the sun.
Click the icon to see a depiction of sun protection.
Sunscreen Guidelines
When choosing a sunscreen, look at the ingredients. Preparations that help block UV radiation are sometimes classified as sunscreens or sunblocks, according to the substances they contain. In general, sunscreens contain organic formulas and sunblocks inorganic formulas. However, the term sunblock is used less and less as sunscreens increasingly contain both kinds of ingredients:
- Organic formulas contain UV-filtering chemicals such as octocrylene, octyl salicylate, homosalate, and octyl methoxycinnamate (block UVB), avobenzone-Parsol 1789 (blocks UVA), cinoxate, ethylhexyl p-methoxycinnamate (blocks UVB and small amounts of UVA), oxybenzone, and benzophenone-3 (blocks UVA/UVB). People should look for a wide-spectrum sunscreen that contains combinations of these ingredients and filter both UVA and UVB. Of note: para-amino benzoic acid (PABA), once a popular ingredient, is now used infrequently. PABA may actually break down in the presence of UV exposure and release harmful oxidants. And many people have an allergic reaction to it. Some products contain PABA derivatives, such as padimate O or octyl dimethyl PABA.
- Inorganic formulas contain the UV-blocking pigments zinc oxide or titanium dioxide. Zinc and titanium oxides lie on top of the skin and are not absorbed. They prevent nearly all UVA and UVB rays from reaching the skin. Older sunblocks are white, pasty, and unattractive, but current products use so-called microfine oxides, either zinc (Z-Cote) or titanium. They are transparent and nearly as protective as the older types. Microfine zinc oxide may be more protective and less pasty-colored than microfine titanium oxide.
Inexpensive products work as well as expensive ones with the same ingredients. Unfortunately, there are still no standards for sunscreens, and even those claiming UVA protection may offer very little.
Organic formulas and inorganic microfine oxides do not protect against visible light, which is a problem for people who have light-sensitive skin conditions, including actinic prurigo, porphyria, and chronic actinic dermatitis.
Calculating the SPF. SPF is a ratio based on the amount of UVB radiation needed to turn sunscreen- or sunblock-treated skin red compared to non-treated skin. For instance, people who sunburn in 5 minutes and who want to stay in the sun for 150 minutes might use an SPF 30. The formula would be: 30 (the SPF number) times 5 (minutes to burn) = 150 minutes in the sun.
Protection offered by sunscreens may be classified as follows:
- Minimal: SPF 2 to 11
- Moderate: SPF 12 through 29
- High: 30+
Although some sunscreens claim SPFs higher than 30, the added protection at such higher levels is insignificant.
SPF Levels by Age Group. Although sunscreens are safe in most toddlers and children, they should not be the first and only lines of defense. All young children should be well-covered with clothing, sunglasses, and hats. Children should be kept out of the sun during peak sunlight periods. Do not use sunscreens on babies younger than 6 months without consulting a doctor.
Older children and adults (even those with darker skin) benefit from using SPFs of 15 and over. Some experts recommend that most people should use SPF 30 on the face and 15 on the body.
Adults who burn easily instead of tanning and anyone with risk factors for skin cancer should use at least SPF 30.
Timing and Amount of Application. Apply sunscreen or sunblock liberally as follows:
- Adults should include sunscreen every day, even if going outdoors for only a short time.
- Apply a large amount to all exposed areas, including ears and feet. To achieve protection as indicated by the sunscreen's SPF, experts recommend half a teaspoon each for the head, neck, and each arm and a teaspoon each for the chest area, the back, and each leg.
- Apply initially 30 minutes before venturing outdoors for best results. This allows time for the sunscreen to be absorbed. Then reapply every 15 - 30 minutes while being in the sunlight.
- Also reapply each time after exercise or swimming. Choose a waterproof or water-resistant formula even if activities don't include swimming. Waterproof formulas last for about 40 minutes in the water, whereas water-resistant formulas last half as long.
- Insect repellents reduce sunscreen SPFs by up to one-third. Use higher SPFs and very liberal application when applying both.
Possible Hazards of Sunscreens, Sun Avoidance, or Both. When used generously and appropriately, sunscreen products and sun avoidance help reduce the severity of many aging skin disorders, including squamous cell cancers. There are certain concerns, however. Sunscreens do not appear to provide protection against melanoma and some basal cell cancers. In fact, some studies have reported a higher association with sunscreen use and these skin malignancies, though not all studies report such negative results.
The reasons for this possible increased risk are unclear, though some theories include:
- Until recently, many sunscreens blocked only or predominantly blocked UVB rays and not UVA, the more deeply penetrating rays now known to be especially dangerous. Studies then may not have reflected the effects of the broad-spectrum sunscreens now available, which block both UVA and UVB.
- People who apply sunscreens may stay out too long during peak sunlight hours. Even if a person doesn't sunburn, UVA rays can still penetrate the skin and do harm.
- People may not put on enough sunscreen. A 2002 study found that people generally apply only 20 - 60% of the recommended amount, which can provide significantly less protection than the given SPF. A later study reported that when applied at the recommended amount, a broad-screen sunscreen prevents DNA damage from UV exposure.
Underexposure to sunlight. There is some major concern that underexposure to sunlight, due to the use of sunscreens or sun-avoidance measures, may produce other health problems such as:
- Vitamin D deficiency. The body makes vitamin D through a chemical reaction to UVB sunlight. Too many sun-protection measures may increase the risk for developing vitamin D deficiency. Vitamin D helps prevent rickets, osteoporosis, and some cancers, including melanoma. People who need to avoid sunlight and whose diet is low in foods that contain vitamin D should check with their doctor about taking supplements. (Warning: Vitamin D is poisonous when taken in high doses.) People with darker skin are at higher risk for deficiencies from sun protection than those with whiter skin.
- Other Cancers. Although sunlight is implicated in skin cancers, it is also associated with lower risks for breast, prostate, ovarian, and colon cancers. Some protection against these cancers may be related to vitamin D production by sunlight.
- Depression. Many people suffer from seasonal affective disorder (SAD), a form of depression that generally occurs in winter and is associated with exposure to less sunlight.
The bottom line is that some sunlight is important and even necessary.
Low-Fat Diet
A study published in 1994 in the New England Journal of Medicine found that persons with a history of nonmelanoma skin cancer who ate a low-fat diet were much less likely to develop actinic keratosis, a precancerous skin condition.
However, the low-fat diet did not appear to have any effect on the development of basal cell cancer.
Chemoprevention
Chemoprevention is the use of a substance to prevent or reduce your risk of cancer. Certain drugs have been used to help block the development of skin cancers, including melanoma. For example, a medicine called imiquimod is approved to prevent skin cancer in certain individuals. This medicine prompts the immune system to fight off foreign substances, including cancer cells. Chemopreventive agents under investigation and showing promise for skin cancer include:
- Nonsteroidal anti-inflammatory drugs
- Difluoromethylornithine (DFMO)
- Catechins (phytochemicals found in certain foods)
- Anti-aging drugs called retinoids (vitamin A derivatives)
Retinoids have been shown to prevent nonmelanoma skin cancer in patients with basal cell nevus syndrome, xeroderma pigmentosum, and transplanted organs. Oral retinoids include isotretinoin and acitretin. They may also prevent the development of squamous cell carcinoma in patients who are taking such medicines to treat psoriasis.
Early animal studies had suggested that cholesterol-lowering statins or fibrates may reduce the risk of skin cancer, but human studies have produced inconsistent results. A review of several studies has concluded that such drugs do not decrease your risk of melanoma. The findings are published in the Journal of the National Cancer Institute.
Researchers are also studying chemopreventative compounds that target genetic mechanisms in the skin. They may prove to be beneficial ingredients in creams or lotions used to prevent skin cancers on a molecular level. They include cytokine interleukin-12 and T4 endonuclease 5 (T4N5).
Exercise
Studies have shown that mice with round-the-clock access to an exercise wheel developed skin cancer more slowly when exposed to UVB. Their tumors were also fewer in number and smaller. Analysis of the data suggested that exercise might trigger the death of the developing cancer cells faster than they can grow. Exercise also made the mice lose weight, and the number of tumors decreased as fat disappeared.
Antioxidants, Vitamins, and Herbal Products
Antioxidants are chemicals or drugs that help prevent cell damage from unstable molecules called free radicals. Antioxidants promote to protect the skin include vitamins C and E, and coenzyme Q10 (CoQ10).
Studies suggest that vitamin E creams, particularly those made from a type of Vitamin E called alpha tocopherol, decreased skin roughness, length of facial lines, and wrinkle depth. Studies on mice have also shown that such creams reduce UV-related skin cancer.
Vitamin C is a very potent antioxidant. It is also called ascorbic acid. Most studies on the effects of antioxidants on the skin have used this vitamin. In laboratory studies, large amounts reduced skin swelling and protected immune factors from sunlight.
Selenium in the form of L-selenomethionine has protected against sun damage and even delayed skin cancer in animal studies. It is not known if such benefits apply to people.
Click the icon to read about the antioxidant selenium.
Antioxidant Skin Creams. There are wide claims about the benefits of antioxidants for wrinkles when used in skin creams. However, to date, only vitamin E, C, and selenium-based skin products have been shown to help reduce sun damage to the skin. However, most available brands contain very low concentrations of these antioxidants. In addition, the antioxidants are also not well absorbed by the skin, so the effect may be short-term.
Antioxidant Pills. One small study found that taking a combination of vitamins C and E supplements by mouth may help reduce sunburn reactions, although the protection is much less than from sunscreens. Taking the vitamins alone does not appear to have the same effect.
Other Natural Substances. The following natural substances have antioxidant properties and are being tried for sun-protection:
- Both green and black tea appear to have properties that may provide some protection against skin cancers and photoaging. A 2001 study using extracts of topical green tea suggested that it might protect against ultraviolet damage. Green tea skin care products are now available, but their quality is unregulated.
- Ginger also appears to have some sun protective qualities.
- Silymarin, a substance found in the milk thistle family (which includes artichokes), may prevent UVB-promoted cancers in animals.
- Garlic has been shown to protect animals against UVB damage. Whether these results may be applied to humans, and what quantities of garlic might be beneficial, is still unknown.
Warning Note: A wide range of herbal products may contribute to dermatological problems. Some Chinese herbal creams have been found to contain corticosteroids. Mercury or arsenic contaminants have been found in some Ayurvedic therapies. In addition, several oral herbal remedies used for medical or emotional conditions may produce irritation in reaction to sunlight (photosensitivity). They include, but are not limited to, St. John's wort, kava, and yohimbe.
Screening
Education and prevention programs have led to improved screening for skin cancer, which in turn has improved diagnosis and survival rates for melanoma. For example, a study published in CANCER has shown that older men are more likely to undergo a whole body skin exam if they were aware of personal risk factors and where they could go to have an exam performed.
Skin Cancer Warning Signs
Skin cancers may have many different appearances. They can be small, shiny, or waxy, scaly and rough, firm and red, crusty or bleeding, or have other features. Itching, tenderness, scaling, bleeding, crusting, or sores can signal potentially cancerous changes in any mole.
A mnemonic device, ABCDE, is used to describe several features that help to distinguish skin cancer from noncancerous growths.
- Asymmetry (A). Skin cancers usually grow in an irregular, asymmetric fashion. That means one half of the abnormal skin area is different than the other half.
- Border Irregularity (B). Noncancerous lesions generally have clearly defined borders. Melanoma lesions often have notched or indistinct borders that may signal ongoing growth and spread of the cancer.
- Color Variation (C). One of the earliest signs of melanoma may be the appearance of various colors within the lesion. Because melanomas arise within pigment-forming cells, they are often varicolored lesions of tan, dark brown, or black, reflecting the production of melanin pigment at different depths within the skin. Occasionally, lesions are flesh colored or surrounded by redness or lighter areas of depigmentation.
- Pink or red areas may result from inflammation of blood vessels within the skin.
- Blue areas reflect pigment in the deeper layers of the skin.
- White areas can arise from dead cancerous tissue.
- Diameter (D). A diameter of 6 millimeters or larger (about the size of a pencil eraser) is worrisome. Melanomas start out small; by the time a lesion has grown this large, other abnormalities will most likely be present. A doctor should examine any suspicious lesion, no matter what size it is.
- Evolution (E). A lesion that is growing or changing deserves evaluation.
The ABCDE plan is a general guide. It will not help detect the early stages of nodular melanoma and may also miss amelanotic melanoma, which is not pigmented.
You should keep in mind that the most important warning sign of melanoma is a new or changing skin lesion, regardless of size or color. Changes that occur over a short period of time (particularly over a few weeks) are most worrisome.
Self-Examinations for General Population
Anyone with risk factors for skin cancer should check the entire body about once a month. People who regularly check moles on their skin may have a lower risk of developing advanced melanoma.
Experts suggest drawing a map of the body, indicating locations of moles, areas of discoloration, lumps, or other blemishes. Whenever a person conducts a self-examination, they should compare their body to the map to check for new lesions, lumps, or moles and for changes in shape, color, and size.
Some experts have defined three specific body areas to look for skin cancers, including melanomas:
- Areas visible to anyone, such as the arms or face -- about 60% of melanomas are found on such areas.
- Areas usually covered with clothing and visible only to the patients or their partners -- about 34% of melanomas are detected in these areas.
- Hidden areas such as the scalp, buttock folds, and mouth -- about 6% of melanomas, usually more advanced, are found here.
Ask a partner to help you check these areas. Turn on a hair dryer to separate hair and examine the scalp.
Professional Examination for High-Risk Individuals
Some experts recommend that everyone, especially those with a high risk of developing melanoma, have a dermatologist perform a whole body skin exam. Dermatologists detect melanoma earlier than other health care providers, according to an article in the Archives of Dermatology.
High-risk people include those with a personal or family history of melanoma and individuals with atypical nevi (irregular moles that are also larger than normal).
Such people should protect themselves from overexposure to sunlight and have a medical examination of the entire skin surface every 3 - 12 months, with the frequency depending on risk factors. Doctors may take photographs of any moles at each visit and compare them with previous photos for any changes.
Examinations for Patients Previously Treated for Melanoma. People who have had melanoma and have been treated successfully are at risk for recurrence or a second primary melanoma. Based on recurrence rates by cancer stage, a team of researchers suggested the following guidelines for being reexamined by the doctor after treatment:
- Stage I patients: Yearly exam
- Stage II patients: Every 6 months for years 1 and 2 and annually thereafter
- Stage III patients: Every 3 months for the first year, every 4 months for year 2, and every 6 months for years 3 to 5
All patients should be checked annually after year 5. These are guidelines only and may be changed, depending on individual patient characteristics.
Some studies also suggest that regular screening of family members of people with melanoma could prevent a number of serious cases. A 2007 report in the Archives of Dermatology has called for expanded melanoma screening programs. The study found that one-time melanoma screening for adults over age 50 seems to be as cost-effective as other recommended cancer screenings. The study authors also found that screening brothers and sisters of someone with melanoma every 2 years may also be cost-effective.
Diagnosis
An experienced doctor should first rule out benign conditions that resemble melanoma, such as a noncancerous mole called a melanocytic nevi.
In rare instances, a melanoma will be difficult to detect. For example, an uncommon form, called a myxoid melanoma, may be mistaken for a benign skin disorder known as a myxoid fibrohistiocytic lesion. Other opinions from a second pathologist, computerized image processing or advanced staining techniques, may help to confirm the diagnosis.
A study published in the Archives of Internal Medicine has found that melanoma tends to be diagnosed at a later stage in persons who are not light-skinned. The study involved nearly 50,000 patients with melanoma, and included Caucasians, Hispanics, Asian/Pacific Islanders, African-Americans, and American Indians.
Dermoscopy
Some doctors now use dermoscopy (also called dermatoscopy or epiluminescence microscopy). This technique uses a handheld scope-like device that enhances the suspected lesion. It is still not clear if such devices are any better than the naked eye of a trained professional. Of interest, however, was a 2002 study suggesting that it was very useful in identifying possible melanomas in suspicious nail abnormalities and therefore avoiding many painful biopsies in this area. A 2004 study confirmed that adding dermoscopy to conventional naked-eye examination leads to fewer biopsies than using naked-eye examination alone.
A recently developed Australian device (the Solarscan) may improve detection. It is shaped like a hair dryer and takes an image of the suspicious lesion; it then reads the image and compares it with a databank of melanoma images to help determine if it is cancerous. It can also store the image of the lesion and compare it for changes with later images taken at subsequent check ups. The device is not yet used in the United States. It still requires FDA approval. Testing is under way to confirm its accuracy.
Skin Biopsy
A skin biopsy is the removal of skin tissue for examination under a microscope. The exact type of biopsy depends on how deep the lesion has penetrated the skin.
- Shave biopsy uses a thin surgical blade to shave off the top layers of skin. The doctor may use this type of biopsy to diagnose basal cell cancer.
- Punch biopsy uses a round, cookie-cutter-like tool. It is used to take a deeper sample skin.
- Incisional and excisional biopsies remove tumors that have grown deep into the skin. An incisional biopsy cuts out part of the tumor. An excisional biopsy removes the entire tumor. These biopsies are used to diagnose melanoma.
All of the above-mentioned biopsies can be done using local anesthesia.
Lymph Node Biopsy
A lymph node biopsy helps the doctor determine whether cancer has spread to one or more lymph nodes.
A procedure called sentinel lymph node (SLN) biopsy is now recommended for cancers that are thicker than 1 millimeter and generally unnecessary for those thinner than 0.75 millimeter, unless they are ulcerated. Although some evidence suggests this procedure may improve survival, no clinical trials have proven to date that this procedure improves the outlook in persons with melanoma.
This procedure involves the following:
- A tiny amount of a tracer, either a radioactively labeled substance (radioisotope) or a blue dye, is injected into the tumor site.
- These substances then flow through the lymph system into the sentinel node, the first lymph node to which any cancer would spread.
- The sentinel lymph node and possibly one or two others are then removed and biopsied.
The results of the biopsy can help doctors decide whether or not to remove other lymph nodes:
- If the sentinel node and others shows signs of cancer then the nearby lymph nodes are removed.
- If they do not, then the remainder of the lymph nodes will likely be cancer-free, and further surgery is not needed.
Secondary Tests
If melanoma has been diagnosed, the doctor will perform other tests to see if the cancer has spread, such as a chest x-ray.
Blood tests that show high levels of lactate dehydrogenase suggest that the cancer has spread. Blood tests to assess liver function and other factors to help determine specific sites where the cancer may appear.
Advanced imaging techniques, such as computed tomography (CT) or positron emission tomography (PET), may also be used. PET is particularly accurate. One study reported that PET was able to diagnose melanoma that had spread even when other tests, including CT, did not. PET can also be very accurate for identifying recurrent melanomas.
Biomarkers for Metastasis
Biomarkers are specific substances that are linked to cancer. Blood tests to detect biomarkers may be used to identify microscopic cancers if sentinel node biopsy results are uncertain. Researchers are continually investigating other biomarkers that may indicate whether the cancer had spread or how severe it is, which would help determine whether treatments should be more or less aggressive.
A number of proteins and other factors detected in blood tests are showing promise as markers for microscopic metastasis. Examples include antibodies to MART-1, Melan-A, tyrosinase, and microphthalmia transcription factor (Mitf). Combinations of some of these factors may improve detection rates.
Staging
Staging is the process used to determine the size of the tumor and where and how far it has spread. When a cancer spreads, its said to have metastasized. Staging helps the health care team plan for appropriate treatment.
- Basal cell cancer is rarely staged, because it doesn't usually spread to other organs. However, it may be staged if it's very, very large.
- Squamous cell cancer may be staged in persons who have a high risk of the cancer spreading.
- Melanoma is always staged.
Health professionals have come up with various methods for staging the cancer. This report uses the TNM staging system recommended by American Joint Committee on Cancer.
- T = tumor. T is followed by a number to indicate thickness.
- N = node. N is followed by numbers to indicate the number of lymph nodes involved.
- M = metastasis. Metastasis is the spread of cancer to far away sites.
In addition a stage will include whether the melanoma is ulcerated or not, an indication of severity. Ulceration is determined if skin layers over the tumor appear indistinct under the microscope.
In general, the thicker the lesion and the farther the cancer has spread, the higher the assigned stage. The higher the stage, the worse the long-term outlook.
- The earliest melanomas, which do not penetrate beneath the surface of the skin and are known as melanoma in situ, are highly curable and are called stage 0 or not given a stage.
- Melanomas less than 4 mm thick suggest Stage I or II cancers, and the next step is to attempt to determine if they have spread or are likely to spread to the lymph nodes.
- Melanomas that are over 4 mm thick indicated later stages. In such cases, the lymph nodes are sometimes removed to attempt to prevent the cancer from spreading, although about 70% of these melanomas have already spread.
Specific stages are as follows:
Stage I. Cure rates are excellent with surgical removal, since they are least likely to have spread.
- Stage 1A. Tumor has not spread to the nodes. It is less than 1 mm and is not ulcerated.
- Stage IB. Tumor has not spread to the nodes. It is less than 1 mm, but is ulcerated, or the tumor is between 1.01 and 2 mm but is not ulcerated.
Stage II. Melanomas can be cured, but the success rate lags behind that of Stage I because a small number of cancer cells may have spread to distant sites. In addition to surgery, other forms of therapy may be recommended.
- Stage IIA. Tumor has not spread to the nodes. It is between 1.01 and 2 mm and is ulcerated, or it is 2.01 to 4 mm without ulceration.
- Stage IIB. Tumor has not spread to the nodes. It is between 2.01 and 4 mm and is ulcerated or greater than 4 mm without ulceration.
Stage III. Survival rate is lower than earlier stages.
- Stage IIIA. Tumor has spread to 1 node and it is up to 4 mm without ulceration. Sentinel biopsy has detected microscopic evidence of tumor cells in the node (micrometastasis).
- Stage IIIB. Tumor is up to 4 mm without ulceration and has spread to one node or there is evidence of micrometastasis in two nodes.
- Stage IIIC. Tumor is any thickness and ulceration may or may not be present. It has spread to 2 or 3 nodes. Additional "satellite" melanomas on the skin more than 2 cm (about an inch) from the original lesion may be present; these are sometimes called "metastases in transit."
Treatment for Melanoma
Treatment for melanoma depends on various factors, including:
- The site of the original lesion
- The stage of the cancer
- The patient's age and general health
Treatment options include:
- Surgery to remove the melanoma cancer cells
- Chemotherapy
- Immunotherapy
- Radiation therapy
- Palliative therapy
Surgery
Surgery is the primary treatment for all stages of melanoma. Some or all of the melanoma is often removed during the diagnosis biopsy. If cancerous tissue still remains after such a biopsy, a surgeon will cut away additional tissue from the surrounding area to remove any stray cancer cells.
Mohs micrographic surgery is a technique used to remove very thin layers of skin one at a time. Each layer is examined immediately under a microscope. When the layers are shown to be cancer-free, the surgery is complete.
The amount of tissue removed depends on the size, depth, and degree of invasion:
- Stage I lesions that are less than 1 mm deep require the smallest surgical cuts, usually about 1 cm off each side and downward from the original lesion.
- For melanomas that are 2 mm or thicker, a margin of 3 cm is important for reducing the risk of recurrence.
- Thicker lesions require wider surgical cuts.
It used to be customary to remove a large area, regardless of the stage of cancer. This potentially disfiguring approach has been abandoned because studies have shown that excising wider margins does not improve survival. Nevertheless, sometimes skin grafts may need to be taken from other body sites to help cover the wound.
Lymph Node Removal. If there is evidence that melanoma has spread to nearby lymph nodes but has not spread beyond, removing them may reduce the chance of recurrence and help patients live longer.
Surgery for Metastatic Melanoma. In some cases, surgical removal of distant tumors may be possible and prolong survival, since often in melanoma the cancer spreads first only to a single site, such as the lung or the brain.
Cryosurgery. Cryosurgery freezes skin tissue and destroys it. This procedure is not useful for most melanomas, but it might have some value in specific situations. For example, it may be effective for smaller melanomas in the eye, a location that is difficult to treat with traditional surgery. It may be useful to eliminate residual cancer cells after standard surgery for lentigo maligna melanomas, an atypical form of melanoma that has a wide surface and is difficult to treat.
Recurrence rates are very high with lentigo maligna after conservative surgery. Although this is a very slowly progressive condition, lentigo maligna can develop into melanoma. Most of these lesions appear on the face and neck, so extensive surgery can be disfiguring. Patients should discuss with their doctor carefully staged surgery to remove all diseased tissue with as little cosmetic harm as possible.
Chemotherapy
Chemotherapy is often used to treat recurrent or metastatic melanomas. This type of therapy is not intended as a cure but can prolong life and improve its quality.
Drugs Used. The following are some of the chemotherapy drugs used to treat melanoma. They may be used alone or in combination under specific situations.
- Methylating agents impair the ability of cancer cells to divide. Dacarbazine (DTIC) and temozolomide (Temodar) are the ones most often used.
- Nitrosoureas, which include carmustine (BCNU) and lomustine (CCNU) are often used.
- Taxanes, such as docetaxel (Taxotere) and paclitaxel (Taxol), are showing some low-level activity against melanoma.
Researchers continue to investigate other chemotherapy drugs and combinations of drugs to see which works best.
Side Effects. Side effects occur with all chemotherapy drugs. They are more severe with higher doses and increase over the course of treatment.
Common side effects include the following:
- Nausea and vomiting
- Diarrhea
- Temporary hair loss
- Weight loss
- Fatigue
- Anemia
- Depression
Serious short- and long-term complications can also occur and may vary depending on the specific agents used. They include the following:
- Increased chance for infection from suppression of the immune system.
- Severe drops in white blood cells (neutropenia). Certain agents, such as taxanes, pose a higher risk for this than other chemotherapeutic drugs. White blood cell count may be improved with the addition of a drug called granulocyte colony-stimulating factor (either filgrastim or lenograstim).
- Liver and kidney damage.
- Abnormal blood clotting (thrombocytopenia).
- Allergic reaction.
- Menstrual abnormalities and infertility in women. A natural hormone medication called a gonadotropin-releasing hormone analogue that puts women in a temporary pre-pubescent state during chemotherapy may preserve fertility in some women.
- Rarely, secondary cancers such as leukemia.
- Problems in concentration, motor function, and memory, which may be long-term.
Treating Side Effects
Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve nausea and vomiting in nearly all patients given moderate drugs and most patients who take more powerful drugs.
Erythropoietin stimulates red blood cell production and can help reduce or prevent anemia related to chemotherapy. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). Aranesp persists longer in the blood than epoetin alfa and so requires fewer injections.
Benefits of Chemotherapy. About 20% of cancers shrink in response to one or more of these drugs, but the effects last only 3 - 6 months. If the tumors completely disappear, the cancer may stay in remission much longer, but in virtually all cases it returns.
Chemotherapeutic Regional Perfusion
Chemotherapeutic regional perfusion (also called isolated limb perfusion) is a technique used to give a person very high-dose chemotherapy. It is often used effectively for metastasized or recurrent melanoma that occurs on the arm or leg. It does not appear to be useful for preventing metastasis after a first occurrence of melanoma in one of these locations.
This technique involves the following:
- The blood supply to the limb with melanoma is temporarily interrupted using a tourniquet and then rechanneled through a heart-lung machine.
- Anticancer drugs are added to the blood in doses up to 10 times the standard doses.
- The blood is then heated to enhance the drug's potency.
- The chemo-infused blood is then sent directly to the melanoma site, minimizing the likelihood of drug toxicity.
- Adverse effects occur in less than 1% of cases and include severe problems in the treated limb (rarely leading to amputation) and drug leakage into the bloodstream. This can severely reduce white blood cells and lead to serious infection.
In addition to arms and legs, perfusion techniques have been tested for the pelvis, head, neck, skin of the breast, and even the abdomen.
Immunotherapy
Immunotherapy uses drugs to boost the patient's own immune system. Immunotherapy after surgery may help prevent recurrence in certain persons with melanoma.
Cytokines. Cytokines are small proteins that play an important role in the body's immune response. Certain cytokines called interferons are used as a therapy for metastatic melanoma. These medicines are usually given along with chemotherapy or other immunotherapies, or both.
A number of cytokines and combinations are being investigated. They include:
- Interferon alpha-2b (Intron) is the only FDA approved immunotherapy for late stage melanoma. The most common side effects are fatigue, depression, and flu-like symptoms, which can be severe. Starting an antidepressant, such as paroxetine (Paxil), several weeks before interferon therapy may help prevent depression.
- Pegylated interferon and natural human interferon are long-acting forms are under investigation. One study showed that low-dose natural interferon after chemotherapy increased the 5-year relapse-free survival rate.
- Interleukin-2 (Proleukin) is a hormone-like substance that stimulates the growth of cancer-fighting white blood cells. High-dose interleukin-2 has been shown to help patients with metastatic melanoma. The drug can cause significant side effects, including very low blood pressure, heart rhythm abnormalities, severe infections, and shortness of breath. The side effects are manageable and nearly always reversible.
- Granulocyte-macrophage colony stimulating factor (GM-CSF, Leukine, Sargramostim) is an injectable cytokine under study. The drug boosts production of immune cells in the blood and bone marrow. An inhaled form of the drug is being tested for melanoma that has spread to the lungs.
- T-cell therapy uses white blood cells, called tumor-infiltrating lymphocytes (TIL), that taken from the patient. The cells are modified so they better fight cancer and are then reinjected back into the patient. T-cell therapy is showing promising results, especially for patients with advanced melanoma who have failed to respond to other treatments.
A chemical called histamine is a powerful inhibitor of reactive oxygen species, ROS, which may inactivate immune cells that fight cancer. Researchers are investigating to see if it can be used along with interleukin-2 cytokine therapy. In one study, the added benefits of histamine were modest except in patients with liver metastatic; in these patients, survival improved by 129 days, which was significant.
Vaccine Immunotherapy. Vaccine immunotherapy is the use of a specific vaccine to treat an existing cancer. In this case, the vaccine targets one or more proteins that are uniquely expressed by melanoma cells.
Many therapeutic melanoma vaccines are in advanced stages of development, but none is approved for use in the United States.
There are two basic types of therapeutic vaccines:
- Autologous vaccines
- Allogenic vaccines
Sometimes a combination of the two are used. In this case, it's called a hybrid.
Autologous vaccines are made from the patient's own cancer cells. This produces a very specific immune response that can target the patient's cancer precisely. Oncophage (HSPPC-96) and M-Vax are autologous vaccines for melanoma that have shown promise in early clinical trials. One problem with the autologous approach is that there is no way to scientifically assess outcome or even guarantee repeated success since each vaccine is unique to the individual patient. This approach is also appropriate only for select patients.
Allogenic vaccines are made in a laboratory using cells from someone other than the patient. They may be made from proteins from tumor cells, genetic material, or even bacteria. One such vaccine is Canvaxin. Early studies showed this vaccine increased survival rates in some patients with Stage 3 melanoma. However, a later trial was halted because the vaccine did not appear to improve make such patients live any longer.
Vaccine immunotherapy requires the body to build up its own defenses. It can take months before beneficial effects occur, but when they do, tumor reduction is much more lasting than with chemotherapy. Vaccines also seem to have fewer side effects than interleukin and interferon.
Antisense Compounds. Antisense compounds can prevent defective cancer genes from being translated into proteins that cause abnormal cell proliferation.
Monoclonal Antibodies (MAb). Antibodies are natural substances produced by immune cells that home in and destroy cancer cells. Scientists are identifying specific antibodies that may attack melanoma cells and cloning them to create monoclonal antibodies. MAbs have shown promise for other cancers and are now being tested for melanoma, often in combination with vaccines and other forms of immunotherapy.
Radiation
In general, radiation is used to help relieve pain and discomfort caused by cancer that has spread or recurred. Radiation is not used as often for treating melanoma as it is for other forms of cancer because melanoma cells tend to be more resistant to its effects. It may be useful in some cases, however.
- In some patients with tumors less than 3 cm deep, however, radiation may help slow down metastasis when combined with a super-heating process using microwaves.
- Brachytherapy, in which radioactive seeds are implanted close to the tumor, has also been used with success for melanoma of the eye.
- Lentigo maligna may sometimes be treated successfully with specific radiation treatments called soft, or Grenz, x-rays.
- Radiotherapy using a so-called gamma knife (very focused gamma radiation) is also effective for cancer that has metastasized to the brain, in some cases halting the growth and, in rare situations, even eliminating it.
Palliative Therapy
The goal of palliative therapy is to improve the patient's quality of life and relieve symptoms. It is not a cure. Advanced melanoma that has spread to distant sites often cannot be cured, although surgical removal of metastatic tumors may provide some benefit by easing pain, increasing the general quality of life, and lengthening survival.
Patients should ask their doctor's about clinical trials, studies that examine new immunotherapies (vaccines, cytokines), gene therapies, chemotherapy combinations, or other treatments.
Experimental Therapies
Tetracyclines. Chemically modified tetracyclines, a common antibiotic, have been shown to modify metalloproteinase, an enzyme in the skin that promotes skin cancers, including melanoma.
Anti-Angiogenesis Agents. An anti-angiogenesis drug is one that blocks the formation of new blood vessels. The growth of new blood vessels helps cancer cells grow and spread. The anti-angiogenesis drug thalidomide (Thalomid) is approved for treatment of melanoma but requires special prescribing precautions. This drug had gained notoriety in the 1960s because of devastating birth defects in the children of women who took it during pregnancy. Scientists are investigating drugs that are chemically similar to thalidomide but have fewer side effects.
Curcumin. The yellow spice found in turmeric and curry powders may contain cancer-fighting properties. In a preliminary laboratory study, curcumin stopped the growth of melanoma cells. It is far too early, however, to recommend curcumin for clinical use.
Treatment for Nonmelanoma Skin Cancer
A number of options are available for treating nonmelanoma skin cancer, including surgery, cryosurgery, phototherapy, radiation, and topical 5-fluorouracil.
Surgery
For any skin cancer and for some keratoses that require removal, surgery is the first treatment. It is usually one of the following:
Excisional Surgery. This is the surgical removal of the cancerous lesion.
Curettage and Electrodesiccation. This procedure involves scraping away of the cancerous tissue followed by electric cauterization to stop the bleeding.
Mohs Micrographic Surgery. Mohs surgery is a meticulous procedure used for skin cancers at high risk for recurrence or becoming invasive. The technique removes very thin layers of skin one at a time. Each layer is examined immediately under a microscope. When the layers are shown to be cancer-free, the surgery is complete. A human skin substitute (Apligraf) is applied to the surgical area. It helps speed up wound healing to achieve a better cosmetic effect.
Good candidates for Mohs surgery include:
- Persons with squamous cell cancer
- Persons with basal cell cancer greater than 1 cm (about half an inch)
- Persons with basal cell cancer on the face, ear, or neck
- Young people with skin cancer
Mohs surgery saves more healthy tissue than other procedures and is highly effective. It results in a 99% cure rate for primary tumors and a 95% cure rate for recurrent ones. It can be safely performed in the doctor's office. Complications are uncommon but can include bleeding and infection.
Lasers. Laser surgery may be useful for certain basal cells and for keratoses that appear on the lips, although it is not clear whether lasers offer any advantages over other surgical treatments. Lasers do not appear to be very effective for thick or tough squamous cell cancers.
Cryosurgery
Cryosurgery removes skin cancer cells or actinic keratoses by freezing the affected tissue with liquid nitrogen. Studies have shown that cyrosurgery can be used to remove even wide areas of actinic keratoses and that it may be more successful over the long term than treatment with 5-fluorouracil, the standard drug. Cryosurgery also appears to reduce the risk for squamous cell cancer in these patients.
A head-to-head comparison of a freezing technique with Mohs micrographic surgery in patients with basal cell cancer reported similar recurrence rates with each approach. Over 85% of the patients with the freezing technique were satisfied with the appearance of the area afterwards. Five-year recurrence rates were only 2.1%.
Cryotherapy achieves good cosmetic results for many patients. However, it may cause blistering and ulceration, leading to pain and infection, as well as harmless, but undesirable, skin-color changes.
Radiation
In unusual cases where the skin cancer may be in an inoperable position (such as the eyelid or the tip of the nose) or if cancer has recurred multiple times, radiation therapy may be indicated. Radiation is directed at the tumor. It may take 1 - 4 weeks with treatments performed several times a week. One technique being investigated for basal and squamous cell cancer uses radiation implants (brachytherapy) and custom-made molds to specifically target the radiation to the cancer site. Studies suggest that this treatment is very effective with few complications.
Topical Phototherapy and Aminolevulinic Acid (ALA)
Topical phototherapy with the drug aminolevulinic acid (ALA) is a nonsurgical method that is proving to be a good choice for treating actinic keratoses and nonmelanoma skin cancers. The technique involves shining blue light onto the cancer area after that patient has taken ALA. ALA accumulates in the skin cells. When the cells are exposed to intense light, the chemical causes them to die. This approach allows precise targeting of one or more lesions, leaving healthy skin unaffected.
It does not penetrate deeper than the epidermis (the top layer of the skin), so it does not produce scarring or changes in skin color, as cryotherapy or other more invasive treatments do.
It can cause pain and irritation, including stinging, itching, and burning, but in one study only 3% of patients stopped using it for these reasons. In a 2002 study, the procedure was more painful for patients with actinic keratoses than for those with nonmelanoma skin cancers. It was also painful when large areas were affected, and men experienced more pain than women.
ALA Phototherapy for Actinic Keratoses. Phototherapy works best on flat lesions performed in two treatments, and is more effective for clearing lesions on the face than those on the scalp. Phototherapy can also treat multiple lesions at the same time instead of sequentially, as in cryotherapy. Studies suggest that it may work as well as cryotherapy and achieve better cosmetic results. (More patients report burning and itching with phototherapy, however.) Phototherapy is also equal to topical 5-fluorouracil in effectiveness and achieving a satisfactory appearance.
ALA Phototherapy for Nonmelanoma Skin Cancers. In patients with squamous cell cancer-in-situ and basal cell cancer, phototherapy has been equal to cryotherapy, with superior healing and appearance afterward. A 2003 study reported that it was more effective than topical 5-fluorouracil for patients with Bowen's disease, and there were fewer side effects.
Some studies have shown that about 10% of patients using phototherapy have a recurrence within 1 year. These recurrence rates are higher than with surgery and other standard treatments. Longer-term studies are required before ALA phototherapy can be recommended for most patients with nonmelanoma skin cancers.
Exfoliation
Chemical peeling, or exfoliation, is useful for solar keratoses on the face, especially in people with fair, dry skin. Alpha-hydroxy acids, for example, are being investigated for keratoses. Dermabrasion, which "sands" the skin, may also be effective, although scarring is possible. A 2002 study found laser resurfacing to treat severe sun damage on the face; however, it may not prevent nonmelanoma skin cancers.
Medications
A number of medications are being used for keratoses and some may be helpful for skin cancers as well. Besides cryotherapy, 5-fluorouracil is the other most commonly used treatment for actinic keratoses. Other medications are also available.
Medications for Keratoses and Common Skin Cancers | |||||
| Medication | Skin Conditions Affected | Oral or Topical | Comments | ||
5-Fluorouracil | Actinic keratoses, Bowen's disease and small nonmelanoma skin cancers. | Topical cream (Efudex, Fluoroplex) or injected gel containing 5-FU and epinephrine (AccuSite). | 5-Fluorouracil (5-FU) removes actinic keratoses and is useful for some patients with a large number of lesions. It requires twice daily application for 3 - 4 weeks. It can cause significant redness, irritation, swelling, and crusting, which takes 2 - 4 weeks to heal. Newer preparations are reducing these side effects. It is still unclear if this medication protects against recurrent keratoses or future skin cancer. Of concern is the possibility that (5-FU) will clear the top of a skin cancer and obscure the rest of the cancer that lies beneath the surface of the skin. A 10-year 2003 study of patients with Bowen's disease reported that 5-FU was safe and effective, with only 2 out of 26 cancers recurring. | ||
Diclofenac and hyaluronan (Solaraze) | Actinic keratoses (approved). Investigated for basal cell. | Topical gel applied twice a day. | Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID). When used to treat actinic keratoses, it is delivered to the skin with hyaluronan, a water-seeking molecule that helps maintain skin tension. It has modest effects and when healing occurs, it may not be evident for at least a month after treatment ends. However, it causes less irritation than 5-FU and may be useful for some people. | ||
Imiquimod (Aldara) | FDA approved for the treatment of superficial basal cell cancer. Previously approved for treating actinic keratoses. Investigated for Bowen's disease and squamous cell cancer. | Imiquimod is a topical cream. | Imiquimod triggers the production of immune factors that help fight cell proliferation. Aldara should be used only when surgery for basal cell cancer is inappropriate. It is not approved for use on the face. | ||
Alpha-Interferons | Basal cell cancer, squamous cell cancer. | Require injections administered three times a week. | Interferons are immune factors that are being used to treat a number of serious conditions. Alpha-interferon injections may be effective against skin cancers that are hard to treat using conventional surgical measures. Cosmetic results reported to be good or very good by 83% of patients. | ||
Prognosis
Virtually all basal and squamous type skin cancers can be cured if treated early.
The outlook for melanoma depends on when it is diagnosed.
If melanoma is detected in its earliest form, the 5-year survival rate is 99%. Other localized forms of melanoma have very favorable outlooks.
If the cancer is found after the melanoma has spread, the 5-year survival rate drops.
- If melanoma spreads to nearby areas (regional metastatic), the rate is 65%.
- If melanoma has spread to distant areas of the body, the survival rate is 15%.
In general, after patients are treated for melanoma, the longer they remain free of cancer recurrence following treatment the better the chance of remaining disease-free. However, relapses are not uncommon in those whose initial melanoma was large.
Anyone who has recovered from melanoma should be especially strict about adhering to preventive guidelines and remain vigilant for suspicious lesions, since the risk for developing a new melanoma is increased even if the first one was successfully cured. Such relapses may occur years after the original diagnosis.
Resources
- www.aad.org -- American Academy of Dermatology
- www.cancer.org -- American Cancer Society
- www.asds.net -- American Society for Dermatologic Surgery
- www.mpip.org -- Melanoma Patients' Information Page
- www.cancer.gov -- National Cancer Institute
- www.nccn.org -- National Comprehensive Cancer Network
- www.skincancer.org -- The Skin Cancer Foundation
- www.epa.gov/sunwise/uvindex.html -- UV index information
References
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Reviewed By: Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.
