Breast cancer survivor offers wisdom at Faulkner satellite center
Call 877-422-3324 today to make an appointment
Make your appointment or second opinion with Dana-Farber today to meet with an onsite specialist.
Can’t get to Boston? Explore our Online Second Opinion service to get expert advice from Dana-Farber oncologists.
Toll-Free Number866-408-DFCI (3324)
Discover the ways to give and how to get involved to support Dana-Farber.
Poet Richard Fox gains insight – and material – through cancer treatment
A family faces cancer in an unfamiliar city – with help
Choosing mastectomy or not: Studying young women's surgical choices
Jeff's targeted therapy has kept his advanced lung cancer at bay.
Basal cell carcinoma is a type of skin cancer that arises from the basal cells, which are small round cells found in the lower part of the epidermis, the outer layer of the skin. Learn about basal cell carcinoma and find information on how we support and care for people with basal cell carcinoma before, during, and after treatment.
Skin Cancer Treatment at the Center for Cutaneous Oncology
At the Center for Cutaneous Oncology, we believe that each case of skin cancer is as unique as the individual facing the diagnosis. Experts from a wide variety of medical fields are here to evaluate and treat your particular skin cancer, no matter how rare or complex.
As a patient in the Center for Cutaneous Oncology, you will be cared for by a dedicated team that focuses exclusively on skin cancers. Our experts include dermatologic oncologists, dermatopathologists, medical oncologists, surgical oncologists, radiation oncologists, radiologists, and other specialists.
Our skin cancer specialists work together, and with you, to create individualized treatment that supports all your medical, nutritional, and emotional needs.
Our clinicians are experts in treating all types of skin cancer, including:
We also treat cutaneous complications of therapy for cancers in general, including:
Learn more about skin cancer treatment at the Center for Cutaneous Oncology
If you have never been seen before at Dana-Farber/Brigham and Women's Cancer Center, please call 877-442-3324 or use this online form to make an appointment.
Established patients: 617-632-6571
Referring physicians: 617-632-6869
Mohs Micrographic Surgery Center
The skin is the body’s largest organ. It protects against heat, sunlight, injury, and infection. Skin also helps control body temperature and stores water, fat, and vitamin D. The skin has several layers, but the two main layers are the epidermis (upper or outer layer) and the dermis (lower or inner layer). Skin cancer begins in the epidermis, which is made up of three kinds of cells:
Skin cancer can occur anywhere on the body, but it is most common in skin that is often exposed to sunlight, such as the face, neck, hands, and arms.
The most common types are basal cell carcinoma and squamous cell carcinoma, which are nonmelanoma skin cancers. Nonmelanoma skin cancers rarely spread to other parts of the body. Melanoma is the rarest form of skin cancer. It is more likely to invade nearby tissues and spread to other parts of the body. Actinic keratosis is a skin condition that sometimes becomes squamous cell carcinoma.
This summary is about nonmelanoma skin cancer and actinic keratosis. See the following PDQ summaries for information on melanoma and other kinds of cancer that affect the skin:
Anything that increases your chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your doctor if you think you may be at risk. Risk factors for basal cell carcinoma and squamous cell carcinoma include the following:
Risk factors for actinic keratosis include the following:
Not all changes in the skin are a sign of nonmelanoma skin cancer or actinic keratosis. Check with your doctor if you notice any changes in your skin.
Signs of nonmelanoma skin cancer include the following:
Signs of actinic keratosis include the following:
The following procedures may be used:
The prognosis (chance of recovery) depends mostly on the stage of the cancer and the type of treatment used to remove the cancer.
Treatment options depend on the following:
The process used to find out if cancer has spread within the skin or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment.
The following tests and procedures may be used in the staging process:
Cancer can spread through tissue, the lymph system, and the blood:
When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.
The metastatic tumor is the same type of cancer as the primary tumor. For example, if skin cancer spreads to the lung, the cancer cells in the lung are actually skin cancer cells. The disease is metastatic skin cancer, not lung cancer.
Staging for nonmelanoma skin cancer that is on the eyelid is different from staging for nonmelanoma skin cancer that affects other parts of the body.
The following are high-risk features for nonmelanoma skin cancer that is not on the eyelid:
In stage 0, abnormalcells are found in the squamous cell or basal cell layer of the epidermis (topmost layer of the skin). These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is also called carcinoma in situ.
In stage I, cancer has formed. The tumor is not larger than 2 centimeters at its widest point and may have one high-risk feature.
In stage II, the tumor is either:
In stage III:
In stage IV, one of the following is true:
In stage 0, abnormalcells are found in the epidermis (topmost layer of the skin). These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is also called carcinoma in situ.
Stage I is divided into stages IA, IB, and IC.
In stage II, one of the following is true:
Stage III is divided into stages IIIA, IIIB, and IIIC.
The tumor has spread to distant parts of the body.
A skin cancer lesion that looks reddish brown and slightly raised.
A skin cancer lesion that looks like an open sore with a pearly rim.
Basal cell carcinoma is the most common type of skin cancer. It usually occurs on areas of the skin that have been in the sun, most often the nose. Often this cancer appears as a raised bump that looks smooth and pearly. Another type looks like a scar and is flat and firm and may be white, yellow, or waxy. Basal cell carcinoma may spread to tissues around the cancer, but it usually does not spread to other parts of the body.
A skin cancer lesion that looks raised and crusty.
A skin cancer lesion that looks pink and raised.
Squamous cell carcinoma occurs on areas of the skin that have been in the sun, such as the ears, lower lip, and the back of the hands. Squamous cell carcinoma may also appear on areas of the skin that have been burned or exposed to chemicals or radiation. Often this cancer appears as a firm red bump. The tumor may feel scaly, bleed, or form a crust. Squamous cell tumors may spread to nearby lymph nodes. Squamous cell carcinoma that has not spread can usually be cured.
Actinic keratosis is a skin condition that is not cancer, but sometimes changes into squamous cell carcinoma. It usually occurs in areas that have been exposed to the sun, such as the face, the back of the hands, and the lower lip. It looks like rough, red, pink, or brown scaly patches on the skin that may be flat or raised, or the lower lip cracks and peels and is not helped by lip balm or petroleum jelly.
Different types of treatment are available for patients with nonmelanoma skin cancer and actinic keratosis. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.
One or more of the following surgical procedures may be used to treat nonmelanoma skin cancer or actinic keratosis:
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiationtherapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Chemotherapy for nonmelanoma skin cancer and actinic keratosis is usually topical (applied to the skin in a cream or lotion). The way the chemotherapy is given depends on the condition being treated.
Retinoids (drugs related to vitamin A) are sometimes used to treat squamous cell carcinoma of the skin.
See Drugs Approved for Basal Cell Carcinoma for more information.
Photodynamic therapy (PDT) is a cancer treatment that uses a drug and a certain type of laser light to kill cancer cells. A drug that is not active until it is exposed to light is injected into a vein. The drug collects more in cancer cells than in normal cells. For skin cancer, laser light is shined onto the skin and the drug becomes active and kills the cancer cells. Photodynamic therapy causes little damage to healthy tissue.
Biologic therapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.
Interferon and imiquimod are biologic agents used to treat skin cancer. Interferon (by injection) may be used to treat squamous cell carcinoma of the skin. Topical imiquimod therapy (a cream applied to the skin) may be used to treat some small basal cell carcinomas.
Information about clinical trials is available from the NCI Web site.
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.
Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.
Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.
Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
Basal cell carcinoma and squamous cell carcinoma are likely to recur (come back), usually within 5 years, or new tumors may form. Talk to your doctor about how often you should have your skin checked for signs of cancer.
Treatment of basal cell carcinoma may include the following:
Treatment of recurrent basal cell carcinoma is usually Mohs micrographic surgery.
Treatment of basal cell carcinoma that is metastatic or cannot be treated with local therapy is usually chemotherapy or a clinical trial of a new treatment.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with basal cell carcinoma of the skin. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
Treatment of squamous cell carcinoma may include the following:
Treatment of recurrent squamous cell carcinoma may include the following:
Treatment of squamous cell carcinoma that is metastatic or cannot be treated with local therapy may include the following:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with squamous cell carcinoma of the skin. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
Actinic keratosis is not cancer but is treated because it may develop into cancer. Treatment of actinic keratosis may include the following:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with actinic keratosis. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
For more information from the National Cancer Institute about skin cancer, see the following:
For general cancer information and other resources from the National Cancer Institute, see the following:
This information is provided by the National Cancer Institute.
This information was last updated on September 2, 2014.
There are three main types of skin cancer:
BCC and SCC are the most common forms of skin cancer and are collectively referred to as nonmelanoma skin cancers. This summary only covers the treatment of nonmelanoma skin cancers. (Refer to the PDQ summary on Melanoma Treatment for more information.)
Nonmelanoma skin cancer is the most commonly occurring cancer in the United States. BCC is the more common type of the two nonmelanoma types, accounting for about three-quarters of nonmelanoma skin cancers. The incidence of nonmelanoma skin cancer appears to be increasing in some, but not all  areas of the United States. Overall U.S. incidence rates have likely been increasing for a number of years. At least some of this increase may be attributable to increasing skin cancer awareness and resulting increasing investigation and biopsy of skin lesions.
Precise estimation of the total numbers and incidence rate of nonmelanoma skin cancer is not possible because reporting to cancer registries is not required. However, based on Medicare fee-for-service data, which were then extrapolated to the U.S. population, an estimated 2,152,500 persons were treated for nonmelanoma skin cancers in 2006. That number would exceed all other cases of cancer estimated by the American Cancer Society for that year, which was about 1.4 million. Although the two types of nonmelanoma skin cancer are the most common of all malignancies, they account for less than 0.1% of patient deaths caused by cancer.
Epidemiologic evidence suggests that exposure to ultraviolet (UV) radiation and the sensitivity of an individual’s skin to UV radiation are risk factors for skin cancer, though the type of exposure (i.e., high-intensity exposure and short-duration exposure vs. chronic exposure) and pattern of exposure (i.e., continuous pattern vs. intermittent pattern) may differ among the three main skin cancer types. All three types of skin cancer are more likely to occur in individuals of light complexion who have had substantial exposure to sunlight, and skin cancers are more common in the southern latitudes of the Northern hemisphere. In addition, the immune system may play a role in pathogenesis of skin cancers.
Organ transplant recipients receiving immunosuppressive drugs are at an elevated risk of skin cancers, particularly SCC. Arsenic exposure also increases the risk of cutaneous SCC. Serologic evidence from a population-based case-control study has shown a possible association between infection with the human papilloma virus (HPV) genus beta-species 1 and SCC.
Note: Other PDQ summaries containing information related to skin cancer include the following:
Reszko A, Aasi SZ, Wilson LD, et al.: Cancer of the skin. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1610-33.
Athas WF, Hunt WC, Key CR: Changes in nonmelanoma skin cancer incidence between 1977-1978 and 1998-1999 in Northcentral New Mexico. Cancer Epidemiol Biomarkers Prev 12 (10): 1105-8, 2003.
Harris RB, Griffith K, Moon TE: Trends in the incidence of nonmelanoma skin cancers in southeastern Arizona, 1985-1996. J Am Acad Dermatol 45 (4): 528-36, 2001.
Rogers HW, Weinstock MA, Harris AR, et al.: Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol 146 (3): 283-7, 2010.
American Cancer Society: Cancer Facts and Figures 2006. Atlanta, Ga: American Cancer Society, 2006. Also available online. Last accessed February 21, 2014.
Koh HK: Cutaneous melanoma. N Engl J Med 325 (3): 171-82, 1991.
Preston DS, Stern RS: Nonmelanoma cancers of the skin. N Engl J Med 327 (23): 1649-62, 1992.
English DR, Armstrong BK, Kricker A, et al.: Case-control study of sun exposure and squamous cell carcinoma of the skin. Int J Cancer 77 (3): 347-53, 1998.
Karagas MR, Nelson HH, Sehr P, et al.: Human papillomavirus infection and incidence of squamous cell and basal cell carcinomas of the skin. J Natl Cancer Inst 98 (6): 389-95, 2006.
Patel AS, Karagas MR, Perry AE, et al.: Exposure profiles and human papillomavirus infection in skin cancer: an analysis of 25 genus beta-types in a population-based study. J Invest Dermatol 128 (12): 2888-93, 2008.
This evidence summary covers basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin, and the related noninvasive lesion actinic keratosis (viewed by some pathologists as a variant of in situ SCC ). Although BCC and SCC are by far the most frequent types of nonmelanoma skin cancers, approximately 82 types of skin malignancies, with a wide range of clinical behaviors, fall into the category of nonmelanoma skin cancer. Other types of malignant disease of the skin include the following:
(Refer to the PDQ summaries on Melanoma Treatment, Merkel Cell Carcinoma Treatment, Mycosis Fungoides and the Sézary Syndrome Treatment, and Kaposi Sarcoma Treatment for more information.)
BCC and SCC are both of epithelial origin.
They are usually diagnosed on the basis of routine histopathology obtained from a shave, punch, or fusiform excisional biopsy.
BCC is at least three times more common than SCC in nonimmunocompromised patients. It usually occurs on sun-exposed areas of skin, and the nose is the most frequent site. Although there are many different clinical presentations for BCC, the most characteristic type is the asymptomatic nodular or nodular ulcerative lesion that is elevated from the surrounding skin, has a pearly quality, and contains telangiectatic vessels.
BCC has a tendency to be locally destructive. High-risk areas for tumor recurrence after initial treatment include the central face (e.g., periorbital region, eyelids, nasolabial fold, or nose-cheek angle), postauricular region, pinna, ear canal, forehead, and scalp. A specific subtype of BCC is the morpheaform type. This subtype typically appears as a scar-like, firm plaque. Because of indistinct clinical tumor margins, the morpheaform type is difficult to treat adequately with traditional treatments.
BCCs are composed of nonkeratinizing cells derived from the basal cell layer of the epidermis. They are slow growing and rarely metastasize. However, they can result in serious deforming damage locally if left untreated or if local recurrences cannot be completely excised. BCCs often have a characteristic mutation in the patched 1 tumor suppressor gene (PTCH1), although the mechanism of carcinogenesis is not clear.
SCCs also tend to occur on sun-exposed portions of the skin, such as the ears, lower lip, and dorsa of the hands. However, SCCs that arise in areas of non–sun-exposed skin or that originate de novo on areas of sun-exposed skin are prognostically worse because they have a greater tendency to metastasize than those that occur on sun-exposed skin that develop from actinic keratosis. People with chronic sun damage, sites of prior burns, arsenic exposure, chronic cutaneous inflammation as seen in longstanding skin ulcers, and sites of previous x-ray therapy are predisposed to the development of SCC.
SCCs are composed of keratinizing cells. These tumors are more aggressive than BCCs and have a range of growth, invasive, and metastatic potential. Prognosis is associated with the degree of differentiation, and tumor grade is reported as part of the staging system. A four-grade system (G1–G4) is most common, but two- and three-grade systems may also be used. Mutations in the PTCH1 tumor suppressor gene have been reported in SCCs removed from patients with a prior history of multiple BCCs.
SCC in situ (also called Bowen disease) is a noninvasive lesion. It may be difficult to distinguish it pathologically from a benign inflammatory process. The risk of development into invasive SCC is low, reportedly in the 3% to 4% range.
Actinic keratoses are potential precursors of SCC, but the rate of progression is extremely low, and the vast majority do not become SCCs. These typically red, scaly patches usually arise on areas of chronically sun-exposed skin and are likely to be found on the face and dorsal aspects of the hand.
Cutaneous squamous cell carcinoma and other cutaneous carcinomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 301–14.
Dubin N, Kopf AW: Multivariate risk score for recurrence of cutaneous basal cell carcinomas. Arch Dermatol 119 (5): 373-7, 1983.
Wagner RF, Casciato DA: Skin cancers. In: Casciato DA, Lowitz BB, eds.: Manual of Clinical Oncology. 4th ed. Philadelphia, Pa: Lippincott, Williams, and Wilkins, 2000, pp 336-373.
Ping XL, Ratner D, Zhang H, et al.: PTCH mutations in squamous cell carcinoma of the skin. J Invest Dermatol 116 (4): 614-6, 2001.
Kao GF: Carcinoma arising in Bowen's disease. Arch Dermatol 122 (10): 1124-6, 1986.
There are separate staging systems in the 7th edition of the American Joint Committee on Cancer’s (AJCC) AJCC Cancer Staging Manual for carcinomas of the eyelid versus other skin surfaces. The staging system for non-eyelid skin cancers is primarily designed for squamous cell carcinomas (SCCs). The staging system for carcinoma of the eyelid addresses carcinomas of all histologies.
Basal cell carcinoma (BCC) rarely metastasizes, thus, a metastatic work-up is
usually not necessary. Regional lymph nodes should be routinely examined in
all cases of SCC, especially for high-risk tumors appearing
on the lips, ears, perianal and perigenital regions, or high-risk areas of the
hand. In addition, regional lymph nodes should be examined with particular care in cases of
SCCs arising in sites of chronic ulceration or inflammation,
burn scars, or sites of previous radiation therapy treatment.
Table 2 has a separate list of risk features that should be evaluated for non-eyelid carcinomas; the relevant risk features should also be evaluated for SCCs of the eyelid. Even with relatively small tumor size, SCCs that occur in immunosuppressed patients tend to have more aggressive behavior than SCCs in nonimmunosuppressed patients. Although not a formal part of the AJCC staging system, it is recommended that centers prospectively studying SCC record the presence and type of immunosuppression in addition to the risk features listed in Table 2.
The American Joint Committee on Cancer has designated staging by TNM
classification. The TNM classification is used to stage both BCC and SCC.
Primary tumor cannot be assessed.
No evidence of primary tumor.
Carcinoma in situ.
Tumor ≤2 cm in greatest dimension with <2 high-risk features.c
Tumor >2 cm in greatest dimension.
Tumor any size with ≥2 high-risk features.c
Tumor with invasion of maxilla, mandible, orbit, or temporal bone.
Tumor with invasion of skeleton (axial or appendicular) or perineural invasion of skull base.
aReprinted with permission from AJCC: Cutaneous squamous cell carcinoma and other cutaneous carcinomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 301-14.
bExcludes cutaneous squamous cell carcinoma of the eyelid.
cHigh-risk features for the primary tumor (T) staging.
>2 mm thickness (Breslow thickness).
Clark level ≥IV.
Primary site ear.
Primary site hair-bearing lip.
Poorly differentiated or undifferentiated.
Regional lymph nodes cannot be assessed.
No regional lymph node metastases.
Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension.
Metastasis in a single ipsilateral lymph node, >3 cm but ≤6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, ≤6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, ≤6 cm in greatest dimension.
Metastasis in a single ipsilateral lymph node, >3 cm but ≤6 cm in greatest dimension.
Metastases in multiple ipsilateral lymph nodes, ≤6 cm in greatest dimension.
Metastases in bilateral or contralateral lymph nodes, ≤6 cm in greatest dimension.
Metastasis in a lymph node, >6 cm in greatest dimension.
No distant metastases.
Patients with a primary cutaneous SCC or other cutaneous carcinoma with no evidence (i.e., clinical, radiologic, or pathologic) of regional or distant metastases are divided into the following two stages:
In instances where there is clinical concern about extension of the tumor into bone and radiologic evaluation has been performed (and is negative), these data may be included to support the stage I versus stage II designation. Tumors that are 2 cm or less in size can be upstaged to stage II if they contain two or more high-risk features.
Stage III patients are those with either of the following:
Stage IV patients are those with any of the following:
The AJCC has designated staging by TNM classification. The TNM classification is used to stage all cell types of eyelid carcinomas.
Tumor ≤5 mm in greatest dimension.
Not invading the tarsal plate or eyelid margin.
Tumor >5 mm but not >10 mm in greatest dimension.
Or, any tumor that invades the tarsal plate or eyelid margin.
Tumor >10 mm but not >20 mm in greatest dimension.
Or, involves full thickness eyelid.
Tumor >20 mm in greatest dimension.
Or, any tumor that invades adjacent ocular or orbital structures.
Any T with perineural tumor invasion.
Complete tumor resection requires enucleation, exenteration, or bone resection.
Tumor is not resectable because of extensive invasion of ocular, orbital, craniofacial structures, or brain.
aReprinted with permission from AJCC: Carcinoma of the Eyelid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 523-6.
No regional lymph node metastasis based upon clinical evaluation or imaging.
No regional lymph node metastasis based upon lymph node biopsy.
Regional lymph node metastasis.
No distant metastasis.
Carcinoma of the Eyelid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 523-6.
There is a wide range of treatment approaches, including excision, radiation therapy, cryosurgery, electrodesiccation and curettage, photodynamic or laser-beam light exposure, and topical therapies. Mohs micrographic surgery is a form of tumor excision that involves progressive radial sectioning and real-time examination of the resection margins until adequate uninvolved margins have been achieved, avoiding wider margins than needed. Each of these methods is useful in specific clinical situations. Depending on case selection, these methods have recurrence-free rates ranging from 85% to 95%.
A systematic review of 27 randomized controlled trials comparing various treatments for BCC has been published. Eighteen of the studies were published in full, and nine were published in abstract form only. Only 19 of the 27 trials were analyzed by intention-to-treat criteria. Because the case fatality rate of BCC is so low, the primary endpoint of most trials is complete response and/or recurrence rate after treatment. Most of the identified studies had short follow-up times (only one study had a follow-up as long as 4 years) and were not of high quality. Short follow-up periods will lead to overestimates of tumor control. A literature review of recurrence rates in case series with long-term follow-up after treatment of BCCs indicated that only 50% of recurrences occurred within the first 2 years, 66% after 3 years, and 18% after 5 years. A rule of thumb was that the 10-year recurrence rates were about double the 2-year recurrence rates.
Treatment options include the following:
Excision with margin evaluation
This traditional surgical treatment usually relies on surgical margins ranging from 3 mm to 10 mm, depending on the diameter of the tumor. Re-excision may be required if the surgical margin is found to be inadequate on permanent sectioning. For example, in one trial, 35 of 199 (18%) primary BCCs were incompletely excised by the initial surgery and underwent a re-excision. In addition, many laboratories examine only a small fraction of the total tumor margin pathologically. Therefore, the declaration of tumor-free margins can be subject to sampling error.
Excision has been compared in randomized trials to radiation therapy, Mohs micrographic surgery, photodynamic therapy (PDT), and cryosurgery:
At 4 years (mean follow-up of 41 months), the actuarial failure rates (confirmed persistent or recurrent tumor) were 0.7% and 7.5% in the surgery and radiation therapy arms, respectively (P = .003). The cosmetic results were also rated as better after surgery by both patients and dermatologists, and also by three independent judges. At 4 years, 87% of surgery patients rated cosmesis as good versus 69% of radiation therapy patients.[Level of evidence: 1iiDii]
After 30 months of follow-up, the recurrence rate was 5 out of 171 tumors (3%) in the excision group and 3 out of 160 (2%) in the Mohs micrographic surgery group (absolute difference = 1%; 95% confidence interval [CI], -2.5%–+3.7%; P = .724). There was no difference in complication rates, and overall cosmetic outcomes were similar. Total operative costs were nearly twice as high in the Mohs group (405.79 Euros vs. 216.86 Euros (P < .001).[Level of evidence 1iiDii]
At 3 months, the complete response (CR) rate in the surgery group was 51 out of 52 lesions (98%) versus 48 out of 53 lesions (91%) in the PDT group (P = .25). CR rates assessed at 12 months were 96% versus 83% (P = .15).[Level of evidence: 1iiDiv] The investigators interpreted the results as noninferiority of PDT, but the study may have been underpowered. Both the investigators and the patients, however, rated the cosmetic results as either excellent or good in a higher proportion of PDT treatments at each time point of follow-up. At 12 months, patient ratings of excellent or good were 98% versus 84% (P = .03) and investigator ratings were 79% versus 38% (P = .001).
At 1 year, there were no recurrences in the excision group versus three in the cryosurgery group (P = NS), but this is a very short follow-up time. Patients and five independent professionals who were blinded to the treatment arm rated the cosmetic outcomes. Their overall assessments favored excision.[Level of evidence 1iiDiv]
Mohs micrographic surgery
Mohs micrographic surgery is a specialized technique used with the intent to achieve the narrowest margins necessary to avoid tumor recurrence, while maximally preserving cosmesis. It is best suited to management of tumors in cosmetically sensitive areas or for tumors that have recurred after initial excision (e.g., eyelid periorbital area, nasolabial fold, nose-cheek angle, posterior cheek sulcus, pinna, ear canal, forehead, scalp, fingers, and genitalia). It is also often used to treat tumors with poorly defined clinical borders.
Mohs micrographic surgery requires special training. The tumor is microscopically delineated, with serial radial resection, until it is completely removed as assessed with real-time frozen sections. Noncontrolled case series suggested that the disease control rates were superior to other treatment methods for BCC. However, as noted in the section on excision, the disease control rate was not clearly better when directly compared to surgical excision of facial BCCs in a randomized trial of primary BCCs.
Radiation therapy is particularly useful in the management of patients with primary lesions that would otherwise require difficult or extensive surgery (e.g., nose or ears). Radiation therapy eliminates the need for skin grafting when surgery would result in an extensive defect. Cosmetic results are generally good, with a small amount of hypopigmentation or telangiectasia in the treatment port. Radiation therapy can also be used for lesions that recur after a primary surgical approach. Radiation therapy is avoided in patients with conditions that predispose them to radiation-induced cancers, such as xeroderma pigmentosum or basal cell nevus syndrome.
As noted above, radiation therapy has been compared to excision in a randomized trial that showed better response and cosmesis associated with surgery.
In a single-center, randomized trial, radiation was superior to cryotherapy in local control at 2 years in 93 patients with primary BCCs. Patients were randomly assigned to receive either EBRT (130 kV x-rays, dosimetry depending upon lesion size) or cryotherapy (two freeze-thaw cycles with liquid nitrogen by spray gun). Patients with lesions on the nose or ear were excluded, since the investigators felt that electron beam therapy is the treatment of choice in these locations. By 1 year, the recurrence rates in the radiation and cryotherapy arms were 4% and 39%, respectively, in a per-protocol analysis. The investigators did not perform a statistical analysis, but the authors of a systematic literature review calculated a relative risk of 0.11 in favor of radiation (95% CI, 0.03–0.43).[Level of evidence 1iiDiv]
Curettage and electrodesiccation
This procedure is also sometimes called electrosurgery. It is a widely employed
method for removing primary BCCs, especially superficial lesions of the neck, trunk, and extremities that are considered to be at low risk for recurrence. A sharp curette is used to scrape away the tumor down to its base, followed by electrodesiccation of the lesion base. Although it is a quick
method for destroying the tumor, the adequacy of treatment cannot be assessed
immediately since the surgeon cannot visually detect the depth of microscopic
A Cochrane Collaboration systematic review found no randomized trials comparing this treatment method with other approaches. In a large, single-center case series of 2,314 previously untreated BCCs managed at a major skin cancer unit, the 5-year recurrence rate of BCCs of the neck, trunk, and extremities was 3.3%. However, rates increased substantially for tumors larger than 6 mm in diameter at other anatomic sites.[Level of evidence 3iiiDii]
Cryosurgery may be considered for patients with small, clinically well-defined primary tumors. It is infrequently used for the management of BCC, but may be useful for patients with
medical conditions that preclude other types of surgery.
Contraindications include abnormal cold
tolerance, cryoglobulinemia, cryofibrinogenemia, Raynaud disease (in the case of lesions on hands and feet), and platelet deficiency disorders.
Additional contraindications to cryosurgery include tumors of the
scalp, ala nasi, nasolabial fold, tragus, postauricular sulcus, free eyelid
margin, upper lip vermillion border, lower legs, and tumors near nerves. Caution should also be used before treating nodular ulcerative neoplasia more than 3 cm in diameter,
carcinomas fixed to the underlying bone or cartilage, tumors situated on the
lateral margins of the fingers and at the ulnar fossa of the elbow, or
recurrent carcinomas following surgical excision.
Edema is common following
treatment, especially around the periorbital region, temple, and forehead.
Treated tumors usually exude necrotic material after which an eschar forms and
persists for about 4 weeks. Permanent pigment loss at the treatment site is
unavoidable, so the treatment is not well suited to dark-skinned patients. Atrophy and hypertrophic scarring have been reported as well as
instances of motor and sensory neuropathy.
As noted in the section above on radiation therapy, a small 93-patient trial comparing cryosurgery to radiation therapy, with only 1 year of follow-up, showed a statistically significant higher recurrence rate with cryosurgery than radiation (39% vs. 4%).
In a small, single-center, randomized study, 88 patients were assigned to either cryosurgery in two freeze-thaw cycles or PDT using delta-aminolevulinic acid as the photosensitizing agent and 635 nm wavelength light with 60 J/cm2 energy delivered by Nd:YAG laser versus cryosurgery in two freeze-thaw cycles. Overall clinical efficacy was similar in evaluable lesions at 1 year (5/39 recurrences for cryosurgery vs. 2/44 recurrences for PDT), but more re-treatments were needed with PDT to achieve complete responses.[Level of evidence 1iiD] Cosmetic outcomes favored PDT (93% good or excellent after PDT vs. 54% after cryosurgery, P < .001). In another randomized study of 118 patients, reported in abstract form only, cryosurgery was compared with PDT with methyl aminolevulinic acid. Tumor control rates at 3 years were similar (74%), but cosmetic outcomes were better in the PDT group. These cryosurgery-PDT comparisons were reported on a per-protocol basis rather than an intent-to-treat basis.[Level of evidence 1iiDiv]
Photodynamic therapy with photosensitizers is used in the management of a wide spectrum of superficial epithelial tumors. A topical photosensitizing agent such as 5-aminolevulinic acid or methyl aminolevulinate is applied to the tumor, followed by exposure to a specific wavelength of light (whether laser or broad band), depending upon the absorption characteristics of the photosensitizer. In the case of multiple BCCs, short-acting systemic (intravenous) photosensitizers such as verteporfin have been used investigationally. Upon light activation, the photosensitizer reacts with oxygen in the tissue to form singlet oxygen species, resulting in local cell destruction.
In case series, PDT has been associated with high initial CR rates. However, substantial regrowth rates of up to 50% have been reported with long-term follow-up. A randomized trial of PDT versus excision is summarized in the section on simple excision above. Two small trials, one reported in abstract form only, comparing PDT with cryosurgery are summarized in the cryosurgery section above, showing similar antitumor efficacy but better cosmesis with PDT.
Topical fluorouracil (5-FU)
Topical 5-FU, as a 5% cream, may be useful in specific limited circumstances. It is a Food and Drug Administration (FDA)-approved treatment for superficial BCCs in patients for whom conventional methods are impractical, such as individuals with multiple lesions or difficult treatment sites. Safety and efficacy in other indications have not been established.[Level of evidence: 3iiiDiv] Given the superficial nature of its effects, nonvisible dermal involvement may persist, giving a false impression of treatment success. In addition, the brisk accompanying inflammatory reaction may cause substantial skin toxicity and discomfort in a large proportion of patients.
Imiquimod topical therapy
Imiquimod is an agonist for the toll-like receptor 7 and/or 8, inducing a helper T-cell cytokine cascade and interferon production. It purportedly acts as an immunomodulator. It is available as a 5% cream and is used in schedules ranging from twice weekly to twice daily over 5 to 15 weeks. Most of the experience is limited to case series of BCCs that are less than 2 cm2 in area and that are not in high-risk locations (i.e., within 1 cm of the hairline, eyes, nose, mouth, ear; or in the anogenital, hand, or foot regions). Follow-up times have also been generally short. Reported CR rates vary widely, from about 40% to 100%.[Level of evidence 3iiiDiv]
There have been a number of randomized trials of imiquimod. However, the designs of all of them make interpretation of long-term efficacy impossible. Most were industry-sponsored dose-finding studies, with small numbers of patients on any given regimen; and patients were only followed for 6 to 12 weeks, with excision at that time to determine histologic response.[Level of evidence 1iDiv] Therefore, although imiquimod is an FDA-approved treatment for superficial BCCs, some investigators in the field do not recommend it for initial monotherapy for BCC; some reserve it for patients with small lesions in low-risk sites who cannot undergo treatment with more established therapies.
Carbon dioxide laser
This method is used very infrequently in the management of BCC because of the difficulty in controlling tumor margins. Few clinicians have extensive experience with the technique for BCC treatment. There are no randomized trials comparing it with other modalities.
After treatment for BCC, patients should be followed clinically and examined regularly. Most recurrences occur within 5 years, but as noted above, about 18% of recurrences are diagnosed beyond that point. Patients who develop a primary BCC are also at increased risk of subsequent primary skin cancers because the susceptibility of their sun-damaged skin to additional cancers persists. This effect is sometimes termed field carcinogenesis. Age at diagnosis of the first BCC (<65 years), red hair, and initial BCC on the upper extremities appear to be associated with higher risk of subsequent new BCCs.
Mohs micrographic surgery is commonly used for local recurrences of BCC. In a separate group within a randomized trial comparing excision to Mohs micrographic surgery for primary BCCs, 204 recurrent BCCs were randomly assigned to excision versus Mohs micrographic surgery. The recurrence rates were 8 out of 102 patients and 2 out of 102 patients, respectively, after a mean follow-up of 2.08 years (P = NS).[Level of evidence 1iiDii] There were more postoperative complications, including wound infections, graft necrosis, or bleeding in the excision group than the Mohs surgery group (19% vs. 8%, P = .021). As with primary tumors, the operative costs associated with Mohs surgery were higher than with excision (489.06 Euros vs. 323.49 Euros [P = .001]).
Metastatic and far-advanced BCC is rare, and reports of systemic therapy are limited to case reports and very small case series with tumor response as the endpoint.[Level of evidence 3iiiDiv] Cisplatin, alone or in combination with other drugs, is the most commonly reported systemic therapy and appears to be associated with the best tumor-response rates. A variety of other agents have been reported but have low-associated response rates, including cyclophosphamide, vinblastine, 5-FU, methotrexate, and doxorubicin.
Since there is no standard therapy, clinical trials are appropriate if available. Because BCCs often exhibit constitutive activation of the Hedgehog/PTCH1-signaling pathway, Hedgehog pathway inhibitors are under investigation. An orally administered Hedgehog pathway inhibitor (GDC-0449) has produced objective responses in patients with advanced or metastatic sporadic BCC, and another topical inhibitor has produced objective responses in patients with nevoid basal cell carcinoma syndrome.[Level of evidence: 3iiiDiv]
Information about ongoing clinical trials is available from the NCI Web site.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with basal cell carcinoma of the skin. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Bath-Hextall FJ, Perkins W, Bong J, et al.: Interventions for basal cell carcinoma of the skin. Cochrane Database Syst Rev (1): CD003412, 2007.
Rowe DE, Carroll RJ, Day CL Jr: Long-term recurrence rates in previously untreated (primary) basal cell carcinoma: implications for patient follow-up. J Dermatol Surg Oncol 15 (3): 315-28, 1989.
Smeets NW, Krekels GA, Ostertag JU, et al.: Surgical excision vs Mohs' micrographic surgery for basal-cell carcinoma of the face: randomised controlled trial. Lancet 364 (9447): 1766-72, 2004 Nov 13-19.
Abide JM, Nahai F, Bennett RG: The meaning of surgical margins. Plast Reconstr Surg 73 (3): 492-7, 1984.
Avril MF, Auperin A, Margulis A, et al.: Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study. Br J Cancer 76 (1): 100-6, 1997.
Petit JY, Avril MF, Margulis A, et al.: Evaluation of cosmetic results of a randomized trial comparing surgery and radiotherapy in the treatment of basal cell carcinoma of the face. Plast Reconstr Surg 105 (7): 2544-51, 2000.
Rhodes LE, de Rie M, Enström Y, et al.: Photodynamic therapy using topical methyl aminolevulinate vs surgery for nodular basal cell carcinoma: results of a multicenter randomized prospective trial. Arch Dermatol 140 (1): 17-23, 2004.
Thissen MR, Nieman FH, Ideler AH, et al.: Cosmetic results of cryosurgery versus surgical excision for primary uncomplicated basal cell carcinomas of the head and neck. Dermatol Surg 26 (8): 759-64, 2000.
Thomas RM, Amonette RA: Mohs micrographic surgery. Am Fam Physician 37 (3): 135-42, 1988.
Rowe DE, Carroll RJ, Day CL Jr: Mohs surgery is the treatment of choice for recurrent (previously treated) basal cell carcinoma. J Dermatol Surg Oncol 15 (4): 424-31, 1989.
Malhotra R, Huilgol SC, Huynh NT, et al.: The Australian Mohs database, part II: periocular basal cell carcinoma outcome at 5-year follow-up. Ophthalmology 111 (4): 631-6, 2004.
Thissen MR, Neumann MH, Schouten LJ: A systematic review of treatment modalities for primary basal cell carcinomas. Arch Dermatol 135 (10): 1177-83, 1999.
Caccialanza M, Piccinno R, Moretti D, et al.: Radiotherapy of carcinomas of the skin overlying the cartilage of the nose: results in 405 lesions. Eur J Dermatol 13 (5): 462-5, 2003 Sep-Oct.
Lovett RD, Perez CA, Shapiro SJ, et al.: External irradiation of epithelial skin cancer. Int J Radiat Oncol Biol Phys 19 (2): 235-42, 1990.
Hall VL, Leppard BJ, McGill J, et al.: Treatment of basal-cell carcinoma: comparison of radiotherapy and cryotherapy. Clin Radiol 37 (1): 33-4, 1986.
Silverman MK, Kopf AW, Grin CM, et al.: Recurrence rates of treated basal cell carcinomas. Part 2: Curettage-electrodesiccation. J Dermatol Surg Oncol 17 (9): 720-6, 1991.
Wang I, Bendsoe N, Klinteberg CA, et al.: Photodynamic therapy vs. cryosurgery of basal cell carcinomas: results of a phase III clinical trial. Br J Dermatol 144 (4): 832-40, 2001.
Basset-Séguin N, Ibbotson S, Emtestam L, et al.: Photodynamic therapy using methyl aminolaevulinate is as efficacious as cryotherapy in basal cell carcinoma, with better cosmetic results. [Abstract] Br J Dermatol 149 (Suppl 64): A-P-66, 46, 2003.
Basset-Séguin N, Ibbotson S, Emtestam L, et al.: Methyl aminolaevulinate photodynamic therapy vs. cryotherapy in primary superficial basal cell carcinoma: results of a 36-month follow-up. [Abstract] Br J Dermatol 153 (Suppl 1): A-P-30, 29. 2005.
Hsi RA, Rosenthal DI, Glatstein E: Photodynamic therapy in the treatment of cancer: current state of the art. Drugs 57 (5): 725-34, 1999.
Lui H, Hobbs L, Tope WD, et al.: Photodynamic therapy of multiple nonmelanoma skin cancers with verteporfin and red light-emitting diodes: two-year results evaluating tumor response and cosmetic outcomes. Arch Dermatol 140 (1): 26-32, 2004.
Efudex® (fluorouracil) cream, 5% [package insert]. Aliso Viejo, Ca: Valeant Pharmaceuticals International, 2005. Available online. Last accessed October 25, 2013.
Love WE, Bernhard JD, Bordeaux JS: Topical imiquimod or fluorouracil therapy for basal and squamous cell carcinoma: a systematic review. Arch Dermatol 145 (12): 1431-8, 2009.
Beutner KR, Geisse JK, Helman D, et al.: Therapeutic response of basal cell carcinoma to the immune response modifier imiquimod 5% cream. J Am Acad Dermatol 41 (6): 1002-7, 1999.
Geisse JK, Rich P, Pandya A, et al.: Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: a double-blind, randomized, vehicle-controlled study. J Am Acad Dermatol 47 (3): 390-8, 2002.
Geisse J, Caro I, Lindholm J, et al.: Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies. J Am Acad Dermatol 50 (5): 722-33, 2004.
Shumack S, Robinson J, Kossard S, et al.: Efficacy of topical 5% imiquimod cream for the treatment of nodular basal cell carcinoma: comparison of dosing regimens. Arch Dermatol 138 (9): 1165-71, 2002.
Marks R, Gebauer K, Shumack S, et al.: Imiquimod 5% cream in the treatment of superficial basal cell carcinoma: results of a multicenter 6-week dose-response trial. J Am Acad Dermatol 44 (5): 807-13, 2001.
Schulze HJ, Cribier B, Requena L, et al.: Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from a randomized vehicle-controlled phase III study in Europe. Br J Dermatol 152 (5): 939-47, 2005.
Robinson JK: Risk of developing another basal cell carcinoma. A 5-year prospective study. Cancer 60 (1): 118-20, 1987.
Karagas MR, Stukel TA, Greenberg ER, et al.: Risk of subsequent basal cell carcinoma and squamous cell carcinoma of the skin among patients with prior skin cancer. Skin Cancer Prevention Study Group. JAMA 267 (24): 3305-10, 1992.
Schinstine M, Goldman GD: Risk of synchronous and metachronous second nonmelanoma skin cancer when referred for Mohs micrographic surgery. J Am Acad Dermatol 44 (3): 497-9, 2001.
Kiiski V, de Vries E, Flohil SC, et al.: Risk factors for single and multiple basal cell carcinomas. Arch Dermatol 146 (8): 848-55, 2010.
Carneiro BA, Watkin WG, Mehta UK, et al.: Metastatic basal cell carcinoma: complete response to chemotherapy and associated pure red cell aplasia. Cancer Invest 24 (4): 396-400, 2006 Jun-Jul.
Pfeiffer P, Hansen O, Rose C: Systemic cytotoxic therapy of basal cell carcinoma. A review of the literature. Eur J Cancer 26 (1): 73-7, 1990.
Khandekar JD: Complete response of metastatic basal cell carcinoma to cisplatin chemotherapy: a report on two patients. Arch Dermatol 126 (12): 1660, 1990.
Low JA, de Sauvage FJ: Clinical experience with Hedgehog pathway inhibitors. J Clin Oncol 28 (36): 5321-6, 2010.
Von Hoff DD, LoRusso PM, Rudin CM, et al.: Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 361 (12): 1164-72, 2009.
Skvara H, Kalthoff F, Meingassner JG, et al.: Topical treatment of Basal cell carcinomas in nevoid Basal cell carcinoma syndrome with a smoothened inhibitor. J Invest Dermatol 131 (8): 1735-44, 2011.
Localized squamous cell carcinoma (SCC) of the skin is a highly curable disease.
There are a variety of treatment approaches to localized SCC, including excision, radiation therapy, cryosurgery, and electrodesiccation and curettage. Mohs micrographic surgery is a form of tumor excision that involves progressive radial sectioning and real-time examination of the resection margins until adequate uninvolved margins have been achieved, avoiding wider margins than needed.
There is little or no good-quality evidence that allows direct comparison of outcomes for patients with sporadic, clinically localized SCCs treated with local therapies. A systematic literature review found only one randomized controlled trial in the management of such patients, and that trial compared adjuvant therapy to observation after initial local therapy rather than different local therapies. In that small single-center trial, 66 patients with high-risk, clinically localized SCC were assigned randomly, after surgical excision of the primary tumor (with or without radiation, depending on clinical judgment), to receive either combined 13-cis-retinoic acid (1 mg/kg orally per day) plus interferon-alpha (3 × 106 U subcutaneously 3 times/week) for 6 months or to observation. In the 65 evaluable patients after a median follow-up of 21.5 months, there was no difference in the combined (primary) endpoint of SCC recurrence or second primary tumor (45% vs. 38%; hazard ratio = 1.13; 95% confidence interval [CI], 0.53–2.41), nor in either of the individual components of the primary endpoint.[Level of evidence 1iiDii]
Absent high-quality evidence from controlled clinical trials, the management of clinically localized cutaneous SCC is based upon case series and consensus statements from experts. The commonly used treatments are listed below.
Surgical excision with margin evaluation
Excision is probably the most common therapy for SCC. This traditional surgical treatment usually relies on surgical margins ranging from 4 mm to 10 mm, depending on the diameter of the tumor and degree of differentiation. In a prospective case series of 141 SCCs, a 4-mm margin was adequate to encompass all subclinical microscopic tumor extension in more than 95% of well-differentiated tumors up to 19 mm in diameter. Wider margins of 6 mm to 10 mm were needed for larger or less-differentiated tumors or tumors in high-risk locations (e.g., scalp, ears, eyelids, nose, and lips). Re-excision may be required if the surgical margin is found to be inadequate on permanent sectioning.
Mohs micrographic surgery is a specialized technique used to achieve the narrowest margins necessary to avoid tumor recurrence, while maximally preserving cosmesis. In case series, it has been associated with a lower local recurrence rate than the other local modalities, but there are no randomized trials allowing direct comparison. This surgery is best suited to the management of tumors in cosmetically sensitive areas or for tumors that have recurred after initial excision (e.g., eyelid periorbital area, nasolabial fold, nose-cheek angle, posterior cheek sulcus, pinna, ear canal, forehead, scalp, fingers, and genitalia).
Mohs micrographic surgery is also often used to treat high-risk tumors with poorly defined clinical borders or with perineural invasion. The method requires special training. The tumor is microscopically delineated, with serial radial resection, until it is completely removed as assessed with real-time frozen sections. Nevertheless, since the technique removes tumor growing in contiguity and may miss noncontiguous in-transit cutaneous micrometastases, some practitioners remove an additional margin of skin in high-risk lesions even after the Mohs surgical procedure confirms uninvolved margins.[Level of evidence: 3iiiDiv]
Radiation therapy is a logical treatment choice, particularly for patients with primary lesions requiring difficult or extensive surgery (e.g., nose, lip, or ears). Radiation therapy eliminates the need for skin grafting when surgery would result in an extensive defect. Cosmetic results are generally good, with a small amount of hypopigmentation or telangiectasia in the treatment port. Radiation therapy can also be used for lesions that recur after a primary surgical approach. Radiation therapy is avoided in patients with conditions that predispose them to radiation-induced cancers, such as xeroderma pigmentosum or basal cell nevus syndrome.
Although radiation therapy, with or without excision of the primary tumor, is used for histologically proven clinical lymph node metastases and has been associated with favorable disease-free survival rates, the retrospective nature of these case series makes it difficult to know the impact of nodal radiation on survival.[Level of evidence 3iiiDii]
This procedure is also sometimes called electrosurgery. A sharp curette is used to scrape the tumor down to its base, followed by electrodesiccation of the lesion base. Although it is a quick method for destroying the tumor, the adequacy of treatment cannot be assessed immediately since the surgeon cannot visually detect the depth of microscopic tumor invasion. Its use is limited to small (<1 cm), well-defined, and well-differentiated tumors.[Level of evidence: 3iiiDii]
Cryosurgery may be considered for patients with small, clinically well-defined primary tumors. It may be useful for patients with medical conditions that preclude other types of surgery. Contraindications include abnormal cold tolerance, cryoglobulinemia,
cryofibrinogenemia, Raynaud disease (in the case of lesions on hands and feet), and platelet deficiency disorders.
Additional contraindications to cryosurgery include tumors of the scalp, ala
nasi, nasolabial fold, tragus, postauricular sulcus, free eyelid margin, upper
lip vermillion border, lower legs, and tumors near nerves. Caution should also be used before
treating nodular ulcerative neoplasia more than 3 cm in diameter, carcinomas fixed to
the underlying bone or cartilage, tumors situated on the lateral margins of the
fingers and at the ulnar fossa of the elbow, or recurrent carcinomas following
Edema is common following treatment, especially around the
periorbital region, temple, and forehead. Treated tumors usually exude
necrotic material after which an eschar forms and persists for about 4 weeks.
Permanent pigment loss at the treatment site is unavoidable, so the treatment is not well suited to dark-skinned patients. Atrophy and
hypertrophic scarring have been reported as well as instances of motor and
The management of SCC in situ (Bowen disease) is similar to good-risk SCC. However, since it is noninvasive, surgical excision, including Mohs micrographic surgery, is usually not necessary. In addition, high complete response (CR) rates are achievable with photodynamic therapy (PDT). In a multicenter trial, 229 patients (209 evaluated in the per-protocol/per-lesion analysis) were randomly assigned to receive PDT (methyl aminolevulinate + 570–670 nm red light; n = 91), placebo cream with red light (n = 15); or treatment by physician choice (cryotherapy, n = 77; topical 5-fluorouracil, n = 26). The sustained complete clinical response rates at 12 months were 80%, 67%, and 69% in the three respective active therapy groups (P = .04 for the comparison between PDT and the two combined physician-choice groups).[Level of evidence 1iiDii] The cosmetic results were best in the PDT group. (For comparison, the CR rates at 3 months for PDT and placebo/PDT were 93% and 21%, respectively.)
SCCs have definite metastatic potential, and patients should be followed regularly after initial treatment. Overall, local recurrence rates after treatment of primary SCCs ranged from about 3% to 23%, depending upon anatomic site. About 58% of local recurrences manifest within 1 year, 83% within 3 years, and 95% within 5 years. The metastatic rate for primary tumors of sun-exposed skin is 5%; for tumors of the external ear, 9%; and for tumors of the lip, 14%. Metastases occur at an even higher rate for primary SCCs in scar carcinomas or in nonexposed areas of skin (about 38%). About 69% of metastases are diagnosed within 1 year, 91% within 3 years, and 96% within 5 years. Tumors that are 2 cm or larger in diameter, 4 mm or greater in depth, or poorly differentiated have a relatively bad prognosis  and even higher local recurrence and metastasis rates than those listed. Reported rates also vary by treatment modality, with the lowest rates associated with Mohs micrographic surgery, but at least some of the variation may be the result of patient selection factors; no randomized trials directly compare the various local treatment modalities.
Recurrent nonmetastatic SCCs are considered high risk and are generally treated with excision, often using Mohs micrographic surgery. Radiation therapy is used for lesions that cannot be completely resected.
As is the case with BCC, patients who develop a primary SCC are also at increased risk of subsequent primary skin cancers because the susceptibility of their sun-damaged skin to additional cancers persists.
As is the case with BCC, metastatic and far-advanced SCC is unusual, and reports of systemic therapy are limited to case reports and very small case series with tumor response as the endpoint.[Level of evidence 3iiiDiv] Cisplatin-based regimens appear to be associated with high initial tumor response rates. High response rates have also been reported with the use of 13-cis-retinoic acid plus interferon-alpha-2a. Since there is no standard therapy, clinical trials are appropriate if available. Information about ongoing clinical trials is available from the NCI Web site.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with squamous cell carcinoma of the skin. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Lansbury L, Leonardi-Bee J, Perkins W, et al.: Interventions for non-metastatic squamous cell carcinoma of the skin. Cochrane Database Syst Rev (4): CD007869, 2010.
Brewster AM, Lee JJ, Clayman GL, et al.: Randomized trial of adjuvant 13-cis-retinoic acid and interferon alfa for patients with aggressive skin squamous cell carcinoma. J Clin Oncol 25 (15): 1974-8, 2007.
Motley R, Kersey P, Lawrence C, et al.: Multiprofessional guidelines for the management of the patient with primary cutaneous squamous cell carcinoma. Br J Dermatol 146 (1): 18-25, 2002.
Brodland DG, Zitelli JA: Surgical margins for excision of primary cutaneous squamous cell carcinoma. J Am Acad Dermatol 27 (2 Pt 1): 241-8, 1992.
Rowe DE, Carroll RJ, Day CL Jr: Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol 26 (6): 976-90, 1992.
Shimm DS, Wilder RB: Radiation therapy for squamous cell carcinoma of the skin. Am J Clin Oncol 14 (5): 383-6, 1991.
Veness MJ, Palme CE, Smith M, et al.: Cutaneous head and neck squamous cell carcinoma metastatic to cervical lymph nodes (nonparotid): a better outcome with surgery and adjuvant radiotherapy. Laryngoscope 113 (10): 1827-33, 2003.
Morton C, Horn M, Leman J, et al.: Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or Fluorouracil for treatment of squamous cell carcinoma in situ: Results of a multicenter randomized trial. Arch Dermatol 142 (6): 729-35, 2006.
Cherpelis BS, Marcusen C, Lang PG: Prognostic factors for metastasis in squamous cell carcinoma of the skin. Dermatol Surg 28 (3): 268-73, 2002.
Luxenberg MN, Guthrie TH Jr: Chemotherapy of basal cell and squamous cell carcinoma of the eyelids and periorbital tissues. Ophthalmology 93 (4): 504-10, 1986.
Sadek H, Azli N, Wendling JL, et al.: Treatment of advanced squamous cell carcinoma of the skin with cisplatin, 5-fluorouracil, and bleomycin. Cancer 66 (8): 1692-6, 1990.
Lippman SM, Parkinson DR, Itri LM, et al.: 13-cis-retinoic acid and interferon alpha-2a: effective combination therapy for advanced squamous cell carcinoma of the skin. J Natl Cancer Inst 84 (4): 235-41, 1992.
Actinic keratoses commonly appear in areas of chronic sun exposure, such as
the face and dorsa of the hands. Actinic cheilitis is a related condition that
usually appears on the lower lips. These conditions represent early epithelial
transformation that may eventually evolve into invasive SCC.
Actinic keratosis is a noninvasive lesion. The progression rate is extremely low. In a prospective study, the progression rate to SCC was less than 1 in 1,000 per year, calling into question the cost effectiveness of treating all actinic keratoses to prevent SCC. Moreover, in a population-based longitudinal study, there was an approximately 26% spontaneous regression rate of solar keratoses within 1 year of a screening examination. Therefore, studies designed to test the efficacy of any treatment for progression of actinic keratoses to SCC are impractical (or impossible). Nevertheless, a variety of treatment approaches have been reviewed.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with actinic keratosis. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Picascia DD, Robinson JK: Actinic cheilitis: a review of the etiology, differential diagnosis, and treatment. J Am Acad Dermatol 17 (2 Pt 1): 255-64, 1987.
Marks R, Rennie G, Selwood TS: Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet 1 (8589): 795-7, 1988.
Marks R, Foley P, Goodman G, et al.: Spontaneous remission of solar keratoses: the case for conservative management. Br J Dermatol 115 (6): 649-55, 1986.
Jorizzo J, Collier A: Actinic keratosis. Waltham, Ma: UpToDate Inc, 2011. Available online. Last accessed October 25, 2013.
This information was last updated on October 25, 2013.
Our licensed social workers are here to help adult patients and their loved ones face the many new concerns and anxieties following a cancer diagnosis, offering emotional support and assistance with obtaining needed resources.
Our support groups are geared to specific cancers and methods of treatment. They give patients the opportunity to meet and share information and moral support. Our experienced, compassionate staff facilitates and guides discussion.
If you are dealing with the death of a loved one, grief can be a lonely and isolating experience. The Bereavement Program provides support to bereaved family members and friends following the death of a patient.
Concierge Services is your one-stop place to learn about Dana-Farber programs, services and resources, as well as information on getting around Boston, finding lodging or restaurants, and activities in the area.
The Expressive Arts Therapy program, sponsored by the Leonard P. Zakim Center for Integrative Therapies, provides adult patients, family members, and caregivers with a variety of options to support well-being during cancer treatment. From live music meditation to painting technique workshops, the program offers a range of creative outlets to suit every interest.
Dana-Farber and Brigham and Women's Hospital, including parking facilities, are fully accessible to people with disabilities. There are wheelchairs at the main entrance, and security staff can provide personal assistance. We also have many educational materials available in large print and audiotape formats.
The Ethics Consultation Service is available for patients and families who may be facing difficult decisions and choices regarding care. Our goal is to bring together patients, families and health care providers to talk about ethical concerns and help everyone involved arrive at a resolution that is right for all.
This comprehensive resource offers guidance, information and resources to support the entire family, including how to talk to children about cancer, advice for the well partner, and creating a support network.
Find practical tips and suggestions for individuals caring for a family member or friend with cancer, including creating a caregiving plan, finding community resources, and looking after your own well-being.
Friends' Place provides personal consultations to help cancer patients of all ages cope with changes in physical appearance that result from cancer treatment. Our experienced, compassionate team provides fittings for compression garments or breast prostheses, helps with wigs and other head coverings, and offers make-up and skincare advice.
The Friends' Corner Gift Shop, located on the first floor of the Yawkey Center for Cancer Care, offers a wide selection of unique gifts and everyday items for patients, families and staff.
Dana-Farber offers several services to help you and your family manage the financial side of cancer treatment. From creating bill payment schedules and estate planning advice to debt management and resource assistance for patients in need, our team is here for you.
Every year, thousands of patients with cancer from around the world come to Dana-Farber for their care. We provide a wide array of logistical and other services for individuals who live outside the United States.
Dana-Farber provides interpreting services for patients whose first language is not English. Interpreters may be requested for any activity, including registration, booking appointments, attending treatments and exams, support groups, and meetings with doctors and other members of your health care team.
Our nutritionists are registered dietitians who can assist you in planning an optimal diet during any stage of your cancer journey, cope with any side effects you may experience, and answer your questions about the latest findings on cancer and nutrition.
One-to-One connects adult patients, family members and caregivers with individuals who have gone through cancer themselves, providing an experienced and reassuring perspective for those facing a cancer diagnosis, treatment and recovery.
The Eleanor and Maxwell Blum Patient and Family Resource Center and its satellite resource rooms are staffed by health care professionals and provide computer stations, books, brochures, videos, and CDs to help you find information and support on a variety of issues about cancer treatment and care.
Patients websites help friends and family members stay up-to-date on their loved ones' condition and write messages of support and encouragement.
The Dana-Farber pharmacy fills prescriptions for all pediatric and adult patients. Our pharmacists are an extension of the patient care team and work closely with your physicians to provide seamless, convenient, safe care.
More than 1,200 Dana-Farber patients and their families have enjoyed free trips to baseball games, theater shows, museums, and other attractions this year through the Recreational Resources program.
The Sexual Health Program provides education, consultation and personalized rehabilitation for patients and their partners who have experienced changes in sexual health during and after cancer treatment.
Through all stages of cancer treatment and survivorship, our Spiritual Care staff is available 24 hours a day to provide emotional and spiritual support for adults and pediatric patients and family members.
Young adults with cancer face very different challenges than patients who were diagnosed earlier in childhood or later in adulthood. The Young Adult Program can help you to find the resources and expertise available at Dana-Farber to help support your cancer experience.
Integrative therapies, also known as complementary therapies, range from acupuncture and massage to nutritional guidance and music therapy. Patients treated at the Zakim Center credit its services with easing nausea, improving circulation, and reducing pain, stress, and anxiety associated with cancer treatment.