Melanoma

Melanoma is a type of cancer that usually starts in the skin, or more rarely, in the eye (ocular melanoma) or mucosal membranes of the body (mucosal melanoma). Melanoma specifically begins in melanocytes, cells that produce melanin, the pigment that gives skin, hair, and eyes their color.

Melanoma is one of the most aggressive and serious types of skin cancer. Although it is much less common than other skin cancers, melanoma is one of the most common types of cancers diagnosed in young adults. Melanocytes often clump together, creating a mole, or nevus, on the surface of the skin, on the mucosal surfaces of the body, or in the eye. The majority of these moles are harmless. However, some nevus types can raise a patient’s risk of developing melanoma and any changes in these moles should be examined by a physician. Because melanocytes are responsible for a change in the pigment of the skin, melanomas are often brown or black. Sometimes melanocytes fail to make pigment—these melanomas appear as pink or white bumps on the skin.

Melanomas also tend to be asymmetrical (unevenly shaped) with dark, ragged edges.

Melanoma is generally curable if diagnosed right away. But it is much more likely than other types of skin cancer to spread to other parts of the body if it isn’t treated early.

While skin melanomas can be found anywhere on the skin, they show up more often in certain areas of the body. In men, melanomas are generally found on the trunk (chest and back) and in women, on the legs. Melanomas often appear on the neck and face as well. Individuals with darker skin are less likely to develop melanomas in these common sites but are no less likely to develop melanomas on the palms of the hands, the soles of the feet (acral melanomas), or inside the oral or genito-anal cavities (mucosal melanomas). These sites account for more than half of all melanomas in African Americans but fewer than one in 10 melanomas in Caucasians.

Types of Melanoma

Cutaneous Melanoma

The most common type of melanoma is skin (cutaneous) melanoma. There are two categories of skin melanoma:

In situ melanoma is confined to the epidermis or upper layer of the skin. It will not spread once the lesion has been removed.

Invasive melanoma has advanced into the deeper layers of the skin called the dermis and the subcutis. In general, the thicker the melanoma is, the more likely it is to invade other parts of the body. When melanoma metastasizes, or spreads to other parts of the body, it commonly involves the lymph nodes, lungs, liver, brain, bones, and digestive tract but can involve any part of the body.

There are four different types of cutaneous melanoma.

Melanoma in the Eyes

Less commonly, melanoma can affect the eyes. Melanoma can affect many parts of your eyes, including:

• The layer of the eye between the retina and the white outer layer of the eye called the choroid. This type of melanoma is called uveal melanoma, which is the most common type of eye melanoma.
• The eyelids
• The clear mucosal surface of the eye called the conjunctiva, which covers the eye’s surface and the inside of the eyelids. This type of melanoma is called conjunctival melanoma.

Mucosal Melanoma

Melanoma can also arise from the mucosal surfaces of the body. Slightly over half of all mucosal melanomas begin in the head and neck region, approximately one quarter of mucosal melanomas arise from the anorectal region, and another 20% arise from the female urogenital tract. Melanomas originating in mucosal surfaces lining the esophagus, gallbladder, bowel, conjunctiva, urethra, and other sites are far less common.

Risk Factors 

According to the American Cancer Society, about 120,000 new cases of melanoma in the US are diagnosed in a year. About 68,000 of these were invasive melanomas, with about 39,000 in males and 29,000 in women.

Melanoma is most often diagnosed in adults, although it can affect children and teenagers, too.
Prolonged exposure to ultraviolet sunlight or tanning beds and a history of severe sunburn increase the chance of developing melanoma. Other risk factors include:

• The presence and the number of atypical moles (also known as dysplastic nevi)
• Personal diagnosis of melanoma or other form of skin cancer
• Family history of skin cancer—two or more relatives diagnosed with skin cancer and melanoma
• Fair skin, freckling, or light hair. Whites are 10 times likelier to develop melanoma than African Americans. Whites with red or blond hair, blue or green eyes, or fair skin that freckles or burns easily are at higher risk.
• Excessive ultraviolet (UV) light exposure, including from tanning beds; history of blistering sunburns especially during childhood
• Age: Melanoma is most common in men over the age of 50 (more common than colon, prostate, and lung cancer). Melanoma is the second most common cancer in teens and young adults and is the most common type of cancer for young adults.
• A weakened immune system caused by AIDS, immunosuppressive drugs, or certain cancers
• Other skin conditions such as xeroderma pigmentosum, a rare inherited condition in which the body cannot repair the DNA of skin cells damaged by UV radiation
• A mutation in gene p53 that normally function as a tumor suppressor. When disabled, this gene can increase the likelihood of developing melanoma.
• A mutation in the BRAF or "switch" gene that allows skin cells to keep growing and dividing. Greater understanding of this gene may lead to the development of new diagnostic tools and treatments for melanoma.
• The CDKN2A (cyclin-dependent kinase inhibitor 2A) gene is also linked to melanoma though testing is usually done only in the context of clinical trials.

The chance of developing melanoma and other types of skin cancer can be minimized by following these general rules:

• Avoid extended periods of sun exposure, especially during peak hours.
• Protect the skin from UV rays with broad-spectrum sunscreen.
• When outdoors, wear sun hats and a protective layer of clothing, and shield the eyes with sunglasses that offer UV protection.
• Do not use sunlamps, tanning beds, or tanning booths, all potentially dangerous sources of UV radiation.
• Regular follow-up with a dermatologist, particularly if you have a history of skin cancer.

Signs of Melanoma

Individuals should examine their skin head-to-toe once a month, looking for any suspicious spots, bumps, or lesions. It is important to tell a physician about any new moles or growths and any changes in the skin. Dermatologists have developed the following criteria to help their patients identify melanoma.

The ABCDE’s of Melanoma

A—asymmetry. A melanoma usually has an uneven appearance, with one side markedly different from the other.
B—border. The edges of this growth may be scalloped or notched.
C—color. A melanoma may be several different colors, combining brown, black, or tan, or red. It may also turn red, black, or some other color.
D—diameter. A melanoma is generally the size of a pencil eraser, measuring ¼ inch across. Early melanomas may be smaller.
E—evolving. Any change in the nature of the lesion—from itching to crusting and bleeding—should be reported to a physician.

The Ugly Duckling

Another warning sign is the discovery of a mole or spot that is different from all the others. If a mole appears markedly larger and darker than its neighbors, it is considered an “ugly duckling” or outlier and should be reported to a physician. The same is true if a small red mole appears in a field of large dark moles. If an individual has few or no other moles, any new or unusual lesion should be considered suspicious.

Diagnosis

Often the possibility of melanoma is brought to a doctor's attention because of a symptom the patient has noticed, like a new or changing mole. If melanoma is suspected, your physician may use one or more of the following ways to understand if you have melanoma or not.

Noninvasive Evaluation

Dermatologists often use a technique called dermatoscopy or skin surface microscopy to evaluate skin spots and pigmented lesions. This technique allows the doctor to see microscopic structures under the skin not visible to the naked eye. Experienced dermatologists using dermatoscopy improve their diagnostic accuracy of melanoma by about 30% while reducing the rate of unnecessary biopsies.

Dermatoscope is a handheld instrument that uses a combination of strong magnifying glass together with a light source (nonpolarized, polarized, and cross-polarized light) enabling the dermatologist to visualize structures below the skin surface, allowing for early diagnosis of melanoma. Dermatoscopy is essential in the surveillance of patients at high risk of melanoma, especially those with many melanocytic nevi or moles.

Another powerful noninvasive technique for early detection of melanoma is full-body digital mole mapping. Using dermatoscopy together with digital mole mapping further improves diagnostic accuracy and allows monitoring of the atypical moles over time, avoiding unnecessary invasive biopsies. The most important predictor of malignancy is change in a mole or a lesion. If there are no changing moles found using digital mole mapping and dermatoscopic images, the moles or other lesions are considered to be benign. Not every change in a mole means malignant transformation, but it is best to see a specialist to evaluate the changing lesion or mole and to make a diagnosis.

Biopsy

A physician may also take a biopsy or skin sample to check the cells under a microscope for any evidence of cancer. The biopsy may involve one or more layers of the skin—the top layer, called the epidermis, the second layer, called the dermis, and the deepest layer, called the subcutis.

A biopsy is generally done on an outpatient basis, with local anesthesia (numbing). A physician will choose one of the following approaches, depending upon the size and nature of the lesion.

Lab Tests

A dematopathologist (a doctor who specializes in evaluating skin cancers) may also perform other tests to determine whether a melanoma is present. These are called immunohistochemistry (IHC) tests.

Fluorescence in situ hybridization (FISH) maps the genetic material in a patient's cells and helps the physician to distinguish a benign nevus from a melanoma.

Comparative genomic hybridization (CGH) further aids the physician in determining whether or not melanoma is present.

Genetic Testing

If an advanced melanoma is found, tumor biopsy samples may be tested for mutations in genes such as BRAF, NRAS, KIT, GNAQ, GNA11, and TRK, among others. Approximately half of cutaneous melanomas have BRAF mutations and several targeted therapies have been developed to treat patients with BRAF mutant melanoma. Other genetic findings such as KIT mutations and TRK fusions may suggest that other targeted therapies may be treatment options.

Imaging Tests

Imaging tests are used mainly to look for the possible spread of melanoma to lymph nodes or other organs in the body. Later, they may help the physicians determine how well a treatment is working or to check for signs of recurrence.

• A chest X-ray may be ordered to discover whether melanoma has spread to the lungs.
• A computed tomography (CT) scan uses X-rays to produce detailed cross-sectional images of the body. This test can show if any lymph nodes are enlarged or if organs such as the lungs or liver have suspicious spots.
• Magnetic resonance imaging (MRI) uses radio waves and strong magnets instead of X-rays to take images of tissue in different parts of the body and can show if the cancer has spread.
• Positron emission tomography (PET) uses radioaactive glucose (sugar) to make detailed computerized pictures of areas inside the body. Because cancer cells often take up more glucose than normal cells, the pictures can be used to find cancer cells and help determine whether melanoma has moved to lymph nodes or other parts of the body.

Blood Tests

If melanoma has become invasive, the patient is likely to have a higher than normal blood level of lactate dehydrogenase (LDH). The results of this test will affect staging of the melanoma and the course of treatment.

Other tests of blood cell counts and blood chemistry levels may be done in a person who has advanced melanoma to see how the bone marrow (the soft spongy area of the bone where new blood cells are made), liver, and kidneys are responding during treatment.