Malignant melanoma is a potentially serious type of skin cancer. It is due to uncontrolled growth of pigment cells, called melanocytes.
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.
Who is at risk of 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:
- Fewer than 1% occurred in those under 20 years
- 13% occurred in people 20 to 40 years
- 36% in those aged 40 to 59 years
- 51% in those aged over 60 years
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:
- Increasing age (see above)
- Previous invasive melanoma or melanoma in situ
- Previous keratinocytic skin cancer
- Many melanocytic naevi (moles)
- Multiple (>5) atypical naevi (funny-looking moles or moles that are histologically dysplastic)
- Strong family history of melanoma with 2 or more first-degree relatives affected
- Fair skin that burns easily
However these risk factors are not important for the less common types of melanoma.
How does a melanoma grow?
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.
Where do you find melanomas?
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:
- Benign melanocytic naevus (normal mole)
- Atypical or dysplastic naevus (funny-looking mole)
- Atypical lentiginous junctional naevus (freckle in heavily sun damaged skin)
- Congenital melanocytic naevus (brown birthmark)
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.
What does a melanoma look like?
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|
Diameter over 6 mm
Evolving (enlarging, changing)
Types of melanoma
Melanomas are described according to their appearance and behaviour. Those that start off as flat patches (i.e. have a horizontal growth phase) include:
- Superficial spreading melanoma (SSM)
- Lentigo maligna melanoma (sun damaged skin of face, scalp and neck), and lentiginous melanoma (on trunk and proximal limbs)
- Acral lentiginous melanoma (on soles of feet, palms of hands or under the nails – the subungual melanoma)
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:
- Nodular melanoma (presenting as a rapidly enlarging lump)
- Spitzoid melanoma (a nodule that resembles a Spitz naevus)
- Mucosal melanoma (arising on lips, eyelids, vulva, penis, anus)
- Neurotropic and desmoplastic melanoma (fibrous tumour with a tendency to grow down nerves)
- Ocular melanoma
Melanoma is also classified according to its relationship with sun exposure, age and number of melanocytic naevi.
Childhood melanomas (below 10 years of age):
- Are extremely rare
- Are less frequently associated with excessive sun exposure
- More often amelanotic (flesh coloured, pink or red), nodular, bleeding and ulcerated compared to melanoma in adults
- May arise within giant congenital melanocytic naevi > 40 cm diameter
- More common in women
- Most common clinical subtype is superficial spreading
- Associated with many melanocytic naevi
- Tend to be seen on lower extremity
- Tends to have BRAFV600E genetic mutation
- Associated with intermittent sun exposure
- More common in men
- Most common clinical subtype is lentigo maligna
- Often occur on head and neck
- Associated with accumulated, lifelong sun exposure
Melanoma is usually epithelial in origin, i.e. starting in the skin, or, less often, mucous membranes. But very rarely, melanoma can start in an internal tissue such as the brain (primary CNS melanoma) or the back of the eye (see ocular melanoma).
SSMM with regression
Lentigo maligna melanoma
Nodular melanoma in lentigo maligna
More images of lentigo maligna melanoma...
Acral lentiginous melanoma
© Dr Ph Abimelec – dermatologue
Amelanotic subungual melanoma
Black nodular melanoma
Amelanotic nodular melanoma
Ulcerated nodular melanoma
Diagnosis of melanoma
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.
- Diagnosis of primary melanoma
- Breslow thickness to the nearest 0.1 mm
- Clark level of invasion
- Margins of excision i.e. the normal tissue around the tumour
- Mitotic rate – a measure of how fast the cells are proliferating
- Whether or not there is ulceration
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).
What is the Clark level of invasion?
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.
Treatment of melanoma
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 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|
Should the lymph nodes be removed?
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, including topical and intralesional immunotherapy for melanoma metastases; and biologics such as ipilimumab, BRAF inhibitors such as dabrafenib and vemurafenib, and MEK inhibitors such as trametinib are showing promise.
What happens at follow-up?
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.
- Self skin examination
- Regular routine skin checks by patient's preferred health professional
- Follow-up intervals are preferably six-monthly for five years for patients with stage 1 disease, three-monthly or four-monthly for five years for patients with stage 2 or 3 disease, and yearly thereafter for all patients.
- Individual patient’s needs should be considered before appropriate follow-up is offered
- Provide education and support to help patient adjust to their illness
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:
- A check of the scar where the primary melanoma was removed
- A feel for the regional lymph nodes
- A general skin examination
- A full physical examination
- In those with many moles or atypical moles, baseline whole body imaging and sequential macro and dermoscopic images of melanocytic lesions of concern ( mole mapping)
In those with more advanced primary disease, follow-up may include:
- Blood tests, including LDH
- Imaging: ultrasound, X-ray, CT, MRI and/or PET scan.
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.
What is the outlook for patients with melanoma?
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.
- Clinical practice guidelines for the management of melanoma in Australia and New Zealand
- Anderson WF, Pfeiffer RM, Tucker MA, Rosenberg PS. Divergent cancer pathways for early-onset and late-onset cutaneous malignant melanoma. Cancer. 2009 Sep 15;115(18):4176-85. doi: 10.1002/cncr.24481. PubMed PMID: 19536874; PubMed Central PMCID: PMC2741537.
- Revised U.K. guidelines for the management of cutaneous melanoma 2010. JR Marsden, JA Newton-Bishop, L Burrows, M Cook, PG Corrie, NH Cox, ME Gore, P Lorigan, R MacKie, P Nathan, H Peach, B Powell, C Walker, BJD, Vol. 163, No. 2, August 2010 (p238-256)
- The prevention, diagnosis, referral and management of melanoma of the skin: concise guidelines (Newton Bishop J, Bataille V, Gavin A, Lens M, Marsden J, Mathews T, Ormerod A, Wheelhouse C). Royal College of Physicians and British Association of Dermatologists. Concise guidance to good practice series, No 7. London : RCP, September 2007
- Richardson et al. The incidence and thickness of cutaneous malignant melanoma in New Zealand 1994–2004. NZ Med J 2008;121:1279
- Ministry of Health. 2011. Cancer: New registrations and deaths 2008. Wellington: Ministry of Health
- Balch CM et al. Final Version of 2009 AJCC Melanoma Staging and Classification. J Clin Oncol 27:6199-6206. PDF file
On DermNet NZ:
- Melanoma – pathology
- Superficial spreading melanoma
- Lentigo maligna
- Lentiginous melanoma
- Nodular melanoma
- Acral lentiginous melanoma
- Subungual melanoma
- Desmoplastic melanoma
- Childhood melanoma
- Ocular melanoma
- Genetics of melanoma
- Genes and melanoma – the simple version
- Mucosal melanoma
- Spitzoid melanoma
- Metastatic melanoma
- Immunotherapy of melanoma
- Topical and intralesional immunotherapy for melanoma metastases
- Your Personal Melanoma Diary – Enhancing Melanoma Survivorship. Australian resource provided to dermnetnz.info by Dr Martin Haskett.
- Atypical naevi
- Mole mapping
- Basal cell carcinoma
- Squamous cell carcinoma
- Sun protection
- Skin self examination
- Sentinel node biopsy
- Melanoma – common skin lesions course
- Superficial spreading melanoma
- Melanoma in situ
- Lentigo maligna melanoma
- Acral lentiginous melanoma
- Subungual melanoma
- Nodular melanoma
- Metastases and rare forms of melanoma
Other web sites:
- Melanoma Foundation of New Zealand
- Melnet: the Melanoma Network of NZ
- Melanoma Research Institute of New Zealand
- Revised U.K. guidelines for the management of cutaneous melanoma 2010 – British Association of Dermatologists, PDF file
- Melanoma – Medline Plus
- Cancer Society of New Zealand
- SkinCancerNet – American Academy of Dermatology
- Melanoma Patients' Information Page
- Melanoma International Foundation and Forum
- Malignant melanoma – Medscape Reference
- Melanoma – Stage 1 – British Association of Dermatologists
- Melanome – Dr Ph Abimelec website (French)
- Melanoma Outcome Calculator – Laboratory for Quantitative Medicine at Massachusetts General Hospital
- Victorian Melanoma Service Melanoma Risk Calculator
- Individualised melanoma patient outcome prediction tools based on AJCC v7
- Patient information: Melanoma skin cancer (The Basics) – UpToDate (for subscribers)
- Patient information: Melanoma treatment; advanced or metastatic melanoma (Beyond the Basics) – UpToDate (for subscribers)
- Patient information: Melanoma treatment; localized melanoma (Beyond the Basics) – UpToDate (for subscribers)