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Important: This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Skin cancer


Table of Contents

GENERAL INFORMATION
CELLULAR CLASSIFICATION
STAGE INFORMATION
Basal cell carcinoma
Squamous cell carcinoma
Actinic keratosis
TREATMENT OPTION OVERVIEW
BASAL CELL CARCINOMA OF THE SKIN
SQUAMOUS CELL CARCINOMA OF THE SKIN
ACTINIC KERATOSIS

GENERAL INFORMATION

(Separate summaries containing information on screening for skin cancer and prevention of skin cancer are also available in PDQ.)

Basal cell carcinoma is the most common form of skin cancer. The second most common type of skin malignancy is squamous cell carcinoma. Although these 2 types of skin cancer are the most common of all malignancies, they account for less than 0.1% of patient deaths due to cancer. Both of these types of skin cancer are more likely to occur in individuals of light complexion who have had significant exposure to sunlight, and both types of skin cancers are more common in the southern latitudes of the Northern hemisphere.[1] The overall cure rate for both types of skin cancer is directly related to the stage of the disease and the type of treatment employed.[2] However, since neither basal cell carcinoma nor squamous cell carcinoma of the skin are reportable diseases, precise 5-year cure rates are not known. Although basal cell carcinoma and squamous cell carcinoma are by far the most frequent types of skin tumors, the skin can also be the site of a large variety of malignant neoplasms. These other types of malignant disease include malignant melanoma, cutaneous T-cell lymphomas (mycosis fungoides), Kaposi's sarcoma, extramammary Paget's disease, apocrine carcinoma of the skin, and metastatic malignancies from various primary sites. Refer to the PDQ summaries on melanoma, cutaneous T-cell lymphoma, and Kaposi's sarcoma for treatment of these diseases. Guidelines for the care of cutaneous squamous cell carcinoma have been published.[3]

References:

  1. Wagner RF, Lowitz BB, Casciato DA: Skin cancers. In: Casciato DA, Lowitz BB, Eds.: Manual of Clinical Oncology. Boston: Little, Brown, and Company, 2nd ed., 1988, pp 250-259.

  2. Rowe DE, Carroll RJ, Day CL: Long-term recurrence rates in previously untreated (primary) basal cell carcinoma: implications for patient follow-up. Journal of Dermatologic Surgery and Oncology 15(3): 315-328, 1989.

  3. Committee on Guidelines of Care, Task Force on Cutaneous Squamous Cell Carcinoma: Guidelines of care for cutaneous squamous cell carcinoma. Journal of the American Academy of Dermatology 28(4): 628-631, 1993.


CELLULAR CLASSIFICATION

Basal cell carcinoma and squamous cell carcinoma are both of epithelial origin. They are usually diagnosed on the basis of routine histopathology.[1] Squamous cell carcinoma is graded 1 to 4 based on the proportion of differentiating cells present, the degree of atypicality of tumor cells, and the depth of tumor penetration.[2] Apocrine carcinomas, which are rare, are associated with an indolent course and usually arise in the axilla.[3]

References:

  1. Lever WF, Schaumburg-Lever G: Histopathology of the Skin. New York: JB Lippincott, 6th ed., 1983.

  2. Immerman SC, Scanlon EF, Christ M, et al.: Recurrent squamous cell carcinoma of the skin. Cancer 51(8): 1537-1540, 1983.

  3. Paties C, Taccagni GL, Papotti M, et al.: Apocrine carcinoma of the skin. Cancer 71(2): 375-381, 1993.


STAGE INFORMATION

Basal cell carcinoma rarely metastasizes, and thus a metastatic work-up is usually not necessary.[1] Regional lymph nodes should be routinely examined in all cases of squamous cell carcinoma, especially for high-risk tumors appearing on the lips, ears, perianal and perigenital regions, or high-risk areas of the hand.[2] In addition, regional lymph nodes should be examined in cases of squamous cell carcinoma arising in sites of chronic ulceration or inflammation, burn scars, or sites of previous radiation therapy treatment. The TNM (primary tumor, nodal involvement, and metastasis) classification is used to stage both basal cell carcinoma and squamous cell carcinoma.[1,3]


Basal cell carcinoma

Basal cell carcinoma is at least 3 times more common than squamous cell carcinoma 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 basal cell carcinoma, the most characteristic type is the asymptomatic nodular or nodular ulcerative lesion that is elevated from the surrounding skin and has a pearly quality and contains telangiectatic vessels. It is recognized that basal cell carcinoma has a tendency to be locally destructive. High-risk areas for tumor recurrence include the central face (periorbital region, eyelids, nasolabial fold, nose-cheek angle), postauricular region, pinna, ear canal, forehead, and scalp.[4] A specific subtype of basal cell carcinoma is the morphea-form type. It typically appears as a scar-like, firm plaque and because of indistinct clinical tumor margins, it is difficult to treat adequately with traditional treatments.[1]


Squamous cell carcinoma

Squamous cell tumors also tend to occur on sun-exposed portions of the skin such as the ears, lower lip, and dorsa of the hand. However, squamous cell carcinomas that arise in areas of non-sun-exposed skin or that originate de novo on areas of sun-exposed skin are prognostically worse since they have a greater tendency to metastasize. Chronic sun damage, sites of prior burns, arsenic exposure, chronic cutaneous inflammation as seen in long standing skin ulcers, and sites of previous x-ray therapy are predisposed to the development of squamous cell carcinoma.[1]


Actinic keratosis

Actinic keratoses are potential precursors of squamous cell carcinoma. These typical 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. Although the vast majority of actinic keratoses do not become squamous cell carcinomas, it is thought that as many as 5% of actinic keratoses will evolve into this locally invasive carcinoma. Due to this premalignant potential, the destruction of actinic keratoses is advocated.[1]

References:

  1. Wagner RF, Lowitz BB, Casciato DA: Skin cancers. In: Casciato DA, Lowitz BB, Eds.: Manual of Clinical Oncology. Boston: Little, Brown, and Company, 2nd ed., 1988, pp 250-259.

  2. Rayner CR: The results of treatment of two hundred and seventy-three carcinomas of the hand. Hand 13(2): 183-186, 1981.

  3. Carcinoma of the skin (excluding eyelid, vulva, and penis). In: American Joint Committee on Cancer: AJCC Cancer Staging Manual. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 157-161.

  4. Dubin N, Kopf AW: Multivariate risk score for recurrence of cutaneous basal cell carcinomas. Archives of Dermatology 119(5): 373-377, 1983.


TREATMENT OPTION OVERVIEW

The designations in PDQ that treatments are "standard" or "under clinical evaluation" are not to be used as a basis for reimbursement determinations.


BASAL CELL CARCINOMA OF THE SKIN

The traditional methods of treatment involve the use of cryosurgery, radiation therapy, electrodesiccation and curettage, and simple excision. Each of these methods is useful in specific clinical situations.[1] Depending on case selection, these methods have cure rates ranging from 85% to 95%. Mohs micrographic surgery, a newer surgical technique, has the highest 5-year cure rates for surgical treatment of both primary (96%) and recurrent (90%) tumors. This method uses microscopic control to evaluate the extent of tumor invasion.

Treatment options:

1. Mohs micrographic surgery.[2] Although this method is complicated and requires special training, it has the highest cure rate of all surgical treatments because the tumor is microscopically delineated until it is completely removed. While other treatment methods for recurrent basal cell carcinoma have failure rates of about 50%, cure rates have been reported at 96% when treated by Mohs micrographic surgery. In addition, it is indicated for the treatment of primary basal cell carcinomas when they occur at sites known to have a high initial treatment failure rate with traditional methods (periorbital area, nasolabial fold, nose-cheek angle, posterior cheek sulcus, pinna, ear canal, forehead, scalp, or tumors arising in a scar). Mohs micrographic surgery is also indicated for tumors with poorly defined clinical borders, tumors with diameters larger than 2 cm, tumors with histopathologic features showing morpheaform or sclerotic patterns, and tumors arising in regions where maximum preservation of uninvolved tissue is desirable, such as eyelid, nose, finger, and genitalia.

2. Simple excision with frozen or permanent sectioning for margin evaluation. This traditional surgical treatment usually relies on surgical margins ranging from 3 to 10 mm, depending on the diameter of the tumor.[3] Tumor recurrence is not uncommon because only a small fraction of the total tumor margin is examined pathologically. Recurrence rate for primary tumors greater than 1.5 cm in diameter is at least 12% within 5 years; if the primary tumor measures larger than 3.0 cm, the 5-year recurrence rate is 23.1%. Primary tumors of the ears, eyes, scalp, and nose have recurrence rates ranging from 12.9% to 25%.

3. Electrodesiccation and curettage. This method is the most widely employed method for removing primary basal cell carcinomas. Although it is a quick method for destroying the tumor, adequacy of treatment cannot be assessed immediately since the surgeon cannot visually detect the depth of microscopic tumor invasion.

Tumors with diameters ranging from 2 to 5 mm have a 15% recurrence rate after treatment with electrodesiccation and curettage. When tumors larger than 3 cm are treated with electrodesiccation and curettage, a 50% recurrence rate should be expected within 5 years.

4. Cryosurgery. Cryosurgery may be considered for small, clinically well defined primary tumors. It is especially useful for debilitated patients with medical conditions that preclude other types of surgery. However, the absolute contraindications for cryosurgery include patients with abnormal cold tolerance, cryoglobulinemia, cryofibrinogenemia, Raynaud's disease (only for treatment of lesions on hands and feet), and platelet deficiency disorders. Morphea or sclerosing basal cell carcinoma should not be treated by cryosurgery. Relative contraindications to cryosurgery include tumors of the scalp, ala nasi, nasolabial fold, tragus, postauricular sulcus, free eyelid margin, upper lip vermillion border, and lower legs. Caution should also be employed before treating nodular ulcerative neoplasia greater than 3 cm, 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. There is significant morbidity associated with the use of cryosurgery. 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. Atrophy and hypertrophic scarring have been reported, as well as instances of motor and sensory neuropathy.

5. Radiation therapy. Radiation is a logical treatment choice, particularly for primary lesions requiring difficult or extensive surgery (e.g., eyelids, nose, ears). It eliminates the need for skin grafting when surgery would result in an extensive defect. Cosmetic results are generally good to excellent with a small amount of hypopigmentation or telangiectasia in the treatment port. Radiation therapy can also be utilized for lesions that recur after a primary surgical approach.[4] Radiation therapy is contraindicated for patients with xeroderma pigmentosum, epidermodysplasia verruciformis, or the basal cell nevus syndrome because it may induce more tumors in the treatment area.

6. Carbon dioxide laser. This method is most frequently applied to the superficial type of basal cell carcinoma. It may be considered when a bleeding diathesis is present, since bleeding is unusual when this laser is used.

7. Topical fluorouracil (5-FU). This method may be helpful in the management of selected superficial basal cell carcinomas. Careful and prolonged follow-up is required, since deep follicular portions of the tumor may escape treatment and result in future tumor recurrence.[5]

8. Systemic retinoids. Although several clinical trials have shown some efficacy for currently available systemic retinoids in both chemotherapy and chemoprevention, the long-term toxicity of these agents generally excludes them as treatment choices for most patients.[6] Studies are exploring their value as cancer preventive agents in patients at high risk for developing multiple tumors.

9. Interferon alfa. Several early studies have shown variable responses of basal cell carcinoma to intralesional interferon alfa.[7,8] Further reports are awaited until this treatment may be recommended for routine clinical practice.

10. Photodynamic therapy.[9] Photodynamic therapy with photosensitizers may be effective treatment for superficial epithelial skin tumors.[10]

Follow-up:

Following treatment for basal cell carcinoma, the patient should be
clinically examined every 6 months for 5 years.[11] Thereafter, the patient
should be examined for recurrent tumor or new primary tumors at yearly
intervals. It has been prospectively found that 36% of patients who develop
a basal cell carcinoma will develop a second primary basal cell carcinoma
within the next 5 years. Early diagnosis and treatment of recurrent basal
cell carcinomas or another primary basal cell carcinoma is desirable since
the treatment of the disease in its earliest stages results in less patient
morbidity.

References:

  1. Preston DS, Stern RS: Nonmelanoma cancers of the skin. New England Journal of Medicine 327(23): 1649-1662, 1992.

  2. Thomas RM, Amonette RA: Mohs micrographic surgery. American Family Physician/GP 37(3): 135-142, 1988.

  3. Abide JM, Nahai F, Bennett RG: The meaning of surgical margins. Plastic and Reconstructive Surgery 73(3): 492-497, 1984.

  4. Lovett RD, Perez CA, Shapiro SJ, et al.: External irradiation of epithelial skin cancer. International Journal of Radiation Oncology, Biology, Physics 19(2): 235-242, 1990.

  5. Dabski K, Helm F: Topical chemotherapy. In: Schwartz RA: Skin Cancer: Recognition and Management. New York, NY: Springer-Verlag, 1988, pp 378-389.

  6. Lippman SM, Shimm DS, Meyskens FL: Nonsurgical treatments for skin cancer: retinoids and alpha-interferon. Journal of Dermatologic Surgery and Oncology 14(8): 862-869, 1988.

  7. Greenway HT, Cornell RC, Tanner DJ, et al.: Treatment of basal cell carcinoma with intralesional interferon. Journal of the American Academy of Dermatology 15(3): 437-443, 1986.

  8. Padovan I, Brodarec I, Ikic D, et al.: Effect of interferon in therapy of skin and head and neck tumors. Journal of Cancer Research and Clinical Oncology 100(3): 295-310, 1981.

  9. Wilson BD, Mang TS, Stoll H, et al.: Photodynamic therapy for the treatment of basal cell carcinoma. Archives of Dermatology 128(12): 1597-1601, 1992.

  10. Wolf P, Rieger E, Kerl H: Topical photodynamic therapy with endogenous porphyrins after application of 5-aminolevulinic acid. Journal of the American Academy of Dermatology 28(1): 17-21, 1993.

  11. Rowe DE, Carroll RJ, Day CL: Long-term recurrence rates in previously untreated (primary) basal cell carcinoma: implications for patient follow-up. Journal of Dermatologic Surgery and Oncology 15(3): 315-328, 1989.


SQUAMOUS CELL CARCINOMA OF THE SKIN

Localized squamous cell carcinoma of the skin is a highly curable disease.[1] The traditional methods of treatment involve the use of cryosurgery, radiation therapy, electrodesiccation and curettage, and simple excision. Each of these methods may be useful in specific clinical situations. Of all treatment methods available, Mohs micrographic surgery has the highest 5-year cure rate for both primary and recurrent tumors. This method uses microscopic control to evaluate the extent of tumor invasion. Lymphadenectomy is indicated when regional lymph nodes are involved.

Treatment options:

1. Mohs micrographic surgery.[2] Although this method is complicated and requires special training, it has the highest cure rate of all surgical treatments because the tumor is microscopically delineated until it is completely removed. It is indicated for the treatment of primary squamous cell carcinomas when they occur at sites known to have a high initial treatment failure rate following traditional methods, primary tumors with poorly defined clinical borders, primary tumors with diameters larger than 2 cm, or primary tumors arising in regions where the maximum preservation of uninvolved tissue is desirable, such as the face, head, and genitalia. It should be used for squamous cell carcinomas that show perineural invasion since tumor transit along nerves may extend many centimeters away from the primary or recurrent tumor site.[3] Recurrent squamous cell carcinomas can also be treated with this technique.

2. Simple excision with frozen or permanent sectioning for margin evaluation. This traditional surgical treatment usually relies on surgical margins ranging from 3 to 10 mm, depending on the diameter of the original tumor.[4] Tumor recurrence is not uncommon because only a small fraction of the total tumor margin is examined pathologically.

3. Electrodesiccation and curettage. This is a quick method for destroying the tumor, but the adequacy of treatment cannot be assessed immediately since the surgeon cannot visually detect the depth of microscopic tumor invasion. It should be reserved for very small primary tumors since this disease has metastatic potential.

4. Cryosurgery. Cryosurgery is used for clinically well defined in situ tumors. It is especially useful for debilitated patients with medical conditions that preclude other types of surgery. However, the absolute contraindications for cryosurgery include patients with abnormal cold tolerance, cryoglobulinemia, cryofibrinogenemia, Raynaud's disease, and platelet deficiency disorders. Relative contraindications to cryosurgery include tumors of the scalp, ala nasi, nasolabial fold, tragus, postauricular sulcus, free eyelid margin, upper lip vermillion border, and lower legs. Caution should also be employed before treating nodular ulcerative neoplasia greater than 3 cm, 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. There is significant morbidity associated with the use of cryosurgery. 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. Atrophy and hypertrophic scarring have been reported, as well as instances of motor and sensory neuropathy.

5. Radiation therapy. Radiation is a logical treatment choice, particularly for primary lesions requiring difficult or extensive surgery (e.g., eyelids, nose, ears). It eliminates the need for skin grafting when surgery would result in an extensive defect. Cosmetic results are generally good to excellent with a small amount of hypopigmentation or telangiectasia in the treatment port. Radiation therapy can also be utilized for lesions that recur after a primary surgical approach.[5] Radiation therapy is contraindicated for patients with xeroderma pigmentosum, epidermodysplasia verruciformis, or the basal cell nevus syndrome because it may induce more tumors in the treatment area.

6. Topical fluorouracil (5-FU). This method may be helpful in the management of selected in situ squamous cell carcinomas (Bowen's disease). Careful and prolonged follow-up is required since deep follicular portions of the tumor may escape treatment and result in future tumor recurrence.[6]

7. Carbon dioxide laser. This method may be helpful in the management of selected squamous cell carcinoma in situ. It may be considered when a bleeding diathesis is present, since bleeding is unusual when this laser is used.

8. Interferon alfa. Clinical trials are ongoing to treat squamous cell carcinoma with intralesional interferon alfa.[7] The results should be available in several years. One report shows the combination of interferon alfa and retinoids is effective treatment for squamous cell carcinoma.[8]

Follow-up:

Since squamous cell carcinomas have definite metastatic potential, these
patients should be re-examined every 3 months for the first several years
and then followed indefinitely at 6-month intervals.

References:

  1. Preston DS, Stern RS: Nonmelanoma cancers of the skin. New England Journal of Medicine 327(23): 1649-1662, 1992.

  2. Thomas RM, Amonette RA: Mohs micrographic surgery. American Family Physician/GP 37(3): 135-142, 1988.

  3. Cottel WI: Perineural invasion by squamous cell carcinoma. Journal of Dermatologic Surgery and Oncology 8(7): 589-600, 1982.

  4. Abide JM, Nahai F, Bennett RG: The meaning of surgical margins. Plastic and Reconstructive Surgery 73(3): 492-497, 1984.

  5. Lovett RD, Perez CA, Shapiro SJ, et al.: External irradiation of epithelial skin cancer. International Journal of Radiation Oncology, Biology, Physics 19(2): 235-242, 1990.

  6. Dabski K, Helm F: Topical chemotherapy. In: Schwartz RA: Skin Cancer: Recognition and Management. New York, NY: Springer-Verlag, 1988, pp 378-389.

  7. Padovan I, Brodarec I, Ikic D, et al.: Effect of interferon in therapy of skin and head and neck tumors. Journal of Cancer Research and Clinical Oncology 100(3): 295-310, 1981.

  8. 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. Journal of the National Cancer Institute 84(4): 235-241, 1992.


ACTINIC KERATOSIS

Actinic keratosis commonly appears in regions 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.[1] They represent early epithelial transformation that may eventually evolve into invasive squamous cell carcinoma. Actinic keratosis is a premalignant condition that should be treated with one of the methods available.[2]

Treatment options:

1. Topical agents:
a) Trichloroacetic acid

b) Phenol

c) Fluorouracil (5-FU): Treats the clinically obvious disease as well

as regions of subclinical involvement. It is usually associated
with a superior cosmetic result.

d) Retinoic acid: Being evaluated for treatment and prevention of
actinic keratosis.

2. Cryosurgery.

3. Electrodesiccation and curettage.

4. Dermabrasion.

5. Shave excision.

6. Carbon dioxide laser.

References:

  1. Picascia DD, Robinson JK: Actinic cheilitis: a review of the etiology, differential diagnosis, and treatment. Journal of the American Academy of Dermatology 17(2, Part 1): 255-264, 1987.

  2. Preston DS, Stern RS: Nonmelanoma cancers of the skin. New England Journal of Medicine 327(23): 1649-1662, 1992.

Date Last Modified: 07/1999



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