Cellular Classification of Skin Cancer
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:
- Melanoma (as noted above).
- Cutaneous T-cell lymphomas (e.g., mycosis fungoides).
- Kaposi sarcoma.
- Extramammary Paget disease.
- Apocrine carcinoma of the skin.
- Metastatic malignancies from various primary sites.
(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.
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, 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.
Squamous Cell Carcinoma
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.
- 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.
- 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. [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]