Melanoma is the most dangerous form of skin cancer. In its advanced state, it can cause serious illness and even death. Fortunately, melanoma rarely strikes without warning. Learn how to identify melanoma, how it spreads and what treatments are available.

What Is Melanoma?

Melanoma is the most serious form of skin cancer. However, if it is recognized and treated early, it is nearly 100 percent curable. But if it is not, the cancer can advance and spread to other parts of the body, where it becomes hard to treat and can be fatal. While it is not the most common of the skin cancers, it causes the most deaths. The American Cancer Society estimates that in 2008, there will be 8,420 fatalities in the U.S., 5,400 in men and 3,020 in women. The number of new cases of invasive melanoma is estimated at 62,480; of these, 34,950 will be in men and 27,350 in women.

Melanoma is a malignant tumor that originates in melanocytes, the cells which produce the pigment melanin that colors our skin, hair, and eyes. The majority of melanomas are black or brown. However, some melanomas are skin-colored, pink, red, purple, blue or white.

Am I at Risk?

Everyone is at some risk for melanoma, but increased risk depends on several factors: sun exposure, number of moles on the skin, skin type and family history (genetics).

• Both UVA and UVB rays are dangerous to the skin, and can induce skin cancer, including melanoma. Blistering sunburns in early childhood increase risk, but cumulative exposure also is a factor. People who live in locations that get more sunlight — like Florida, Hawaii, and Australia — get more skin cancer. Avoid using a tanning booth or tanning bed, since it increases your exposure to UV rays, increasing your risk of developing melanoma and other skin cancers.

• Moles

  There are two kinds of moles: normal moles — the small brown blemishes, growths, or "beauty marks" that appear in the first few decades of life in almost everyone — and atypical moles, also known as dysplastic nevi. Regardless of type, the more moles you have, the greater your risk for melanoma.

• Skin Type

  As with all skin cancers, people with fairer skin are at increased risk.

• Family History

  About one in every ten patients diagnosed with the disease has a family member with a history of melanoma. If your mother, father, siblings or children have had a melanoma, you are in a melanoma-prone family. Each person with a first-degree relative diagnosed with melanoma has a 50 percent greater chance of developing the disease than people who do not have a family history. If the cancer occurred in a grandmother, grandfather, aunt, uncle, niece or nephew, there is still an increase in risk, although it is not as great. Read more on family history, below.

• Personal History

  Once you have had melanoma, you run an increased chance of recurrence. Also, people who have or had basal cell carcinoma and squamous cell carcinoma are at increased risk for developing melanoma.

• Weakened Immune System

  Compromised immune systems as the result of chemotherapy, an organ transplant, excessive sun exposure, and diseases such as HIV/AIDS or lymphoma can increase your risk of melanoma.

If you are in any of these risk groups, you can protect yourself and your children by practicing safe sun habits, remembering to examine yourself regularly, watching for the warning signs and getting yearly exams by a dermatologist or other physician experienced in skin care.

We are all at risk for melanoma. However, some people are more at risk than others. Heredity plays a major role. If your mother, father, siblings, or children (first-degree relatives) have had a melanoma, you are part of a melanoma-prone family. Each person with a first-degree relative diagnosed with melanoma has a 50 percent greater chance of developing the disease than members of the general public who do not have a family history of the disease. If the cancer occurred in a grandmother, grandfather, aunt, uncle, niece, or nephew (second-degree relatives), there is still an increase in risk compared to the general population, though it is not as great.

About one of every ten patients diagnosed with the disease has a family member with a history of melanoma. If melanoma is present in your family, you can protect yourself and your children by being particularly vigilant in watching for the early warning signs and finding the cancer when it is easiest to treat.

Close Relatives Examined

When this skin cancer is diagnosed, it is standard practice for physicians to recommend that close relatives be examined immediately for melanoma and for the presence of unusual or atypical moles. These moles are also called "dysplastic nevi." You can read more about atypical moles here.

Family Syndrome

When atypical moles are found in an individual belonging to a melanoma family, the condition is known as FAMMM, standing for Familial Atypical Multiple Mole Melanoma Syndrome. People with this syndrome are at the greatest risk of developing melanoma. In contrast, a research study found that those family members who did not have atypical moles were much less likely to develop melanoma.

Genetic Risk Factors

A mutation (alteration) in a recently discovered gene, the BRAF, may play a part in causing melanoma. In one study, this mutated gene was found in two-thirds of the melanoma cells analyzed. BRAF is called a "switch" gene, because it turns on to allow the cells to grow and divide. Mutations in this gene can lead to uncontrolled cell growth and cancer. The discovery is an exciting research breakthrough, but physicians and patients are still years away from reaping the rewards. Ultimately, the understanding of the BRAF gene could lead to the development of diagnostic tools and drug therapies. The mutations most commonly seen in familial melanoma occur in another gene, p53. When this gene is in its normal state, its main function is to give damaged cells time to repair themselves and not progress to cancer. However, when the gene is altered, it becomes unable to perform this function, and cancer can result. A number of gene mutations in addition to p53 and BRAF have been associated with familial melanoma. In the future, families might be screened so as to identify those members who are carrying a defective gene.

Moles in an Active Stage

Moles in people belonging to melanoma-prone families are subject to change at certain times of life. They may get larger or show alterations in color or elevation, so for those periods, they are described as being active. While the reasons for these changes are not fully known, there could be a hormonal component: Moles are more active at puberty and during pregnancy. Many — but not all — physicians advise high-risk individuals not to take hormonal medications, such as oral contraceptives or hormone replacement therapy.

Examination Scheduling

Individuals with the Atypical Mole Syndrome can improve their chances of early detection by increasing the frequency of skin self-examination and by visiting a physician more often. The clinician may take photographs to document whether there are new moles or changes in older ones.

Children: A Special Case

Children in melanoma-prone families need special care, because familial melanoma is likely to make its appearance early in life. Even though these cancers usually do not appear until after adolescence, they may arise in much younger children who have a family history of melanoma. Most physicians, therefore, advise parents to make a point of studying a child's skin frequently from infancy on.

Physician examination should start at the age of ten and continue on a twice-a-year basis thereafter. Particular care should be taken at puberty and during adolescence when hormonal changes activate the moles. Here is some encouraging news: Because melanoma families are on the lookout for the disease and seek professional consultation early, the survival rate for familial melanoma is even higher than that for non-familial melanomas.

Moles, brown spots and growths on the skin are usually harmless — but not always. Anyone who has more than 100 moles is at greater risk for melanoma. The first signs can appear in one or more atypical moles. That's why it's so important to get to know your skin very well and to recognize any changes in the moles on your body. Look for the ABCDEs of melanoma, and if you see one or more, make an appointment with a physician immediately.

	Asymmetry If you draw a line through this mole, the two halves will not match.
	Border The borders of an early melanoma tend to be uneven. The edges may be scalloped or notched.
	Color Having a variety of colors is another warning signal. A number of different shades of brown, tan or black could appear. A melanoma may also become red, blue or some other color.
	Diameter Melanomas usually are larger in diameter than the size of the eraser on your pencil (1/4 inch or 6 mm), but they may sometimes be smaller when first detected.
	Evolving Any change — in size, shape, color, elevation, or another trait, or any new symptom such as bleeding, itching or crusting — points to danger.

Prompt action is your best protection. The pictures below show atypical normal moles and melanomas.

	Benign	Malignant
Symmetrical			Asymmetrical
Borders are even			Borders are uneven
One shade			Two or more shades
Smaller than 1/4 inch			Larger than 1/4

Oprima aqui para ver esto en espaňol.

The Four Basic TypesMelanomas fall into four basic categories. Three of them begin in situ — meaning they occupy only the top layers of the skin — and sometimes become invasive; the fourth is invasive from the start. Invasive melanomas are more serious, as they have penetrated deeper into the skin and may have spread to other areas of the body.

Superficial spreading melanoma is by far the most common type, accounting for about 70 percent of all cases. This is the one most often seen in young people. As the name suggests, this melanoma travels along the top layer of the skin for a fairly long time before penetrating more deeply.

The first sign is the appearance of a flat or slightly raised discolored patch that has irregular borders and is somewhat geometrical in form. The color varies, and you may see areas of tan, brown, black, red, blue or white. This type of melanoma can occur in a previously benign mole. The melanoma can be found almost anywhere on the body, but is most likely to occur on the trunk in men, the legs in women, and the upper back in both.

Lentigo maligna is similar to the superficial spreading type, as it also remains close to the skin surface for quite a while, and usually appears as a flat or mildly elevated mottled tan, brown or dark brown discoloration. This type of in situ melanoma is found most often in the elderly, arising on chronically sun-exposed, damaged skin on the face, ears, arms and upper trunk. Lentigo maligna is the most common form of melanoma in Hawaii. When this cancer becomes invasive, it is referred to as lentigo maligna melanoma.

Acral lentiginous melanoma also spreads superficially before penetrating more deeply. It is quite different from the others, though, as it usually appears as a black or brown discoloration under the nails or on the soles of the feet or palms of the hands. It is the most common melanoma in African-Americans and Asians, and the least common among Caucasians.

Nodular melanoma is usually invasive at the time it is first diagnosed. The malignancy is recognized when it becomes a bump. It is usually black, but occasionally is blue, gray, white, brown, tan, red or skin tone.

The most frequent locations are the trunk, legs, and arms, mainly of elderly people, as well as the scalp in men. This is the most aggressive of the melanomas, and is found in 10 to 15 percent of cases.

Once the type of melanoma has been established, the next step is to classify the disease as to its degree of severity.

Classifications for melanomas are called stages. The stage refers to the thickness, depth of penetration, and the degree to which the melanoma has spread. The staging is used to determine treatment.

Early melanomas (Stages I and II) are localized, and more advanced melanomas (Stages III and IV) have spread (metastasized) to other parts of the body. There are also subdivisions within stages.

Guide to Staging
The most important factors in the staging system are the thickness of the tumor, known as Breslow's thickness, and the presence of microscopic ulceration, indicating that the epidermis covering the tumor is not intact.

Breslow's thickness measures in millimeters the distance between the upper layer of the epidermis and the deepest point of the tumor's penetration. The thinner the melanoma, the better the chance of a cure.

• In situ melanoma remains confined to the epidermis
• Very thin tumors are less than 1.0 millimeter
• Thin tumors are 1.01-2.0 mm
• Intermediate tumors are 2.0-4.0 mm
• Thick melanomas are 4.00 mm or more.

The presence of microscopic ulceration moves the tumor into a later stage, so your doctor may elect to treat such a tumor with ulceration more aggressively.

Very thin tumors are classified according to Clark's level of invasion, based on the number of layers of skin penetrated by the tumor.

• Clark's level I. The melanoma occupies only the epidermis.
• Clark's level II. The melanoma penetrates to the layer immediately under the epidermis, the papillary dermis.
• Clark's level III. The melanoma fills the papillary dermis and impinges on the reticular dermis, the next layer down.
• Clark's level IV. The melanoma penetrates into the reticular or deep dermis.
• Clark's level V. The melanoma invades the subcutaneous fat.

Sentinel Node in Diagnosis

One of the most important indicators of the severity of a melanoma is whether it has spread. The initial spread is most likely to be in the lymph node closest to the primary tumor--the sentinel node. This is identified by lymphoscintigraphy, a procedure based on injecting a small amount of radioactive substance to trace a blue dye through the lymphatic fluid. The dye is first picked up by the sentinel node. This is then excised (sentinel node biopsy) and studied in the laboratory for the presence of melanoma cells. If they are found, the other nodes in the region are also excised. If there are no melanoma cells, the other nodes are not removed.

Metastasis is a factor to be considered in all tumors more than 1.0 mm in thickness or when a thinner tumor shows evidence of ulceration.

Stage I. This category is subdivided according to the thickness of the primary (original) tumor.

• Stage 1a: The tumor is less than 1.0 mm in Breslow's thickness without ulceration and is in Clark's level II or III.
• Stage Ib: The tumor is less than 1.0 mm in Breslow's thickness with ulceration and/or Clark's level III or IV, or it is 1.01 - 2.0 mm in thickness without ulceration, and may have spread to the closest lymph nodes.

Stage II. This is also subdivided according to gradations in thickness and/or depth, the presence or absence of ulceration, and potential regional lymph node metastases.

• Stage IIa: The tumor is 1.01 - 2.0 mm in Breslow's thickness with ulceration, or is 2.01-4.0 mm in thickness without ulceration.
• Stage IIb: The tumor is 2.01-4.0 mm in Breslow's thickness with ulceration, or is greater than 4.0 mm in thickness without ulceration.
• Stage IIc: The tumor is greater than 4.0 mm in Breslow's thickness with ulceration.

If a melanoma is suspected to have spread to the lymph nodes at any point in Stage I or II, a test called a sentinel node biopsy is done to confirm this. This technique involves removing and examining the node nearest the tumor, which is called the sentinel node. Such a biopsy is now frequently done when a tumor is more than 1 mm in thickness, or when a thinner melanoma shows evidence of ulceration. If the sentinel node is found to be positive for melanoma, the rest of the surrounding lymph nodes are removed.

As the sentinel node biopsy is not considered necessary in all cases, you may wish to discuss the matter with your physician.

Later Stages — Stages III and IV

Stage III. Once a melanoma is known to have reached the local or regional lymph nodes, the disease is said to have reached Stage III. Breslow's thickness is no longer used in staging, but the presence of microscopic ulceration continues to be used, as it has an important effect on the progression of the disease.

In-transit or satellite metastases are also included in Stage III. In this case, the spread is to skin or underlying tissue (subcutaneous) for a distance of more than 2 centimeters (1 cm equals 0.4 inch) from the primary tumor, but not beyond the regional lymph nodes. In addition, the new staging system includes metastases so tiny they can be seen only through the microscope.

Stage IV. The melanoma has metastasized to lymph nodes far away from the primary tumor or to internal organs, most often the lungs, followed in descending order of frequency by the liver, brain, bone and gastrointestinal tract.

Treatment

When it comes to the early stages of the disease, the future is bright. Most people with thin, localized melanomas are cured by appropriate surgery. Early detection still remains the best weapon in fighting skin cancer.

More treatments are available for more advanced disease. The cure rate continues to rise. Research has produced a greater understanding of melanoma, leading to the development of new drugs.

Surgical Excision: The first step in treatment is the removal of the melanoma, usually by surgical excision (cutting it out). Most surgical excisions, also called resections, are done in a doctor's office or as an outpatient procedure with local anesthesia. Scars are usually small and improve over time. Surgery is less extensive than in the past, so scars are smaller.

Discolorations and areas that are depressed or raised following the surgery can be concealed with cosmetics specially formulated to provide camouflage. If the melanoma is larger and requires more extensive surgery, a better cosmetic appearance can be obtained with flaps made from skin that is near the tumor, or with grafts of skin taken from another part of the body. For grafting, the skin is removed from areas that are normally or easily covered with clothing.

There is now a trend towards performing a sentinel lymph node biopsy and tumor removal at the same time.

Setting the Margins

In today's technique, much less of the normal skin around the tumor is removed. The borders of the entire area to be excised — both tumor and healthy skin — are known as the margins. Margins are much narrower than they ever were before. Most surgeons today are following the guidelines recommended by the National Institutes of Health (NIH) and the American Academy of Dermatology Task Force on Cutaneous Melanoma:

• When there is an in situ melanoma, the surgeon excises 0.5 centimeter of the normal skin surrounding the tumor and takes off the skin layers down to the fat.
• In removing a melanoma that is 1 mm or less in thickness, the margins of surrounding skin are extended to 1 cm, and the excision goes through all skin layers and down to the fascia.
• If the melanoma is equal to or greater than 2 mm in Breslow's thickness, a margin of 2–3 cm is taken.

The lymph nodes must be evaluated before treatment is selected. To find out whether melanoma cells have spread, the physician starts by feeling the nearby lymph nodes. If the melanoma is on the arm, the nearest nodes are in the armpit; if on the leg, they are in the groin. For a melanoma on the head, the closest lymph nodes are usually on the neck on the same side. For a tumor on the trunk, the nodes in either the armpit or the groin could be involved.

When an enlargement or lump in a lymph node can be recognized by touch, it is called palpable. A palpable lymph node will be surgically removed in a node biopsy.

This node is sent to the pathology laboratory to be tested for the presence of malignant cells. If any are found, the patient usually has the other nodes in that lymph node basin removed. Then, additional, or adjuvant, treatments that stimulate the immune system and/or chemotherapy will be recommended.

Non-Palpable Nodes

Sometimes the lymph nodes are not palpable. When that is the case, one of two approaches will usually be followed:

• Wait-and-See: Some physicians advise a "wait-and-see" policy. No further surgery is done at this time, but the patient is asked to return at regular intervals for checkups.
• Remove nodes. Other physicians believe in removing all the nodes in the region of the tumor on the chance that there are hidden cancer cells. You will hear this procedure described by the technical term of a "radical node dissection." There is no definite proof that non-palpable lymph node removal should be performed as a preventive measure. It is a good idea for a melanoma patient to ask the physician about these options and the reasons why one or the other is recommended.
• Selective removal of lymph nodes. In this approach, only the sentinel node and nodes in the region of the primary tumor are removed. This method is being used with increasing frequency for melanomas that are more than 1.00 mm in depth. The surgery is less extensive than the radical node dissection, and studies have found that patients do well.

Microscopic nodal involvement

Palpable nodes may — or may not — be a sign of melanoma. The diagnosis must be confirmed by microscopic evaluation. This is also the procedure for sentinel nodes that are non-palpable, but may still contain cancerous cells. Research is now going on into special biochemical techniques that can identify those melanoma cells that do not show up under routine microscopic examination.

Local vs. Distant Spread

In local forms of the disease, the metastases can reach skin or subcutaneous tissue more than 2 cm from the primary tumor, but not beyond the regional lymph nodes. Once the disease has advanced to Stage IV, melanoma cells have traveled through the body via the bloodstream or lymph vessels, going far from the original tumor site. They may have reached distant lymph nodes or invaded the internal organs. This can be in addition to or instead of the local spread to the lymph nodes or in-transit metastases.

When distant metastases are suspected, they can be traced by scans of the
chest, head, abdomen and pelvis with a CT scan (computed tomography) in which special x-ray equipment and a computer program show a cross-section of body tissues or organs; an MRI (magnetic resonance imaging) which uses a magnet instead of x-ray to create a map of the patient's body; and by PET (positron emission tomography), an evolving radiographic technique. For PET scanning, radioactive sugar, the basic carbohydrate utilized by the body for energy, is injected intravenously into the patient. This sugar is taken up rapidly by any melanoma cells that are present.

For patients with Stages III and IV disease, surgery may be followed with adjuvant therapy. Ask your physician to explain the possibilities and grounds for selection of one treatment over the other.

Chemotherapy

A number of drugs that are active in fighting cancer cells are being used to treat melanoma, either one at a time or incombinations. Currently, Dacarbazine (DTIC), given by injection, is the only chemotherapy approved by the FDA. DTIC may be combined with carmustin (BCNU) and tamoxifen, or with cisplatin and vinblastine. Another drug, temozolomide, can be given orally. Unfortunately, to date, the response of melanomas to chemotherapy has been limited, but a great deal of research into new drugs and new approaches is being carried out.

Another class of drugs, based on a different principle, has come into use more recently. They are anti-angiogenic, which means that they prevent new blood vessels from forming. The reason this is important is that they cut off the blood supply that would otherwise nourish the cancer cells and enable them to grow. These drugs are still experimental and a good deal of research into improving and combining them with others is going on. Studies are underway with the anti-angiogenic drug, thalidomide, combined with the chemotherapeutic agent, temozolomide. Angiostatin and endostatin are two other drugs in this class that have shown some degree of activity against melanoma in preliminary studies.

The isolation-perfusion method is sometimes used as a palliative (pain-relieving) treatment when the melanoma is on an arm or leg. "Isolation" means that the chemotherapy is "perfused" (added to) the blood flowing through the affected limb, and no other part of the body.

Immunotherapy/Biochemotherapy

This is one of the most exciting and changing fields in medicine, based on drugs that act on the body's immune system. A number of newly-developed treatments are now being tested with some success. Among the immunotherapies, several types of experimental melanoma vaccines are now viewed as promising. Unlike the influenza vaccine, given when you are well to prevent disease, these are given to people who already have melanoma. Clinical trials of various types of vaccine are underway with patients whose disease is in Stages III and IV. The vaccines are intended to stimulate the immune system so that it reacts more strongly against a patient's melanoma cells, destroying the cancer or slowing the progression. These vaccines are not a part of routine treatment at this time, so patients with advanced melanomas may wish to discuss this possibility with their physicians.

Another type of immunotherapy (also known as biologic therapy) makes use of chemicals that occur naturally in the body. The one you are most likely to hear about is interferon-alpha. This is the only systemic drug with FDA approval, and it has been shown to improve five-year survival of Stage III patients. Tumor necrosis factor (tumor-killing) factor is another of these naturally occurring substances. Both of these — especially interferon-alpha — are produced by white cells (lymphocytes) when they come in contact with tumor cells, viruses or other harmful substances, and have been shown to kill a number of tumors, including melanomas. They have some anti-angiogenic properties as well. However, both drugs have significant side effects which can limit their use.

Lymphokines, which are chemicals occurring naturally in small quantities in the body, are being used for Stage IV patients. They may also be produced by white blood cells (lymphocytes) which have been specially stimulated by antigens, a basic part of the immune system, to make them better "killers" of malignant cells. The best known of these therapies uses the lymphokine, interleukin-2, with or without the addition of interferon alpha, which enters and attacks melanoma cells. However, interleukin-2 is associated with very significant side effects when given in high doses. This form of immunotherapy is still in the experimental stage.

Gene therapy

A gene is the basic unit of genetic material. It is the code or "blueprint" by which our body's proteins are made. Alterations in these codes can result in uncontrolled cell growth as in cancer.

On the other hand, selected genes can be altered so as to correct genetic defects or enhance the cancer-fighting potential of cells. There is hope that making changes in genes will lead to successes in treating a wide range of illnesses, so this kind of therapy frequently gets newspaper headlines. However, keep in mind that this treatment is in the very early stages of research, and its effectiveness is yet to be proven.

One form of gene therapy is based on creating alterations in the white blood cells or in the tumor-infiltrating lymphocytes so that they will attack the melanoma. This is achieved by removing these cells from the patient, growing them outside the body and treating them so as to increase their number. The next step is the addition of genetic material that produces one of the many growth factors which make the lymphocytes more aggressive as cancer-fighters. These more aggressive lymphocytes are returned to the patient's body in an effort to stimulate the immune system to kill the melanoma and its metastases.

The focus of current research is the identification of genes for specific melanoma antigens. These are molecules found on the cell wall that stimulate the production of antibodies, which are a part of the body's immune defense system. An antibody attaches itself to only one type of antigen. By injecting the gene for the melanoma antigens, the hope is to increase their number and produce a broad attack by the patient's immune system.

Clinical Trials

Many patients, especially those with advanced disease, are participating in clinical trials in order to get new treatments while they are still experimental and not generally available.

Patients who have Stage III and IV melanoma might consider enrolling in a clinical trial, a new or experimental treatment. There are risks involved in enrolling in a clinical trial, but there can be benefits, as well.

What You Need to Know

Hearing the words "It's cancer" can be overwhelming. Often, people are too stunned to be able to ask physicians for the information they need. When discussing your diagnosis and treatment options with your physician, it can be helpful to have questions prepared ahead of time, so that you don't forget anything important. Take a pen and paper to write down the answers, or a portable tape recorder so that you can play back the answers later. Studies have shown that people who are more informed about their cancer have a more positive attitude and respond better to treatment.

Questions to Ask Your Physician

• How advanced is my melanoma? What stage is it in?
• What are my chances of recovery?
• What treatments are available?
• Will I be given a choice of options?
• If I need surgery, will there be a scar?
• Which treatment do you think is best for me? Why?
• What are the side effects? Can they be treated, too?
• Will my health insurance or Medicare/Medicaid cover the cost?
• Will I be able to work and lead a normal life during treatment?
• What tests will be performed to show that the melanoma is cured?
• What are the chance of it coming back?
• Is there anything I can do to prevent a recurrence?