Wednesday, April 4, 2012

Squamous Cell Carcinoma of the Skin

Author: Dr Bryan Cho University of California SF 2009-01-22
Squamous Cell Carcinoma of the Skin: Appearance,Risk Factors, Treatment and Prevention

Squamous cell carcinoma (SCC) is a cancer of cells that make up the uppermost layer of the skin. Cancer is a condition where skin cells grow haphazardly, invade surrounding tissue and disrupt normal tissue function.  When diagnosed and treated early, most SCCs are not serious and can be cured. About 98-99% of SCCs are localized—the cancer is only present in the skin. However, if treatment is significantly delayed, SCC can spread and invade surrounding bone, cartilage or muscle. Only in rare cases can SCC metastasize (travel to nearby lymph nodes or distant organs) which can be life threatening. When SCC occurs in the most superficial layers of the skin it is called in situ. Squamous cell carcinoma that has invaded the underlying skin layers is known as invasive.
Squamous cell carcinoma is the second most common form of skin cancer with over 250,000 new cases per year in the United States. Roughly twenty percent of the skin cancers diagnosed each year is SCC.

 


Appearance

Because SCC is a tumor of the skin, the most common presentation is a new skin growth that does not go away. Most often they are flat reddish patches or raised red bumps. Sometimes, there may be an open sore within the tumor. Most SCCs grow slowly but they can grow rapidly in patients with a depressed immune system. Sometimes, the only clue that skin cancer is present is a new bump that persists or sore that will not heal.
If you are concerned you may have SCC, contact your primary care physician or local dermatologist so they may examine the skin lesion that you are concerned with.  If they suspect that the lesion may be cancerous, they might perform a skin biopsy to confirm their clinical diagnosis. 
 

Location

Squamous cell carcinoma most commonly occurs on areas of the body that have had many years of sun exposure. Face, ears, scalp, back of the hands and forearms are the most common sites. Sun damaged skin can be identified by the presence of wrinkles, age spots and persistent red blood vessels. In many cases, precancerous skin lesions called actinic keratosis may be nearby. 
Some body sites are at higher risk for recurrent tumor or metastasis; these include SCCs on the lip, ear and nose.


Risk Factors 
Sun Exposure

The most common cause of SCC is overexposure to sunlight.  Ultraviolet radiation within sunlight can damage the DNA of skin cells. Both UVA and UVB radiation can penetrate the skin to cause skin cancer.  After many years of sun exposure, damage accumulates and skin cancers begin to form. Factors that increase exposure to UV radiation and elevate risk for SCC include:
  • Jobs or leisure activities that occur primarily outdoors
  • Living in sunny climates
  • Sunbathing
  • Tanning booths
  • Sunburns
Because sun damage adds up over time, it is important to practice good sun protection measures over a lifetime.

Skin Type
Anyone can develop SCC, but people with fair complexions are the most susceptible. A convenient way to identify your skin type is to use the following scale.
Fitzpatrick Skin Type
  • I      Extremely fair skin, always burns, never tans
  • II    Fair skin, always burns, sometimes tans
  • III   Medium skin, somtimes burns, always tans
  • IV  Olive skin, rarely burns, always tans
  • V   Moderately pigmented brown skin, never burns, always tans
  • VI  Markedly pigmented black skin, never burns, always tans
The lower your skin type number, (e.g. type I skin) the higher your risk for developing skin cancer following significant sun exposure.


Previous Skin Cancer

Once you’ve had one SCC, you are at elevated risk for developing additional SCCs in the future.  You are also at elevated risk for developing other types of skin cancer including basal cell carcinoma and melanoma.  Most patients with a history of SCC should see their dermatologist for a full skin evaluation at least once a year.  The dermatologist may recommend more frequent skin evaluations in some cases.


Immune Status

People with weakened immune systems due to illness or medication may develop SCC more frequently, especially if they have other risk factors. Examples of immunosuppressive illnesses include HIV/AIDS and lymphoma.
The frequency of SCC in transplant recipients is 65-fold higher than the general population (1). The risk of skin cancer increases each year following transplantation and the cancers that occur may develop more quickly and be more aggressive. The current ITSCC (International Transplant Skin Cancer Consortium) guidelines recommend that all transplant recipients have a full body skin exam by a dermatologist at least once yearly (2).
To learn more about skin cancer in transplant recipients see:


Exposures

Chronically inflamed skin such as that found in ulcers or burn injuries can evolve into SCC. Areas of skin that have been exposed to relatively high doses of radiation such as those used to treat cancer (e.g. radiotherapy) or used to treat acne (done prior to 1950) may be at elevated risk for skin cancer.  Toxic materials such as arsenic can also increase risk for developing SCC. 
Genetic disease

Individuals with a rare disease called Xeroderma Pigmentosum have a condition that prevents repair of skin cells damaged by the UV radiation in sunlight.  These individuals develop SCC at a very young age that can be life threatening.
Precancers

Squamous cell carcinoma has a precursor condition called an actinic keratosis. Actinic keratoses are considered the earliest stage in the development of SCC. Up to 1% of these lesions can become cancerous. More than 10 million Americans develop actinic keratosis as a result of sun overexposure. Having one actinic keratosis means you will likely develop more in the future and are at risk for developing SCC. When actinic keratoses occur on the lip the condition is called actinic chelitis.
Actinic keratoses are pink, scaly, rough spots that reoccur in the same location and are usually less than the size of a dime.
Actinic keratoses are most common in people older than 40, but can also appear in younger individuals with extensive sun exposure. Because they can turn cancerous, affected areas should be regularly examined and treated to prevent their change to cancer.

Diagnosis


If you or your doctor finds a bump or spot that is suspicious for skin cancer, a biopsy may be performed. A biopsy is a diagnostic test but not a treatment. Further treatment is necessary to ensure the cancer is removed completely.
To perform a biopsy, the skin is numbed with local anesthesia then a sample of skin is removed to analyze under a microscope. Other than the injected anesthesia, the procedure is painless. Most biopsy sites require local wound care and will heal within three to four weeks.

Treatment


There are several medical and surgical treatments for SCC.  Most surgical treatments are done in a physician’s office under local anesthesia. Which treatment method used is determined by many factors including:
  • Size
  • Location
  • Primary or recurrent skin cancer
  • Subtype of skin cancer
  • Invasion of underlying structures, nerves or metastatic spread
  • Health of the patient
  • Preference of the patient
  • Preference of the physician
You and your physician should discuss the various treatment options and decide which best suits your particular diagnosis.
Medical

Topical Chemotherapy

5-fluorouracil is a topical (used on top of the skin) anticancer agent that is typically used to selectively eliminate precancers of the skin (actinic keratosis). Under certain circumstances (such as those patients who are unable to tolerate surgery), this treatment can be used to treat very superficial forms of SCC (squamous cell carcinoma in situ) however this is generally not recommended. Use of this medication requires close medical supervision and follow-up. The cream is applied twice per day for 3 to 9 weeks (3). Side effects include redness, painful burning, oozing, and itching. It may be difficult to tell the difference between the expected action of 5-fluorouracil on your skin versus an allergic reaction or infection.

Topical Immunomodulators

Imiquimod is a chemical that stimulates an immune response against abnormal skin cells. Clinical trials for Imiquimod as a treatment for SCC are ongoing but early results are encouraging (4). Use of Imiquimod for SCC is an off-label use.  This means that the FDA has not approved the medication for use in this condition. The current dosing regimen for SCC is once a day for 16-weeks.

Chemoprevention

Acetretin is an oral retinoid medication that has been shown to decrease the development of new SCCs (5). Because of the potential for many and serious side effects, this medication is only used in high risk skin cancer patients who generally develop greater than five skin cancers per year. The chemopreventative actions of the medication only persist while taking the medication and once discontinued, new skin cancers will develop.
Surgical

Curettage and Electrodessication

Tumor cells are scraped away with a curette, a sharp, spoon like instrument and then the area is cauterized (electrodessicated) with an electric needle to control bleeding and kill any remaining tumor cells. The procedure is repeated for up to three cycles to ensure that any remaining tumor cells are destroyed.  This procedure is appropriate for superficial forms of SCC (e.g. squamous cell carcinoma in situ). Cure rates from 90 to 95% are generally achieved. This procedure is quick but typically leaves a circular scar.

Surgical Excision

Surgical excision is the most common procedure used to treat SCC. The area is anesthetized with local anesthesia and the cancer is removed along with a border of healthy appearing skin, called a margin. A margin is necessary because it is impossible to tell with the naked eye where the tumor stops and normal skin begins. The width of the margin varies depending on body site and subtype of SCC but is typically about 4mm. All layers of the skin are removed as well as a portion underlying fat and the wound is sewn closed. Excision wounds typically heal in one to two weeks depending on the body site. The tumor specimen is sent to a lab to see if any cancer remains. If tumor is still present, additional surgery is required. The cure rate for excisional surgery is about 95%.

Mohs Micrographic Surgery 

Mohs surgery is a type of surgical technique used for high risk SCC. The cancer is removed in layers; each layer is checked under a microscope until the entire tumor is removed. The processing of each layer takes about one hour; most surgeries can be completed in a day. By removing the cancerous tissue but as little normal tissue as possible, the functional and cosmetic outcome is maximized. Because the entire margin is examined, Mohs surgery has the highest five-year cure rate for surgical treatment of both skin cancers primary (96-98%).
Mohs surgery is generally used to remove large tumors, tumors in high risk sites (eyelids, nose, ears and lips) or for cancers that were treated previously and have recurred.  It is also the treatment of choice for high risk skin cancer patients such as organ transplant recipients.  This method should only be performed by physicians who are specially trained in this type of surgery. The surgery is performed under local anesthesia.
For more information about Mohs surgery see: http://www.mohssurgery.org/pdfs/patient_information_brochure.pdf
Photodynamic therapy

An agent called a photosensitizer is applied to the skin and accumulates preferentially within tumor cells. When exposed to a specific type of light, the photosensitizer is activated and kills the cancer.  This treatment is currently approved for treatment of precancers.  Treatment of superficial SCC is considered an off-label use (not approved by the FDA).

Radiation therapy

Radiation is used to treat SCC that has invaded surrounding nerves (perineural spread) or for metastatic SCC that has invaded nearby skin lymphatics (in transit metastasis) or draining lymph nodes. For these type of SCC, radiation is used in conjunction with surgical treatments.  Radiation can also be used to treat SCC in patients too ill to undergo surgery or for unresectable tumors for palliation. Multiple cycles of radiation are usually required.

Prevention


Self skin exam
Examine your skin once a month for any suspicious changes.  The single most important feature that may signal the presence of a skin cancer is a new, changing, enlarging skin growth that persists.  Sores that do not heal may also indicate cancerous or precancerous conditions of the skin that need attention. Early intervention is critical to successful treatment. If you have a history of SCC, you should see your dermatologist at least once per year for a full skin check.  In some cases, the dermatologist may recommend more frequent skin evaluations.
To learn how to perform skin self exams: http://www.skincancer.org/early-detection/self-examination.html

Ultraviolet Radiation
Some exposure to sunlight can be enjoyable, but too much sunlight can be dangerous.  Sunlight consists of two types of ultraviolet (UV) radiation: UVB and UVA.  Both UVB and UVA radiation contribute to freckling, skin wrinkling and the development of skin cancer.
UVB radiation (290-320nm) has the most energy and causes the most damage when it penetrates the skin.  UVB is only partially blocked by clouds or fog; therefore, it is important to wear sunblock even on cloudy days.  This type of radiation intensifies during the summer and with higher elevations and can do damage more quickly than UVA radiation. Because of its damaging affect to the DNA of skin cells, UVB radiation is the main cause of sunburn and skin cancer.  Over the past 25-years, the thinning ozone has meant more UVB penetrates the atmosphere so the risk for UVB-related sun damage has gone up. 
UVA radiation (320-400nm) is less powerful than UVB, but it penetrates deeper into the skin.  Small daily doses of UVA causes long-term skin injury, even without signs of sunburn. UVA light is used in tanning booths. Tanning booths not only inflict the same type of skin and eye damage as natural sunlight, they may also be as much as 20 times stronger.

Sun protection
Squamous cell carcinoma is largely preventable. Studies have shown ~90% of skin cancers are linked to sun exposure.  Therefore good sun protection is an important way to prevent the development of both sun-related skin damage (freckles, fine wrinkles, etc…) and sun-related skin cancers. Sun protection has three components:
  • Application of a broad spectrum, daily sunblock
  • Sun protective clothing
  • Sun avoidance

Sunblock
Chemical sunblocks absorb UV radiation and convert light energy to heat. Physical sunblocks (Zinc oxide or titanium dioxide) reflect UV radiation away from your skin. 
All sunblocks have a Sun Protection Factor (SPF) rating. The SPF rating indicates how long a sunscreen remains effective on the skin. A user can determine the how long their sunblock will be effective by multiplying the SPF factor by the length of time it takes for him or her to suffer a burn without sunscreen. 
For instance, if you normally develop a sunburn in 10 minutes without wearing a sunscreen, a sunscreen with an SPF of 15 will protect you for 150 minutes (10 minutes multiplied by the SPF of 15). Although sunscreen use helps minimize sun damage, no sunscreen completely blocks the all wavelengths of UV light. Wearing sun protective clothing and minimizing your sun exposure from 10 a.m. to 3 p.m. will also help protect your skin from overexposure and minimize sun damage.
If you have had SCC or want to use sunblock as a preventative measure against sun damage, a general recommendation would be to use a broad spectrum sunblock with UVA and UVB protection with an SPF rating of at least 30. Sunblock should be applied daily as part of your morning routine. All sunblocks should be applied 15-20 minutes before sun exposure to allow a protective film to develop, then reapplied after water contact or sweating.  Some sunblocks can lose effectiveness after two hours, so reapply frequently.
Water resistant sunblocks are available for active individuals or those involved in sports.  It’s important to check the label to ensure they say “water-resistant” or “very water-resistant.” 
  • Water-Resistant sunblock maintains the SPF level after 40 minutes of water immersion
  • Very Water-Resistant sunblock maintains the SPF level after 80 minutes of water immersion
A website that has details of over 1000 sunblocks/sunscreens and allows easy indentification of those which are physical blockers or chemically-based can be found at:  
 

Sun Protective Clothing:
Clothing is a simple sun protection tool since it provides a physical barrier from the sun that doesn't wash or wear off and can protect the skin from both UVA and UVB radiation. Long-sleeved shirts and pants, hats with broad brims and sunglasses are all effective forms of sun protective clothing. 
The ideal sun-protective fabrics are lightweight, comfortable, and protect against exposure even when wet. Several companies in the U.S. manufacture clothing that is specifically designed to be UV-protective.  Their products include outerwear, pants, shirts, and hats for all sizes and shapes including children.
For more information see the following websites:

Sun Protective Clothing Additives: SunGuard Detergent
SunGuard detergent is an UV blocking additive that can be added to your laundry to change everyday clothing into sun protective clothing with a SPF 30. SunGuard is odorless and colorless and last for approximately 30 washes before losing its effectiveness.
For more information see http://www.ritsunguard.com/

Sun avoidance
Avoiding sunshine can help protect you from developing SCC.
  • Limit your time in the sun between 10 a.m. and 3 p.m.
  • Plan your outdoor activities so you can avoid the intense, mid-day sun
  • Whenever possible, seek shade

References
1. Jensen P. et al. J Am Acad Dermatol. 2000; 42, p307
2. Stasko T et al. Dermatol Surg. 2004;30(4 Pt 2),p642
3. Bargman H. et al. J Cutan Med Surg. 2003;7:p101
4.  Mackenzie-Wood A. et al. J Am Acad Dermatol. 2001;44:p462
5.  Lebwohl M, Tannis C et al.J Dermatolog Treat. 2003;14 Suppl 2:p3
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