Melanoma Treatment

Melanoma is a disease in which malignant (cancer) cells form in melanocytes (cells that color the skin).

The skin is the body’s largest organ. It protects against heat, sunlight, injury, and infection. Skin also helps control body temperature and stores water, fat, and vitamin D. The skin has several layers, but the two main layers are the epidermis (upper or outer layer) and the dermis (lower or inner layer). Skin cancer begins in the epidermis, which is made up of three kinds of cells:

• Squamous cells: Thin, flat cells that form the top layer of the epidermis.
• Basal cells: Round cells under the squamous cells.
• Melanocytes: Cells that make melanin and are found in the lower part of the epidermis. Melanin is the pigment that gives skin its natural color. When skin is exposed to the sun or artificial light, melanocytes make more pigment and cause the skin to darken.

From 2010 to 2019, the number of new cases of melanoma increased by about 1% per year, though the number of deaths each year from melanoma continues to decrease. Melanoma is most common in adults, but it is sometimes found in children and adolescents. For more information, see Childhood Melanoma Treatment.

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Anatomy of the skin, showing the epidermis, dermis, and subcutaneous tissue. Melanocytes are in the layer of basal cells at the deepest part of the epidermis.

There are different types of cancer that start in the skin.

There are two main forms of skin cancer: melanoma and nonmelanoma.

Melanoma is a rare form of skin cancer. It is more likely to invade nearby tissues and spread to other parts of the body than other types of skin cancer. When melanoma starts in the skin, it is called cutaneous melanoma. Melanoma may also occur in mucous membranes (thin, moist layers of tissue that cover surfaces such as the lips). This summary is about cutaneous (skin) melanoma and melanoma that affects the mucous membranes.

The most common types of skin cancer are basal cell carcinoma and squamous cell carcinoma. They are nonmelanoma skin cancers. Nonmelanoma skin cancers rarely spread to other parts of the body. For more information, see Skin Cancer Treatment.

Melanoma can occur anywhere on the skin.

In men, melanoma is often found on the trunk (the area from the shoulders to the hips) or the head and neck. In women, melanoma forms most often on the arms and legs.

When melanoma occurs in the eye, it is called intraocular or ocular melanoma. For more information, see Intraocular (Uveal) Melanoma Treatment.

Unusual moles, exposure to sunlight, and health history can affect the risk of melanoma.

Anything that increases a person's chance of getting a disease is called a risk factor. Not every person with one or more of these risk factors will develop melanoma, and it will develop in some people who don't have any known risk factors. Talk with your doctor if you think you may be at risk.

Risk factors for melanoma include the following:

• Having a fair complexion, which includes the following:
  • Fair skin that freckles and burns easily, does not tan, or tans poorly.
  • Blue or green or other light-colored eyes.
  • Red or blond hair.
• Being exposed to natural sunlight or artificial sunlight (such as from tanning beds).
• Being exposed to certain factors in the environment (in the air, your home or workplace, and your food and water). Some of the environmental risk factors for melanoma are radiation, solvents, vinyl chloride, and PCBs.
• Having a history of many blistering sunburns, especially as a child or teenager.
• Having several large or many small moles.
• Having a family history of unusual moles (atypical nevus syndrome).
• Having a family or personal history of melanoma.
• Being White.
• Having a weakened immune system.
• Having certain changes in the genes that are linked to melanoma.

Being White or having a fair complexion increases the risk of melanoma, but anyone can have melanoma, including people with dark skin.

For more information on risk factors for melanoma, see the following:

• Genetics of Skin Cancer
• Skin Cancer Prevention

Signs of melanoma include a change in the way a mole or pigmented area looks.

These and other signs and symptoms may be caused by melanoma or by other conditions. Check with your doctor if you have any of the following:

• A mole that:
  • changes in size, shape, or color.
  • has irregular edges or borders.
  • is more than one color.
  • is asymmetrical (if the mole is divided in half, the 2 halves are different in size or shape).
  • itches.
  • oozes, bleeds, or is ulcerated (a hole forms in the skin when the top layer of cells breaks down and the tissue below shows through).
• A change in pigmented (colored) skin.
• Satellite moles (new moles that grow near an existing mole).

For pictures and descriptions of common moles and melanoma, see Common Moles, Dysplastic Nevi, and Risk of Melanoma.

Tests that examine the skin are used to diagnose melanoma.

In addition to asking about your personal and family health history and doing a physical exam, your doctor may perform the following tests and procedures to find and diagnose melanoma:

• Skin exam: A doctor or nurse checks the skin for moles, birthmarks, or other pigmented areas that look abnormal in color, size, shape, or texture.
• Biopsy: A procedure to remove the abnormal tissue and a small amount of normal tissue around it. A pathologist looks at the tissue under a microscope to check for cancer cells. It can be hard to tell the difference between a colored mole and an early melanoma lesion. Patients may want to have the sample of tissue checked by a second pathologist. If the abnormal mole or lesion is cancer, the sample of tissue may also be tested for certain gene changes.

  There are four main types of skin biopsies. The type of biopsy done depends on where the abnormal area formed and the size of the area.

  • Shave biopsy: A sterile razor blade is used to “shave-off” the abnormal-looking growth.
  • Punch biopsy: A special instrument called a punch or a trephine is used to remove a circle of tissue from the abnormal-looking growth.
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    Punch biopsy. A sharp, hollow, circular instrument is used to remove a small, round piece of tissue from a lesion on the skin. The instrument is turned clockwise and counterclockwise to cut about 4 millimeters (mm) down to the layer of fatty tissue below the skin and remove the sample of tissue. Skin thickness is different on different parts of the body.
    

  • Incisional biopsy: A scalpel is used to remove part of a growth.
  • Excisional biopsy: A scalpel is used to remove the entire growth.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis and treatment options depend on the following:

• The thickness of the tumor and where it is in the body.
• How quickly the cancer cells are dividing.
• Whether there was bleeding or ulceration of the tumor.
• How much cancer is in the lymph nodes.
• The number of places cancer has spread to in the body.
• The level of lactate dehydrogenase (LDH) in the blood.
• Whether the cancer has certain mutations (changes) in a gene called BRAF.
• The patient’s age and general health.

After melanoma has been diagnosed, tests may be done to find out if cancer cells have spread within the skin or to other parts of the body.

The process used to find out whether cancer has spread within the skin or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment.

For melanoma that is not likely to spread to other parts of the body or recur, more tests may not be needed. For melanoma that is likely to spread to other parts of the body or recur, the following tests and procedures may be done after surgery to remove the melanoma:

• Lymph node mapping and sentinel lymph node biopsy: The removal of the sentinel lymph node during surgery. The sentinel lymph node is the first lymph node in a group of lymph nodes to receive lymphatic drainage from the primary tumor. It is the first lymph node the cancer is likely to spread to from the primary tumor. A radioactive substance and/or blue dye is injected near the tumor. The substance or dye flows through the lymph ducts to the lymph nodes. The first lymph node to receive the substance or dye is removed. A pathologist views the tissue under a microscope to look for cancer cells. If cancer cells are not found, it may not be necessary to remove more lymph nodes. Sometimes, a sentinel lymph node is found in more than one group of nodes.
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. For melanoma, pictures may be taken of the neck, chest, abdomen, and pelvis.
• PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
• MRI (magnetic resonance imaging) with gadolinium: A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body, such as the brain. A substance called gadolinium is injected into a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues, such as lymph nodes, or organs and make echoes. The echoes form a picture of body tissues called a sonogram. The picture can be printed to be looked at later.
• Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. For melanoma, the blood is checked for an enzyme called lactate dehydrogenase (LDH). High LDH levels may predict a poor response to treatment in patients with metastatic disease.

The results of these tests are viewed together with the results of the tumor biopsy to find out the stage of the melanoma.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

• Tissue. The cancer spreads from where it began by growing into nearby areas.
• Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
• Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

• Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
• Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if melanoma spreads to the lung, the cancer cells in the lung are actually melanoma cells. The disease is metastatic melanoma, not lung cancer.

The stage of melanoma depends on the thickness of the tumor, whether cancer has spread to lymph nodes or other parts of the body, and other factors.

To find out the stage of melanoma, the tumor is completely removed and nearby lymph nodes are checked for signs of cancer. The stage of the cancer is used to determine which treatment is best. Check with your doctor to find out which stage of cancer you have.

The stage of melanoma depends on the following:

• The thickness of the tumor. The thickness of the tumor is measured from the surface of the skin to the deepest part of the tumor.

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• Whether the tumor is ulcerated (has broken through the skin).

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• Whether cancer is found in lymph nodes by a physical exam, imaging tests, or a sentinel lymph node biopsy.

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• Whether the lymph nodes are matted (joined together).

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• Whether there are:
  • Satellite tumors: Small groups of tumor cells that have spread within 2 centimeters of the primary tumor.
  • Microsatellite tumors: Small groups of tumor cells that have spread to an area right beside or below the primary tumor.
  • In-transit metastases: Tumors that have spread to lymph vessels in the skin more than 2 centimeters away from the primary tumor, but not to the lymph nodes.

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• Whether the cancer has spread to other parts of the body, such as the lung, liver, brain, soft tissue (including muscle), gastrointestinal tract, and/or distant lymph nodes. Cancer may have spread to places in the skin far away from where it first formed.

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The following stages are used for melanoma:

Stage 0 (Melanoma in Situ)

In stage 0, abnormal melanocytes are found in the epidermis. These abnormal melanocytes may become cancer and spread into nearby normal tissue. Stage 0 is also called melanoma in situ.

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Stage 0 melanoma. Abnormal melanocytes are found in the epidermis (outer layer of the skin). These abnormal melanocytes may become cancer and spread into nearby normal tissue.

Stage I

In stage I, cancer has formed. Stage I is divided into stages IA and IB.

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Millimeters (mm). A sharp pencil point is about 1 mm, a new crayon point is about 2 mm, and a new pencil eraser is about 5 mm.

• Stage IA: The tumor is not more than 1 millimeter thick, with or without ulceration.
• Stage IB: The tumor is more than 1 but not more than 2 millimeters thick, without ulceration.
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  Stage I melanoma. In stage IA, the tumor is not more than 1 millimeter thick, with or without ulceration (a break in the skin). In stage IB, the tumor is more than 1 but not more than 2 millimeters thick, without ulceration. Skin thickness is different on different parts of the body.
  

Stage IV

In stage IV, the cancer has spread to other parts of the body, such as the lung, liver, brain, spinal cord, bone, soft tissue (including muscle), gastrointestinal (GI) tract, and/or distant lymph nodes. Cancer may have spread to places in the skin far away from where it first started.

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Stage IV melanoma. Cancer has spread to other parts of the body, such as the brain, spinal cord, lung, liver, gastrointestinal (GI) tract, bone, muscle, and/or distant lymph nodes. Cancer may have spread to places in the skin far away from where it first started.

Melanoma can recur (come back) after it has been treated.

The cancer may come back in the area where it first started or in other parts of the body, such as the lungs or liver.

There are different types of treatment for patients with melanoma.

Different types of treatment are available for patients with melanoma. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

The following types of treatment are used:

Immunotherapy

Immunotherapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer.

The following types of immunotherapy are being used in the treatment of melanoma:

• Immune checkpoint inhibitor therapy: Immune checkpoint inhibitors block proteins called checkpoints that are made by some types of immune system cells, such as T cells, and some cancer cells. These checkpoints help keep immune responses from being too strong and sometimes can keep T cells from killing cancer cells. When these checkpoints are blocked, T cells can kill cancer cells better. They are used to treat some patients with advanced melanoma or tumors that cannot be removed by surgery.

  There are two types of immune checkpoint inhibitor therapy:

  • CTLA-4 inhibitor therapy: CTLA-4 is a protein on the surface of T cells that helps keep the body’s immune responses in check. When CTLA-4 attaches to another protein called B7 on a cancer cell, it stops the T cell from killing the cancer cell. CTLA-4 inhibitors attach to CTLA-4 and allow the T cells to kill cancer cells. Ipilimumab is a type of CTLA-4 inhibitor.
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    Immune checkpoint inhibitor. Checkpoint proteins, such as B7-1/B7-2 on antigen-presenting cells (APC) and CTLA-4 on T cells, help keep the body’s immune responses in check. When the T-cell receptor (TCR) binds to antigen and major histocompatibility complex (MHC) proteins on the APC and CD28 binds to B7-1/B7-2 on the APC, the T cell can be activated. However, the binding of B7-1/B7-2 to CTLA-4 keeps the T cells in the inactive state so they are not able to kill tumor cells in the body (left panel). Blocking the binding of B7-1/B7-2 to CTLA-4 with an immune checkpoint inhibitor (anti-CTLA-4 antibody) allows the T cells to be active and to kill tumor cells (right panel).
    

  • PD-1 and PD-L1 inhibitor therapy: PD-1 is a protein on the surface of T cells that helps keep the body’s immune responses in check. PD-L1 is a protein found on some types of cancer cells. When PD-1 attaches to PD-L1, it stops the T cell from killing the cancer cell. PD-1 and PD-L1 inhibitors keep PD-1 and PD-L1 proteins from attaching to each other. This allows the T cells to kill cancer cells. Pembrolizumab and nivolumab are types of PD-1 inhibitors. Atezolizumab is a PD-L1 inhibitor that is being studied in combination with cobimetinib and vemurafenib (types of targeted therapy).

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Immune checkpoint inhibitor. Checkpoint proteins, such as PD-L1 on tumor cells and PD-1 on T cells, help keep immune responses in check. The binding of PD-L1 to PD-1 keeps T cells from killing tumor cells in the body (left panel). Blocking the binding of PD-L1 to PD-1 with an immune checkpoint inhibitor (anti-PD-L1 or anti-PD-1) allows the T cells to kill tumor cells (right panel).

• Interleukin-2 (IL-2): IL-2 boosts the growth and activity of many immune cells, especially lymphocytes (a type of white blood cell). Lymphocytes can attack and kill cancer cells.
• Tumor necrosis factor (TNF) therapy: TNF is a protein made by white blood cells in response to an antigen or infection. TNF is made in the laboratory and used as a treatment to kill cancer cells. It is being studied in the treatment of melanoma.

See Drugs Approved for Melanoma for more information.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI website.

Treatment for melanoma may cause side effects.

For information about side effects caused by treatment for cancer, visit our Side Effects page.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. Information about clinical trials supported by NCI can be found on NCI’s clinical trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

Follow-up tests may be needed.

As you go through treatment, you will have follow-up tests or check-ups. Some tests that were done to diagnose or stage the cancer may be repeated to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back).

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PDQ® Adult Treatment Editorial Board. PDQ Melanoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/skin/patient/melanoma-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389388]

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