Skin Cancer

Skin cancers are broadly classified as melanoma and nonmelanomas. More than 1 million cases of nonmelanoma are diagnosed each year, making it the most common cancer in the United States. Melanoma occurs less frequently, with approximately 60,000 new cases diagnosed in 2007.

The number of people affected by both types of skin cancer has increased substantially over the past several decades. Increased exposure to the sun is thought to be the cause of this increase.

Melanomas and nonmelanomas are cancers that originate in the outer layer of the skin, or the epidermis. The epidermis is made up of three kinds of cells. Skin cancers are defined by the type of cell from which they develop. Squamous cell carcinoma arises from squamous cells, — thin flat cells that make up the top layer of the epidermis. Basal cell carcinoma develops in basal cells — round cells that lie beneath the layer of squamous cells.

These two types of skin cancer are referred to as nonmelanoma to distinguish them from melanoma, which develops in melanocytes. Melanocytes form the bottom layer of the epidermis and determine the skin color of an individual. Nonmelanomas are relatively slow growing and rarely spread (metastasize). In contrast, melanoma cells are much more likely to invade nearby lymphatic vessels and/or spread to other parts of the body, making them potentially more harmful. They are the focus here.

A biopsy must be done to confirm the diagnosis of a nonmelanoma or melanoma. An excisional biopsy or a deep-shave biopsy is most often used if the lesion is thought to be melanoma, as this method involves excision (removal) of the entire lesion.

The factors considered in classifying the melanoma according to the tumor (T) staging category in the AJCC system are the thickness of the lesion and the presence or absence of ulceration. (Ulceration means that the layer of skin over the melanoma is disrupted.)

The T categories are as follows:

Each T classification is also subcategorized according to whether ulceration is absent (subcategory a) or present (subcategory b). For example, an ulcerated lesion that is 1 mm thick is classified as T1b. The pathologist will also report on the level of invasion, a measure of how deep into the dermis the melanoma has invaded.

The node (N) classification is used to describe the spread of the melanoma to lymph nodes in terms of both the number of lymph nodes involved and the amount of cancer cells in the lymph nodes. If the cancer cells in the lymph node are found with use of a microscope, the metastasis is considered to be microscopic. If there are enough cancer cells in the lymph node to make the node appear as a palpable mass, it is said to be macroscopic.

The N categories are as follows:

The N1, N2 and N3 categories include subcategories to indicate whether metastasis to the lymph nodes is microscopic; that is, not clinically detectable (subcategory a); or macroscopic; that is, detectable by clinical or x-ray exam (subcategory b). In addition, N2 and N3 also include a subcategory of c to indicate in-transient or satellite metastasis, which is the presence of cancer cells in the lymphatic vessels leading to a lymph node.

Lastly, the melanoma is classified according to whether the cancer has metastasized. The M categories are as follows:

One of the most important indicators of survival after treatment of a melanoma is whether it has spread. When melanoma spreads, the first place it is most likely to be found is the regional lymph node closest to the melanoma. This lymph node is referred to as the sentinel node. A procedure called lymphoscintigraphy, otherwise known as sentinel node mapping, is done to determine the exact drainage of lymph from the skin surrounding the melanoma into the sentinel lymph node. This procedure is usually considered for melanomas that are more than 1 mm thick.

With sentinel node mapping, a small amount of radioactive substance is injected into the skin around the biopsy site of the melanoma and a device that detects radioactivity is used to follow the path of the substance as it travels to the nearest group of lymph nodes. The surgeon will also inject a small amount of blue dye into the skin around the melanoma at the beginning of the operation as a second tracer to precisely identify the sentinel node. The surgeon then makes a small incision in the area of the lymph nodes and removes the sentinel node that has turned blue and/or become radioactive. The surgeon will remove the sentinel node (sentinel node biopsy), and a pathologist will examine it to determine if melanoma cells are present. If no cancer cells are detected in the sentinel node, it is highly unlikely that the melanoma has spread to any lymph nodes.

Sentinel node mapping and biopsy may not be necessary in every case of melanoma, and an individual should discuss this issue with his or her physician.

The treatment of skin cancers depends on whether the lesion is a nonmelanoma or a melanoma. Several treatment options are available for nonmelanomas, and the choice depends on many factors, such as the location and characteristics of the tumor (size, depth, and location); the individual’s age, general health condition, and personal preference; and the potential cosmetic result.

Generally, this can be accomplished by excision of the skin cancer with a small margin of the surrounding skin. The surgeon and the pathologist will generally verify that the skin cancer is generally removed with a “quick stain” during the operative procedure. If there is still residual tumor, then more skin must be excised. For melanomas, surgical treatment involves a wider excision of skin surrounding the melanoma in an amount that varies according to tumor thickness. The goals are to remove all cancerous tissue and to minimize the likelihood that the cancer will recur (grow back). Surgical excision is usually the preferred treatment for both types of skin cancer.

In addition to surgical excision of a melanoma, dissection (removal) of lymph nodes that contain cancer cells may also necessary. Surgery is the most effective treatment in this circumstance. If a melanoma is thick or has spread to one or more lymph nodes, the physician may recommend adjuvant therapy after the surgery, which is treatment given after the primary treatment.

The goal of adjuvant therapy is to kill cancer cells that are not yet detectable, and this treatment increases the likelihood that the melanoma will not recur. Adjuvant therapy may include biological therapy (also called immunotherapy) or radiation therapy or both. At present, there is no documented benefit of chemotherapy after surgery. When melanoma is metastatic at the time it is diagnosed, a combination of surgery and radiation therapy may be recommended to eliminate the primary melanoma as well as control the metastatic disease.

Surgical excision involves removal of the melanoma and a small amount of normal tissue around the lesion (known as the surgical margin). The normal tissue is removed to make sure that all cancer cells have been eliminated. This procedure is known as a wide local excision. How wide the excision should be is determined by how thick the tumor is, but it is generally recommended at either a half-inch or an inch of skin surrounding the melanoma. After the lesion has been removed, the margins of the wound are sewn together.

If sentinel node biopsy was done previously and showed that melanoma had spread, the lymph nodes in the area of the sentinel node may have to be dissected. Sentinel lymph node mapping and biopsy may be done at the time of removal of the melanoma if the physician finds that the melanoma has adverse features, such as cancer cells in the margins. If this testing indicates that the cancer has spread to the sentinel node, another surgical procedure is performed at a later time to remove additional nearby lymph nodes. If stage III melanoma involving pathologically documented spread of cancer to the lymph nodes is found, lymph node dissection is done during the same procedure as the wide excision.

A combination of treatments that may include surgery to remove the melanoma and chemotherapy to treat the metastasis, is needed for stage IV melanoma. Chemotherapy is known as systemic therapy because anticancer drugs travel through the bloodstream to kill cancer cells that have spread beyond the site of the melanoma.

The chemotherapy drugs most commonly used to treat metastatic melanoma include:
DTIC (dacarbazine) alone
Combination of DTIC, BCNU (carmustine), and Platinol (cisplatin)
Combination of DTIC, Platinol, and Velban (vinblastine)
Temodar (temozolomide — similar to DTIC but in pill form)

Chemotherapy drugs may be associated with side effects, such as nausea and vomiting, hair loss and mouth sores. These side effects are usually temporary, and treatments are available to help manage them. In addition, chemotherapy can decrease the number of healthy blood cells, which can leave a person feeling tired and weak. A low level of healthy blood cells also makes a person more susceptible to infection or to bruising and bleeding when injured. It is important for individuals to tell their doctor, nurse or other member of the health-care team about side effects so that appropriate treatments can be prescribed to relieve discomfort.

Another treatment option for some melanomas is immunotherapy, or treatment that stimulates the individual’s own immune system to kill cancer cells. The two most commonly used drugs for immunotherapy are interferon-alpha and interleukin-2 (IL-2). These drugs are given in high doses and are most often used for individuals who are participating in a clinical trial.

Immunotherapy may be appropriate if an individual has several melanomas and it is not possible to perform an appropriate wide excision on all of them. Immunotherapy may also be used as adjuvant therapy for melanomas that are thick or have spread to lymph nodes.

Immunotherapy is associated with several side effects, including chills, fever, aches and extreme tiredness. Individuals who are considering immunotherapy should discuss this treatment with their physician to learn about the potential benefits, the likelihood of side effects, and the options for managing these side effects.

For patients treated for melanoma, follow-up for a second melanoma is critical. The National Comprehensive Cancer Network offers guidelines for follow-up based on the stage of disease (Table 1). In addition to a physical examination that focuses on evaluation of the skin and lymph nodes, follow-up may include blood work and computerized tomography to determine if there are signs of growth or recurrence, especially if signs and symptoms are apparent.

Recurrent melanoma may be treated with surgical excision if it is localized, and treatment in a clinical trial may involve chemotherapy or immunotherapy.

Table 1. Recommendations for Follow-Up after Treatment for Melanoma*

*Recommendations according to guidelines developed by the National Comprehensive Cancer Network.
LDH = lactate dehydrogenase; CBC = complete blood count; LFT = liver function studies; CT = computerized tomography.

• Aim at Melanoma: www.aimatmelanoma.org
• ASCO’s Patient Web site: www.cancer.net
• Joanna M. Nicolay Melanoma Foundation: www.melanomaresource.org
• Melanoma Research Foundation: www.melanoma.org
• Melanoma Research Alliance: melanomaresearchalliance.org
• National Cancer Institute: www.cancer.gov/cancertopics/types/melanoma
• National Comprehensive Cancer Network: www.nccn.org

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