Carolyn Vachani, MSN, RN, AOCN & Suzanne McGettigan, MSN, CRNP, AOCN
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 13, 2011
A melanocyte is a normal cell found in the skin that produces melanin. Melanin is a black or dark brown pigment that is seen in the skin, hair, and parts of the eye. Melanin is transferred from the melanocytes into nearby skin and hair cells. The concentrated areas of color seen on the skin are known as moles or nevi.
Melanoma is a type of cancer that forms from melanocytes. Melanoma is the most serious form of skin cancer. Other more common, but usually less serious, types of skin cancer include basal cell carcinoma and squamous cell carcinoma.
Of the many different types of melanoma, most are seen in the skin (this also includes nail beds, soles of the feet, and scalp), but melanoma can also occur in the eye, or on mucosal surfaces which include the anal canal, rectum, and vagina. In 2010, there will be an estimated 68,130 new cases of invasive melanoma diagnosed in the United States, accounting for 5% of all new cancer diagnoses in men and 4% of new cancer diagnoses in women. The number of new cases of melanoma has steadily increased for 30 years. The increased number of cases of melanoma being diagnosed is also associated with increased survival due to early detection.
Risk factors for cutaneous melanoma, or melanoma that arises in the skin, include fair skin or complexion, a history of sunburns and/or prolonged exposure to ultraviolet light (both sun and artificial UV light), multiple moles, older age, a personal or family history of non-melanoma skin cancer and a personal or family history of melanoma.
As we age, our years of sun exposure increase, and therefore the risk of melanoma increases.
Researchers have found that the risk of melanoma is 2.24 times higher in people with a first-degree relative with the diagnosis; therefore it is important to be aware of your family history. If you have been diagnosed with melanoma, it is important to share this information with your relatives so that they can undergo appropriate screening. Certain types of moles, called dysplastic nevi, are associated with a higher incidence of melanoma. These moles are typically large (>5mm in diameter) and have uneven pigmentation and borders. A single dysplastic nevi is associated with a 2-fold increased risk, while 10 or more nevi indicate a 12- fold increased risk of developing melanoma.
People with fair skin, light eyes, or those who have a tendency to freckle or burn easily are all at higher risk. Melanoma rates are 20 times higher in Caucasians than in Blacks. The melanin in dark-skinned people has been found to have a natural sun protection factor (SPF) and can filter twice as much ultraviolet light as that of a light-skinned person. This protection, however, is not complete, and melanoma can develop in dark-skinned people. Melanoma is more commonly found on soles, palms, or nail beds in dark-skinned people.
A history of 3 or more sunburns, particularly blistering sunburns, before age 20 greatly increases risk. A history of severe sunburns in childhood and adolescence may actually double the risk of melanoma in adulthood. For many years, the tanning industry has promoted tanning salons as a safe alternative to natural sun, or a way to prevent sunburn. This is because the tanning machines were said to produce only UVA rays, without producing UVB rays, which are responsible for most sunburns. Researchers have since learned that tanning beds do produce UVB rays in varying amounts, depending on the machine. They have also learned that UVA is not as safe as once thought. Despite the fact that UVA is less likely to cause sunburn, it has many biologic effects that can cause long-term damage. As for using tanning beds to prevent sunburn on a vacation, this is also untrue. A visit to a tanning bed, followed by natural sun exposure, causes a cumulative effect on skin cells and can cause an unexpected burn. Bottom line: Tanned skin is not healthy and actually indicates that the skin has been damaged.
The best way to prevent melanoma is to protect the skin from sun exposure (both natural and artificial). Avoid sun exposure between 10am and 4pm, wear protective clothing (including a hat) when in the sun, and use sunscreen with a sun protection factor (SPF) of 15 or greater everyday, even in the winter! Sunscreen use is especially important for children due to the fact that sunburns during childhood greatly increase the risk of melanoma in adulthood. Consistent use of sunscreen has even shown the ability to reduce further skin damage in people with a history of extensive sun exposure.
You should examine your own skin regularly. Be aware of the shapes and coloring of any moles you have. Melanoma often develops from an existing mole, causing its appearance to change. Examine your skin routinely in a mirror, including your back, bottom of your feet, nail beds, and scalp. Look for changes in existing moles, or the development of new ones. Concerning moles are ones that have the "ABCDE" characteristics. "A" is for asymmetry. If an asymmetric mole were divided in half, one side would not look like the other. "B" is for border irregularity. The border of the mole may appear blurry and uneven. "C" is for color. This can be a change in the color the mole has always been, the development of a black mole, or color variation within a mole, meaning that a single mole may have red, brown, and black colors within it. "D" is for diameter. You should have any mole that has changed in size or color, particularly those greater than 6mm in diameter, checked by a physician. "E" is for evolution meaning that a mole has changed in appearance over time, color, shape, or elevation. These rules are not set in stone, which is why you should be aware of your own moles, and report any changes in moles to a physician.
The best screening is a skin examination. Your physician should examine your skin during routine physicals, but you should also examine your skin routinely at home. Because you see your skin everyday, you are most likely to notice any changes early on. Prognosis is best when lesions are found early, making skin examination very important.
Melanoma usually presents as an irregular mole, with the "ABCDE" characteristics described above. This can be a preexisting mole that has changed or a newly developed mole. More advanced lesions may have inflammation, oozing, crusting, itching, ulceration or bleeding. However, some melanomas don't fit the mold- they may not have the typical coloring of a mole or may have no color at all. They may be smaller than 5mm, when moles larger than 5mm and often said to be of greater concern. They may occur in areas that are never exposed to sunlight. Your best bet is to know your skin's normal appearance and bring any changes to the attention of your healthcare provider.
When melanoma is suspected, an excisional biopsy should be performed. This biopsy removes the lesion and the layers beneath it, allowing the depth of the lesion to be accurately determined. The depth of the lesion determines prognosis and treatment, so it is important for this to be accurate.
There are four general types of melanoma: superficial spreading melanoma, lentigo malignant melanoma, acral lentiginous melanoma, and nodular melanoma. Additionally, melanoma can arise in the mucosal surfaces or in the ocular region, known as mucosal melanoma (i.e. gastrointestinal tract, urinary tract and vagina) and ocular (eye) melanoma, respectively.
After the initial biopsy is performed, and again after the wide excision, a pathology report is issued by the dermatopathologist. This pathology report further describes many aspects of the melanoma, including the type, the depth of invasion, the tissue level of invasion, the presence or absence of a lymphatic response, ulceration, regression, satellite lesions, and blood/lymph/nerve invasion. Additionally, the pathology report will describe if the excised lesion is a primary melanoma, in which case it would be described using the terms above, or a metastatic melanoma deposit. Metastatic melanoma is when the cancer cells spread within the subcutaneous skin tissue in the site of the original tumor. These lesions are often called "in-transit metastases".
The depth is described in two ways: Breslow thickness, which is the depth of invasion in millimeters, and Clark's level, which describes depth of invasion by the tissue it invades (levels I-V). Clark's Level I involves the epidermis only. Clark's Level II involves the epidermis and the layer of skin immediately below, the papillary dermis. Clark's Level III goes one layer deeper into the reticular dermis. Clark's Level IV involves the deep dermis. Clark's Level V invades beyond the skin layers into the subcutaneous fat. Clark's levels are often confused with the staging of melanoma, but Clark's level is an indication of the depth of penetration of the melanoma only, not the stage of disease.
The staging is based on these measurements, and is classified as follows:
Depending on the stage of the melanoma, patients will have a chest x-ray and liver function studies to assess for metastases. In patients with stages II-IV, further evaluation for metastases is needed; this may include cat scans, PET scans, and lymph node dissection (with or without sentinel node biopsy).
Surgery is the mainstay of treatment for melanoma. After a melanoma is diagnosed by a biopsy, the next step is to have a "wide excision". This surgical procedure removes an area of normal tissue around where the lesion was located. The amount of tissue removed is based on the depth of the melanoma. This area of normal skin is referred to as the "margins".
If the melanoma is deeper than 1mm or invades to Clark's level IV or greater, a sentinel lymph node biopsy may be performed. In a sentinel lymph node biopsy, a blue dye with a radioactive tracer is injected into the site of the original tumor. The dye spreads to the "sentinel node" (the first node that to which the cancer would spread). These blue lymph nodes are removed, examined under a microscope and tested for cancer. If any of these lymph nodes are positive, the remaining lymph nodes in the region are removed, a procedure known as a lymph node dissection. If the sentinel nodes do not contain melanoma, a completion lymph node dissection can be avoided.
Patients with early stage melanoma and negative lymph nodes are monitored regularly with skin examinations, chest x-rays, and liver function tests for the development of any recurrence or a second melanoma. These patients have a good prognosis, with 95 percent of patients alive 5 years after diagnosis. However, having one melanoma in a patient's lifetime places him/her at higher risk for developing a second melanoma and follow up with a dermatologist is a mainstay of on-going treatment.
Patients with lymph node involvement are considered to have Stage III disease. Theoretically, in Stage III melanoma, the cancer has been removed by the surgery and lymph node dissection. Unfortunately, there are often tumor cells circulating in the body that we cannot see. For this reason, the patient may be offered treatment with radiation therapy, immunotherapy, chemotherapy (DTIC, cisplatin, carboplatin, temozolomide), vaccine therapies, and/or a clinical trials of new therapies to destroy any remaining cancer cells and prevent further spread of the cancer. Radiation therapy can be used to treat a local area thought to be at risk for recurrence of the melanoma. An immunotherapy agent (interferon, interleukin-2, GM-CSF, Bacille Calmette-Guerin (BCG) bacteria) can be used to stimulate the patient's own immune system against cancer.
Melanoma can also spread into the region between the original site and the lymph nodes. These lesions are called "in-transit metastases." These may often be treated with the treatment modalities used in Stage III disease. One technique being used in patients with tumors confined to one limb is isolated limb perfusion. This involves temporarily cutting off circulation to the affected limb and administering high doses of chemotherapy to the limb, sparing the rest of the body of the medication's toxicities.
When the cancer has spread beyond the regional lymph nodes, into another organ, it is considered Stage IV melanoma. Stage IV disease has a poorer prognosis. In some instances, patients with isolated areas of metastasis are able to have these surgically removed. Chemotherapy, immunotherapy, and/or participation in a clinical trial may also be treatment options used to treat Stage IV melanoma.
A newer immune therapy, called ipilimumab, was approved in 2011 for use in the treatment of metastatic or unresectable melanoma. Ipilimumab is a type of monoclonal antibody therapy, which works to stimulate the immune system to destroy cancer cells. T-cells are a type of white blood cell that are very important to the normal functioning of the immune system. Ipilimumab blocks the activity of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a molecule found on T cells that normally suppress immune activity. By blocking CTLA-4, T-cells function better and the immune response is stimulated. This is the first therapy that has shown improved survival for people with advanced melanoma.
Clinical trials are testing many new agents for the treatment of melanoma. These may include: vaccines, which can be made from the patient's own tumor cells or parts of the melanoma cells; varying combinations of chemotherapy; immunotherapy agents; and surgical techniques. One technique being tested in patients with tumors confined to one limb is isolated limb perfusion. This involves temporarily cutting off circulation to the affected limb and administering high doses of chemotherapy to the limb, sparing the rest of the body of the medication's toxicities. New medications and techniques are continually being tested to find more effective therapies for this disease.
About 5 percent of patients will develop a second melanoma in their lifetime, while others may develop metastases from the original tumor, and therefore all patients require follow-up. Patients should be evaluated every 3 to 6 months for the first 3 years after diagnosis, then every 6 to 12 months for 2 years, and then annually. Chest x-ray and liver function tests may be done each year, and CT scans, if appropriate, for a particular case.
This article is meant to give you a better understanding of melanoma. Use this knowledge when meeting with your physician, making treatment decisions, and continuing your search for information. You can learn more about melanoma on OncoLink through the related links on the left.
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