Squamous cell carcinoma of the skin

Definition

A squamous cell carcinoma is a skin cancer that originates from squamous keratinocytes in the epidermis, the top layer of the skin. Squamous is a term that indicates a surface with a scaly nature.

Description

Squamous keratinocytes are flattened, unpigmented skin cells in the middle of the epidermis. When they become cancerous, these cells invade the dermis (the layer of skin just below the epidermis) and spread out into the normal skin. They become visible as a small growth or area of change in the skin's appearance.

Most squamous cell carcinomas appear on areas that have been exposed to the sun: the head and neck, forearms, backs of the hands, upper part of the torso, and lower legs. Many develop in precancerous patches called actinic keratoses. Actinic keratoses are rough, scaly patches on the skin that usually start to show up in middle age. They are associated with a lifetime's exposure to the sun. Estimates of the chance that an actinic keratosis will turn into a squamous cell carcinoma vary from 0.24% to 20%.

Squamous cell carcinomas can also originate in old scars and burns, long-standing sores, and other areas of chronic skin irritation. These tumors tend to be more dangerous than those that arise in actinic keratoses.

The least dangerous type of squamous cell carcinoma is called Bowen's disease , intraepithelial squamous cell carcinoma, or squamous cell carcinoma in situ. Bowen's disease can show up anywhere on the skin, but it is especially common on the head and neck. This cancer usually grows slowly; but may evolve into a more serious, spreading form if it is not removed.

Other types of squamous cell carcinomas grow fairly quickly and can develop within a few months. These tumors may spread in the skin along the blood vessels, nerves, and muscles. They can also metastasize, or spread to other areas. On the average, 2-6% of squamous cell carcinomas metastasize, but this varies with the tumor site. At least 95% of the tumors that originate in actinic keratoses remain in the skin; but up to 38% of the cancers from scars are metastatic. Metastasis is also more likely when the cancer originates on the ear, lip, or genitalia, is large or deep, or develops in someone with a severely suppressed immune system. Cancers that regrow after treatment, and tumors that spread along the nerves are particularly dangerous.

Demographics

Squamous cell carcinomas are more common in the older adult population rather than the young. Overall, the chance of developing one is about 7% to 11%. The likelihood increases with exposure to the sun, and is greatest for fair-skinned individuals who tan poorly. Living near the equator, where ultraviolet light is more intense, also increases the risk. A weakened immune system— for instance, from an organ transplant, or AIDS—can also increase the risk of developing a squamous cell carcinoma by a factor of 5 to 250.

Squamous cell carcinomas tend to be most dangerous in individuals with dark skin. The mortality rate for African-Americans with squamous cell carcinomas is 17-24%, much higher than the 2% death rate for white males with nonmelanoma skin cancer. One reason for this disparity is that the cancers that develop in dark skin are more likely to come from old scars and burns than from actinic keratoses.

Causes and symptoms

Squamous cell carcinoma is caused by genetic damage to a skin cell. A number of factors can increase the risk that this will happen, but the exact cause is rarely known.

Any of the following changes may be a warning sign that an actinic keratosis is developing into a squamous cell carcinoma:

• pain
• increased redness
• sores or bleeding
• hardening or thickening
• increased size

Most squamous cell carcinomas begin as a small red bump on the skin. More advanced squamous cell carcinomas have the following characteristics:

• a few millimeters to a few centimeters in diameter
• reddish-brown, flesh-colored, pink, or red
• bumpy or flat
• sharp, irregular edges in Bowen's disease; others may have no definite edge
• may be crusted or scaly
• may contain bleeding sores

Diagnosis

Squamous cell carcinomas are usually diagnosed with a skin biopsy taken in the doctor's office. This is generally a brief, simple procedure. After numbing the skin with an injection of local anesthetic, the doctor snips out the tumor or a piece of it. This skin sample is sent to a pathologist to be read. It can take up to a week for the biopsy results to come back. Squamous cell carcinomas are graded into categories of one through four. The grading is based on how deeply the tumor penetrates in the skin and how abnormal its cells are. Higher grades are more serious.

Treatment team

Primary care physicians remove some squamous cell carcinomas; other cancers, including larger or more complicated tumors, may be referred to a dermatologist. The services of a plastic surgeon are occasionally necessary. Metastatic tumors are often treated by an oncologist, surgeons, specially trained nurses, and specialists in radiation treatment.

Clinical staging, treatments, and prognosis

Staging

In stage 0 (Bowen's disease), the cancer is very small and has not yet spread from the epidermis to the dermis.

In stage I, the cancer is less than 2 cm (0.8 inches) in diameter. No cancer cells can be found in lymph nodes or other internal organs.

In stage II, the cancer is more than 2 cm (0.8 inches) in diameter. No cancer cells can be found in lymph nodes or other internal organs.

In stage III, cancer cells have been found in nearby lymph nodes or in the bone, muscle, or cartilage beneath the skin.

A stage IV cancer can be any size. In this stage, cancer cells have been discovered in internal organs that are distant from the skin. Squamous cell carcinomas tend to spread to nearby lymph nodes, the liver, and the lungs.

Treatment

The treatment options for a squamous cell carcinoma depend on the size of the tumor, its location, and the likelihood that it will spread aggressively or metastasize. All of the treatments described below generally have cure rates of approximately 90% to 99% for small, localized cancers. The five-year cure rates are highest with Moh's surgery , also called Moh's micrographic surgery.

One option is conventional surgery. The doctor numbs the area with an injection of local anesthetic, then cuts out the tumor and a small margin of normal skin around it. The wound is closed with a few stitches. One advantage of conventional surgery is that the wound usually heals quickly. Another benefit is that the complete cancer can be sent to a pathologist for evaluation. If cancer cells are found in the skin around the tumor, additional treatments can be done.

Laser surgery may be an alternative. A disadvantage to laser surgery is that the wounds from some lasers heal more slowly than cuts from a scalpel. The advantage is that bleeding is minimal.

Another option is Moh's micrographic surgery. This technique is a variation of conventional surgery. In this procedure, the surgeon examines each piece of skin under the microscope as it is removed. If any cancer cells remain, another slice is taken from that area and checked. These steps are repeated until the edges of the wound are clear of tumor cells, then the wound is closed. The advantage to this technique is that all of the visible cancer cells are removed but as much normal skin as possible is spared. Mohs surgery is often used for larger or higher risk tumors and when cosmetic considerations are important. The main disadvantage is that it takes much longer than conventional surgery and requires a specially trained surgeon.

In cryosurgery, liquid nitrogen is used to freeze the tumor and destroy it. This treatment is another type of blind destruction; there is no skin sample to make sure the cancer cells have all been killed. Patients report swelling and pain after cryosurgery, and a wound appears a few days later where the cells were destroyed. Healing takes about four to six weeks. When the site heals, it has usually lost its normal pigment. There is a risk of nerve damage with this technique. Cryosurgery is generally used only for small cancers in stage 0 and stage I.

In electro dessication and curettage, the physician scoops out the cancer cells with a spoon-shaped instrument called a curette. After most of the tumor is gone, the rest is destroyed with heat from an electrical current. The wound is left open to heal like an abrasion. It leaks fluid, crusts over, and heals during the next two to six weeks. This method is generally used only for the smallest squamous cell carcinomas (stage 0 and stage I). One disadvantage is that there is no skin sample to confirm that the tumor is completely gone. The electrical current used during this surgery can interfere with some pacemakers.

Some cases of Bowen's disease can be treated by applying a lotion containing fluorouracil for several weeks. This treatment usually gives good cosmetic results. The side effects from fluorouracil include allergies to the ingredients, infections, redness, peeling, and crusting, sensitivity to the sun, and changes in skin color. The main disadvantage to this treatment is that the drug cannot penetrate very far and cancer cells in the deeper parts of the tumor may not be destroyed.

Radiation therapy is sometimes used for squamous cell carcinomas, especially when the tumor is at a site where surgery would be difficult or remove a sizeable amount of tissue. This treatment is sometimes combined with surgery for cancers that have metastasized or are likely to. One disadvantage is that tumors returning after radiation tend to grow more quickly than the original cancer. In addition, x rays may promote new skin cancers. The cosmetic results are usually good. In some cases the skin may lose a little pigment, or develop spider veins. Some doctors reserve radiation treatment for those over 60.

Chemotherapy is often added to surgery or radiation for stage IV cancers. Retinoids and interferon are experimental treatments that may be helpful.

Prognosis

Because many squamous cell carcinomas are not staged, precise five-year survival rates for each stage are not available. In general, the prognosis is very good for small squamous cell carcinomas that originate in actinic keratoses. However, cancers that were not completely destroyed may regrow. Tumors can redevelop in the scar from the surgery, on the edges of the surgery site, or deep in the skin. Larger or higher risk tumors, cancers that regrow after treatment, and tumors that have invaded local tissues or metastasized are more difficult to cure. Most metastases show up within the first two years after a skin tumor has been removed. The five-year survival rate for metastatic cancers is 34%.

Alternative and complementary therapies

Alternative treatments for squamous cell carcinoma usually attempt to prevent rather than treat this cancer. Options being tested include antioxidant vitamins , minerals, and green tea extracts.

Coping with cancer treatment

Most squamous cell carcinomas are removed with techniques that cause few, if any, lasting side effects. Patients who have cosmetic concerns may wish to discuss them with their doctors.

Clinical trials

The medical community considers the following treatments to be experimental.

Clinical trials are testing whether interferon alpha, injected into the tumor, can destroy some squamous cell carcinomas. An early report from a combination of inter-feron alpha and retinoids is promising.

Ongoing trials are also evaluating whether small squamous cell carcinomas can be cured with photodynamic laser therapy. In this technique, a dye activated by laser light destroys the cancer. This dye is spread onto the skin, injected, or drunk. During a waiting period, normal cells clear the dye, then a laser activates the remainder. As of 2001, this technique was only useful for cancers very near the surface of the skin. One side effect after treatment is a period of excessive sun-sensitivity.

Other clinical trials are testing whether retinoids, spread onto the skin, can prevent or treat squamous cell carcinoma.

Prevention

The most important risk factor for squamous cell carcinoma is exposure to the sun (or other source of ultraviolet light) combined with a lighter complexion and inability to tan. Other risk factors include:

• increasing age
• actinic keratoses
• a previous skin cancer
• exposure to arsenic or the chemicals in coal tars
• radiation treatments
• treatment with psoralen and ultraviolet light for psoriasis
• chronic skin damage such as burn scars and ulcers
• infection with some varieties of human papillomavirus
• genetic disorders such as xeroderma pigmentosum and albinism
• a weakened immune system

Most people will receive 80% of their lifetime exposure to the sun before they reach the age of 20. For this reason, prevention should start during childhood and adolescence. Some important steps to prevent squamous cell carcinoma, as well as other skin cancers include:

• Wear protective clothing and a wide-brimmed hat in the sun.
• Stay out of the sun from 10 A. M. to 4 P. M.
• Use a sunscreen that has a sun protection factor (SPF) of at least 15.
• Avoid suntanning booths.

Drugs related to vitamin A (including beta-carotene and retinoids), vitamin E, nonsteroidal anti-inflammatory drugs (NSAIDS), and selenium might be able to prevent some skin cancers. In 2001, their effectiveness was still in question.

Special concerns

Because many squamous cell carcinomas are found on the face and neck, cosmetic concerns are a priority for many patients. If there is a risk of noticeable scarring or damage, a patient may wish to ask about alternative types of removal or inquire about the services of a plastic surgeon.

After treatment, it is important to return to the doctor periodically to check for regrowth or new skin cancers. Approximately a third to a half of all patients with nonmelanoma skin cancers find a new skin cancer within the next five years. Having a squamous cell carcinoma before the age of 60 may also increase the chance of developing other cancers in internal organs; however, this idea is still very controversial.

See Also Basal cell carcinoma; Chemoprevention; Reconstructive surgery

Resources

BOOKS

Keefe, Kristin A., and Frank L. Meyskens, Jr. "Cancer Prevention." In Clinical Oncology, 2nd ed., edited by Martin D. Abeloff, James O. Armitage, Allen S. Lichter, and John E. Niederhuber. Philadelphia: Churchhill Livingstone, 2000, pp.339-42.

Rohrer, Thomas E. "Cancer of the Skin." In Conn's Current Therapy; Latest Approved Methods of Treatment for the Practicing Physician, 52nd ed., edited by Robert E. Rakel et al. Philadelphia: W. B. Saunders, 2000, pp.763-5.

Waldorf, Heidi A. "Premalignant Lesions." In Conn's Current Therapy; Latest Approved Methods of Treatment for the Practicing Physician, 52nd ed., edited by Robert E. Rakel et al. Philadelphia: W. B. Saunders, 2000, pp.792-4.

Wolfe, Jonathan. "Nonmelanoma Skin Cancers: Basal Cell and Squamous Cell Carcinoma." In Clinical Oncology, 2nd ed., edited by Martin D. Abeloff, James O. Armitage, Allen S. Lichter, and John E. Niederhuber. Philadelphia: Churchhill Livingstone, 2000, pp.1351-8.

PERIODICALS

Elmets C.A., D. Singh, K. Tubesing, M. Matsui. S. Katiyar, and H. Mukhtar. "Cutaneous photoprotection from ultraviolet injury by green tea polyphenols." Journal of the American Academy of Dermatology 44, no. 3 (March 2001): 425-32.

Garner, Kyle L., and Wm. Macmillian Rodney. "Basal and Squamous Cell Carcinoma." Primary Care; Clinics in Office Practice 27, no. 2 (June 2000): 477-8.

"Is Sunscreen an Enabler?" Harvard Health Letter 25, no. 9 (July 2000): 1-3.

Jerant, Anthony F., Jennifer T. Johnson, Catherine Demastes Sheridan, and Timothy J. Caffrey. "Early Detection and Treatment of Skin Cancer." American Family Physician 62 (15 July 2000): 357-68, 375-6, 381-2.

Keller, Karen Laszlo, and Neil A. Fenske. "Use of Vitamins A, C, and E and Related Compounds in Dermatology: A Review." Journal of the American Academy of Dermatol ogy 38, no. 4 (October 1998): 611-25.

ORGANIZATIONS

American Skin Association. 150 East 58th Street, 32nd Floor, New York, NY, 10155-0002. (212) 753-8260.

Skin Cancer Foundation. 245 Fifth Avenue, Suite 2402, New York, NY 10016. (212) 725-5176.

OTHER

"Nonmelanoma Skin Cancer Treatment—Health Professionals." CancerNet. Aug. 2000 National Cancer Institute. 15 Mar. 2001 <http://cancernet.nci.nih.gov/pdq.html>.

"Non-melanoma Staging." Oncology Channel. Mar. 2001. 26 June 2001. <http://oncologychannel.com/nonmelanoma/staging.shtml>

"Prevention of Skin Cancer. Prevention—Health Profession als." CancerNet. Mar. 2001 National Cancer Institute. 26 June 2001. <http://cancernet.nci.nih.gov/pdq.html>.

Skin Cancer. CancerLinksUSA. 1999. 26 June 2001. <http://www.cancerlinksusa.com/skin/index.htm>.

Anna Rovid Spickler, D.V.M., Ph.D.

KEY TERMS

Actinic keratosis (plural actinic keratoses)

—A rough, dry, scaly patch on the skin associated with sun exposure.

Albinism

—A genetic disease characterized by the absence of the normal skin pigment, melanin.

Antioxidant

—A substance that can neutralize free radicals. Free radicals are damaging molecules formed from oxygen. Antioxidant vitamins include vitamin E, C, and beta-carotene, a form of vitamin A.

Biopsy

—A sample of an organ taken to look for abnormalities. Also, the technique used to take such samples.

Chronic

—Long-standing.

Dermis

—A layer of skin sandwiched between the epidermis and the fat under the skin. It contains the blood vessels, nerves, sweat glands, and hair follicles.

Epidermis

—The thin layer of skin cells at the surface of the skin.

Fluorouracil

—A cancer drug.

Interferon alpha

—A chemical made naturally by the immune system and also manufactured as a drug.

Local anesthetic

—A liquid used to numb a small area of the skin.

Lymph node

—A small organ full of immune cells, found in clusters throughout the body. Lymph nodes are where reactions to infections usually begin.

Nonmelanoma skin cancer

—A squamous cell carcinoma or basal cell carcinoma.

Nonsteroidal anti-inflammatory drugs (NSAIDS)

— A class of drugs that suppresses inflammation. Includes a wide variety of drugs, including aspirin.

Papillomavirus

—A member of a group of viruses associated with warts and cervical cancer.

Pathologist

—A doctor who specializes in examining cells and other parts of the body for abnormalities.

Precancerous

—Abnormal and with a high probability of turning into cancer, but not yet a cancer.

Oncologist

—A doctor who specializes in the treatment of cancer.

Retinoids

—A class of drugs related to vitamin A.

Selenium

—A mineral needed in extremely small quantities by the body. Large amounts can be very toxic.

Xeroderma pigmentosum

—A genetic disease characterized by the inability to repair damaged DNA. Individuals with this disease develop an excessive number of skin cancers.

QUESTIONS TO ASK THE DOCTOR

• What treatment (s) would you recommend for my tumor?
• How effective would you expect each of them to be, for a tumor of this size and in this location?
• How much cosmetic damage am I likely to see with each?
• Are there any alternatives?
• How should I prepare for the procedure?
• What is the risk that my tumor in particular will grow again?