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Melanoma

Melanoma Definition

Melanoma, the most serious type of skin cancer, develops in the cells that produce melanin — the pigment that gives your skin its color. Melanoma can also form in your eyes and, rarely, in internal organs, such as your intestines.

The exact cause of all melanomas isn't clear, but exposure to ultraviolet (UV) radiation from sunlight or tanning lamps and beds greatly increases your risk of developing melanoma.

Avoiding excessive sun exposure can prevent many melanomas. And making sure you know the warning signs of skin cancer can help ensure that cancerous changes are detected and treated before they have a chance to spread. Melanoma can be successfully treated if you catch it early.

Melanoma Symptoms

Melanomas can develop anywhere on your body, but most often develop in areas that have had exposure to the sun, such as your back, legs, arms and face. Melanoma can occur in areas that don't receive much sun exposure, such as the soles of your feet, palms of your hands and on fingernail beds.

The first melanoma symptoms often are:

• A change in an existing mole, or
• The development of a new, unusual-looking growth on your skin

But melanoma can also occur on otherwise normal-appearing skin.

Normal moles
Normal moles are generally a uniform color, such as tan, brown or black, with a distinct border separating the mole from your surrounding skin. They're oval or round in shape and about 1/4 inch, or 6 millimeters (mm), in diameter — the size of a pencil eraser.

Most people have between 10 and 40 moles. Many of these develop by age 20, although moles may change in appearance over time — some may even disappear with age. Some people may have one or more large (more than 1/2 inch, or 12 mm, in diameter), flat moles with irregular borders and a mixture of colors, including tan, brown, and either red or pink. Known medically as dysplastic nevi, these moles are much more likely to become cancerous (malignant) than normal moles are.

Unusual moles that may indicate melanoma
Characteristics of unusual moles that may indicate melanomas or other skin cancers follow the A-B-C-D-E guide developed by the American Academy of Dermatology:

• A is for asymmetrical shape. Look for moles with irregular shapes, such as two very different-looking halves.
• B is for irregular border. Look for moles with irregular, notched or scalloped borders — the characteristics of melanomas.
• C is for changes in color. Look for growths that have many colors or an uneven distribution of color.
• D is for diameter. Look for new growth in a mole larger than about 1/4 inch (6 millimeters).
• E is for evolving. Look for changes over time, such as a mole that grows in size or that changes color or shape. Moles may also evolve to develop new signs and symptoms, such as new itchiness or bleeding.

Other suspicious changes in a mole may include:

• Scaliness
• Itching
• Change in texture — for instance, becoming hard or lumpy
• Spreading of pigment from the mole into the surrounding skin
• Oozing or bleeding

Malignant moles vary greatly in appearance. Some may show all of the changes listed above, while others may have only one or two unusual characteristics.

Hidden melanomas
Melanomas can also develop in areas of your body that have little or no exposure to the sun, such as the spaces between your toes and on your palms, soles, scalp or genitals. These are sometimes referred to as hidden melanomas because they occur in places most people wouldn't think to check. When melanoma occurs in people with dark skin tones, it's more likely to occur in a hidden area.

Hidden melanomas include:

• Melanoma under a nail. Subungual melanoma is a rare form of melanoma that occurs under a nail, most often on the thumb or big toe. It's especially common in blacks and in other people with darker skin pigment. The first indication of a subungual melanoma is usually a brown or black discoloration that's often mistaken for a bruise (hematoma). See your dermatologist if you develop a nail discoloration that increases in size, spreads to involve the cuticle or that doesn't heal after two months.
• Melanoma in the mouth, digestive tract, urinary tract or vagina. Mucosal melanoma develops in the mucous membrane that lines the nose, mouth, esophagus, anus, urinary tract and vagina. Mucosal melanomas are especially difficult to detect because they can easily be mistaken for other, far more common conditions. A melanoma in a woman's genital tract may result in itching and bleeding — signs and symptoms that commonly result from a yeast infection or menstrual irregularities. And symptoms of anorectal melanoma are similar to those caused by hemorrhoids. Your dentist is trained to spot melanomas that occur in your mouth. Regular pelvic exams can help detect melanomas in the vagina.
• Melanoma in the eye. Ocular melanomas sometimes develop in the pigment-containing cells in the back portion of your eye (retina). These melanomas usually don't produce symptoms and are only detected during eye exams. On the other hand, melanomas that occur in the lining of your eyelid (conjunctiva) or the pigmented coating within your eyeball (choroid) may cause a scratchy feeling under your eyelid or a dark spot in your vision. The best way to prevent ocular melanoma, which has been linked to chronic sun exposure, is to wear glasses rated to block 99 percent to 100 percent of ultraviolet A light when you're in the sun.

Melanoma Causes

Melanoma is the most serious and deadly type of skin cancer. Although melanomas make up the smallest percentage of all skin cancers, they cause the greatest number of deaths. That's because they're more likely to spread to different parts of your body. And the incidence of melanoma is on the rise.

Melanoma occurs when something goes awry in the melanin-producing cells (melanocytes) that give color to your skin. Normally, skin cells develop in a controlled and orderly way — healthy new cells push older cells toward your skin's surface, where they die and eventually are sloughed off. This process is controlled by DNA — the genetic material that contains the instructions for every chemical and biological process in your body. But when DNA is damaged, new cells may begin to grow out of control and can eventually form a mass of cancerous cells.

Just what damages DNA in skin cells and how this leads to melanoma is a matter of intense study. Cancer is a complex disease that often results from a combination of factors, including environmental and genetic factors, rather than from a single cause. Still, excessive exposure to ultraviolet (UV) radiation is a leading factor in the development of melanoma, whether the radiation is from the sun or from tanning lamps and beds.

UV radiation and melanoma
UV radiation is produced by the sun. UV light is divided into three wavelength bands — ultraviolet A (UVA), ultraviolet B (UVB) and ultraviolet C (UVC). Only UVA and UVB rays reach the earth — UVC radiation is completely absorbed by atmospheric ozone, a naturally occurring substance that filters UV radiation. Commercial tanning lamps and tanning beds also produce UV radiation.

UVB light causes harmful changes in skin cell DNA, including the activation of oncogenes — a type of gene that, when turned on, can change a normal cell into a cancerous one. But UVA light may be more likely to damage melanocytes, leading to melanoma. Tanning lamps and beds mainly produce UVA radiation.

UV radiation is most intense at the equator and at high elevations, but no matter where you live, your skin absorbs UV radiation whenever you're outdoors unless you wear protective clothing and sunscreen.

Other causes of melanoma
UV light doesn't cause all melanomas, especially those that occur in places on your body that don't receive exposure to sunlight. This indicates that other factors may contribute to your risk of melanoma.

Melanoma Risk factors

Factors that may increase your risk of skin cancer include:

• Fair skin. Having less pigment (melanin) in your skin means you have less protection from damaging UV radiation. If you have blond or red hair, light-colored eyes, and you freckle or sunburn easily, you're more likely to develop melanoma than is someone with a darker complexion. Fair-skinned people of Northern European ancestry are particularly at risk. Queensland, Australia, has the highest skin cancer rate in the world because it has unusually high levels of UV radiation and because most of its inhabitants are of English or Irish descent.

  Though less common, melanoma can develop in people with darker complexions, including Hispanics and blacks. For these people, melanoma is often diagnosed in the later stages, when the lesions are deeper and more advanced. Survival from melanoma is strongly correlated to the depth and spread of cancer at the time of diagnosis. So it's important that people of all ethnic backgrounds be aware of melanoma and take precautions against UV radiation.

• A history of sunburn. Every time you burn your skin, you increase your risk of developing skin cancer. People who have had one or more severe, blistering sunburns as a child or teenager are at increased risk of skin cancer as an adult. For that reason, it's particularly important to protect children from the sun, not just with sunscreen but also with a hat, protective clothing and dark glasses. Although sunburns in adulthood also are a risk factor, the greatest damage seems to occur before you're 18. Infants are particularly vulnerable because the melanin in their skin isn't yet fully developed.
• Excessive sun exposure. Exposure to UV radiation is the leading cause of all skin cancers, including melanoma.
• Sunny or high-altitude climates. Living in a sunny climate exposes you to more UV radiation than does living in a cool, cloudy climate. In the United States, skin cancer is far more common in Arizona than in Minnesota. In addition, if you live at a high elevation you're exposed to more UV radiation.
• Moles. Having just one dysplastic mole doubles your risk of melanoma. But it's not only atypical moles that make you more susceptible to melanoma — having more than 50 ordinary moles also increases your risk.
• A family history of melanoma. If a close relative, such as a parent, child or sibling, has had melanoma, you have a greater chance of developing it too. In addition, some families are affected by a condition called familial atypical mole-malignant melanoma (FAMMM) syndrome. The hallmarks of FAMMM include a history of melanoma in one or more close relatives and having more than 50 moles, some of which are atypical. People with this syndrome have an extremely high risk of developing melanoma.
• Weakened immune system. People with weakened immune systems are at greater risk of many diseases, including skin cancer. This includes people who have chronic leukemias, other cancers or HIV/AIDS, and those who have undergone organ transplants or who are taking medications that suppress the immune system.
• Exposure to carcinogens. The American Cancer Society has identified several substances that may contribute to melanoma, including coal tar, the wood preservative creosote, arsenic compounds in pesticides and radium.
• Rare genetic disorder. People with xeroderma pigmentosum, which causes an extreme sensitivity to sunlight, have a greatly increased risk of developing melanoma because they have little or no ability to repair damage to the skin from ultraviolet light.

Melanoma When to seek medical advice

Make an appointment with your doctor if you notice a new skin growth, a change in an existing mole or a sore that doesn't heal in two weeks.

Melanoma Tests and diagnosis

Skin cancer screening
The American Cancer Society (ACS) recommends having a complete skin exam every year if you're older than 40, or more often if you're at high risk of developing skin cancer. These screening exams involve a head-to-toe inspection of your skin by someone qualified to diagnose skin cancer, such as a dermatologist or nurse specialist. If you have risk factors for skin cancer — fair skin, a history of severe sunburns, one or more dysplastic moles, or a family history of melanoma — talk to your doctor about more frequent screenings. Sometimes frequent screenings are recommended for all close family members of a person with melanoma.

In addition, the ACS recommends monthly self-exams. This helps you learn the moles, freckles and other skin marks that are normal for you, so you can notice any changes. It's best to do this standing in front of a full-length mirror while using a hand-held mirror to inspect hard-to-see areas. Be sure to check the fronts, backs and sides of your arms and legs. In addition, check your groin, scalp and fingernails, and your soles and the spaces between your toes.

Diagnosing melanoma
Sometimes cancer can be detected simply by looking at your skin, but the only way to accurately diagnose melanoma is with a biopsy. In this procedure, your doctor or dermatologist removes all or part of the suspicious mole or growth, and a pathologist analyzes the sample.

If the mole is small, your doctor is likely to perform an excisional biopsy — such as a punch biopsy or an elliptical excision. In this procedure, the entire mole or growth is removed, along with a small border of normal-appearing skin. An incisional biopsy is more likely to be used for large moles (larger than 3/8 inch, or 10 millimeters), or for those in places where scars would be more obvious. With an incisional biopsy, only the most irregular part of a mole or growth is taken for laboratory analysis. Contrary to common belief, incisional biopsies don't cause melanoma to spread.

Staging
If you receive a diagnosis of melanoma, the next step is to determine the extent, or stage, of the cancer. Melanoma is staged using these criteria:

• Thickness and depth. A pathologist determines the thickness and depth of a melanoma by carefully examining it under a microscope. The thickness of a cancerous lesion is the most important factor in deciding on a treatment plan. In general, the thicker the tumor, the more serious the disease.

• Spread. It's also important to determine whether melanoma cells have spread to your lymph nodes. To do so, your surgeon may use a procedure known as a sentinel node biopsy. Doctors are developing and evaluating criteria to determine who should undergo this procedure. Sentinel node biopsy isn't used for the most superficial forms of melanoma.

  Until recently, surgeons would remove as many lymph nodes as possible to verify that the nodes didn't contain cancer cells. But this greatly increased the risk of lymphedema — severe swelling of the involved area — and other side effects. That's why a new procedure was developed that focuses on finding the sentinel nodes — the first nodes to receive the drainage from malignant tumors and therefore the first to develop cancer. If a sentinel node is removed, examined and found to be healthy, the chance of finding cancer in any of the remaining nodes is very small and no other nodes need to be removed.

Melanoma is staged using the numbers 0 through IV:

• Stage 0. This melanoma is also called in situ melanoma. At this stage, the cancer is confined to the epidermis and hasn't begun to spread. Treatment consists of complete surgical removal only.  Finding and treating a cancerous tumor at this stage offers the best chance for a full recovery.
• Stages I through IV. These cancers are invasive tumors that have the ability to spread to other areas. A stage I cancer is small and well localized and has a very successful treatment rate. But the higher the stage number, the lower the chances of a full recovery. By stage IV, the cancer has spread beyond your skin to other organs, such as your lungs, liver and bone. Although it may not be possible to eliminate the cancer at this stage, treatment with radiation or biological or experimental therapies may help alleviate signs and symptoms.

Melanoma Treatments and drugs

The best treatment for you depends on your stage of cancer and your age, overall health and personal preferences.

Ask your doctor and other members of your melanoma treatment team any questions you have so that you can fully understand the different treatments and the potential risks and side effects of each treatment. Consider seeking a second opinion, especially from a doctor who specializes in treating melanoma. In some cases, after weighing your options you may choose not to treat the melanoma itself but rather to try to relieve any symptoms the cancer may cause.

Treating early-stage melanomas
The best treatment for early-stage melanomas is surgical removal (simple excision). Very thin melanomas may have been entirely removed during the biopsy and require no further treatment. Otherwise, your surgeon will excise the cancer as well as a small border of normal skin and a layer of tissue beneath the skin. In almost every case this eliminates the cancer.

At one time, surgery for more invasive early-stage tumors involved cutting out the cancer along with a large border of normal skin (wide local excision). This usually meant having a skin graft — a procedure in which skin from another part of the body is used to replace the skin that's removed. But taking smaller amounts of normal skin in some cases of invasive melanomas may be just as effective in treating cancer and may eliminate the need for skin grafts.

Treating melanomas that have spread beyond the skin
If melanoma has spread beyond the skin, treatment options may include:

• Surgical removal. It's very difficult to cure melanomas that have spread beyond the skin. But surgically removing a melanoma that has spread (metastatic melanoma) can often provide relief of symptoms — sometimes for years. Whether this is an option for you will depend on where the cancer is located and how severe it is, as well as on your own wishes and overall health.
• Chemotherapy. This form of treatment uses drugs to destroy cancer cells. Two or more drugs are often given in combination and may be administered intravenously, in pill form or both — usually for four to six months. Melanoma has long been thought to be resistant to most forms of chemotherapy, but new chemotherapy regimens are being studied and developed. In the meantime, chemotherapy is sometimes used to relieve symptoms in people with advanced metastatic melanoma.
• Radiation therapy. This treatment uses high-energy X-rays to kill cancer cells. It's sometimes used to help relieve symptoms of melanoma that has spread to another organ. Fatigue is a common side effect of radiation therapy, but your energy usually returns once the treatment is completed.
• Biological therapy (immunotherapy). Biological therapy boosts your immune system to help your body fight cancer. These treatments are made of substances produced by the body or similar substances produced in a laboratory. Biological therapies used to treat melanoma include interferon and interleukin-2. Side effects of these treatments are similar to those of the flu, including chills, fatigue, fever, headache and muscle aches.

Clinical trials
Clinical trials are studies of new therapies that aren't yet approved for treatment of melanoma. Doctors use clinical trails to determine whether a treatment is safe and effective. People who enroll in clinical trials have a chance to try evolving therapies, but a cure isn't guaranteed. And sometimes the potential side effects aren't known.

Some melanoma treatments being studied in clinical trials include:

• Chemoimmunotherapy. Combining chemotherapy and biological therapy drugs may increase the success of both of these treatments. However, combining treatments can make severe side effects more likely.
• Gene therapy. Researchers hope replacing faulty genes that allow cancer cells to proliferate might cause the cancer cells to die. Another approach to gene therapy involves placing genes into cancer cells to make them sensitive to normally harmless drugs. That way only the cancer cells would die when the drug is released into the body.
• Targeted therapy. Targeted therapies interrupt a specific process in cancer cells in order to control cancer. For instance, the process by which cancers develop blood vessels to draw nutrients from your body could be stopped so that tumors remain small and localized. In another approach, specific chemicals that stimulate cancer cells to grow rapidly could be inactivated.
• Vaccine treatment. Vaccines for treating cancer are different from vaccines used to prevent diseases. Vaccine treatment for melanoma might involve injecting altered cancer cells into the body in order to draw the attention of the immune system.

Melanoma Prevention

The best news about melanoma is that many cases of skin cancer can be prevented by following these straightforward precautions:

• Avoid the sun between 10 a.m. and 4 p.m. Because the sun's rays are strongest during this period, try to schedule outdoor activities for other times of the day, even in winter or when the sky is cloudy. You absorb UV radiation year-round, and clouds offer little protection from damaging rays.

• Wear sunscreen year-round. Sunscreens don't filter out all harmful UV radiation. While sunscreens block UVB rays very well, most don't block all UVA rays. For this reason, sunscreen should be just one part of your overall sun protection strategy. Sunscreens that contain ingredients such as titanium dioxide and mexoryl do a better job at blocking UVA rays. Choose a broad-spectrum sunscreen that has a sun protection factor (SPF) of at least 15. Use a generous amount of sunscreen on all exposed skin, including your lips, the tips of your ears, and the backs of your hands and neck.

  For the most protection, apply sunscreen 20 to 30 minutes before sun exposure and reapply it every two hours throughout the day. Also be sure to reapply it after swimming or exercising. Apply sunscreen to young children before they go outdoors, and teach older children and teens how to use sunscreen to protect themselves. Keep a bottle of sunscreen in your car as well as with your gardening tools, and sports and camping gear.

• Wear protective clothing. Sunscreens don't provide complete protection from UV rays. That's why it's a good idea to also wear tightly woven clothing that covers your arms and legs, and a broad-brimmed hat, which provides more protection than a baseball cap or visor does. Some companies also sell photoprotective clothing. Your dermatologist can recommend an appropriate brand. Don't forget sunglasses. Look for those that block both UVA and UVB rays.
• Avoid tanning beds and tan-accelerating agents. Tanning beds emit UVA rays, which may be as dangerous as UVB rays — especially since UVA light penetrates deeper into your skin and causes precancerous skin lesions.
• Be aware of sun-sensitizing medications. Some common prescription and over-the-counter drugs — including antibiotics; certain cholesterol, high blood pressure and diabetes medications; birth control pills; nonsteroidal anti-inflammatory drugs such as ibuprofen (Advil, Motrin, others); and the acne medicine isotretinoin (Accutane) — can make your skin more sensitive to sunlight. Ask your doctor or pharmacist about the side effects of any medications you take. If they increase your sensitivity to sunlight, be sure to take extra precautions.
• Check your skin regularly and report changes to your doctor. Examine your skin often for new skin growths or changes in existing moles, freckles, bumps and birthmarks. With the help of mirrors, check your face, neck, ears and scalp. Examine your chest and trunk, and the tops and undersides of your arms and hands. Examine both the front and back of your legs, and your feet, including the soles and the spaces between your toes. Also check your genital area, and between your buttocks.
• Have regular skin exams. Consult your doctor for a complete skin exam every year if you're older than 40, or more often if you're at high risk of developing melanoma.

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