| Basal Cell Cancer of the SkinDefinition - A type of nonmelanoma skin cancer that arises from epidermal basal cells
- Subtypes
- Superficial: least invasive
- Nodular
- Morpheaform (fibrosing): most invasive
 Epidemiology - Nonmelanoma skin cancer
- Most common cancer in the U.S.
- Basal-cell carcinomas (BCCs) account for 70–80% of nonmelanoma skin cancers.
- Lifetime risk of BCC among white persons in North America is 30%.
- Incidence
- Highest rates in Australia
- Incidence increases with decreasing latitude
- In U.S.
- Estimated at > 1.5 million cases annually
- 407 cases per 100,000 white men
- 212 cases per 100,000 white women
- Age and sex
- Rates highest among elderly men
- Incidence increasing in young women
- Race
- Uncommon in black persons and dark-skinned persons
Risk Factors - Cumulative exposure to sunlight
- Most significant factor
- Principally ultraviolet B (UV-B) spectrum
- Most tumors develop on sun-exposed areas of the head and neck.
- More common on the left side of the body in the U.S. and on the right side in the United Kingdom
- Presumably because of exposure during driving
- Male sex
- Older age
- Celtic descent
- Fair complexion
- Light-colored eyes
- Red or blond hair
- Tendency to sunburn easily
- Outdoor occupation
- Exposure to arsenic in well water or from industrial sources
- Exposure to cyclic aromatic hydrocarbons in tar, soot, or shale
- Immunosuppression induced by disease or drugs
- HIV infection
- Skin cancer may be more aggressive in this setting.
- Solid organ transplant recipients
- Ionizing radiation (including therapeutic radiation)
- Thermal burn scars
- Chronic ulcerations
- Heritable conditions: albinism, xeroderma pigmentosum, and basal-cell nevus syndrome
- History of BCC
- 10-fold risk of subsequent occurrences compared with controls
Etiology - Multifactorial
- Cumulative exposure to sunlight, principally the UV-B spectrum, is the most significant factor.
- Emerging data suggest that ultraviolet A radiation may be more carcinogenic than previously believed.
- Mutations in the tumor suppressor patch gene have been implicated in development of BCC.
Symptoms & Signs - Arise mainly in body areas exposed to sun
- Head and neck (80%)
- Trunk (15%)
- Arms and legs (5%)
- Often asymptomatic
- Advanced lesions
- Nonhealing ulceration
- Bleeding
- Pain
- Superficial BCC
- Truncal erythematous, scaling plaques that slowly enlarge
- Nodular BCC
- Small, slow-growing pearly nodule, with a rolled-edge appearance of its borders, often with small telangiectatic vessels on its surface
- Ulceration is frequent.
- Ulcerated nodular BCC is called a "rodent ulcer."
- Pigmented BCC
- Variant of nodular BCC with presence of melanin
- Morpheaform (fibrosing) BCC
- Solitary, flat or slightly depressed, indurated, whitish or yellowish plaque
- Borders typically indistinct
Differential Diagnosis - Benign inflammatory dermatoses
- May be confused with superficial BCC
- Pigmented nodular BCC
- May lead to erroneous diagnosis of malignant melanoma
- Early nodular BCC without ulceration may mimic nevi.
- Ulcerated BCC can be confused with squamous-cell cancer or keratoacanthoma.
Diagnostic Approach - Perform biopsy of suspicious skin lesions to confirm the diagnosis.
Laboratory Tests Imaging Diagnostic Procedures - Biopsy is needed to confirm the diagnosis.
Treatment Approach - Goals
- Total removal of tumor
- Preservation of function and cosmesis
- Options include:
- Most effective, recommended for all high-risk lesions
- Surgery: lowest failure rates[1]
- Radiotherapy
- Other options for low-risk, superficial lesions
- Cryotherapy
- Topical immunomodulators or chemotherapy
- Phototherapy
- Factors to consider in choosing therapy
- Tumor characteristics
- Patient age
- Medical status
- Preferences of patient
Specific Treatments Excision- Offers advantage of histologic control
- Usually selected for:
- More aggressive tumors
- Those in high-risk locations
- Cosmetic appearance
Mohs micrographic surgery- Specialized method of surgical excision
- Permits best histologic control and preservation of uninvolved tissue
- Associated with cure rates > 98%
- Preferred technique for:
- Recurrent lesions
- Lesions in a high-risk location
- Large and ill-defined lesions
- Lesions where maximal tissue conservation is critical (e.g., the eyelids)
Radiation therapy- Not used as often as surgical techniques
- Offers excellent chance of cure in many cases
- Useful in:
- Patients not considered surgical candidates
- As surgical adjunct in high-risk tumors
- Guidelines recommend reserving this treatment for patients > 60 years because of long-term sequelae.
- Contraindicated in genetic conditions predisposing to skin cancer and connective tissue diseases
Cryosurgery using liquid nitrogen- May be used in certain low-risk tumors
- Requires specialized equipment (cryoprobes) to be effective for advanced neoplasms
Electrodesiccation and curettage- Method most commonly used by dermatologists
- Selected for low-risk tumors
- Small primary tumor of a less aggressive subtype in a favorable location
Topical 5-fluorouracilTopical immunomodulators- Show promise in efficacy at treating superficial and nodular BCCs
- Ongoing trial is comparing imiquimod with surgery.[1]
- Imiquimod
- Approved for biopsy-proved primary superficial lesions < 20 mm on trunk, neck, or arms or legs of adults with normal immune systems[2]
- Relatively well-tolerated as a 5% cream applied 1–3 times daily for 6 weeks
- Improved rates of cure with increased frequency and duration of treatment
- Twice daily dosing may be limited by local skin reactions.
- Not indicated for morpheaform, infiltrative, nodular, or recurrent BCC or for lesions on the head
Photodynamic therapy - Selective activation of a photoactive drug by visible light
- May have improved cosmetic outcomes compared with surgery
- Effective for clearance but high recurrence rate
Other treatments- Have been used successfully in patients with numerous tumors
- T4N5 liposome lotion (topical endonuclease)
- Has been shown to repair DNA and may decrease the rate of nonmelanoma skin cancer in xeroderma pigmentosum
- Laser therapy
- Despite rapidly advancing technology in development, long-term efficacy in treating infiltrative or recurrent lesions still unknown.
Monitoring - Patients with a history of skin cancer
- Long-term follow-up for detection of recurrence, metastasis, and new skin cancers should be emphasized.
- Follow up every 6 months for the first year, then annually.
- 50% of recurrences occur within 2 years, and 67% occur within 3 years.
Complications - Invasion of surrounding tissue resulting in disfigurement or loss of function of invaded structure (e.g., nose, eyes, ears)
Prognosis - 5-year cure rate with surgical excision
- Any size on neck, trunk, limbs: >99%
- Head, < 6mm diameter: 97%
- Head, > 6mm diameter: 92%
- Mohs surgery has lowest 5-year recurrence rate of any treatment.
- Natural history
- Slowly enlarging, locally invasive neoplasia
- Degree of local destruction and risk of recurrence vary by:
- Size
- Small nodular, pigmented, cystic, or superficial BCCs respond well to most treatments.
- Large lesions (>10 mm on face, >20 mm in other areas) or morpheaform subtype may be more aggressive.
- Longer duration associated with higher risk
- Location
- Location on central face, eyelids, ears, or scalp associated with higher risk.
- Histologic subtype of tumor, high risk from:
- Poorly defined borders
- Morpheaform, sclerosing, mixed infiltrative, micronodular
- Presence of recurrent disease
- Previous radiation therapy at that site
- Patient’s immune status
- Immunosuppression associated with high risk
- Greatest risk of recurrence is within first 5 years.
- Metastatic potential
- Has been estimated to be 0.0028–0.1%
- Predictors of subsequent BCC after index case
- Initial truncal occurrence
- Age > 60 years
- Superficial histologic subtype
- Male sex
- Risk of subsequent skin cancers (melanoma and nonmelanoma types)
- Estimated to be up to 40% in 5 years
- BCC rarely causes death.
Prevention - Patient and physician education
- Visual examination of all skin surfaces by the patient or by a health care provider is used in screening for BCC.
- No prospective, randomized study has been performed to look for a mortality decrease.
- Screening may reinforce sun avoidance and other skin cancer prevention behaviors.
- Could dramatically reduce incidence of skin cancer
- Emphasis should be placed on preventive measures beginning early in life.
- Damage from UV-B radiation begins early, even though cancers develop years later.
- Regular use of sunscreens and protective clothing should be encouraged.
- Avoidance of tanning salons and midday (10 A.M. to 2 P.M.) sun exposure is recommended.
- Precancerous and in situ lesions should be treated early.
- Early detection of small tumors allows simpler treatments to be used, with higher cure rates and less morbidity.
- Chemoprophylaxis using synthetic retinoids
- Useful in controlling new lesions in some patients with multiple tumors
- Preventive measures in high-risk patients
- Small trials have shown some benefit for the following:[3]
- T4N5 liposome lotion in people with xeroderma pigmentosum
- Acitretin in renal transplant recipients
- Authors of meta-analysis suggest that small numbers and inconsistent results limit ability to draw firm conclusions.
ICD-9-CM - 173.9 Malignant neoplasm of skin, site unspecified
- 198.2 Secondary malignant neoplasm of the skin
- 232.9 Carcinoma in situ of skin, site unspecified Basal cell cancer of the skin
See Also Internet Sites References - Bath-Hextall F et al: Interventions for basal cell carcinoma of the skin. Cochrane Database Syst Rev , 2007 [PMID:17253489]
- Rubin AI, Chen EH, Ratner D: Basal-cell carcinoma. N Engl J Med 353:2262, 2005 [PMID:16306523]
- Bath-Hextall F et al: Interventions for preventing non-melanoma skin cancers in high-risk groups. Cochrane Database Syst Rev , 2007 [PMID:17943854]
General Bibliography - Drake LA et al: Guidelines of care for basal cell carcinoma. The American Academy of Dermatology Committee on Guidelines of Care. J Am Acad Dermatol 26:117, 1992 [PMID:1732317]
- Friedman RI et al (eds): Cancer of the Skin. Philadelphia, Saunders, 1991, pp 27-94
- Geisse JK et al: Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: a double-blind, randomized, vehicle-controlled study. J Am Acad Dermatol 47:390, 2002 [PMID:12196749]
- Marks R: An overview of skin cancers. Incidence and causation. Cancer 75:607, 1995 [PMID:7804986]
- Neville JA, Welch E, Leffell DJ: Management of nonmelanoma skin cancer in 2007. Nat Clin Pract Oncol 4:462, 2007 [PMID:17657251]
- This topic is based on Harrison’s Principles of Internal Medicine, 17th edition, chapter 83, Cancer of the Skin by AJ Sober, H Tsao, CV Washington.
PEARLS - In the Women’s Health Initiative study, women who developed nonmelanoma skin cancer were 2.3-fold more likely to report a history of a second noncutaneous cancer than were women without previous skin cancer.
- In black women, risk of a noncutaneous cancer was 7-fold higher in women with previous skin cancer.
- Basal cell carcinoma may present as a persistent non-healing skin ulcer.
- Biopsy should be performed to rule out the diagnosis.
- Eczema patches refractory to usual management may also be due to basal cell carcinoma.
- Basal cell carcinomas can be a feature of an X-linked inherited syndrome called Bazex Syndrome characterized by a triad of congenital hypotrichosis; follicular atrophoderma affecting the dorsa of the hands and feet, the face, and extensor surfaces of the elbows or knees; and the development of basal cell neoplasms.
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