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Melanoma
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Important Resources for Melanoma:
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Types
There are four main types of melanoma arising in the skin:
- Superficial spreading is the most common type, accounting for about 70% of cases. It occurs most often on the lower leg or back. The cells grow outward at first, parallel to the skin surface ("radial growth") before invading deeper structures.
- Nodular melanoma does not have a radial growth phase like that seen in superficial spreading melanoma. Instead, the lesion is an elevated and often bizarrely colored nodule that grows quickly, most often seen on the head, neck, and trunk.
- Lentigo maligna melanoma is most often found on sun-exposed areas, especially the face. It grows laterally and (fortunately) quite slowly, and has a relatively low tendency to metastasize.
- Acral lentiginous melanoma is the most common type in nonwhite populations. It occurs on the palms and soles and sometimes under fingernails or toenails. It has a prolonged noninvasive stage.
In addition to the cutaneous (skin) melanoma mentioned above, melanocytes in the eye can also become cancerous, causing ocular or uveal melanoma.
Signs and Symptoms
Almost all cases are initially asymptomatic. The appearance of a suspicious lesion is the sign that initiates medical attention.
Causes
The causes of melanoma can be categorized as intrinsic (unavoidable) and extrinsic (avoidable). As with other types of skin cancer, an important extrinsic cause of melanoma is sun exposure in the form of ultraviolet radiation. UV radiation is widely known to cause damage to and induce mutations in cells' DNA molecules. Occasionally these mutations can result in oncogenic transformation, which enables the cells to grow and migrate without regard to the usual control mechanisms. An important intrinsic cause of melanoma is found in the genes CDKN2A and CDK4, mutations of which have been found in melanoma-prone families.[1]
Diagnosis
Diagnosis proceeds systematically, starting with initial evaluation of the lesion, which may be noted as part of a screening exam by the patient or the patient's physician. A biopsy usually comes next, with evaluation of the skin sample by a pathologist. Microscopic examination can confirm or refute the diagnosis in almost all cases. The last diagnostic step is evaluation of the disease's extent in the body. This usually involves invasive imaging studies carried out by surgeons and radiologists in cooperation with pathologists.
Screening
Patients or their family members may notice suspicious lesions and make use of the "ABCDE" acronym to decide whether a suspicious area merits a trip to the doctor. The letters stand for criteria with which to judge a lesion:
- A stands for asymmetry of the lesion, an unfavorable finding.
- B stands for border, with an irregular or indistinct border being an unfavorable sign.
- C stands for color, with multiple colors being an unfavorable sign.
- D stands for diameter, larger being an unfavorable sign. Lesions larger than 6 mm are considered "large."
- E stands for evolution, or changing over time. Lesions that grow or change their appearance with time are more worrisome.
Melanoma showing Asymmetry, an irregular Border, and variation in Color. Source: NCI.
Microscopic
The diagnosis of melanoma is made based on the microscopic appearance of the cells. Grading refers to how the cells look in the microscope. Especially worrisome features characteristic of a "high grade" lesion include malignant cells invading surrounding normal tissue, large nuclei in the malignant cells, and the appearance of active cell division among the malignant cells. Immunohistochemistry is often used to characterize the malignant cells further based on which antigens are expressed. This is especially useful when melanoma must be distinguished from other types of cancer that do not express melanoma-specific antigens.
Staging
Staging refers to accurate determination of how far the cancer has spread. Several surgical and imaging techniques are employed for accurate staging. Once the examination is complete, the disease's stage can be determined to help decide on treatment.
Surgical and imaging techniques
- Lymph node mapping and sentinel lymph node biopsy: Procedures in which a radioactive substance and/or blue dye is injected near the tumor. The substance or dye flows through lymph ducts to the sentinel node or nodes (the first lymph node or nodes where cancer cells are likely to have spread). The surgeon removes only the nodes with the radioactive substance or dye. A pathologist then checks the sentinel lymph nodes for cancer cells. If no cancer cells are detected, it may not be necessary to remove additional 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 chest, abdomen, and pelvis.
- MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
- 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.
Stages
Stage 0 (in situ)
In stage 0, 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 0 is also called melanoma in situ.
Stage I
In stage I, cancer has formed. Stage I is divided into stages IA and IB.
- Stage IA: In stage IA, the tumor is not more than one millimeter thick, with no ulceration. The tumor is in the epidermis and upper layer of the dermis.
- Stage IB: In stage IB, the tumor is either:
- Not more than one millimeter thick, with ulceration, and may have spread into the dermis or the tissues below the skin; or
- One to two millimeters thick, with no ulceration.
Stage II
Stage II is divided into stages IIA, IIB, and IIC.
- Stage IIA: In stage IIA, the tumor is either:
- 1 to 2 millimeters thick, with ulceration; or
- 2 to 4 millimeters thick, with no ulceration.
- Stage IIB: In stage IIB, the tumor is either:
- 2 to 4 millimeters thick, with ulceration; or
- More than 4 millimeters thick, with no ulceration.
- Stage IIC: In stage IIC, the tumor is more than 4 millimeters thick, with ulceration.
Stage III
In stage III, the tumor may be any thickness, with or without ulceration, and:
- Has spread to 1 or more lymph nodes; or
- Has spread into the nearby lymph system but not into nearby lymph nodes; or
- Has spread to lymph nodes that are matted (not moveable); or
- Satellite tumors (additional tumor growths within 2 centimeters of the original tumor) are present and nearby lymph nodes are involved.
Stage IV
In stage IV, the tumor may be any thickness, with or without ulceration, may have spread to 1 or more nearby lymph nodes, and has spread to other places in the body.
Treatment
Successful treatment of melanoma implies complete removal of the malignant cells. Comprehensive treatment usually involves removal of as much of the cancer as possible by surgery, followed by chemotherapy and/or radiotherapy and/or biologic therapy.
Surgery
Surgery to remove the tumor is the primary treatment of all stages of melanoma. The doctor may remove the tumor using the following operations:
- Local excision: Taking out the melanoma and some of the normal tissue around it.
- Wide local excision with or without removal of lymph nodes.
- Lymphadenectomy: A surgical procedure in which the lymph nodes are removed and examined to see whether they contain cancer.
- Sentinel lymph node biopsy: The removal of the sentinel lymph node (the first lymph node the cancer is likely to spread to from the tumor) during surgery. 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 for biopsy. 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.
Even if the doctor removes all the melanoma that can be seen at the time of the operation, some patients may be offered chemotherapy after surgery to kill any cancer cells that are left. Chemotherapy given after surgery, to increase the chances of a cure, is called adjuvant therapy.
Chemotherapy
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy).
In treating melanoma, anticancer drugs may be given as a hyperthermic isolated limb perfusion. This technique sends anticancer drugs directly to the arm or leg in which the cancer is located. The flow of blood to and from the limb is temporarily stopped with a tourniquet, and a warm solution containing anticancer drugs is put directly into the blood of the limb. This allows the patient to receive a high dose of drugs in the area where the cancer occurred.
Radiation therapy
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.
Biologic therapy
Biologic therapy 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 natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.
Chemoimmunotherapy
Chemoimmunotherapy is the use of anticancer drugs combined with biologic therapy to boost the immune system to kill cancer cells.
Treatment Options by Stage
Treatment of stage 0 is usually surgery to remove the area of abnormal cells and a small amount of normal tissue around it.
Treatment of stage I melanoma may include the following:
- Surgery to remove the tumor and some of the normal tissue around it.
- A clinical trial of surgery to remove the tumor and some of the normal tissue around it, with or without lymph node mapping and selective lymphadenectomy.
- A clinical trial of new techniques to detect cancer cells in the lymph nodes.
- A clinical trial of lymphadenectomy with or without adjuvant therapy.
Treatment of stage II melanoma may include the following:
- Surgery to remove the tumor and some of the normal tissue around it, followed by removal of nearby lymph node s.
- Lymph node mapping and sentinel lymph node biopsy, followed by surgery to remove the tumor and some of the normal tissue around it. If cancer is found in the sentinel lymph node, a second surgical procedure can be performed to remove additional nearby lymph nodes.
- Surgery followed by high- dose biologic therapy.
- A clinical trial of adjuvant chemotherapy and/or biologic therapy, or immunotherapy.
- A clinical trial of new techniques to detect cancer cells in the lymph nodes.
Treatment of stage III melanoma may include the following:
- Surgery to remove the tumor and some of the normal tissue around it.
- Surgery to remove the tumor with skin grafting to cover the wound caused by surgery.
- Surgery followed by biologic therapy.
- A clinical trial of surgery followed by chemotherapy and/or biologic therapy.
- A clinical trial of biologic therapy.
- A clinical trial comparing surgery alone to surgery with biologic therapy.
- A clinical trial of chemoimmunotherapy or biologic therapy.
- A clinical trial of hyperthermic isolated limb perfusion using chemotherapy and biologic therapy.
- A clinical trial of biologic therapy and radiation therapy.
Treatment of stage IV melanoma may include the following:
- Surgery or radiation therapy as palliative therapy to relieve symptoms and improve quality of life.
- Chemotherapy and/or biologic therapy.
- A clinical trial of new chemotherapy and/or biologic therapy, or vaccine therapy.
- A clinical trial of radiation therapy as palliative therapy to relieve symptoms and improve quality of life.
- A clinical trial of surgery to remove all known cancer.
Treatment Options for Recurrent Melanoma
Treatment of recurrent melanoma may include the following:
- Surgery to remove the tumor.
- Hyperthermic isolated limb perfusion.
- Radiation therapy as palliative therapy to relieve symptoms and improve quality of life.
- Palliative treatment with biologic therapy.
- A clinical trial of biologic therapy and/or chemotherapy as palliative therapy to relieve symptoms and improve quality of life.
Followup
Unfortunately, a history of melanoma puts one at greater risk of additional melanoma, which may represent a recurrence of the original disease or a completely independent event. Regular and thorough skin examinations are essential for melanoma survivors.
Risk Factors
Several risk factors have been identified:
- Unusual moles
- Exposure to natural sunlight
- Exposure to artificial ultraviolet light (tanning booth)
- Family or personal history of melanoma
- Being white and older than 20 years
- Red or blond hair
- White or light-colored skin and freckles
- Blue eyes
Clinical Trials
Several clinical trials are focused on immunotherapy for melanoma. Since melanocytes express several antigens that are uncommon in other cells, sensitizing the patient's immune system to recognize and attack cells with melanoma-specific antigens is a promising approach. These and many others are listed at ClinicalTrials.gov.
Expected Outcome
Five-year survival rates with appropriate treatment are estimated at 100% for Stage 0, 85-95% for Stage I, 40-85% for Stage II, 25-60% for Stage III, and 9-15% for Stave IV.
Epidemiology
1 in 75 Americans will develop melanoma, the most dangerous form of skin cancer, at some point in their life.
Other Resources
Chat online
The NCI's LiveHelp online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 9:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.
References
Links to Clinical Images
External Links
Melanoma International Foundation
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