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Harvard Commentaries
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Harvard Commentaries
Reviewed by the Faculty of Harvard Medical School


Nonmelanoma Skin Cancers


November 29, 2010

Skin Cancer
8297
Basics
Nonmelanoma Skin Cancers
Nonmelanoma Skin Cancers
htmCZNonMelanoma
The two most common forms of nonmelanoma skin cancer are basal cell cancers, which account for 80% of all skin cancers, and squamous cell cancers, which account for 15% of cases.
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InteliHealth
2010-11-29
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InteliHealth Medical Content
2013-10-01

Reviewed by the Faculty of Harvard Medical School

Nonmelanoma Skin Cancer

Overview

Nonmelanoma skin cancers include basal cell cancers, which account for 80% of all skin cancers, and squamous cell cancers, which account for 15% of skin cancer cases.

Basal cell cancers originate in the deepest cells, or basal cells, of the epidermis, the outermost layer of the skin. They usually develop on areas of the body that have been exposed to the sun — the face, ears, neck, scalp, shoulders and back. Most cases probably are caused by ultraviolet B (UVB) radiation. These slow-growing cancers rarely spread internally. People who have had one basal cell carcinoma have a 35% to 50% chance of developing a new one within five years, usually at another site that has been exposed to the sun.

Squamous cell cancers occur in the epidermis and usually appear on sun-exposed surfaces of the face, ear, neck, lip, backs of the hands, arms, chest, back and legs. Often, squamous cell cancer forms in an area with precancerous skin changes, known as actinic keratosis (solar keratosis). In rare cases, these cancers may develop in skin that has been damaged or diseased by a process other than sun exposure: in scars from severe burns, in skin ulcers and, less often, in the genital area. Genital squamous cell cancers can arise as a result of a sexually transmitted infection with the human papilloma virus (a virus associated with genital warts and cervical cancer). Squamous cell cancer is more aggressive than basal cell carcinoma, with approximately 3% spreading to distant areas of the body.

 

Risk Factors

Sun Exposure
The single greatest risk factor for most skin cancers is unprotected exposure to the sun's UV rays. The damage that can lead to skin cancers results from two types of the UV rays — UVB, which damages skin and produces cancer-causing mutations, and UVA, which is capable of penetrating more deeply beneath the skin's surface. Both may affect the skin's immune system and result in skin cancer.

The amount of UV radiation received depends on the strength of the light, the length of exposure and whether the skin is protected. People who live in areas where it's sunny year-round are at higher risk. For example, the risk of nonmelanoma skin cancer is twice as high in Arizona as in Minnesota. Spending a lot of time outdoors without protection with clothing or sunscreen increases risk.

Gender and Age
Men have twice the rate of basal cell carcinoma and three times the rate of squamous cell carcinoma as women, perhaps because of outdoor occupations that expose them to the sun. The risk of basal cell and squamous cell cancers increases with age.

Fair Skin
The risk of skin cancer is more than 20 times higher for whites than for dark-skinned African Americans. Those with fair skin that freckles or burns easily face the highest risk. This is because darker skin has more skin pigment, which offers a protective effect against the sun's UV rays.

Radiation Exposure
People who have had radiation treatment have a greater risk of developing nonmelanoma skin cancer in the area that was treated. This risk begins about 20 years after the radiation treatment.

Reduced Immunity
People with weakened immune systems are more likely to develop nonmelanoma skin cancer. This includes individuals with HIV infection and organ transplant recipients, who usually are given medications that suppress their immune system to prevent their body from rejecting the new organ.

Chemical Exposure
Exposure to industrial tar, coal and some types of oil can increase the risk of squamous cell cancer. Arsenic, a naturally occurring substance in rock formations and soil, is contained in wood preservatives and is a byproduct of brass and bronze manufacture, copper smelting and glass making. It can contaminate drinking water and has been associated with both types of nonmelanoma skin cancer.

Genetic Syndromes
Several rare inherited syndromes can predispose an individual to nonmelanoma skin cancer:

  • Xeroderma pigmentosum is a defect in the ability to repair DNA that has been damaged by UV light. Skin cancers often are first seen in early childhood.

     

  • Nevoid basal cell carcinoma syndrome is an inherited disorder characterized by multiple basal cell carcinomas, pits in the palms and soles, cysts in the jaws and a variety of skeletal abnormalities. Skin cancers usually begin to develop in the early teen years.

     

  • Albinism is a rare congenital condition in which there is no pigment in skin or hair.

     

  • Epidermodysplasia verruciformis is an inherited disease characterized by multiple warts on the hands and feet and also distinctive skin changes on the arms and chest. It is linked to susceptibility to infection by certain subtypes of human papilloma virus (HPV). HPV causes all common viral warts, including genital warts, foot warts and hand warts.

Skin Injury and Inflammation
Skin cancer can develop in ulcers, scars and other skin injuries that don't heal. There is a small risk of developing nonmelanoma cancer in skin affected by skin diseases such as discoid lupus erythematosus.

Prevention

The best way to reduce the risk of nonmelanoma skin cancer is to limit unprotected exposure to the sun, especially when sunlight is the most intense (generally from 10 a.m. to 3 p.m.). Also avoid tanning parlors and sun lamps because the UV radiation they deliver can cause skin cancer.

You can protect your skin with clothing and a hat with a broad brim. Wrap-around sunglasses provide the best protection for the area around the eyes. Use sunscreens with an SPF factor of 30 or more on areas exposed to the sun, particularly when the sun is strong. People with fair skin and people who burn easily should be particularly vigilant about applying sunscreen on all exposed areas before going outdoors — even on overcast days. Even with sunscreen, it's best to limit exposure during the time when the sun's rays are strongest. Be sure to reapply sunscreen often; always reapply after swimming or sweating. Older, fair-skinned people commonly react to longstanding sun exposure by developing rough pink spots or patches that are covered by a scratchy white or yellow crust. These are actinic keratoses (solar keratoses) that may progress to squamous cell cancers and should therefore be treated. Treatment of actinic keratoses decreases the risk of progression to squamous cell cancer.

Many people form multiple actinic keratoses. Sun protection is of utmost importance. A low-fat diet has also been shown to decrease the tendency to form these precancerous areas and is a prudent preventive measure for anyone who has had nonmelanoma skin cancer.

Signs and Symptoms

Basal cell carcinoma usually develops on the skin of the face, chest, back and legs. Squamous cell carcinoma usually develops on sun-exposed skin but also can occur on the unexposed areas such as the external genitalia, fingers, toes and the soles of the feet. Basal cell carcinoma can vary in appearance, so watch for any of the following:

  • A translucent pink or red bump
  • A flat, red, scaly growth.
  • An unexpected scar-like growth, usually ivory-colored with irregular borders.
  • A sore or pimple that doesn't heal.

Screening

Any skin change of concern should be examined promptly by a physician so that a simple skin biopsy can be performed if appropriate. People who have had skin cancer in the past or who have many moles should have their skin checked annually or biannually by a health professional. Regularly scheduled skin checks to look for nonmelanoma skin cancers have not been proven worthwhile for people who aren't at higher risk of skin cancer and don't have any worrisome skin changes.

Diagnosis

An examination of the suspicious growth or skin change by a physician is the first step in diagnosis. Your doctor will want to know when you first noticed the growth and when you became aware that it had enlarged or changed. If the doctor suspects a skin cancer, a skin biopsy will be performed.

Most skin biopsies are done in the doctor's office. The surrounding skin is numbed with a local anesthetic, and part or all of the growth is removed for microscopic examination in the laboratory.

Biopsy results will reveal whether the growth is malignant (cancerous). Since basal cell carcinoma and squamous cell carcinoma rarely spread, it usually isn't necessary to stage the disease by determining whether it has invaded other organs. Occasionally, with very large or long-standing tumors, staging may be necessary.

Treatment

Surgery
Almost all cases of basal cell and squamous cell skin cancers can be cured with surgery. For advanced squamous cell cancer, additional treatment with chemotherapy or radiation therapy may be required. The type of surgeries include:

  • Excision. A local anesthetic is used to numb the area, and the cancerous growth and some surrounding skin are surgically removed. The surrounding skin edges are pulled together, leaving a linear scar. This is generally an outpatient procedure performed in a doctor's office. In most cases, this is all the treatment needed.

     

  • Electrodesiccation and curettage. A local anesthetic is used to numb the area. Basal cell and squamous cell skin cancers are removed with a scraping instrument called a curette. The area is then treated with an electric needle to destroy any remaining cancer cells. This treatment leaves a flat, white scar.

     

  • Mohs' micrographic surgery. Also known as microscopically controlled surgery, this procedure involves shaving off the growth layer by layer and immediately checking each sample under a microscope. If malignant cells are seen, the surgeon removes another layer, and then another and so on, checking each time for malignancy until a layer of skin proves cancer-free. This technique is the most accurate that exists for removing skin cancers, and it preserves normal skin adjacent to the tumor, thus providing the smallest possible defect for cosmetic closure. A local anesthetic is used. The extent of scarring depends on the size and location of the growth.

     

  • Cryosurgery. Liquid nitrogen is used to freeze and kill skin cancer cells. This procedure may be recommended for premalignant conditions and small basal cell and squamous cell cancers. Anesthetic rarely is needed, but after the frozen skin thaws, there may be some blistering, crusting, pain and swelling that lasts for several weeks. A white scar may develop at the treated area.
  • Laser surgery. Lasers can be used in place of scalpels to cut away cancerous tissue. Other types of laser light therapies directly destroy cancer cells.

Some nonmelanoma cancers require other types of treatment in addition to or instead of surgery.

Topical Therapies
Topical chemotherapy involves placing anticancer drugs directly on the skin. The drug most commonly used is 5-fluorouracil (5-FU). Because it can destroy only cancer cells near the surface, not those that have penetrated into the skin or spread to other body sites, 5-FU is used primarily for precancerous skin conditions. Treated skin will be red and sensitive for several weeks. The area also will be sensitive to the sun for a few weeks and must be protected.

Imiquimod (Aldara) cream is a topical therapy that doctors prescribe to treat superficial basal cell cancers and actinic keratoses (precancerous skin abnormalities). Imiquimod activates the immune system. The activated immune cells attack cancerous and precancerous skin cells.

Systemic Chemotherapy
Systemic chemotherapy is used for skin cancer that has spread internally. Chemotherapy drugs are injected into a vein or given by mouth. These drugs travel through the bloodstream to all parts of the body to kill cancer cells.

In contrast to topical chemotherapy, systemic chemotherapy can attack cancer cells that have already spread beyond the skin to lymph nodes and other organs. These drugs kill cancer cells but also can damage normal cells, possibly causing side effects such as nausea, vomiting, loss of appetite, hair loss, sores in the mouth or vagina, susceptibility to infections, anemia, fatigue and infertility.

Radiation Therapy
Radiation therapy may be recommended instead of surgery if a tumor is very large or located in an area of skin that makes surgery difficult, such as the eyelid, the tip of the nose or the ear. Radiation therapy also may be used for patients who are not good candidates for surgery because of advanced age or poor health. In rare cases, radiation may be recommended after surgery to destroy cancer cells not visible during surgery or to treat nonmelanoma skin cancer that has spread to the lymph nodes or other organs. Side effects include skin irritation, redness and drying and development of skin cancer years later.

What's on the Horizon

Treatment of skin cancer has been evolving rapidly, and more changes are on the horizon. Among the new approaches to treating nonmelanoma skin cancer are the following:

  • Photodynamic therapy. This treatment involves administering a drug that is absorbed by the body's cells, making them sensitive to a particular wavelength of light. After a certain period, the drug leaves the healthy cells but remains in the cancer cells. When these light-sensitive cancer cells are exposed to a laser light, the drug in the cells absorbs the light and produces a chemical change that destroys the cancer cells. In this way, cancer cells can be destroyed with minimal damage to healthy cells. The laser light can pass only superficially into the skin, so this therapy is best used for superficial tumors. The main side effect, skin sensitivity to sun and light exposure, may last four hours or up to six weeks.
  • Retinoids. These drugs are related chemically to vitamin A. Researchers currently are investigating the use of retinoids to prevent nonmelanoma skin cancer, especially for people at high risk of developing multiple skin cancers and recurrences. These drugs include isotretinoin, etretinate and acitretin. Taken orally, these drugs seem to help reduce the incidence of nonmelanoma skin cancers and solar keratoses. These still experimental drugs can cause serious side effects, including birth defects, liver abnormalities, raised blood lipids, drying of the lips and mucous membranes in the nose, and peeling of the palms and soles.

 

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