Melanoma

Who Are Affected by Melanoma

Melanoma is the fourth most common major malignancy in Australia, and we have the world's highest incidence of any country in the world.

Melanoma is more commonly diagnosed in men than women. 1 in 17 Australians will get melanoma. This means in your life you will know several people who will be diagnosed with this disease. Anyone with a history of sun exposure can develop melanoma.

Unfortunately, 1 out of every 120 Australians will die from Skin Cancer, but survival has been improving. 

Melanoma Risk Factors

Everyone is at some risk for melanoma, but the increased risk depends on several factors including:

Moles - Irrespective of the mole type, the more moles you have, the greater your risk of melanoma.
People with large numbers of moles, especially unusual or unique looking moles (Dysplastic Naevi). 

• Congenital - the small brown blemishes, growths, or "beauty marks'' that appear in the first few years of life in almost everyone and - 
• Acquired moles arise up to the age of 40 and tend to go away (regress) after the age of 70
  

The nature of the moles on your body is also significant. Atypical moles, also known as Dysplastic Naevi, confer a higher risk. Atypical moles can be precursors to melanoma, and having them puts you at a much higher risk of melanoma. These are usually multiple and are uniquely different from each other in size, shape, colour, outline and so on. 
Some people with a large number of (>50) Dysplastic Naevi who have had one removed and confirmed to be either precancerous (Dysplastic) or melanoma, are considered to have Dysplastic Naevus Syndrome which confers an increased risk of melanoma in the order of 20-30 times.

Sun Exposure - Both UVA and UVB rays are dangerous to the skin and can induce skin cancer. Blistering sunburns in early childhood especially increases the risk, but sunburns later in life and cumulative exposure also may be factors. 

Skin Type - As with all skin cancers, people with fairer skin are at the highest risk. Common risk attributes like fair skin, freckles, blond or red hair, and blue, green, or grey eyes. They have a tendency to burn rather than tan.

Personal History - People who have had one melanoma are at risk of developing others, in the same area or elsewhere on the body. If you’ve had melanoma you have a 10 times higher risk of developing another skin cancer of any type and so routine reviews are advised on a 6 monthly basis.
In simple terms, every cancerous and precancerous skin lesion you’ve had numerically contributes to your risk of melanoma.

Compromised Immune System - Compromised immune systems as a result of chemotherapy, an organ transplant, excessive sun exposure, and diseases such as HIV/AIDS or lymphoma can increase your risk of melanoma.

Family History - Heredity plays a major role in melanoma. About one in every 10 patients diagnosed with the disease has a family member with a history of melanoma. If your mother, father, siblings or children have had a melanoma, you are in a melanoma-prone family. Each person with a first-degree relative diagnosed with melanoma has a 50 per cent higher chance of developing the disease than people who do not have a family history of the disease.
This is especially relevant where a close family member was diagnosed with melanoma under the age of 40.

Genetic Risk Factors - A DNA mutation in the BRAF gene can play a part in causing many melanomas. This mutated gene is found in about half of all melanomas. BRAF is called a "switch" gene, because mutations can turn it on abnormally, leading to uncontrolled cell growth and cancer.

What Causes Melanoma?

Melanoma risk increases with exposure to UV radiation, particularly with episodes of sunburn (especially during childhood). 95% of melanomas in Australia result from skin damage caused by:

• Cumulative long-term sun exposure 
• Intermittent overexposure to ultraviolet (UV) radiation from the sun (typically leading to sunburn) 

Most melanomas occur on parts of the body exposed to the sun — especially the face, ears, neck, scalp, shoulders, back, and back of the calves, but many can be found in areas that are only burned or exposed occasionally - such as the abdomen or upper thighs

It is not possible to pinpoint a precise, single cause for a specific tumour, especially tumours found on a sun-protected (rarely exposed) area of the body or in an extremely young individual. Some melanoma can also result from less common causes such as contact with arsenic. 

Symptoms of Melanoma? 

Melanoma may have no visible symptoms, however, it can be associated with observable changes in a mole. Other symptoms may include new and evolving dark areas under nails or on membranes lining the mouth, vagina, or anus.

As a general rule, to spot either melanomas or non-melanoma skin cancers (such as Basal Cell Carcinoma and Squamous Cell Carcinoma), take note of any new moles or growths, and any existing lesions that begin to grow or change noticeably.

If you observe two or more of the signs below, you should consult the Sydney Sarcoma Unit immediately.

Changing Mole - This could be size (gets larger or rarely smaller), shape (becomes irregular), colour (darkens, lightens, or becomes irregularly coloured), or the border becomes more irregular or less well defined

New Mole - The appearance of a new mole. Over 40 years of age this is a rare event and should prompt professional evaluation to rule out melanoma. 

Mole Appearance - Asymmetrical shape, irregularly bordered, multi-coloured or tan/brown spot or growth, a shiny bump or nodule that is often black/brown, pink, red, blue, or white. Especially one which is new, or has changed rapidly over just a few weeks or months

Open Sore - That bleeds, oozes, or crusts and remains open for a few weeks, only to heal up and then bleed again. A persistent, non­–healing sore is a worrying sign for melanoma especially if it occurs on a mole

Reddish Patch - An irritated area, which may develop a crust. It may itch or hurt. Mostly they are not tender and have no associated discomfort Pigment growing in a scar - any pigmented patch growing in a previous surgical or another scar, A scar-like area that is white, yellow or waxy, and often has poorly defined borders; the skin itself appears shiny and taut. This warning sign may indicate the presence of an invasive melanoma that is larger than it appears to be on the surface

Melanoma can sometimes resemble non-cancerous skin conditions such as psoriasis or eczema, the clue being that melanomas don’t seem to go away or respond like benign conditions often do Moles, brown spots and growths on the skin are usually harmless — but not always. 

Types of Melanoma

There are several types of melanoma and they vary in their appearance, characteristics, site, and natural history. Invasive melanomas are more serious, as they penetrate deeper into the skin and are more likely to spread to other areas of the body.

Superficial Spreading Melanoma - Also known as in-situ melanoma is by far the most common type, accounting for about 50 per cent of all cases. This is the one most often seen in young people up to 40-50yo. As the name suggests, this melanoma can grow along with the top layer of the skin for a long time in what is known as a radial growth phase. They may shift into a vertical growth phase and invade the skin and at this point are more likely to spread. The first sign is the appearance of a flat or slightly raised discoloured patch that has irregular borders and is somewhat asymmetrical in form. The colour varies, and you may see areas of tan, brown, black, red, blue or white. This type of melanoma can occur in a previously benign mole. This melanoma can be found almost anywhere on the body but is most likely to occur on the trunk in men, the legs in women, and the upper back in both.

Lentigo Maligna Melanoma - Is similar to the superficial spreading type, accounting for 10% of all cases. It also has a prolonged radial growth phase on the surface, and usually appears as a flat or mildly elevated mottled tan, brown or dark brown discolouration in the mask area of the face (near eyes, cheeks, forehead, nose). This type of in situ melanoma is found most often in the elderly, arising on chronically sun-exposed, damaged skin on the face, ears, arms and upper trunk. When this cancer becomes invasive, it is referred to as lentigo maligna melanoma.

Acral Lentiginous Melanoma - A unique as it usually appears as a black or brown discolouration under the nails (Subungual melanoma) or on the soles of the feet or palms of the hands. It accounts for around 5% of melanoma cases. This type of melanoma is sometimes found in dark-skinned people and may advance more rapidly than superficial spreading melanoma and lentigo maligna. It is the most common melanoma in African-Americans and Asians, and the least common among Caucasians.

Nodular Melanoma - The most aggressive of the more common types of melanoma and is usually invasive at the time it is first diagnosed. It is one of the most dangerous forms of human cancer and accounts for 15-20% of all cases. They are often distinguished by being Elevated, Firm, and Growing (EFG). They are usually black, but occasionally are blue, grey, white, brown, tan, red or even skin coloured. The most frequent locations are the trunk, legs, and arms, mainly of elderly people, as well as the scalp in men. 20% of nodular melanomas have very little to no pigment, making a history of change the most reliable feature in diagnosing these lesions. The more rapidly these lesions grow the more important early removal is to survival rates.

Desmoplastic Melanoma - A rare form of melanoma accounting for less than 1% of cases. It is a form of melanoma that is surrounded by fibrous tissue and may involve nerve fibres, when it does so it is called neurotropic melanoma. Desmoplastic melanoma is an aggressive form that needs to be considered whenever there is a lump (or nodule) that is growing on/in the skin, or when there is a change in a previously stable scar on the skin.

Uveal Melanoma - May arise from the melanocytes that give the eye its colour on the iris, or from the melanocytes in the retina at the back of the eye (choroidal melanoma). These lesions are very rare and account for less than 1% of cases. They can be very aggressive.

Mucosal Melanoma - This does not arise in the skin but instead arises from mucous membranes in areas such as the mouth, lips, sinuses, vagina, anorectal area, urethra, and so on. It is very rare accounting for less than 1% of cases, and there appears to be no link to UV exposure or to any of the other risk factors for melanoma, and these lesions are genetically distinct from other forms of melanoma.

They are often diagnosed at a late stage (for obvious reasons) and survival rates are generally quite low reflecting the delay in diagnosis.

Stages of Melanoma

Once the type of melanoma has been established, the next step is to classify the disease as to its degree of severity. 

The general stages of melanoma are:

• T - stands for the main (primary) tumour (its size, location, and how far it has spread within the skin and to nearby tissues).
• N - stands for spread to nearby lymph nodes (bean-sized collections of immune system cells, to which cancers often spread first).
• M - is for metastasis (spread to other parts of the body).

Clark Levels are useful when melanomas have penetrated less than 1mm, and for more invasive lesions we use TNM Staging. There are five Clark Levels:

• Level 1 - melanoma confined to the epidermis (in situ melanoma)
• Level 2 - Invasion into the papillary dermis
• Level 3 - Invasion to the junction of the papillary and reticular dermis
• Level 4 - Invasion into the reticular dermis
• Level 5 - Invasion into the subcutaneous fat

Some melanomas are aggressive and can grow and spread (metastasise) quickly. If melanoma is advanced the outcome (prognosis) can vary and affect your treatment choices. More advanced melanomas (Stages III and IV) have spread (metastasized) to other parts of the body. There are also subdivisions within stages.

Stage III Melanoma

By the time a melanoma advances to Stage III or beyond, an important change has occurred. At this point, the tumour has either spread to the lymph nodes or to the skin between the primary tumour and the nearby lymph nodes. (All tissues are bathed in lymph — a colourless, watery fluid consisting mainly of white blood cells — which drains into lymphatic vessels and lymph nodes throughout the body, potentially carrying cancer cells to distant organs).

Stage IV Melanoma

The melanoma has metastasized to lymph nodes distant from the primary tumour or to internal organs, most often the lung, followed in descending order of frequency by the liver, brain, bone, and gastrointestinal tract.

The two main factors in determining how advanced the melanoma is into Stage IV (the “M” category, for “metastases”) are the site of the distant metastases (non-visceral, lung, or any other visceral metastatic sites) and elevated serum lactate dehydrogenase (LDH) level.

Lymph Node Involvement

Once melanoma has progressed beyond Stage II, it has spread beyond the original site. It is most likely to have reached the lymph nodes that are closest to the tumour.

An enlarged lymph node may instead be surgically removed and sent to the pathology laboratory to be tested microscopically for the presence of malignant cells. If any are found, the rest of the nodes in that basin will also be removed, and treatments that stimulate the immune system and/or therapies directly targeting the melanoma may be recommended.

Lymphoscintigraphy (Mapping) & Sentinel Node Biopsy - Lymphoscintigraphy is a technique for mapping the lymphatic pathway to track whether melanoma cells have metastasized from the primary melanoma tumour to the local lymph nodes. A small amount of a harmless radioactive substance is injected at the site of the melanoma to trace the flow of lymph fluid draining from it to the nodes. Then, with the help of a scanner, the drainage pattern of the lymph fluid is determined.

Most often, a second lymphatic mapping technique is then also used to increase certainty: Blue dye is injected into the skin around the tumour, and the dye passes into the lymph fluid, tracing its path. The blue colour is picked up first by the node closest to the tumour, which is referred to as the sentinel node. Sometimes there are one or more other sentinel nodes as well, which should also show up in the dye and radioactive tracer tests. Armed with the findings from this lymphatic mapping, the surgeon can at first remove only the sentinel nodes.

Once a specific area (basin) of lymph drainage has been pinpointed by the dye or tracer, the sentinel node(s) can be removed surgically and tested in the pathology laboratory, the premise being that if any melanoma cells reach the local nodal basin, they will show up in the sentinel node(s). If no cancer cells are found in the sentinel nodes, no further surgery is performed. If cancer cells are present in the sentinel nodes, the rest of the nodes in this lymphatic basin will also usually be removed and examined. Once melanoma cells are confirmed in the lymph nodes, the patient is reclassified as Stage III.

Local vs Distant Spread

Once the disease has advanced to Stage IV, melanoma cells have travelled through the body via the bloodstream or lymph vessels, going far from the original tumour site. They may have reached distant lymph nodes or invaded the internal organs. This can be in addition to or instead of in-transit metastases or local spread to the regional lymph nodes. In local forms of the disease, the metastases can reach skin or subcutaneous tissue more than 2 cm from the primary tumour, but not beyond the regional lymph nodes.

When distant metastases are suspected, they can be traced by scans of the chest, head, abdomen, and pelvis with a CT (computed tomography) scan in which special X-ray equipment and a computer program show a cross-section of body tissues or organs; an MRI (magnetic resonance imaging) scan that uses a magnet instead of X rays to create a map of the patient’s body and brain; and by PET (positron emission tomography), an evolving radiographic technique. 

For PET scanning, radioactive sugar, the basic carbohydrate utilized by the body for energy, is injected intravenously into the patient. This sugar is preferentially taken up by any melanoma cells than surrounding normal tissues.

Melanoma Diagnosis

An excision biopsy is generally required to confirm the diagnosis and to guide effective treatment. This diagnostic process involves a Doctor taking a tissue sample for biopsy by removing the lesion surgically under local anaesthetic to a margin of 2mm and sending it for histopathological evaluation.

An excision biopsy is sufficient to establish the diagnosis of melanoma. In the rare case of suspected metastatic melanoma, lymph nodes may be examined by the Doctor to see if cancer has spread or by the use of imaging technologies like ultrasound, CT, or PET scanning.

Surgical Removal for Melanoma

Surgical removal of melanoma is the most common treatment. Melanomas are almost always surgically removed under local anaesthetic. This approach offers:

• High cure rates
• Is immediate
• Margins are checked to confirm complete removal
• The presence of any invasive component can be accurately assessed guiding further treatment

In more advanced skin cancers, some of the surrounding tissue may also be removed to make sure that all of the cancerous cells are cleared.

Excision Treatment Process

After careful administration of local anaesthetic, the surgeon:

• uses a scalpel to remove the entire growth, along with surrounding apparently normal skin as a safety margin.
• The wound around the surgical site is then closed with sutures (stitches).

Excision Treatment Recovery -

• Scarring is usually quite acceptable. Pain or discomfort is usually minor.
• For a few days post excision there may be minor bruising and swelling.
• Typically, where sutures are used, they are removed soon afterwards.

Wide-Area Local Excision

A second excision is usually performed on the site after the melanoma has been diagnosed on excisional biopsy.

The desired safety margins are determined by the type of melanoma to be between 5 mm and 20mm based on the level of invasion and a second excision known as a wide-area local excision is performed to achieve this amount of safety margin around the melanoma excision site. In cases of superficial spreading melanoma, the desired margin is 5 mm to the side and deep, and highly invasive melanomas may require up to 20mm margins to the side and deep to reach the lowest risk of spread or local recurrence.

General Prognosis After Melanoma Treatment

The most important factor in melanoma survival is early diagnosis and treatment. An individual’s prognosis depends on the type and stage of cancer, as well as their age and general health at the time of diagnosis. The 5-year survival rate is 90%, and when treated early the majority of melanomas are curable.

If the spread is within the region of the primary melanoma (i.e. to local lymph nodes or to the skin in the local area), the five-year survival is 65%, dropping to 15% if the disease is widespread and goes untreated.

What if a Melanoma is Untreated

Melanomas can spread to vital organs but respond well to early treatment. If untreated the consequences could include:

• Disfigurement
• Nerve, or muscle injury, or other injuries to nearby unique structures like eyelids from the melanoma itself or its required treatment
• They are most likely to be lethal in almost all cases if untreated.

The larger the tumour has grown, the more extensive any surgical or adjuvant treatment would be and the associated risks would also increase.