Also called: Malignant Melanoma, Skin Melanoma, Multiple Melanoma, Melanoma Mole, Melanoma in Situ
Mark Oren, M.D., FACP
Skin cancer is the most common of all cancers, accounting for as much as half of all cancer diagnoses, according to the American Cancer Society (ACS). Skin cancer is divided into two main categories – melanoma and non-melanoma.
Melanoma is a malignant skin cancer that originates in melanocytes, the cells that produce the skin’s pigment (melanin). Like all cancers, melanoma results from unrepaired damage to DNA, genetic material that is present in every cell.
Melanoma is the least common of the two types of skin cancer, accounting for about 4 percent of all skin cancer cases. However, it is the most deadly form of skin cancer and is responsible for about 75 percent of skin cancer–related deaths each year, according to the Occupational Safety and Health Administration (OSHA). It can spread to almost every organ or tissue in the body. Untreated, melanoma can cause death within a year of diagnosis.
However, melanoma is highly curable when detected and treated early. Patients can learn to recognize the warning signs, which include a darkening and enlarging of an existing mole or an irregular and raised shape. Moles that change color, itch or become crusted can also indicate melanoma.
Melanoma is strongly associated with excessive exposure to ultraviolet radiation (UV), which can come from sunlight or tanning booths and beds. In the United States, the number of diagnosed cases of melanoma is increasing despite warnings about the harmful effects of the sun.
It should be remembered that most moles do not signal melanoma. Some types of benign skin growths may appear similar to melanoma.
Nevertheless, patients should bring any suspicious mole to the attention of a physician, who is trained to recognize melanomas. Although melanoma is highly treatable, the survival rate drops drastically after it has spread to nearby or, more importantly, distant sites.
Not all skin cancers are melanomas. Melanoma is most commonly diagnosed by physical examination and biopsy. When caught early, melanoma is often treated by surgically removing the tumor. If the cancer has spread, then chemotherapy and radiation therapy may become necessary as treatment.
Melanoma is a type of skin cancer that originates in cells called melanocytes. The skin is the largest organ of the body, protecting the internal organs from injury and invasion from harmful substances. It is composed of three layers – the epidermis, the dermis and the subcutis. The top layer is called the epidermis.
Melanocytes, which protect the skin from the harmful rays of the sun, are located in the epidermis, which is about 1/100th of an inch (or 0.2 millimeters [mm]) thick. Melanocytes produce melanin,the pigment that gives skin its color.
Within the epidermis layer are four sublayers. The outermost sublayer (stratum corneum) of the epidermis is composed of dead keratinocytes (also called squamous cells). Below this level are live keratinocytes, which produce an important protein that helps protect the body. The lowest sublayer is composed of basal cells.
Like all cancers, melanoma results from unrepaired damage to DNA, genetic material that is present in every cell. This damage causes the cells to multiply continuously until they form a growth or tumor (a mass of excess tissue), usually appearing as a mole on the skin or sometimes in the eye. At an early stage, melanoma is usually highly curable by simply excising (cutting out) the mole.
However, melanoma is capable of spreading to every tissue and organ in the body. Melanoma can spread outward on the surface of the skin or deep into the layers of the skin (reaching the lymphatic system and bloodstream).
While the vast majority of melanomas develop on the skin, they have also been found in the eye (intraocular melanoma).
Although melanoma can spread to any organ or tissue, the most common sites for metastasis are the lungs and liver. It is also known to spread to the brain and spinal cord and to the bones.
Melanoma is strongly linked to excessive exposure to ultraviolet (UV) radiation, primarily from the sun. It is believed that intense, intermittent exposure to UV rays creates a greater risk for melanoma than prolonged low-grade exposure. People who work for long periods in the sun appear to be less at risk than those who get occasional but intense exposure to the sun, such as indoor workers who spend several hours in the sun on weekends.
Most cases occur in white people, and it most often appears on the trunks of fair-skinned men and the lower legs of fair-skinned women. People who have darker pigment are at lower risk but they also can develop melanoma.
Melanoma accounts for 4 percent of all skin cancers, but is responsible for about 75 percent of skin-cancer related deaths, according to the American Cancer Society (ACS). Since 1973, mortality has sharply increased by 50 percent, mostly among older white men. Although the number of new cases of melanoma has slowed among both men and women, the disease remains on the rise. The ACS estimates that there will be 62,190 new cases of melanoma in the United States in 2006 and nearly 8,000 people will die of the this cancer.
Melanoma is highly curable, with a five-year survival rate of 97 percent when caught at a localized stage (meaning it has not spread), according to the Centers for Disease Control and Prevention. The survival rate drops to 63 percent for melanoma that has spread to nearby areas and to 18 percent if the cancer has spread to distant organs.
Melanoma can be confused with other forms of skin cancer that are less dangerous.
Types and differences of melanoma
Melanoma is composed of one type of cell – the melanocyte. However, variations of melanoma exist, based on their shape:
- Superficial spreading melanoma (SSM). The most common form of melanoma. SSM is commonly found on women’s legs or on the backs or upper arms of men. African Americans and Asians are sometimes diagnosed with SSM on the palms of their hands or the soles of their feet.
- Nodular melanoma (NM). This form of the disease is by far the most aggressive. NM often starts as a small, round bump with a smooth border. Some NMs are brown, blue, gray or red, but most are black. Since it is known to spread so rapidly, NM is rarely caught in its early stages.
- Acral-lentiginous melanoma (ALM). While melanoma mostly affects whites, ALM is the most common melanoma diagnosis in African Americans and Asians. As with SSM, it is often found on the palms of the hands or the soles of the feet.
- Lentigo maligna melanoma (LM). LM is considered the least aggressive form of this disease. It is often found on the cheeks or nose of older adults. Usually appearing in tan, brown or black, LM rarely spreads to other parts of the body.
In some cases, melanoma develops in inconspicuous places. These more rare forms of the disease include:
- Ocular melanoma. This rare form of melanoma develops in the skin of the eyelid or in the pigmented coating of the inner eyeball.
- Subungual melanoma. This type of melanoma is extremely rare. It develops under a nail, usually on the thumb or big toe. It is more often diagnosed in African Americans or other people with darker skin pigment.
- Mucosal melanoma. This type of melanoma is fairly uncommon. It can develop in the mucosal tissue lining of the nose, mouth, esophagus, anus, urinary tract or vagina. This form of melanoma is frequently diagnosed at later stages because it can be mistaken for other more common conditions.
Risk factors for melanoma
The main environmental risk factor that leads to melanoma is exposure to the sun’s ultraviolet (UV) rays. This means that melanoma is a highly preventable type of cancer. Other forms of artificial UV light can be just as dangerous as the UV rays of the sun, such as the light emitted by tanning beds and sun lamps.
Some risk factors may increase a person’s chances of developing melanoma. For instance, people with a large number of moles or certain types of moles, such as dysplastic nevi (nevus is the medical term for mole), are at higher risk.
Normally, these nevi have a single color – usually tan, brown or black. They are characterized by a distinct border that separates the mole from the surrounding skin. Some individuals have moles that are not uniform in color or have irregular shapes or borders. These types of moles are known as dysplastic nevi, and they are far more likely to develop a malignancy than normal moles. Dysplastic nevi can run in families. Patients with these moles have a lifetime risk of 6 to 10 percent of developing melanoma, according to the American Cancer Society (ACS).
Having fair skin, light eyes or hair color, and having many freckles may increase a person’s risk as well. Caucasians are 20 times more likely to develop melanoma than African Americans who are more protected by their skin pigment, according to the ACS. However, it should be noted that people of color can also develop melanoma. Other risk factors include:
- Family history of melanoma. Approximately 10 percent of those diagnosed with melanoma have a family history of the disease, according to the ACS. Genetic mutations are seen in as much as 40 percent of families with a high incidence of melanoma.
- Immunosuppressive therapy. People being treated with medications that may suppress the immune system, such as those who have undergone an organ transplant, are at greater risk of developing melanoma.
- Age. According to the ACS, the incidence of melanoma among 70-year-olds is twice that of 45-year-olds. However, among cancers, melanoma is one of hte more common ones that occurs under age 30.
- Smoking. Tobacco use – particularly smoking cigarettes – increases a person’s risk of developing melanoma.
- Gender. Men are more likely to develop melanoma than women (a risk of 1 in 52 versus 1 in 77), according the ACS.
- Xeroderma pigmentosum. This rare, inherited condition causes people to be less likely to repair DNA damage caused by sunlight.
- Previous melanoma. After a person has had a melanoma, the risk of developing another melanoma is increased.
- Living in a sunny or high-altitude climate. People who live in sunny climates, such as in the southern United States, and those who live at high altitudes with little or no cloud cover for protection are at an increased risk of developing melanoma.
- Exposure to carcinogens (cancer-causing substances), such as coal, tar, creosote (a wood preservative), arsenic compounds in pesticides and radium increases the risk of melanoma.
Signs and symptoms of melanoma
Patients can be trained to recognize skin cancer. The most important warning sign to look for is a spot on the skin, such as a mole, that changes in size, shape, texture or color. This change may occur over a period of several weeks to one to two years. Such changes should be evaluated immediately by a dermatologist(a doctor who specializes in the physiology or pathology of the skin) or other qualified physician.
The American Academy of Dermatology lists the ABCDs of spotting malignant (cancerous) melanoma. These include:
- A is for asymmetry. One half of the mole or lesion looks different from the other half.
- B is for border. A border around the mole that is irregular, scalloped or undefined.
- C is for color. If the color is different in one part of the mole than the rest.
- D is for diameter. Moles or lesions that are larger than 6 millimeters.
Some physicians add “E” for elevated: a mole that becomes raised or three-dimensional in texture.
The signs and symptoms of melanoma should be thoroughly reviewed by a qualified physician. Some common symptoms of a suspicious mole include:
- Darker or variable discoloration
- Scaliness or itching
- An increase in size
- Development of satellites (spreading of pigment form the mole to surrounding skin)
- Ulceration or bleeding (later signs)
- Change in texture of the mole (possibly becoming hard, lumpy or rough)
It is important to note that many skin changes do not indicate the presence of cancer. However, patients should immediately notify their physician if any of these changes occur.
Diagnosis methods for melanoma
Individuals should seek medical advice if a new skin growth appears or an existing mole or skin growth changes and does not heal in two weeks. In most cases, individuals will be referred to a dermatologist, a physician who specializes in conditions of the skin. A medical history and complete physical examination will most likely be the first steps in diagnosing the changes to a mole. To diagnose melanoma, the physician will biopsy the suspicious area by local excision. The sample will then be sent to an experienced pathologist who can view the specimen under a microscope for evidence of cancer. The pathologist can determine the type and stage of the cancer with a biopsy.
An incisional or excisional biopsy is usually recommended to remove suspected melanomas. An incisional biopsy removes a portion of the tumor to be examined later whereas an excisional biopsy removes the entire tumor.
The National Cancer Institute (NCI) recommends that suspected melanomas never be shaved off or cauterized for removal. In addition, NCI recommends that a second review by an independent qualified pathologist who is specialist in skin conditions and diseases be performed to reduce the possibility of misdiagnosis.
After melanoma is diagnosed, a physician will examine surrounding lymph nodes for signs of enlargement. If the nodes are enlarged, a lymph node dissection may be performed. This procedure involves removing several lymph nodes and examining the tissue for indication that the cancer has spread. An alternative to a complete lymph node dissection is a sentinel node biopsy, which is a procedure done by a surgeon with specialized training. It involves the removal of one or a very limited number of lymph nodes that are most likely to contain cancer cells that have spread. This procedure can predict the likelihood of more extensive lymph node involvement.
The information on lymph node involvement (whether or not they contain any cancer cells) is used for staging the cancer, treatment planning and prognosis. If the melanoma is suspected to have spread, a number of imaging tests may be ordered. These tests include the following:
- Chest x-ray. A painless test in which an image is created of part of the body by using low doses of electromagnetic radiation that are reflected on film paper or fluorescent screens.
- MRI (magnetic resonance imaging). A powerful magnetic field is used to create images of structures and organs within the body. MRI can be used to help detect several types of cancer, including melanoma that has metastasized to the brain, spinal cord or organs.
- CAT scan (computed axial tomography). A painless test that uses multiple x-ray images, taken from different angles, to create three-dimensional images of body structures.
Sometimes melanoma can develop in the eye. This is referred to as intraocular melanoma, which is a rare form of the disease. Malignant cells develop in a part of the eye called the uvea, which, like the skin, contains melanocytes. This type of melanoma often appears as a dark spot on the iris but can be inside the eye and not visible without special instruments to examine the eye’s interior. If the melanoma develops on another part of the uvea, it may cause blurry vision or it may produce no symptoms at all. This form of melanoma is often diagnosed during a routine eye examination and may require an ultrasound for further classification.
Treatment options for melanoma
The goal of treating melanoma skin cancer is to destroy or remove the cancer completely with minimal scarring of the patient’s skin. The treatment options for melanoma depend on a number of factors, including the location of the melanoma and the type and stage of the cancer. Generally, the treatment for melanoma will depend on the following:
- The thickness of the melanoma
- Whether or not it has spread to deeper levels of the skin or other areas of the body
- The mitotic index (an indication of how quickly the cancer cells are growing and reproducing)
- The number of regional lymph nodes involved
- Ulceration or bleeding at the primary site
- Microscopic satellites
- Age and general health of the patient
When caught early, melanoma may be treated by simple excision. This is a minor surgical procedure in which the tumor is cut out along with a small margin of healthy skin around the edges of the melanoma, usually less than an inch (2 centimeters). It may be removed as treatment or as part of a biopsy to confirm a diagnosis of melanoma. A wide excision (re-excision) may be performed to ensure that the cancer has not spread to nearby cells.
If the melanoma has spread, additional surgery and other options may be necessary, including:
- Chemotherapy. Chemotherapy is a method of treating various cancers that involves the use of powerful anti-cancer drugs. It works by destroying cancer cells and keeping them from growing, dividing and spreading. Chemotherapy with a single drug is only effective for a small percentage of melanoma patients with advanced disease. However, high-dose chemotherapy followed by bone marrow or stem cell replacements is considered to be more successful in treating advanced melanoma.
- Radiation therapy. Radiation therapy uses precise x-ray beams to kill or shrink cancer cells. Radiation targets dividing cancer cells and disrupts or destroys their genetic material, preventing the cells from continuing to grow and spread throughout the body. Often, radiation is often used to treat melanoma that has spread to nearby lymph nodes or to areas that cannot be treated surgically. Radiation may be used to shrink large melanomas and also to relieve pain. However, due to melanoma’s level of resistance to radiation, high individual doses are normally required in order to be effective.
- Biological therapy. Also called immunotherapy, this form of therapy stimulates the body’s immune system to recognize and fightcancer cells. Immunotherapy uses certain proteins to trigger the body’s immune system to produce more white blood cells, which attack and kill cancer cells. In some forms, biological therapy directly attacks the cancer cells. It also can help reduce the side effects associated with cancer treatments such as chemotherapy. With this type of treatment, the side effects are normally minor tenderness at the injection site or, at times, lumps that are painful. However, these usually arise only after a long series of treatments. A limited response has been seen with this type of treatment.
- Surgery. Surgical options may be limited once melanoma has spread to other areas of the body. Even if melanoma invades just one or two sites, surgical removal may not provide a cure. However, removing metastases in some areas, such as the brain, may be considered if it will enhance the patient’s quality of life.
- To determine whether or not the cancer has spread, many surgeons will also perform a lymph node dissection. This procedure removes some or all of the lymph nodes that are closest to the lesion for inspection by the pathologist for evidence of cancer. An alternative to a complete lymph node dissection is a sentinel node biopsy, a relatively new treatment that requires removal of only one lymph node to determine if the cancer has spread.
Prevention methods for melanoma
It is important for all individuals to be aware that exposure to the sun and its ultraviolet (UV) rays can cause skin cancer. The Occupation Safety and Health Administration(OSHA) recommends the following steps to prevent skin cancers, including melanoma:
- Cover up. Tightly woven clothing and special sun-resistant clothing are more effective at blocking out sun and keeping it from damaging the skin.
- Use sunscreen. Frequently apply sunscreen with a sun protection factor (SPF) of at least 15, which will block 93 percent of UV rays. It is important to follow the directions on the bottle, including when to reapply. Note: SPF ratings refer only to UVB protection. Be sure to choose a product that includes protection against both UVA and UVB rays (e.g., products containing zinc oxide or titanium dioxide). Sunsreen for the lips should also be considered as part of the protection. Sunscreen should be applied 30 minutes before going outside and reapplied after swimming or sweating. In addition, there is some UV radiation even on seemingly cloudy days and sunscreen should be worn whenever individuals are outside.
- Wear a hat. A baseball cap or visor offers little or no protection for the ears and neck. A wide-brimmed hat is a far better choice since it will protect the ears, neck, eyes, forehead, nose and scalp.
- Wear UV-absorbent sunglasses. Even inexpensive sunglasses can be effective. Look for ones that block 99 to 100 percent of UVA and UVB radiation. Wrap-around glasses offer the best protection as they shade the sides of the eyes as well.
- Limit sun exposure. The rays of the sun are the strongest, and thus cause the most damage, between 10 a.m. and 4 p.m. If it is not possible to avoid being outdoors during those hours, seek shade under a tree, beach umbrella or tent.
- Avoid tanning beds. In addition to the possibility of infections and warts, tanning beds are not a safe way to get a tan because they also expose the skin to UV radiation, just like the sun.
- Checking medications. Some prescription drugs increase a person’s sensitivity to sunlight, putting them at greater risk for sunburn. Common medications that increase sensitivity include thiazides, diuretics, tetracycline, sulfa antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen.
- Regular examinations by a physician. Routine examinations by a physician qualified to diagnose skin cancer are important to those with a low or normal risk, and especially those with an increased risk of developing melanoma skin cancer. From ages 20 to 39, a full-body screening by a dermatologist(a doctor who specializes in the physiology or pathology of the skin) is recommended every three years. After the age of 40, patients should be examined annually. For individuals who have had skin cancer before, it is best to follow the treating physician’s recommendations for follow-up care. In between clinical exams, monthly self-examinations are recommended.
The damaging effects of the sun can be more dramatic at higher elevations where there are little or no clouds or haze to filter the sunlight. Just like direct sunlight, snow (as well as sand or water) can reflect the UV rays of the sun and can lead to sunburn and permanent damage to the skin.
Ongoing research regarding melanoma
The incidence of melanoma has increased dramatically over the last several years. Researchers are continually looking for novel ways to treat this potentially deadly form of skin cancer. Thus patients with all stages of melanoma may be candidates for clinical trials. Patients with stage IV melanoma that has spread to distant sites are rarely helped by standard therapy. These patients are considered candidates for clinical trials that are studying new forms of treatment, including:
- Combination chemotherapy
- Gene therapy. This novel form of treatment adds certain genes to the cancer cells in an effort to help the cells regulate their malignant behavior.
- Retinoids (synthetic vitamin A). Preliminary studies show that retinoids can have a protective effect in reducing the incidence of skin cancer in those most at risk.
- Vaccine immunotherapy. This form of therapy seeks to find new ways of controlling the response of the immune system to the melanoma.
- Molecular targeting. New drugs combined with chemotherapy are being evaluated for their role in attacking genes related to melanoma. The BRAF gene is abnormal in melanoma cells and medications that block its activity are being studied in clinical trials.
Patients who are interested in enlisting in a clinical trial should speak with their oncologist (cancer doctor). Information on clinical trials is also available online from the National Cancer Institute (NCI).
The prognosis (predicted outlook or chance of survival) of a particular cancer depends on its stage or how widespread it is in the body. Physicians treating melanoma have used several different staging systems with differing criteria. Some determinations are made based on the clinical examination, while other stage determinations are made after the biopsy is completed.
Many types of cancer are staged using the TNM system, where:
- “T” describes the extent of a tumor’s invasion into surrounding tissues and organs.
- “N” describes whether or not the cancer has spread to surrounding lymph nodes and, if so, the size of the lymph nodes. Lymph nodes are groups of immune system filtering cells that help ward off infections and cancers. They are typically the size of a bean.
- “M” describes whether or not the cancer has metastasized or spread to distant organs.
Melanomas can be staged several ways. The major stage groups for melanoma are:
- Stage 0. The melanoma is in the epidermis but has not spread to the dermis.
- Stage I. The melanoma is localized in the skin.
- Stage II. The melanoma is still localized in the skin, but may be thicker or ulcerated.
- Stage III. The melanoma has spread to local lymph nodes.
- Stage IV. The melanoma has spread beyond local lymph nodes to distant organs, areas of the skin or lymph nodes.
According to the ACS, the 5-year survival rate for melanoma according to stage is as follow:
|Stage||Five-year survival rate|
|I||90 to 95 percent|
|II||45 to 78 percent|
|III||28 to 70 percent|
Another method of staging melanoma is use of the Clark’s level for diagnosis. The Clark’s classification serves to explain the anatomic level of invasion. These levels include:
- Level I. This is the earliest stage of melanoma. The lesion is still at the surface of the skin and has not invaded surrounding tissue.
- Level II. The melanoma that has gone below the epidermis (top layer of the skin) to reach the dermis (second layer of the skin).
- Level III. The melanoma has grown down into one of the middle layers of the dermis.
- Level IV. The melanoma has reached the bottom layer of the dermis, but not subcutaneous tissue.
- Level V. The melanoma has penetrated the top two layers of the skin and has reached the third layer.
The Clark’s classification is frequently combined with information from the Breslow’s method of classification. The Breslow classification refers to the vertical thickness of the melanoma in millimeters (mm) and is used for staging and treatment decisions. It is a more accurate prognostic indicator than the older Clark’s levels.
The third method of classification is Breslow’s method. The Breslow classification refers to the vertical thickness of the melanoma in millimeters (mm), which is determined during the biopsy. It is used for staging and treatment decisions.
In Breslow’s method, the tumor thickness levels compare to four of the five Clark’s levels:
- Up to 0.75 mm thickness compares to Clark’s level II
- From 0.75 to 1.5 mm thickness compares to Clark’s level III
- From 1.5 to 4.0 mm thickness compares to Clark’s level IV
- Greater than 4.0 mm thickness compares to Clark’s level V
The National Cancer Institute (NCI) reports that a small number of malignant melanomas spontaneously regress. At less than 1 percent of the total number of cases, these events are extremely rare.
Questions for your doctor about melanoma
Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about melanoma:
- What type of tests will be performed to diagnose my skin cancer?
- What type of melanoma do I have?
- How large and thick is my melanoma?
- Will I need a lymph node dissection?
- What is the stage of my cancer?
- What is the best treatment option for my condition?
- What are the risks and benefits of this treatment?
- If my growth is removed, will I have a scar?
- What are the chances that my cancer will return?
- How often should I be checked since I have had melanoma?
- Are my family members at higher risk for melanoma?
- Should my family members be screened more often because of my diagnosis?