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18 March 2011

Melanoma

Melanoma is a potentially serious skin cancer that develops from normal skin cells called melanocytes.

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Summary

  • Melanoma is a form of skin cancer that develops from cells called melanocytes.
  • Melanocytes also can grow to form benign (not cancerous) moles.
  • If a mole shows changes in size, shape, colour or becomes ulcerated it may indicate that it has transformed into a melanoma.
  • Melanoma can be cured if detected early, before it spreads (metastasises) to other areas of the body.
  • Diagnosis of melanoma is confirmed with an excision biopsy of the suspicious lesion.
  • Treatment of melanoma depends on the extent of disease.
  • Sun exposure, particularly sunburn, can cause skin damage that can lead to melanoma.

Description

Melanoma is a potentially serious type of skin cancer that develops from normal skin cells called melanocytes (these cells produce the skin pigment melanin, which gives the skin its natural colour). The cells become malignant and start growing uncontrollably, subsequently aggressively invading surrounding healthy tissues.

Melanoma may arise from the skin (most commonly) or other sites where there are melanocytes (eyes, mucous membranes and brain tissue), and may spread (metastasise) through the blood or lymph systems to organs and bones.

This cancer can develop in a mole or other mark on the skin, but also often develops in unmarked skin. Commonly, it starts on the upper back or trunk of men and women and the legs in women, but it can occur anywhere. Melanoma is most common in light-skinned people, but affects people of all races.

Melanomas can vary in size, shape and colour, and often they consist of mixed colours. Most often a melanoma looks like a flat, brown or black mole, irregular in shape and at least 6 mm across. A melanoma may be lumpy or rounded, change colour, become crusty, ooze or bleed. Any change in shape, size or colour of a mole may indicate melanoma and should be treated suspiciously and preferably biopsied by removing the lesion and sending it to the laboratory for microscopic examination.
Early removal ensures optimal outcome.

Melanoma can grow extremely aggressively and invade surrounding healthy tissue, growing mostly downwards. The five-year cure rate for early and very superficial lesions can be close to 100%, but they have a 90% chance of being fatal within 10 years after they have started to spread (metastasise).

Classification

There are four types of melanoma:

1. Lentigo-malignant melanoma: This appears mostly on the face of elderly people as an asymptomatic, large (2 to 6 cm), flat, tan or brown disc with darker brown or black spots scattered on the surface. After variable periods, a large amount of lentigo malignas start to invade the skin and therefore early excision (before the lesion becomes large) is recommended.

2. Superficial spreading melanoma: This is initially much smaller than the lentigo-malignant melanoma and occurs most commonly on women’s legs and men’s torsos. You may become suspicious when there is enlargement or irregular colour changes are seen in a mole, with blue, black, red or white spots and surface indentations.

3. Nodular melanoma: 10 to 15% of all melanoma. This may occur anywhere on the body as dark, protuberant papules or a plaque that varies in colour from pearl to grey to black. Sometimes the lesion ulcerates. It can also be unpigmented (not dark).

4. Acrolentiginous melanoma: This is most common in black races, and arises on the surface of hands or feet, or underneath nails.

Cause

Melanoma develops when normal pigment-producing skin cells start dividing uncontrollably. Common causes of malignant transformation are:

  • Damage to the DNA of melanocytes by exposure to the sun. Exposure to the sun, measured by length (hours or days) and intensity (degree of sunburn), is the single most important cause of melanoma. Because it can cause cancer, the sun is considered a carcinogen. This effect is now exacerbated by the absence of ozone in the upper atmosphere, especially around the South Pole (the so-called ozone hole). The result has been a steadily increasing incidence of melanoma in South Africa, Australia and New Zealand. Melanoma can, however, also arise in skin areas or other organs that are never exposed to sunlight.
  • An inherited predisposition towards melanoma. This is most common in people who have atypical moles (dysplastic naevi), and where the original tumour develops in tissue such as eyes or brain. In some families, many members have a large number of atypical moles, and some have had melanoma. Members of these families are at very high risk. It is important for them to have frequent check-ups (every three to six months) so that any problems may be detected early. The doctor may take pictures of a person's skin to help detect any changes.
  • Melanoma may also develop when the immune system is suppressed, especially in kidney transplant recipients and people with leukaemia (cancer in which there is an excess of white blood cells) or lymphoma (tumour of the lymph tissue).

Symptoms

The early signs of melanoma can be a change in a mole or similar pigmented lesion. These include changes in:

  • Colour, especially darkening or turning black, brown, white, red or blue. It is also possible that part of a mole will lose colour (regression).
  • Colour distribution, especially spread of colour from the edge of a mole into surrounding skin
  • Size, especially rapid growth
  • Shape, especially when irregular borders appear
  • Elevation – when a previously flat mole thickens or becomes raised above the rest of the skin
  • Surface, especially erosion, scaling, indentations, oozing, bleeding or crusting
  • Surrounding skin, especially redness, swelling or satellite pigmentations (small new patches of colour around a larger lesion)
  • Sensation, especially itching, tingling or burning
  • Consistency, especially softening or friability (small pieces breaking off easily)

To summarise:

  • A - Asymmetry
  • B - Irregular or spreading border
  • C - Irregular colour
  • D - Diameter 6mm or more

Later symptoms include:

  • Ulceration or bleeding of a mole or other coloured skin lesion.
  • Pain in a mole or lesion.

Advanced cancer can develop in one to 12% of patients who never had obvious melanoma on the skin. Symptoms of metastatic melanoma may include:

  • Swollen lymph nodes (lymphadenopathy), especially in the armpit or groin
  • Colourless lump or thickening under the skin
  • Unexplained weight loss
  • Skin turning a slate-grey colour (melanosis)

Prevalence

Melanoma is not the most common kind of skin cancer, but six out of every seven deaths from skin cancer are due to melanoma. In older people the risk of developing melanoma is higher but it can affect even young children.

The incidence has risen dramatically worldwide in the last 40 years. Yet, the morbidity (death rate) of melanomas has dropped significantly due to early detection.

Course

Melanoma usually occurs in single numbers. Many melanomas begin in an existing mole or other lesion, but 25 to 50% start in previously unmarked skin.

Melanoma usually follows a predictable pattern of growth through skin layers. If not treated, almost all melanomas eventually spread to other parts of the body. Spontaneous regression is rare. Early detection and surgical removal cures most cases of primary melanoma.

A person's chance of survival (prognosis) with primary melanoma is indicated by the following factors:

  • Thickness and infiltration of the tumour (the main factor).
  • Site of primary tumour: the survival rate is higher if the tumour is on an arm or leg and lower if it is on the torso, head, or neck (or under fingernail or toenail).
  • Sex: the five-year survival rate for women is 83% to 86%, compared with 67% to 68% for men.
  • Age: survival is higher in adults under 60 years old.

Metastatic melanoma is cancer that has spread (metastasised) via the lymph system to nearby skin (in-transit metastases) or to lymph nodes, or via the bloodstream to distant organs. Metastatic melanoma is usually fatal, even with treatment. Early detection and removal of primary melanoma before it metastasises can prevent death from melanoma.

Risk factors

  • Previous history of exposure to the sun. This is the single most important risk factor. Extensive exposure to the sun can occur during childhood, in jobs that require the person to work outside, and during leisure-time activities.
  • History of sunburns, particularly severe (blistering) sunburns in childhood.
  • White race, especially with fair skin that burns rather than tans.
  • Red hair or blue eyes.
  • Family history of melanoma or atypical moles.
  • Atypical moles and some types of congenital moles.
  • 50 or more moles.
  • Marked (extensive) freckles on the upper back.
  • Previous melanoma or other skin cancer.
  • Immunosuppression.

Risk factors for melanoma in children include the following:

  • Moles present at birth, especially if larger than 20 cm (giant congenital melanocytic naevus).
  • Atypical moles.
  • Immunosuppression.
  • Albinism.
  • A rare hereditary disease in which the body cannot repair damage done to cells by ultraviolet radiation from the sun (xeroderma pigmentosum).

When to see your doctor

  • Any change in a mole, including in its size, shape or colour, or if it becomes painful.
  • A bleeding mole.
  • A discoloured area under a fingernail or toenail (not caused by an injury).
  • A general darkening of the skin unrelated to sun exposure.

If you have been diagnosed with melanoma, contact your health professional immediately when you have any of the following:

  • Loss of weight.
  • Difficulty breathing or swallowing.
  • Coughing or spitting up blood (bloody sputum).
  • Blood in vomit or bowel movement (redness not caused by eating beets).
  • Black urine or bowel movement (not caused by taking iron).

Watchful waiting
It is inappropriate to watch and wait, because this condition can be fatal if not treated as early as possible. Consult a doctor immediately regarding suspicious changes in a mole. Nearly all melanomas can be cured if diagnosed early, before they grow large or deep, or spread.

Diagnosis

1. Evaluation of a skin lesion
Your doctor will physically examine your skin to evaluate suspicious moles or lesions. He or she will do this through biopsy, which is the only way to make a definite diagnosis. It will be done in either of the following ways:

  • Complete removal of lesion for examination (excisional biopsy)
  • Acquisition of a small sample of the lesion for examination (incisional biopsy). This procedure is usually only done on very large lesions.

The specimen is examined by a histopathologist (a doctor specialised in evaluation of body tissues for disease). Sometimes it is helpful for more than one pathologist to look at the tissue to determine whether melanoma is present. If the diagnosis is melanoma, the pathologist will determine its thickness.

2. Digital imaging
Many countries now have MoleMax machines. These computerised imaging systems have an automatic focus video head to record moles plus (most importantly), a second head which shoots polarised (non-reflecting) light that can show the pattern of pigment in the mole.

This can stop many irregular moles in young people being removed; or aid the decision as to how many actually need to be excised. It can also pick up a 2% change (the naked eye picks up at 20% change only!).

3. Further testing
When the melanoma is thicker than 1 mm, other testing may include:

  • Chest X-ray
  • Liver-function blood tests
  • Whole-body computerised axial tomography (CAT) scan. This produces images of the body by computer-analysed X-rays, which show structures or variations in the density of different types of tissue.

4. Evaluation of lymph nodes
After melanoma is diagnosed, the next step may be an evaluation of the lymph nodes to see if the melanoma has started to spread through the lymphatic system to nearby (regional) lymph nodes.

This might not be necessary if the original melanoma is thinner than 0.76 mm, as the probability for tumour spread is very low. On the other hand, the lymph nodes may also not be tested if the primary melanoma is thicker than 4 mm, as in this case it is very likely that the cancer has already spread to distant organs (metastasised). Testing the lymph nodes will not change treatment decisions.

The lymph nodes around the melanoma need to be clinically examined as the first step in diagnosing lymph-node metastases. Additionally, lymphoscintigraphy can be used. It allows removal of the node (sentinel node) to which the tumour may be draining. The routine removal of all potential draining lymph nodes is not regarded as best practice any more.

Tender or enlarged lymph nodes may or may not be a sign that the melanoma has metastasised. Your doctor will do a biopsy of an enlarged lymph node by inserting a needle and removing cells from it, or by surgical removal of the entire node.

5. Evaluation of metastases
A complete medical history and comprehensive physical examination will be done. A CAT scan or magnetic resonance imaging (MRI) scan may be done to identify metastases in other parts of the body. MRI uses magnetic fields to produce an image that provides information about physical structures and biochemistry.

Your physician will "stage" the melanoma, in other words determine how far it has progressed. This is needed to plan treatment and provide an indication of survival. To stage melanoma, the physician looks at the entire clinical picture, including:

  • The pathologist's report on tumour thickness
  • Where the primary tumour is (arm, leg, back, neck)
  • Whether the melanoma has spread to nearby skin (in-transit or satellite metastases)
  • Whether the melanoma has spread to the lymph nodes
  • Whether the melanoma has spread to distant organs

If abnormalities besides the primary tumour are found, the following tests may be done:

  • Other skin lesions: an excisional or incisional biopsy is performed to determine if the lesion is a skin metastasis or a second primary melanoma.
  • Respiratory symptoms or abnormal chest X-ray: follow-up tests include lung tomogram or a CAT scan of the chest.
  • Abdominal symptoms (weight loss, inability to eat, pain) or abnormal liver function tests: follow-up diagnostic tests may include an abdominal CAT scan. However, CAT scans may miss small metastases, which can be picked up with MRI scans. If there are suspicious abdominal symptoms (spitting up blood, vomiting blood, rectal bleeding), an endoscopy or colonoscopy, upper gastrointestinal barium swallow, or barium enema may be useful.
  • Central nervous system symptoms (headache, numbness, and disturbances in vision or balance): a complete neurological exam is performed. This may be followed by a CAT scan or MRI of the brain.
  • Bone pain: Pain in bone tissue is evaluated by a bone scan and by blood tests.

Treatment

Surgery
About 95% of patients with melanoma are treated with surgery. Treatment is based on tumour depth, level of invasion, risk of metastases, and patient/physician preference.

  • Primary melanoma is treated by surgical removal (excision) of the lesion. If the melanoma is thin (usually less than 1.5 mm) and has not deeply invaded surrounding healthy tissues, excision cures the cancer. The excision might involve removing a considerable margin around the lesion to maximise chances of cure.
  • If the melanoma is thicker or when there are symptoms of lymph node involvement, nearby nodes may be surgically removed (lymphadenectomy) as well. Lymphadenectomy is usually not done if the primary tumour is 4 mm thick or more, because it is likely that the cancer has already spread past the lymph nodes.
  • Metastases to the lymph nodes are associated with metastases to distant organs (liver, lung, bones and brain) in 85% of patients. Metastatic melanoma responds poorly to most forms of cancer therapy. Treatment for metastatic cancer aims at relieving symptoms and prolonging life. The chance of dying within 10 years is greater than 90%. Patients may want to consider entering a clinical trial of new drugs or other treatments.
  • Ocular melanoma (a rare melanoma in the eye) has traditionally been treated by enucleation (removal of the eyeball), but radiation is now an alternative treatment.
  • Melanoma on the skin of a finger or toe, or under a nail – which is also rare – is treated by amputation of that finger or toe.

When surgery is performed to remove a primary skin melanoma, it might necessitate a skin graft. For this procedure, the doctor uses skin from another part of the body to replace the skin that was removed. This might be required for cosmetic reasons or to restore body function when melanoma occurs on the face, hands, feet, forearm, or lower leg.

After surgery, a patient should have follow-up skin examinations:

  • Every six months for two years, then yearly examination after two years.
  • Every three to six months for two years if you have atypical moles

Because the tendency to develop melanoma runs in families, it is important that relatives of people who have had melanoma have frequent skin examinations as well.

Medication

Chemotherapy
People with thick melanoma and those with regional and distant metastases may benefit from chemotherapy. Chemotherapy (treatment with anti-cancer drugs) is a systemic treatment, meaning that it can affect cancer cells throughout the body. Chemotherapy is primarily designed to relieve symptoms and prolong life. In most cases, it does not cure the cancer.

One or more anti-cancer drugs are given by mouth or by injection into a blood vessel. Either way, the drugs enter the bloodstream and travel through the body. When melanoma occurs only on an arm or leg, doctors sometimes use a technique called perfusion. With this technique, the flow of blood to and from the limb is stopped for a while with a tourniquet. Anti-cancer drugs are then put into the blood of the limb. In this way the patient receives high doses of drugs in the area where the melanoma is located.

Most responses to chemotherapy last only a few months. However, new forms of chemotherapy are constantly being discovered and tested. The success of new drugs and new drug combinations is determined through controlled testing of a new therapy (clinical trial). These trials are designed to answer scientific questions and to determine whether a new treatment is safe and effective. Patients who take part in clinical trials make an important contribution to medical science and may have the first chance to benefit from improved treatment methods.

Immunotherapy
Immunotherapy (also called biological therapy) helps the body's immune system fight disease more effectively and often involves the use of substances called biological response modifiers (BRMs). This therapy is mostly considered if melanoma has spread. The body normally produces BRMs in small amounts in response to infection and disease. Using modern laboratory techniques, scientists can produce these substances in large amounts for use in cancer treatment.

Adjuvant therapy
Doctors do not yet know whether chemotherapy or biological therapy given soon after surgery can help prevent melanoma from recurring. This form of treatment, known as adjuvant therapy, is under study in clinical trials. Doctors may suggest that certain patients who are at high risk for recurrence, such as those whose melanoma is deep or has spread to nearby tissue, participate in a clinical trial.

Other
Radiation therapy (also called radiotherapy) is occasionally used to treat melanoma that has spread: it involves the use of high-energy rays to damage cancer cells and stop them from growing. Radiation therapy is most commonly used to help control melanoma that has spread to the brain.

Side effects
Often the resulting scars from surgery to remove an early-stage melanoma are small (2.5 to 5 cm long) and fade with time. In larger and thicker tumours, more surrounding skin and tissue (even including muscle) are removed. Although skin grafts reduce scarring, these scars will often be quite noticeable.

The removal of lymph nodes from the underarm or groin may damage the lymphatic system and slow the flow of lymph in the arm or leg. Lymph may build up in a limb and cause swelling (lymphoedema). There are methods available to reduce swelling if it becomes a problem. Additionally, following removal of lymph nodes, it is more difficult for the body to fight infection in a limb. Thus it is important to protect the affected arm or leg from injuries that can lead to infection. When an infection does develop, see your doctor.

Although chemotherapy, biological therapy and radiation therapy are very carefully tailored to a particular case, it is difficult to limit the effects of these treatments so that only cancer cells are destroyed. Because healthy cells can also be damaged, cancer treatments often cause unpleasant side effects.

Side effects of chemotherapy depend on the drugs given. In general, anti-cancer drugs affect cells that divide rapidly. These include blood cells, which fight infection, cause the blood to clot, and carry oxygen to all parts of the body. When blood cells are affected by anti-cancer drugs, patients are more susceptible to fever or infection, can bruise or bleed more easily, and may have less energy. Cells in the hair follicles and those that line the digestive tract also divide rapidly. Thus chemotherapy can cause hair loss and other problems such as mouth sores, poor appetite, nausea and vomiting.

The drugs commonly used to treat melanoma can also cause shortness of breath, kidney problems, tingling or numbness of the fingers, toes, or face, and some hearing loss. Most of the side effects of chemotherapy resolve after treatment stops. However, some side effects, such as tingling, numbness, and hearing loss, may continue even after chemotherapy is over.

Side effects of biological therapies vary with the type of treatment. Often, these treatments cause flu-like symptoms such as chills, fever, muscle aches, weakness, loss of appetite, nausea, vomiting, and diarrhoea. Sometimes, patients develop a rash, bleed or bruise easily, or retain fluid. These problems can be severe, and patients may need to be hospitalised during treatment.

Side effects of radiation therapy depend on the amount of radiation given and the area being treated. For melanoma that has spread to the brain, treatment usually continues for two weeks. Side effects during treatment may include headache and fatigue. Patients often lose their hair, but it usually grows back after treatment.

Loss of appetite can be a problem during therapy. People may not feel hungry when they are uncomfortable or tired. Also, some of the common side effects of cancer treatment, such as nausea, vomiting, or a change in the person's sense of taste, can make eating difficult. Yet good nutrition is important because patients who eat well generally feel better and have more energy. In addition, they may be better able to withstand the side effects of treatment. This means patients have to receive enough calories and protein to help prevent weight loss, regain strength, and rebuild normal tissues. Many patients find that eating several small meals and snacks during the day works better than having three large meals.

Prevention

As at least two thirds of all cases of melanoma are caused by excessive exposure to ultraviolet radiation from the sun, this is the obvious factor to eliminate. Some sources claim that exposure to sunlight in childhood, especially severe sunburns, is a major cause of melanoma.

Sunscreens are rated in strength according to a sun protection factor (SPF), which ranges from 2 to 15 and higher. Those rated 15 or higher provide the best protection. One study estimated that if children regularly used a sunscreen of SPF 15 or higher during their first 18 years of life, they would cut their lifetime risk of melanoma by 78%. Parental guidance (insisting on sunscreen use and wearing of hats and T-shirts) and peer modelling (for example, when lifeguards are seen wearing hats, sunglasses, shirts and sunscreen) are a positive influence on teenagers.

However, other experts think that the link between childhood exposure and later melanoma exists because most people get most of their total exposure to the sun before they are 18. People who live in warm, sunny climates or who have jobs that require them to be outdoors most of the time have a higher risk of developing melanoma whether or not they got sunburnt as children.

People who burn rather than tan, especially those who have red hair or blue eyes, are also at higher risk. You can decrease your risk for melanoma by avoiding ultraviolet light from the sun (sunburns) or tanning booths, and by using a sunscreen whenever you are going to be outside for a while. The most damaging sun exposure is from 10 am to 3 pm. Thus you should avoid exposure to the midday sun whenever possible. Another simple rule is to protect yourself from the sun when your shadow is shorter than you are. Wearing a hat and long sleeves offers protection. Lotions or creams that contain sunscreens can help prevent sunburn.

Previously reviewed by Dr D. Presbury (MB BC, FRCP)

Reviewed by Dr David Eedes, Oncologist, March 2011

 
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