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Melanoma

(Malignant Melanoma)

By

Vinod E. Nambudiri

, MD, MBA, EdM, Harvard Medical School

Reviewed/Revised Jan 2024
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Melanoma is a skin cancer that begins in the pigment-producing cells of the skin (melanocytes).

  • Melanomas can begin on normal skin or in existing moles.

  • They may be irregular, flat or raised brown patches of skin with spots of different colors or firm black or gray lumps.

  • To diagnose melanoma, doctors do a biopsy.

  • Melanomas are removed.

  • If they have spread, chemotherapy and radiation therapy are used, but cure is difficult.

Melanocytes are the pigment-producing cells in the skin that give skin its distinctive color. Sunlight stimulates melanocytes to produce more melanin (the pigment that darkens the skin) and increases the risk of melanoma.

In 2023, approximately 97,610 new cases of melanoma are estimated to occur in the United States, causing an estimated 7,990 deaths. Although melanoma accounts for less than 2% of all skin cancers Overview of Skin Cancer Skin cancer is the most common type of cancer, and people of all skin tones can be affected. People who have light skin are particularly susceptible to developing most forms of skin cancer because... read more diagnosed in the United States, it causes the most skin cancer deaths.

Melanoma usually begins on normal skin as a new, small, pigmented growth, most often on sun-exposed areas. About 1 in 3 melanomas develops in a preexisting mole Moles Moles are small, usually dark, skin growths that develop from pigment-producing cells in the skin (melanocytes). Most people have some moles, but the tendency to develop atypical moles is sometimes... read more Moles . Melanoma may also occur around and inside the eyes, in the mouth, on the genitals and rectal areas, in the brain, and in the nail beds.

Melanoma readily spreads (metastasizes) to distant parts of the body, where it continues to grow and destroy tissue.

The two most common types of melanoma are

  • Superficial spreading melanoma: This type accounts for 70% of melanomas and occurs most commonly on women’s legs and men’s torsos. The tumor cells commonly have mutations in the BRAF gene.

  • Nodular melanoma: This type accounts for 15 to 30% of melanomas, occurs anywhere on the body, and grows rapidly.

Risk Factors for Melanoma

Risk factors for melanoma include the following:

People who have had melanoma are at increased risk of developing a new melanoma.

Melanoma is less common among people who have dark skin. When melanoma does develop in people who have dark skin, it often develops in the nail beds and on the palms and soles.

Melanomas are very rare in childhood. However, congenital melanocytic nevus is a dark-colored patch of skin, like a mole or a birthmark, that is present at birth. When large in size, for example, more than about 8 inches (about 20 centimeters), congenital melanocytic nevus is a risk factor for malignant melanoma.

Although melanomas occur during pregnancy, pregnancy does not increase the likelihood that a mole will become a melanoma. Moles frequently change in size and darken during pregnancy.

All people should know the ABCDEs of melanoma The ABCDEs of Melanoma The ABCDEs of Melanoma so they can check their moles for any malignant (cancerous) changes.

Symptoms of Melanoma

Melanomas can vary in appearance. Some are flat, irregular brown patches containing small black spots. Others are raised brown patches with red, white, black, or blue spots. Sometimes melanoma appears as a firm red, black, or gray lump.

Less than 10% of melanomas produce no pigment. These so-called amelanotic melanomas may be pink, red, or slightly light-brown and may look like noncancerous growths or a form of nonmelanoma skin cancer.

Diagnosis of Melanoma

  • Biopsy

A new mole or changes in a mole—such as enlargement (especially with an irregular border), darkening, inflammation, spotty color changes, bleeding, itching, tenderness, and pain—are warning signs of possible melanoma and so are the ABCDEs of melanoma The ABCDEs of Melanoma The ABCDEs of Melanoma . If these or other findings lead doctors to suspect melanoma, they do a biopsy.

The ABCDEs of Melanoma

These warning signs are known as the ABCDEs of melanoma.

  • A—Asymmetry: Asymmetric (irregular) appearance (the two halves of the mole are not equal)

  • B—Borders: Irregular borders (that is, borders seem to blend in with the surrounding skin or are not round or oval)

  • C—Color: Changes in color of an existing mole, especially the spread of brown, black, red, white, or blue pigmentation or a color significantly different or darker than the person's other moles

  • D—Diameter: More than ¼ inch (about 6 millimeters) wide, about the size of most pencil erasers

  • E—Evolution: A new mole in a person over age 30 or a changing mole

For the biopsy Biopsy Doctors can identify many skin disorders simply by looking at the skin. A full skin examination includes examination of the scalp, nails, and mucous membranes. Sometimes the doctor uses a hand-held... read more Biopsy , doctors remove the entire growth if it is small or only part of it if it is large. They then examine the sample under a microscope to determine whether the growth is a melanoma and, if so, whether all the cancer has been removed. If the biopsy shows that the growth is a melanoma and the growth has not been completely removed, it is then completely removed. A growth that is a melanoma is often tested for genetic mutations because results may further help doctors determine treatment.

Most darkly pigmented growths that are removed for biopsy are not melanoma but, rather, simple moles Moles Moles are small, usually dark, skin growths that develop from pigment-producing cells in the skin (melanocytes). Most people have some moles, but the tendency to develop atypical moles is sometimes... read more Moles . Nonetheless, removing even many harmless moles is preferable to allowing a single cancer to grow. Some growths are neither simple moles nor melanomas, but something in between. These growths, called atypical moles Atypical moles Moles are small, usually dark, skin growths that develop from pigment-producing cells in the skin (melanocytes). Most people have some moles, but the tendency to develop atypical moles is sometimes... read more Atypical moles (dysplastic nevi), sometimes turn into melanoma later.

There are additional tools that doctors may use to help distinguish an atypical mole from a melanoma. These tools include polarized light and dermoscopy, which help to better evaluate the growths.

Treatment of Melanoma

  • Removal of the tumors

  • Possibly imiquimod, cryotherapy, or radiation therapy

  • For tumors that have spread, immunotherapy, targeted therapy, chemotherapy, or radiation therapy

Doctors treat melanomas by cutting them out (sometimes using Mohs microscopically controlled surgery Mohs Microscopically Controlled Surgery Mohs Microscopically Controlled Surgery ), taking a border of almost ½ inch (1 centimeter) or more of skin around the tumor.

For people who have the most shallow melanomas (that is, melanomas that have not invaded past the epidermis—called melanoma in situ) and who cannot have surgery (for example, because their health is too poor) or choose not to (for example, because their melanomas are in cosmetically important areas), doctors may treat with imiquimod cream or may use extreme cold (cryosurgery) to destroy the melanomas.

Did You Know...

  • If diagnosed early, surgery can cure almost 100% of shallow melanomas.

Melanoma that has spread

If melanoma has spread to distant areas (metastasized), surgery is generally not an option, but sometimes localized areas of cancer (for example, the affected lymph nodes) may be surgically removed.

The new immunotherapies Immunotherapy for Cancer Immunotherapy is used to stimulate the body's immune system against cancer. These treatments target specific genetic characteristics of the tumor cells. The genetic characteristics of tumors... read more pembrolizumab and nivolumab are used to help the body's immune system destroy the cancer. These medications are called PD-1 inhibitors because they block the action of a protein on the surface of the cancer cell called programmed cell death protein 1. This protein protects the cancer cell from the effects of the immune system. When PD-1 inhibitors block the protein, the immune system is able to attack the cancer cell and kill it. PD-1 inhibitors are proving to be very effective treatments for metastatic melanoma. Ipilimumab is another immunotherapy that helps activate certain white blood cells to attack cancer cells and improves survival. The combination of nivolumab and ipilimumab is often the best treatment. Nivolumab can also be used in combination with another immunotherapy called relatlimab.

Targeted therapy consists of medications that attack a cancer cell's innate biologic mechanisms. In targeted therapy, medications attack specific parts of cells that are present only in the cancerous cells with specific gene mutations. Use of these medications has improved cancer survival in some people. One class of medications targets cells with a BRAF gene mutation. These medications include dabrafenib, encorafenib, and vemurafenib. For people who cannot be treated with immunotherapy, a combination of targeted therapies can be used.

Chemotherapy Chemotherapy and Other Systemic Cancer Treatments Systemic treatments are those that have effects throughout the body rather than being applied directly to the cancer. Chemotherapy is a form of systemic treatment that uses drugs to kill cancer... read more drugs, such as dacarbazine and temozolomide, have not been proved to prolong survival, but they are sometimes given to treat melanomas that have spread in people who do not have other treatment options.

Radiation therapy Radiation Therapy for Cancer Radiation is a form of intense energy generated by a radioactive substance, such as cobalt, or by specialized equipment, such as an atomic particle (linear) accelerator. Radiation preferentially... read more may be used in people when complete removal of a melanoma is not possible because of its location, when it recurs in an area where it had originally been removed, and when it has spread to the brain.

Prognosis for Melanoma

Melanoma may spread rapidly and cause death within months of diagnosis. The less a melanoma has grown deeper into the skin, the greater the chance that surgery will cure it. Almost 100% of the earliest, most shallow melanomas are cured by surgery. However, melanomas that have grown deeper than about 1/32 inch (about 1 millimeter) into the skin have a higher risk of metastasizing to the lymph nodes and blood vessels.

Once melanoma has metastasized to distant parts of the body, the 5-year survival rate is approximately 35%. Some people live for less than 9 months. However, the course of the disease varies greatly and depends in part on the strength of the body’s immune defenses. Some people survive in apparent good health for several years despite the spread of the melanoma.

Prevention of Melanoma

Doctors do not know with certainty whether these measures decrease the chances of people developing or dying of melanoma. However, using tanning beds, particularly by young people, does seem to increase the risk of melanoma.

Anyone who has had a melanoma is at risk of developing other melanomas. Therefore, such people need regular skin examinations.

People who have many moles should have a total body skin examination at least once a year. People can be taught to examine themselves to detect changes in existing moles and to recognize features suggesting melanoma The ABCDEs of Melanoma The ABCDEs of Melanoma . In people without risk factors, doctors do not know whether routine yearly skin examinations reduce the number of deaths from melanoma.

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

Drugs Mentioned In This Article

Generic Name Select Brand Names
Aldara, Zyclara
Keytruda
Opdivo
YERVOY
Tafinlar
BRAFTOVI
Zelboraf
DTIC-Dome
TEMODAR
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