Melanoma

Melanoma is a malignant tumor of melanocytes. Melanocytes predominantly occur in the skin but can be found elsewhere, especially the eye. The vast majority of melanomas originate in the skin. Melanomas are the most lethal form of skin cancer. Early detection and treatment is associated with a good prognosis. Late detection can lead to a grim prognosis.

Contents
1 Causes
2 Prevention
2.1 Primary
3 Diagnosis
4 Types of Primary Melanoma
5 Prognostic factors
6 Staging
7 Treatment
7.1 Surgery 
 
Causes
Epidemiologic studies from Australia suggest that exposure to ultraviolet radiation is one of the major contributors to the development of melanoma. Few dermatologists question the association between sunlight and melanoma. It is widely believed that occasional extreme sun exposure (resulting in "sunburn") is causally related to melanoma. Those with more chronic long term exposure (outdoor workers) may develop protective mechanisms. Melanoma is most common on the back in men and on legs in women (areas of intermittent sun exposure) and is more common in indoor workers than outdoor workers (in a British study). Other factors are mutations in or total loss of tumor suppressor genes. Use of sunbeds (with deeply penetrating UVA rays) has been linked to the development of skin cancers, including melanoma.

Possible significant elements in determining risk include the intensity and duration of sun exposure, the age at which sun exposure occurs, and the degree of skin pigmentation.

Exposure during childhood is a more important risk factor than exposure in adulthood. This is seen in migration studies in Australia where people tend to retain the risk profile of their country of birth if they migrate to Australia as an adult.

Fair and red-headed people are at greater risk for developing melanoma. A person with multiple atypical nevi or dysplastic nevi are at a significant risk. Although constant exposure to sun can cause melanoma, it is a larger risk factor for other less serious skin cancers, such as basal cell carcinoma and squamous cell carcinoma. Individuals with blistering or peeling sunburns (especially in the first twenty years of life) have a significantly greater risk for melanoma.

A family history of melanoma greatly increases a person's risk. It is critical that individuals with family members who have been diagnosed with melanoma be checked regularly for skin cancer.

Prevention

Primary
To prevent or detect melanomas (and increase survival rates), it is recommended that the public:

Learn what they look like (see "ABCDE" mnemonic below.)
Are aware of moles and check for changes (shape, size, color, itching or bleeding)
Show any suspicious moles to a doctor (preferably a dermatologist).
Minimize exposure to sources of ultraviolet radiation (the sun and sunbeds)
Follow sun protection measures. Wearing protective clothing (long-sleeved shirts, long trousers, and broad-brimmed hats.) offers the best protection. Use a sunscreen with an SPF rating of 30 or better on exposed areas.
A popular method for remembering the signs and symptoms of melanoma is the mnemonic "ABCDE":

Asymmetrical skin lesion.
Border of the lesion is irregular.
Color: melanomas usually have multiple colors.
Diameter: moles greater than 5mm are more likely to be melanomas than smaller moles.
Evolution: The evolution (ie change) of a mole or lesion may be a hint that the lesion is becoming malignant.
If you have a personal or family history of skin cancer or of dysplastic nevus syndrome (multiple atypical moles) you should see a dermatologist at least once a year.

Diagnosis
Any mole that is irregular in color or shape should be examined by a doctor to determine if it is a malignant melanoma, the most serious and life-threatening form of skin cancer. Following a visual examination and a dermatoscopic exam (an instrument that illuminates a mole, revealing it's underlying pigment and vascular network structure), the doctor may biopsy the suspicious mole. If it is malignant, the mole and an area around it will need excision. This may require a referral to a surgeon or dermatologist.

The diagnosis of melanoma requires experience, as early stages may look identical to harmless moles or not have any color at all. Where any doubt exists, the patient will be referred to a specialist dermatologist. Beyond this expert knowledge a biopsy performed under local anesthesia is often required to assist in making or confirming the diagnosis and in defining the severity of the melanoma.

One method is a punch biopsy, using a surgical punch (an instrument similar to a tiny cookie cutter with a handle, with an opening ranging in size from 1 to 6 mm). The punch is used to remove a plug of skin (down to the subcutaneous layer) from a portion of a large suspicious lesion, or to completely remove a smaller lesion. Preferably, an excisional biopsy can be performed, where the suspect lesion is totally removed by cutting an ellipse of tissue around it. Both methods will include the epidermal, dermal, and subcutaneous layers of the skin in the biopsy specimen, enabling the pathologist to determine the depth of penetration of the melanoma by microscopic examination. This is described by Clark's level (involvement of skin structures) and Breslow's depth (measured in millimeters).

Lactate dehydrogenase (LDH) tests are often used to screen for metastases, although many patients with metastases (even end-stage) have a normal LDH; extraordinarily high LDH often indicates metastatic spread of the disease to the liver. It is common for patients diagnosed with melanoma to have chest X-rays and an LDH test, and in some cases CT, MRI, PET and/or PET/CT scans. Although controversial, sentinel lymph node biopsies and examination of the lymph nodes are also performed in patients to assess spread to the lymph nodes.

Sometimes the skin lesion may bleed, itch, or ulcerate, although this is very late sign. A slow-healing lesion should be watched closely, as that may be a sign of melanoma. Be aware also that in circumstances that are still poorly understood, melanomas may "regress" or spontaneously become smaller or invisible - however the malignancy is still present. Amelanotic (colorless or flesh-colored) melanomas do not have pigment and may not even be visible. Lentigo maligna, a superficial melanoma confined to the topmost layers of the skin (found primarily in older patients) is often described as a "stain" on the skin. Some patients with metastatic melanoma do not have an obvious detectable primary tumor.

Treatment
Treatment of malignant melanoma is best performed from a multidisciplinary approach including dermatologists, medical oncologists, radiation oncologists, surgical oncologists, general surgeons, neurologists, neurosurgeons, otorynolaryngologists, radiologists, pathologists/dermatopathologists, research scientists, nurse practitioners and physician assistants, and palliative care experts. Nurse practitioners (NPs) and physician assistants (PAs) are qualified to evaluate and treat patients on behalf of their supervising physicians, so it should not be a surprise when visiting a dermatologist to see an NP or PA.

Surgery
Diagnostic punch or excisional biopsies may appear to excise (and in some cases may indeed actually remove) the tumor, but further surgery is often necessary to reduce the risk of recurrence.

Complete surgical excision with adequate margins and assessment for the presence of detectable metastatic disease along with short and long term follow up is standard. Often this is done by a "wide local excision" (WLE) with 1.0 cm margins.

More recently, Mohs micrographic surgery is becoming increasingly popular for smaller melanomas, especially of the face. In this surgery, performed by specially-trained dermatologists, a small layer of tissue is excised and prepared as a frozen tissue section. This section can be prepared and examined by the dermatologist/dermatopathologist within one hour, and the patient will return for further stages of excision as needed, with each excised tissue layer being examined until clear margins are obtained. Although the amount of stages required can range from one to five or more, on average only two stages will be necessary to excise the tumor. If a tumor is found to be more invasive or widespread than previously thought, a WLE may on rare occasions be performed after Mohs surgery has begun. Although the risk of recurrence is slightly higher, the procedure is much less invasive and patients undergoing Mohs surgery have a similar survival rate to patients undergoing WLE.