Melanoma is a unique type of cancer normally arising in the skin arising from melanocytes. Melanocytes make a cell pigment melanin; this is present to protect the skin from ultraviolet damage. A melanoma may begin in a mole but can also begin in other pigmented tissues such as in the eye or the intestines.
Causes of melanoma
Repetitive scorching burning by sunshine/ultraviolet light particularly when suffered by fair skinned individuals in youth, is a predisposing factor for the development of melanoma. This explains why the disease is more common in Caucasian races living nearer the equator, and the lower incidences in black races. There are some data that suggest that ultraviolet dependent melanoma has a slightly better prognosis than other types. Studies from Western Canada and other regions of the world strongly suggest that intermittent burning exposure of unacclimatised Caucasian skin is a major risk factor for the development of melanoma.
Other predisposing factors are the dysplastic naevus syndrome, a familial condition of multiple congenital dysplastic naevi (‘moles’) and the cancer predisposition syndrome, the Li Fraumeni syndrome, which runs heavily in families and runs to multiple other primary cancers. There are three genes currently identified which influence melanoma risk. The majority of cases arise in patients with no obvious predisposing cause.
Malignant melanoma is a relatively uncommon cancer in the UK where it comprises only 1% of cancers and only 1200 deaths per year; however, there are some data to suggest that the incidence is rising. By contrast, the incidence in Queensland, Australia, where a Caucasian population are heavily exposed to sunlight, is 5 per 1,000 of the population indicating the breadth of incidence of this highly fatal cancer across the globe. Whilst the incidence of melanoma is highest in Australia, there is good evidence that the incidence in Europe and America is rising. In the European population, the increase in incidence has been linked to a greater opportunity for foreign travel and sunbathing holidays. This increased chance of taking holidays in the sun may in part explain why there is a higher incidence of the disease in higher social classes In America, the Surveillance, Epidemiology and End Results (SEER) study showed a steady increase in incidence of cutaneous melanoma at various latitudes, again reinforcing the sunshine exposure risk factor. The disease is more common in women by a factor of approximately twofold – in Europe and America (but not in Australia). Also, there is a tendency for melanoma to occur on the trunk in men and extremities in women; facial melanoma tends to be a disease of the elderly. Mucosal melanoma is relatively more common in dark skinned races, in whom the incidence of skin melanoma is less frequent.
Symptoms & diagnosis: Melanoma
The most characteristic feature associated with a melanoma is the black colour of the skin lesion. Whilst some malignant melanomas arise from benign naevi (‘moles’) the majority arise from normal skin. The development of a black skin lesion must never be ignored and the changes within a pre-existing skin lesion, particularly of its size, shape and colour should all alert the patient and doctors. The development of bleeding, crusting and a change in sensation or inflammation in a skin lesion merits further assessment.
A proportion of patients may present with signs or symptoms of disseminated melanoma. These may include the development of lymph nodes or skin nodules; pain from metastases, weight loss or neurological symptoms if there has been spread to the brain or spine.
There are several clinically recognised types of presentation: the first is the superficial spreading type of melanoma (up to 2/3 of cases) where a flat, coloured skin lesion progressively grows irregularly in the skin, typically on the limbs.
The nodular melanoma has more substance to it, is frequently faster growing and tends to be a rounder nodular skin lump, such nodular cases account for up to 20% of all cases.
The rarer types of melanoma are the lentigo maligna melanoma which is a very slow growing flat skin lesion growing on the face of typically elderly and female patients and the acral type which is found on the palms and soles and mucosal membranes and typically encountered in Asian and black peoples.
To determine if the abnormality is a melanoma, a small piece of the area (or if it is small, the entire area) is removed and examined under a microscope to determine if precancerous or cancerous cells are present.
The staging for melanoma will include assessing the local extent of the primary tumour, whether there is further spread to the local skin or lymph node areas and the presence of metastatic disease.
The extent of the primary melanoma in terms of depth of invasion at microscopic assessment has a significant impact on outcome. Patients with stage 1 disease have a 90% ten year survival, stage 2 has a 60% and stage 3 has a 30% ten year survival. Only five per cent of patients with stage 4 disease survive five years.
The assessment of lymph nodes spread can be undertaken by clinical examination and imaging investigations. CT scanning of the body would be offered to patients with a medium to high risk of metastases. Other imaging tests including a Chest x-ray, liver ultrasound may also be used to identify disease. PET scanning may be considered in selected cases. The assessment of urinary melanogen and a serum protein S100 remain poorly validated.
Thus the staging is based on the depth/thickness of invasion for stages 1-2 disease; the overall staging is thus:
Stage 1A. Localised: Less than 0.75mm depth
Stage 1B. Localised: 0.76-1.5 mm depth
Stage 2A. Localised: 1.5 – 4mm depth
Stage 2B. Localised: More than 4mm depth
Stage 3. Nodal metastases in the regional draining nodes
Stage 4. Metastatic disease to other organs
Treatment and outcomes: Melanoma
In most patients, surgery is required to remove (or excise) the entire tumour. Generally, one to two centimetres of normal skin surrounding the lesion must also be removed. Occasionally, skin grafting may be necessary to promote healing and replace skin that has been removed.
If an enlarged lymph node (or gland) is present, it may be biopsied at the time of the wide local excision. Even if enlarged lymph nodes cannot be detected, the lymph nodes may be evaluated during or after the surgical removal of the melanoma.
In the majority of cases, enlarged lymph nodes are not visible, and the only way to determine if they are affected is to take a sample of the lymph node during surgery. The sample is then examined under a microscope to determine if abnormal cells are present. This is typically accomplished with a surgical technique known as sentinel lymph node (SLN) biopsy.
The sentinel lymph node (SLN) technique is based upon the theory that when tumour cells migrate, they spread to one or a few lymph nodes before involving other nodes. Further, these nodes can be identified by injecting a blue dye or radioactive material around the primary tumour before the wide local excision, and then searching for the node that has taken up the dye or the radioactive tracer at the time of surgery.
SLN biopsy has become the standard technique for assessing the status of regional lymph nodes and is recommended for staging of most patients with newly diagnosed primary melanomas. However, patients whose melanomas are less than 1 mm in thickness (thin melanomas) may not require SLN, since the likelihood of tumour spread to the regional lymph nodes is less than 10 percent.
In contrast, SLN biopsy may be advised for thin melanomas with other high-risk features, such as ulceration, Clark’s level IV or V (the tumour has invaded deeper levels of the skin), or if there are significant areas of regression (spontaneous loss of tumour cells).
Based upon the pathologic disease stage, the optimal treatment is chosen. For patients with localized disease who have no evidence of distant metastases, the goals of treatment are:
- Complete surgical removal of the primary melanoma
- Evaluation of regional lymph nodes for evidence of tumour involvement
- Preventing further spread or disease recurrence
There are now data, not convincing to all but enough to have changed current, standard practice in the USA, to support the routine use of adjuvant alpha interferon (in high dosage and after surgery) for such high risk patients without metastatic disease to distant organs.
Alpha interferon adjuvant therapy in stage 2 and 3 disease is still under investigation, but at present it is the only
Treatment of advanced metastatic melanoma focuses on shrinking or eliminating the metastatic lesions, preventing further spread of the disease, and ensuring patient comfort. In most cases, it is not possible to completely eliminate the cancer. Depending on the location and extent of the metastases, treatment may involve the use of medical treatments (chemotherapy or immunotherapy), surgery, or radiation therapy.
Chemotherapy and immunotherapy treatments may be given alone or in combination. Most of these treatments must be given into a vein (intravenously) or injected under the skin, although a few can be given in pill form.
Each medication is given over a period of time, often several months or more, depending upon how the patient responds. Patients are monitored for signs of drug toxicity or side effects. Many side effects are temporary and can be managed so that patient discomfort is minimised.
The vast majority of early, thin (stage 1) melanomas are cured by the surgical excision described above. The prognosis for patients who have thicker tumours or who have relapsed is much more uncertain. The therapy of relapsed patients with melanoma remains a difficult task for the doctors as this tumour does not respond well to systemic therapy.
In patients who have not previously received chemotherapy, then the chemotherapeutic drugs mentioned above will be considered, sometimes together with immunotherapy agents such as interferon; other times immunotherapy will be tried alone. The vaccine programmes are a developing area for patients who have failed standard therapy but are yet to be validated and all such patients will be in clinical trials. For individual problems, other therapies may be indicated. For example, brain radiotherapy may be useful for brain metastatic spread and for single brain metastases in otherwise better performance status patients then surgical resection or stereotactic radiosurgical (see brain tumour section) approaches may be used before or in lieu of whole brain radiotherapy.
Similarly, radiotherapy may be useful for painful bone metastases and in occasional other palliative settings.
There is no formal screening programme but in Australia and other areas where the incidence is high, a very extensive public awareness programme is present which, through script and graphics, demonstrates to the population what to report immediately if found on the skin.
Melanoma: Recommended books
If you or a relative or friend is suffering from melanoma, you may find one of these books of interest
Select the book title for more information, and price details.
What You Really Need to Know About Moles and Melanoma Publisher – Johns Hopkins University Press The authors provide comprehensive information about melanoma for patients and family members, as well as those who are concerned about getting the…