General Information About Skin Cancer
There are three main types of skin cancer:
- Basal cell carcinoma (BCC).
- Squamous cell carcinoma (SCC).
BCC and SCC are the most common forms of skin cancer and together are referred to as nonmelanoma skin cancers. This summary addresses the treatment of BCC and SCC of the skin and the related noninvasive lesion actinic keratosis. Refer to the PDQ summary on Melanoma Treatment for information about the treatment of melanoma.
Incidence and Mortality
Nonmelanoma skin cancer is the most common cancer in the United States. BCC is the more common type of nonmelanoma, 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 the resulting examination and biopsy of skin lesions.
The total number and incidence rate of nonmelanoma skin cancers cannot be estimated precisely because reporting to cancer registries is not required. However, based on extrapolation of Medicare fee-for-service data to the U.S. population, it has been estimated that the total number of persons treated for nonmelanoma skin cancers in 2012 was about 3 million.[5,6] That number exceeds all other cases of cancer estimated by the American Cancer Society for that year, which totaled about 1.6 million. Although nonmelanoma skin cancer is the most common of all malignancies, it accounts for less than 0.1% of patient deaths caused by cancer.
Risk factors for nonmelanoma skin cancer include the following:
- Sun and UV radiation exposure (including tanning beds). Epidemiologic evidence suggests that cumulative exposure to 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.[8-10] Skin cancers are more common in the southern latitudes of the Northern hemisphere.
- History of sunburns. People who have had sunburns are predisposed to the development of SCC.
- Light complexion and eye color. Individuals with a light complexion (fair skin that freckles and burns easily), light-colored eyes (blue, green, or other light-colored eyes), and light-colored hair (red or blond) who have had substantial exposure to sunlight are at increased risk of developing nonmelanoma skin cancer.
- Family history or personal history of BCC, SCC, actinic keratosis, familial dysplastic nevus syndrome, or atypical nevi.
- Chronic cutaneous inflammation. People with chronic cutaneous inflammation, as seen in long-standing skin ulcers, are predisposed to the development of SCC.
- Immune suppression. Organ transplant recipients receiving immunosuppressive drugs and individuals with immunosuppressive diseases are at an elevated risk of developing skin cancers, particularly SCC.
- Other environmental exposure. Arsenic exposure and therapeutic radiation increase the risk of cutaneous SCC.
Types of Skin Cancer
This evidence-based 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). BCC and SCC are both of epithelial origin. 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:
- Melanoma. (Refer to the PDQ summary on Melanoma Treatment for more information.)
- Merkel cell carcinoma. (Refer to the PDQ summary on Merkel Cell Carcinoma Treatment for more information.)
- Cutaneous T-cell lymphomas (e.g., mycosis fungoides). (Refer to the PDQ summary on Mycosis Fungoides [Including Sézary Syndrome] Treatment for more information.)
- Kaposi sarcoma. (Refer to the PDQ summary on Kaposi Sarcoma Treatment for more information.)
- Extramammary Paget disease.
- Apocrine carcinoma of the skin.
- Metastatic malignancies from various primary sites.
Basal cell carcinoma
BCC is at least three times more common than SCC in nonimmunocompromised patients. It usually occurs on sun-exposed areas of skin, with the nose being the most common 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.
BCCs are composed of nonkeratinizing cells derived from the basal cell layer of the epidermis. They are slow growing and rarely metastasize. BCC has a tendency to be locally destructive and can result in serious deforming damage if left untreated or if local recurrences cannot be completely excised. 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 often have a characteristic mutation in the patched 1 tumor suppressor gene (PTCH1), although the mechanism of carcinogenesis is not clear.
Squamous cell carcinoma
People with chronic sun damage, history of sunburns, arsenic exposure, chronic cutaneous inflammation (as seen in long-standing skin ulcers), and previous radiation therapy are predisposed to the development of SCC. SCCs tend to occur on sun-exposed portions of the skin, such as the ears, lower lip, and dorsa of the hands. SCCs that develop from actinic keratosis on sun-exposed skin are less likely to metastasize and have a better prognosis than those that develop de novo, or on non–sun-exposed skin.
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. Distinguishing SCC in situpathologically from a benign inflammatory process may be difficult. The risk of development into invasive SCC is low, reportedly in the range of 3% to 4%.
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.
Diagnostic and Staging Evaluation
BCC and SCC are usually diagnosed on the basis of routine histopathology obtained from a shave, punch, incisional, or excisional biopsy.
Other tests and procedures may be incorporated into the diagnosis and staging of BCC and SCC of the skin when appropriate and include the following:
- Physical examination, including skin examination and history.
- Chest x-ray.
- Computed tomography (CT) scan or positron emission tomography (PET)–CT scan of the head and neck or chest.
- Ultrasonography of the regional lymph nodes.
- Lymph node biopsy.
Ophthalmic examination or evaluation is performed for the diagnosis and staging of eyelid carcinoma.
Other PDQ summaries containing information related to nonmelanoma 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. [PUBMED Abstract]
- 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. [PUBMED Abstract]
- 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. [PUBMED Abstract]
- Rogers HW, Weinstock MA, Feldman SR, et al.: Incidence Estimate of Nonmelanoma Skin Cancer (Keratinocyte Carcinomas) in the U.S. Population, 2012. JAMA Dermatol 151 (10): 1081-6, 2015. [PUBMED Abstract]
- American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. Available online. Last accessed June 15, 2018.
- American Cancer Society: Cancer Facts and Figures 2012. Atlanta, Ga: American Cancer Society, 2012. Available online. Last accessed August 8, 2018.
- Koh HK: Cutaneous melanoma. N Engl J Med 325 (3): 171-82, 1991. [PUBMED Abstract]
- Preston DS, Stern RS: Nonmelanoma cancers of the skin. N Engl J Med 327 (23): 1649-62, 1992. [PUBMED Abstract]
- 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. [PUBMED Abstract]
- Cutaneous carcinoma of the head and neck. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 171–81.
- Dubin N, Kopf AW: Multivariate risk score for recurrence of cutaneous basal cell carcinomas. Arch Dermatol 119 (5): 373-7, 1983. [PUBMED Abstract]
- 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. [PUBMED Abstract]
- Kao GF: Carcinoma arising in Bowen’s disease. Arch Dermatol 122 (10): 1124-6, 1986. [PUBMED Abstract]