What Is Melanoma?

Who Gets Melanoma?

Australia and New Zealand have the highest reported incidence and mortality of melanoma globally.

About 1 in 15-18 white-skinned Australians and New Zealanders are expected to develop melanoma in their lifetime.

Melanoma is the third most common cancer in Australia and New Zealand.

In 2019, there were 2,727 melanoma registrations in New Zealand. There were 362 deaths from melanoma in 2016.

Melanoma can occur in adults of any age but is very rare in children.

According to the Australian Institute of Health and Welfare, in 2021:

• 7.9% of people diagnosed with melanoma were aged under 40 years
• 10.7% were aged 40-49
• 17.8% were aged 50-59
• 23.9% were aged 60-69
• 23.7% were aged 70-79
• 16% were aged 80 or older.

The mean age for melanoma diagnosis is 65.7 years among men and 62.4 years among women.

Melanoma is the most common cancer diagnosed in young Australians aged 15–29 years, accounting for 15% of all cancers in this age group.

The main risk factors for developing the more common type of melanoma (eg, superficial spreading melanoma) include:

• Increasing age
• Previous invasive melanoma or melanoma in situ
• Previous basal cell or squamous cell carcinoma
• Many melanocytic naevi (moles)
• Multiple (>5) atypical naevi (large or histologically dysplastic moles)
• A strong family history of melanoma with two or more first-degree relatives affected
• White/fair skin
• Parkinson disease
• UV exposure
• History of sunburn
• Weakened immune system or cancer-prone syndromes.

These risk factors are not as relevant to rarer types of melanoma.

Although the presence of a large number of common nevi is a strong risk factor for cutaneous melanoma, the majority of melanomas arise de novo. A 2017 meta-analysis of 38 studies including over 20,000 melanomas found that only 29 percent were nevus-associated, with the rest arising de novo.

What Causes Melanoma?

Melanoma is thought to begin as an uncontrolled proliferation of melanin-producing cells (melanocytic stem cells) that have undergone a genetic transformation.

The cause of these cell mutations can be acquired or inherited.

• Acquired 'sporadic' mutations are the most common cause of cancer. They occur from damage to a cell during a person's life. The most common cause of melanoma is overexposure to UV radiation, eg, sun exposure, sunbed use.
• Germline 'inherited' mutations are passed down from the parent. Inherited (familial) melanoma is far less common (<10%). CDKN2A (also called p16INK4A or MTS1) is the gene primarily linked in up to 20–40% of familial melanomas. However, in recent years, a growing number of other genes have been implicated, including CDK4, MC1R, MITF, TERT, ACD, BAP1, POT1, and TERF2IP.

Cutaneous melanoma can arise from otherwise normal-appearing skin (in about 75% of melanomas) or from within a pre-existing mole or freckle, which starts to grow larger and change in appearance.

Precursor lesions include:

• Benign melanocytic naevus (normal mole)
• Atypical or dysplastic naevus (unusual-looking mole)
• Atypical lentiginous junctional naevus (flat naevus in heavily sun-damaged skin) or atypical solar lentigo
• Large or giant-sized congenital melanocytic naevus (brown birthmark).

Melanomas have two growth phases, radial and vertical.

Most melanomas arise as superficial tumours confined to the epidermis (ie, they have a horizontal growth phase; in situ). These generally grow slowly, but at any time, further genetic changes may cause the tumour to progress to the vertical growth phase, in which the malignant cells breach the basement membrane, invading deeper tissues, resulting in invasive melanoma.

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 bloodstream 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 the skin.

What are the Clinical Features of Melanoma?

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 in men), and the most common site in women is the leg (around 35% of melanomas in women).

Although melanoma usually starts as a skin lesion, it can also grow on mucous membranes (mucosal melanoma), 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 and may itch or bleed. Melanomas may grow across the skin (known as the radial growth phase) or grow in depth (known as the vertical growth phase).

Melanoma may be detected at an early stage when it is only a few millimetres in diameter, but it may grow to several centimetres in diameter before it is 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, raised, and palpable.

Some melanomas are itchy or tender. More advanced lesions may bleed easily or crust over.

Most melanomas have characteristics described by the ABCDE+EFG melanoma criteria or the Glasgow 7-point checklist.

Taking a thorough history is important, and any lesion that changes in size, shape, colour, or elevation for more than one month should be reviewed by a specialist or biopsied.

Glasgow 7 Point Checklist

Major features

• Change in size
• Irregular shape
• Irregular colour

Minor features

• Diameter >7 mm
• Inflammation
• Oozing
• Change in sensation

How do Clinical Features vary in different types of Skin?

White or pale skin colour is an independent but significant risk factor for melanoma across diverse ethnic groups. However, people of all skin colours with a family history of melanoma are at increased risk of developing melanoma due to a genetic predisposition.

In skin of colour, it can be harder to identify melanomas, their growth phase, and their pattern as the surrounding skin may mask or match the colour of the melanoma.

People with skin of colour tend to have:

• Thicker melanomas at diagnosis and higher mortality rates
• Significantly higher rates of melanomas in areas not exposed to the sun, including the subungual, palmar, and plantar surfaces (eg, acral lentiginous melanoma in Pacific Islanders, blacks, and Asians)
• Non-cutaneous melanomas (eg, mucosal melanoma, ocular melanoma).

What are the complications of Melanoma?

• Metastasis and related systemic effects
• Side effects from systemic or radiation therapy
• Death



Complications due to surgery:

• Wound infection
• Inability to close
• Dehiscence
• Skin necrosis
• Incomplete resection
• Seromas, lymphoedema, and lymphoceles with node dissection.

How is Melanoma Diagnosed?

Melanoma may be suspected because of a lesion's clinical features or a history of change.

A thorough history and skin examination will be performed using the "ugly duckling" sign, ABCDE rule, and the Glasgow revised seven-point checklist (described above).

This may be supported by dermoscopy, confocal microscopy, total body photography (mole mapping), and adhesive patch genomic analysis, among other methods.

• Dermoscopy — Some melanomas are extremely difficult to recognise clinically. The dermatoscopic appearance is helpful in the diagnosis of melanoma. Melanoma-specific criteria often include an atypical pigment network; brown-black dots/globules; multiple (5–6) colours asymmetrically distributed; blue-white veil; depigmentation; and irregular vascular pattern. Dermoscopy monitoring should only be considered for flat or slightly raised lesions, whereas any suspicious or nodular lesions should be excised.
• Confocal Microscopy — Where available, reflectance confocal microscopy (RCM) may be useful for clinical and dermoscopic examination of suspected melanoma lesions. RCM is a live imaging technology that allows for instant viewing of the epidermis and papillary dermis with nearly histologic resolution. Areas of higher melanin concentration appear as bright areas on a confocal image. This technology is especially useful for identifying amelanotic or hypomelanotic melanomas, mapping surgical margins pre-operatively, and monitoring lesions over time.
• Photographic skin surveillance — Where available, total body photography (TBP), eg, MoleMap, should be considered for high-risk individuals, particularly those with high naevus counts and dysplastic naevi. TBP provides a baseline for monitoring new lesions and changes in pre-existing naevi. While not all changed lesions need to be excised, if there is clinical or dermoscopic evidence for melanoma at any point, excision is recommended.
• Radiographic investigations — Imaging, such as CT or PET, may be appropriate for staging or surveillance of melanomas that are at significant risk for distant metastases.
• Adhesive patch genomic analysis — skin surface tape stripping is a non-invasive test that can be used on pigmented lesions to obtain their genomic signature. It can be used to assist in the diagnosis of melanoma.

How Do You Prevent Melanoma?

Preventative measures involve addressing risk factors such as:

• exposure to UV radiation
• wearing protective clothing
• using sunscreen (SPF 50)
• avoiding tanning beds.