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Malignant melanoma is a potentially serious type of skin cancer. It is due to uncontrolled growth of pigment cells, called melanocytes.
New Clinical Guidelines on the Management of Melanoma in Australia and New Zealand have been released by the New Zealand Guidelines Group and the Australian Cancer Network. Please refer to these for up to date information on the care of patients with this disease.
Normal melanocytes are found in the basal layer of the epidermis, i.e. the bottom part of the outer layer of the skin. The melanocytes produce a protein called melanin, which protects the skin by absorbing ultraviolet (UV) radiation. Melanocytes are found in equal numbers in black and in white skin, but the melanocytes in black skin produce much more melanin. People with dark brown or black skin are very much less likely to be damaged by UV radiation than those with white skin.
Non-cancerous growth of melanocytes results in moles (properly called benign melanocytic naevi) and freckles (ephelides and lentigines). Cancerous growth of melanocytes results in melanoma.
Melanoma is most common in white skinned individuals, but it may rarely develop in those with dark skin as well. About one in fifteen white skinned New Zealanders are expected to develop melanoma in their lifetime – Australia and New Zealand have the highest reported rates of melanoma in the world. It was the third most common cancer in New Zealand in 2008.
Melanoma can occur in adults of any age but is very rare in children. In New Zealand in 2003:
According to New Zealand Cancer Registry data, 2256 invasive melanomas were diagnosed in 2008; 48% were in males. There were 371 deaths from all types of melanoma in 2008 (69% were male).
The main risk factors for developing the most common type of melanoma (superficial spreading melanoma) include:
However these risk factors are not important for the less common types of melanoma.
Cancers proliferate at an uncontrolled rate because of abnormalities in the genes that control cell growth. Further genetic changes promote invasion into surrounding tissue. Melanoma is now thought to begin as uncontrolled proliferation of transformed melanocytic stem cells.
Superficial forms of melanoma spread out within the outside layer of skin (the epidermis). A pathologist may report this as the radial or horizontal growth phase. If all the melanoma cells are confined to the epidermis, it is melanoma in situ. Lentigo maligna is a special kind of melanoma in situ that occurs around hair follicles on the sun damaged skin of the face or neck. Melanoma in situ is always cured by excision because it has no potential to spread round the body.
When the cancerous cells have grown through the basement membrane into the deeper layer of the skin (the dermis), it is known as invasive melanoma. The pathologist may state that the tumour has a vertical growth phase, which is potentially more dangerous than the horizontal growth phase. Nodular melanoma appears to be invasive from the beginning, and has little or no relationship to sun exposure.
Once the melanoma cells have reached the dermis, they may spread to other tissues via the lymphatic system to the local lymph nodes or via the blood stream to other organs such as the lungs or brain. This is known as metastatic disease or secondary spread. The chance of this happening mainly depends on how deep the cells have penetrated into the skin. So early detection of melanoma is vital.
Melanoma can arise from otherwise normal appearing skin (75% of melanomas) or from within a mole or freckle, which starts to grow larger and change in appearance. Precursor lesions include:
Melanomas can occur anywhere on the body, not only in areas that get a lot of sun. In New Zealand, the most common site in men is the back (around 40% of melanomas), and the most common site in women is the leg (also around 40%).
Although melanoma usually starts as a skin lesion, it can also rarely grow on mucous membranes such as the lips or genitals. Occasionally it occurs in other parts of the body such as the eye, brain, mouth or vagina.
The first sign of a melanoma is usually an unusual looking freckle or mole. A melanoma may be detected at an early stage when it is only a few millimetres in diameter, but they may grow to several centimetres in diameter before they are diagnosed.
A melanoma may have a variety of colours including tan, dark brown, black, blue, red and, occasionally, light grey. Melanomas that are lacking pigment are called amelanotic melanoma. There may be areas of regression that are the colour of normal skin, or white and scarred.
During its horizontal phase of growth, a melanoma is normally flat. As the vertical phase develops, the melanoma becomes thickened and raised.
Some melanomas are itchy or tender. More advanced lesions may bleed easily or crust over.
A pigmented lesion (mole or freckle) should be checked by an experienced doctor if it has any of the characteristics described by the Glasgow 7-point checklist or by the ABCDE's of melanoma. Not all such lesions prove to be malignant. Not all melanomas show these characteristics.
| Major features | Minor features |
|---|---|
| Change in size | Diameter >7mm |
| Irregular shape | Inflammation |
| Irregular color | Oozing |
| Change in sensation |
A
B
C
D
E Asymmetry
Border irregularity
Colour variation
Diameter over 6 mm
Evolving (enlarging, changing)
Melanomas are described according to their appearance and behaviour. Those that start off as flat patches (i.e. have a horizontal growth phase) include:
These superficial forms of melanoma tend to grow slowly, but at any time, they may begin to thicken up or develop a nodule (i.e. progress to a vertical growth phase).
Melanomas that quickly involve deeper tissues include:
Combinations may arise e.g. nodular melanoma arising within a superficial spreading melanoma or desmoplastic melanoma arising within a lentigo maligna.
Melanoma may be suspected because of the history of change (if known) or the appearance of the skin lesion. The dermoscopic appearance is particularly helpful in the diagnosis of early melanoma. Dermoscopy requires special training. Dermoscopy is not necessary if the lesion has the typical clinical appearance of melanoma.
A suspected melanoma should be surgically removed with a 2 to 3-mm margin (excision biopsy) and sent to a pathology laboratory for examination under a microscope (histology). A small biopsy is best avoided, except in unusually large lesions. An incisional or punch biopsy could be misleading.
The pathological diagnosis of melanoma can be very difficult. Histological features of superficial spreading melanoma in situ include the presence of buckshot (pagetoid) scatter of atypical melanocytes within the epidermis. These cells may be enlarged with unusual nuclei. Dermal invasion results in melanoma cells within the dermis or deeper into subcutaneous fat.
Extra tests using immunohistochemical stains may be necessary.
The pathologist's report should include a macroscopic description of the specimen and melanoma (the naked eye view), and a microscopic description. The following features should be reported if there is invasive melanoma.
The report may also include comments about the cell type and its growth pattern, invasion of blood vessels or nerves, inflammatory response, regression and whether there is associated in-situ disease and/or associated naevus (original mole).
The Breslow thickness is reported for invasive melanomas. It is measured vertically in millimetres from the top of the granular layer (or base of superficial ulceration) to the deepest point of tumour involvement. It is a strong predictor of outcome; the thicker the melanoma, the more likely it is to metastasise (spread).
The Clark level indicates the anatomic plane of invasion.
| Level 1 | In situ melanoma |
| Level 2 | Melanoma has invaded papillary dermis |
| Level 3 | Melanoma has filled papillary dermis |
| Level 4 | Melanoma has invaded reticular dermis |
| Level 5 | Melanoma has invaded subcutaneous tissue |
The deeper the Clark level, the greater the risk of metastasis (secondary spread). It is useful in predicting outcome in thin tumours, and less useful for thicker ones in comparison to the value of the Breslow thickness.
Melanomas are removed surgically. The extent of surgery depends on the thickness of the melanoma and its site. Most thin melanomas do not need extensive surgery. The lesion is removed using a local anaesthetic, and the defect stitched up. A small area of normal skin around the melanoma is also excised to make sure that all the melanoma cells have been removed. Often this is done as a second procedure (re-excision) when the pathology has confirmed melanoma.
For thicker melanomas (those over 1 mm or so in thickness), a much wider area of skin is cut out. A skin graft might be necessary, which replaces the removed skin with skin taken from another part of the body.
Melanoma staging means finding out if the melanoma has spread from its original site in the skin. Most melanoma specialists refer to the American Joint Committee on Cancer (AJCC) cutaneous melanoma staging guidelines (2009). In essence, the stages are:
| Stage | Characteristics |
|---|---|
| Stage 0 | In situ melanoma |
| Stage 1 | Thin melanoma < 2 mm in thickness |
| Stage 2 | Thick melanoma > 2 mm in thickness |
| Stage 3 | Melanoma spread to involve local lymph nodes |
| Stage 4 | Distant metastases have been detected |
If the local lymph nodes are enlarged due to metastatic melanoma, they should be completely removed. This requires a surgical procedure, usually under general anaesthetic. If they are not enlarged, they may be tested to see if there is any microscopic spread of melanoma. The test is known as a sentinel node biopsy.
In New Zealand, many surgeons recommend sentinel node biopsy for melanomas thicker than 1 mm, especially in younger persons. However, although the biopsy may help in staging the cancer, it does not offer any survival advantage. The necessity for sentinel node biopsy is controversial at present.
Lymph nodes containing metastatic melanoma often increase in size quickly. An involved node is usually non-tender and firm to hard in consistency. If this occurs between planned follow-up visits, let your doctor know promptly.
If the melanoma is widespread, other forms of treatment may be necessary, but are not always successful in eradicating the cancer. Immunotherapy and biologics such as ipilimumab and vemurafenib are showing promise.
The main purpose of follow-up is to detect recurrences early but it also offers an opportunity to diagnose a new primary melanoma at the first possible opportunity. A second invasive melanoma occurs in 5-10% patients; an unrelated melanoma in situ affects in more than 20% of melanoma patients.
The Australian and New Zealand Guidelines for the Management of Melanoma (2008) make the following recommendations for follow-up for patients with invasive melanoma.
The follow-up appointments may be undertaken by the patient's general practitioner or specialist or they may be shared.
Follow-up appointments may include:
In those with more advanced primary disease, follow-up may include:
Tests are not typically worthwhile for stage 1/2 melanoma patients unless there are signs or symptoms of disease recurrence or metastasis. And no tests are thought necessary for healthy patients who have remained well for 5 years or longer after removal of their melanoma, whatever stage.
Melanoma in situ is not dangerous; it only becomes potentially life threatening if an invasive melanoma develops within it. The rates of melanoma in situ are not reported by cancer registries. The risk of spread and ultimate death from invasive melanoma depends on several factors, but the main one is the measured thickness of the melanoma at the time it was surgically removed.
The Melanoma Guidelines report that metastases are rare for melanomas < 0.75mm and the risk for tumours 0.75–1 mm thick is about 5%. The risk steadily increases with thickness so that melanomas >4 mm have a risk of metastasis of about 40%.
New Zealand statistics gathered by the Cancer Registry between 1994 and 2004 revealed 15,839 invasive melanomas. Of these, 52% were under 0.75 mm in thickness, 22% were between 0.76 and 1.49 mm, 15% were between 1.5 and 3 mm in thickness and 11% were more than 3 mm in thickness. Thicker tumours were slightly more likely to be diagnosed in males, and more likely in older people than younger ones.
