What is melanoma?
Melanoma of the skin is a form of skin cancer that arises from the pigment cells (melanocytes), which are present throughout the skin. Compared with other types of skin cancer, melanoma is an aggressively growing tumour that tends to spread (metastasise) relatively quickly.
What are melanocytes?
Normal melanocytes protect the skin against the harmful effects of sunlight. When melanocytes occur in clusters, visible pigment spots can appear — these are the pigment spots we all know as moles. Like other cells in the body, melanocytes can change into cancer cells. This can happen both to melanocytes within moles and to melanocytes elsewhere in the skin.
Who is at risk of melanoma?
Whereas most forms of cancer are mainly seen in older people, melanoma is a tumour that occurs relatively often in young patients. Together with conditions such as leukaemia, it is one of the most important cancers occurring in young adults. Melanoma in childhood, however, is extremely rare.
Melanoma is sometimes a familial disease: several members of a family, or even a single household, may have melanoma. People who are part of such a family are advised to contact a dermatologist.
What are the risk factors for melanoma?
The most important risk factors are:
- A fair skin type. People with a very fair skin type (who burn easily) have a greater risk of melanoma.
- Sunburn, particularly in childhood. Repeated sunburn before the age of about five appears to increase the risk of developing melanoma later in life.
- Moles. Some moles carry an increased risk of turning into a melanoma. This applies especially to atypical moles and very large congenital moles.
- Inherited susceptibility. Melanoma can occur very frequently in certain families as a result of a genetic defect. Carriers of these gene mutations have a very strongly increased risk of developing melanoma.
What signs should you look out for?
Melanomas often develop within an existing mole, causing the mole to change. Such changes may include:
- a change in the colour of the mole; new dark areas, or conversely lighter areas, are suspicious;
- a change in the shape of the mole — if it develops an irregular border or becomes thicker, this may mean a melanoma is developing;
- itching;
- pain;
- bleeding.
Note: not all of these signs need to be present when a mole changes into a melanoma. When a melanoma arises spontaneously from melanocytes in normal skin, a spot appears that at first looks like an ordinary mole, but which can then develop the same changes described above.
What types of melanoma are there?
Melanoma in situ. This is not yet a melanoma, but the last stage of change before a true melanoma develops. Cancer cells are already present, but they are still confined to the uppermost layer of the skin (the epidermis). A separate page on melanoma in situ is available.
Superficial spreading melanoma. Most melanomas fall into this category. These melanomas often have a relatively large surface area but usually do not yet grow deep into the skin.
Nodular melanoma. In this type, a tumour-like accumulation of melanoma cells is present at a relatively early stage. On the surface this is often visible as a dark grey or dark blue “bump” within the mole.
Acral lentiginous melanoma. This type, rare in North-Western Europe, is seen on the hands (palm, fingers, nails) and feet (sole, toes, nails).
Mucosal melanoma. Rarely, melanoma occurs on the lining of the mouth, the inner side of the eyelids, or the vagina.
Ocular melanoma. Melanomas can also occur in the eye, in addition to the skin and mucous membranes. This specific melanoma is not discussed further here.
Amelanotic (non-pigmented) melanoma. This is a colourless variant of ordinary melanoma. It is a notorious type, because it does not look like a melanoma and is therefore often discovered late. Amelanotic melanomas are relatively rare but appear to have become more common in recent years.
How is melanoma treated?
Treatment (1) – surgical removal
When a doctor suspects a melanoma, the patient is usually referred to a dermatologist. The dermatologist assesses the suspicious lesion with the naked eye and often also with a special magnifier placed on the skin (the “dermatoscope”). If a melanoma is suspected, the suspicious spot is removed surgically with a margin of a few millimetres.
The removed piece of skin is examined by a pathologist. If it is indeed a melanoma, the pathologist measures the thickness of the melanoma (the “Breslow thickness”). Many studies have shown that the thickness of the melanoma is the most important predictive factor for the prognosis: the thinner the melanoma, the better the survival chances.
Treatment (2) – re-excision of the scar
Once the thickness of the melanoma is known, further management is planned. For melanomas thinner than 2 millimetres, the original scar is removed again, usually with a margin of 1 centimetre measured from the edge of the original melanoma. In many cases the sentinel lymph node procedure is then also carried out (see below). For thicker melanomas (more than 2 millimetres), the scar is removed surgically with a larger margin (usually 2 cm). Here too, the sentinel node procedure is usually advised.
Treatment (3) – lymph node assessment and the sentinel node procedure
Once the diagnosis of melanoma is certain, the treating doctor feels the lymph nodes. When melanomas spread, they can lodge in the lymph nodes, and if this has already happened, further treatment is adjusted accordingly. In most cases suspicious lymph nodes are removed for examination.
When a melanoma is 0.8 mm thick or thicker and no enlarged lymph nodes are felt, a special technique is often used to check whether spread has occurred. This is called the sentinel node procedure. With this examination, the lymph node most likely to be affected first in the event of spread can be located. For most melanomas thinner than 0.8 mm, no additional lymph node examination is usually performed beyond feeling the nodes (unless the melanoma was “ulcerated”).
Many patients with a positive sentinel node may now be eligible for treatment with melanoma-inhibiting medicines. Because identifying sentinel nodes containing spread now has direct consequences for further treatment, the procedure has become more valuable than in the past. Whether the sentinel node procedure is possible and advisable in your situation is best discussed with your treating dermatologist or surgeon.
Treatment (4) – additional treatments
In most patients in whom melanoma is found, no further treatment is needed after local removal as described above. If, however, the melanoma has spread further, additional treatments may be chosen. Knowledge and available medicines have developed rapidly in recent years, particularly in the fields of immunotherapy and molecular (targeted) therapy. Your treating doctor can check whether you are eligible for treatment with one or more of these medicines. Additional treatments may include:
Radiotherapy. Radiotherapy is sometimes given to the skin area where the melanoma was removed, and sometimes also at the site of metastases, particularly in the brain. Cancer cells tolerate radiation less well than normal cells; the dose is chosen so that the melanoma cells are destroyed while normal tissue is damaged as little as possible.
Chemotherapy. For metastatic melanoma, chemotherapy is sometimes chosen. Medicines such as dacarbazine may be prescribed. These agents can cause serious side effects.
Immunotherapy. Immunotherapy uses the patient’s own immune system to attack and clear the melanoma cells. Several types of immunotherapy for melanoma have been developed. The most important are:
- Immune checkpoint inhibitors. The immune system uses “checkpoints” to switch the defence on or off. Melanoma cells are sometimes able to use these checkpoints to prevent the immune system from attacking them. Medicines have been developed that act on these checkpoints so that the immune system can attack the melanoma cells after all. Examples that activate the immune system are the PD-1 inhibitors pembrolizumab and nivolumab and the CTLA-4 inhibitor ipilimumab.
- Other immunotherapy. Other types of immunotherapy are also in development, usually vaccines against melanoma cells or “engineered” white blood cells intended to selectively attack the tumour. Immunotherapy is carried out in specialised centres. As far as is known, these agents can suppress the tumours but do not achieve a complete cure of melanoma.
Targeted molecular therapy. In recent years, several treatments have been developed that can very specifically target metastatic melanoma cells, slowing the process of spread.
- BRAF. About half of melanomas have an altered BRAF gene, producing an abnormal BRAF protein that can drive the growth of these melanoma cells. Switching off these proteins can sometimes slow melanoma growth. Examples of BRAF inhibitors are vemurafenib and dabrafenib.
- MEK. The MEK gene works together with the BRAF gene. MEK inhibitors can therefore also help slow tumour growth in some patients with metastatic melanoma. Examples are trametinib and cobimetinib.
- C-KIT. Some melanomas have growth-promoting changes in the C-KIT gene, particularly melanomas that started on the fingers, toes, palms, soles or mucous membranes. A C-KIT inhibitor such as imatinib may then help slow melanoma growth.
Disadvantages of these medicines include sometimes serious side effects and the fact that the average gain in life expectancy is limited. On the other hand, some patients with widely spread melanoma can achieve a considerable health benefit. A challenge for science is to identify in advance those patients for whom a particular treatment will be effective.
Follow-up
After treatment, the patient is monitored for 5 to 10 years, usually by the dermatologist, or by the dermatologist and surgeon together. The frequency of follow-up depends on the thickness of the melanoma.
For an uncomplicated melanoma with a Breslow thickness up to 1 mm, a single follow-up visit one month after removal is recommended for evaluation; in practice, many patients and doctors prefer regular checks for a few years. For melanomas with a Breslow thickness above 1 mm, checks take place every 3 months in the first year, every 6 months in the second year, and once a year thereafter up to the fifth year. People who have had a melanoma with a Breslow thickness above 2 mm are additionally checked yearly from the sixth to the tenth year. A check-up consists of inspecting the scar, feeling the lymph nodes and examining the skin for suspicious moles. In special situations, more extensive investigation is carried out.
What is the outlook?
One of the first things someone confronted with a diagnosis of melanoma wants to know is their survival chances. Predictions are difficult: every case of melanoma is different, and many factors can influence the prognosis. Survival depends strongly on whether the melanoma has already formed metastases.
If the melanoma has been completely removed and there are no metastases, the outlook is excellent. Unfortunately, it can never be said with certainty at the moment of removal that a melanoma has not spread: individual melanoma cells may already have detached from the original tumour and may over time form a new tumour elsewhere. These “micro-metastases” are often difficult or impossible to detect early in the follow-up period. Large studies show repeatedly that the chance of metastasis clearly increases as the original melanoma is thicker. In roughly 90–95% of patients with a melanoma thinner than 1 mm, the disease does not return; as the melanoma becomes thicker, the proportion of patients free of metastasis after 5 years gradually decreases. When metastases are present, the outlook becomes less favourable.
Preventing melanoma
Sensible sun exposure. The sun appears to play a role in the development of most melanomas. Repeated sunburn, especially before the age of five, increases the chance of later melanoma development. Protect the skin — and especially children’s skin — well against sunburn.
Self-examination. Melanoma of the skin is a special cancer because it can be noticed by the patient at an early stage. Regularly examining your own skin is therefore very important. If there are skin changes showing one or more of the warning signs mentioned above, do not hesitate — contact a doctor promptly.
When to see a doctor
Seek prompt assessment for any new or changing mole or skin growth — especially rapid growth, several colours, an irregular outline, thickening, itching, pain, bleeding, or a lesion that looks unlike your others. After a melanoma, report any change in the scar, a new lump or an unexplained persistent symptom without waiting for the next scheduled appointment.