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Am Fam Physician. 2020;102(6):339-346

Related editorial: Keratinocyte Carcinomas: Should We Screen for Them?

Patient information: A handout on this topic is available at https://familydoctor.org/condition/skin-cancer/.

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial affiliations.

Keratinocyte carcinoma, traditionally referred to as nonmelanoma skin cancer, includes basal cell and cutaneous squamous cell carcinoma and is the most common skin cancer malignancy found in humans. The U.S. Preventive Services Task Force recommends counseling about minimizing exposure to ultraviolet radiation for people aged six months to 24 years with fair skin types to decrease their risk of skin cancer. Routine screening for skin cancer is controversial. The U.S. Preventive Services Task Force concludes that current evidence is insufficient to assess the balance of benefits and harms of a routine whole-body skin examination to screen for skin cancer. Basal cell carcinoma commonly appears as a shiny, pearly papule with a smooth surface, rolled borders, and arborizing telangiectatic surface vessels. Cutaneous squamous cell carcinoma commonly appears as a firm, smooth, or hyperkeratotic papule or plaque, and may have central ulceration. Initial tissue sampling for diagnosis is a shave technique if the lesion is raised, or a punch biopsy of the most abnormal-appearing area of skin. High-risk factors for recurrence and metastasis include prior tumors, ill-defined borders, aggressive histologic patterns, and perineural invasion. Mohs micrographic surgery has the lowest recurrence rate among treatments but is best considered for large, high-risk tumors or tumors in sensitive anatomic locations. Smaller, lower-risk tumors are treated with surgical excision, electrodesiccation and curettage, or cryotherapy. Topical imiquimod and fluorouracil are also treatment options for superficial basal cell carcinoma and squamous cell carcinoma in situ. There are no clear guidelines for follow up after an index keratinocyte carcinoma, but monitoring for recurrence is important because the five-year risk of subsequent skin cancer is 41%. After more than one diagnosis, the five-year risk increases to 82%.

Keratinocyte carcinoma, referred to as nonmelanoma skin cancer, comprises basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC). BCC is the most common skin cancer malignancy and affects more than 3.3 million people annually in the United States.1 CSCC is the second most common skin cancer, with up to 400,000 U.S. cases and more than 3,000 disease-related deaths annually.2 Lifetime risk of keratinocyte carcinoma in the United States is at least 20% and is greater than 30% for White patients.3

Reported incidence rates of BCC vary depending on factors such as geographic latitude and sun exposure. Although BCCs can develop early in life, sporadically, and with certain genetic syndromes, age is an independent risk factor. The incidence of BCC increases after age 40. Incidence in younger people is increasing and may be the result of increased sun exposure.4 The proportion of keratinocyte carcinomas represented by CSCC has increased to 30% or greater, primarily in older patients, and is attributed to cumulative ultraviolet light exposure.3

Risk Factors and Prevention

Intermittent sun exposure (e.g., recreational tanning, occupational exposure, childhood sunburns) is the predominant risk factor for BCC. Cumulative sun exposure plays a critical role in CSCC carcinogenesis. The presence of any nevus on an extremity is associated with a higher risk of BCC. One study found that people with 15 or more nevi on the extremities had a 40% greater likelihood of BCC compared with those without any nevi on the extremities. No association between nevus count and CSCC has been observed.5

In addition to cumulative sun exposure, other risk factors for CSCC include chronically diseased or injured skin (e.g., ulcers, sinus tracts), exposure to ionizing or ultraviolet B radiation, immunosuppression (including HIV and drug-induced immunosuppression following organ transplantation), and xeroderma pigmentosum. Organ transplant recipients are 65 times more likely to develop CSCC compared with age-matched control patients. Lesions appear an average of two to four years after transplantation with increasing frequency over time.6

The U.S. Preventive Services Task Force (USPSTF) recommends behavior therapy aimed at minimizing exposure to ultraviolet radiation to decrease the risk of skin cancer for people aged six months to 24 years with fair skin types (i.e., ivory or pale skin, light eye color, red or blond hair, freckles, and those who sunburn easily). The USPSTF also recommends selective counseling for adults 25 years and older with fair skin types, noting that there is limited benefit to counseling all adults. There is insufficient evidence to include people without a fair skin type in the recommendation statement.7 The USPSTF stated the evidence is insufficient to assess the balance of benefits and harms for counseling adults about skin self-examination and routine screening of healthy adults for skin cancer.8

A 2016 Cochrane review found no difference in the incidence of BCC or CSCC with daily sunscreen use compared with occasional use.9 The single randomized trial included in the review demonstrated a 39% reduction in the number of CSCC tumors in the group using sunscreen daily compared with the never-used group.10 No studies evaluated other sun-protection measures, including sun-protective clothing, sunglasses, or hats, or seeking the shade when outdoors.9 Tanning bed use imparts a session-dependent increase in the risk of BCC, with a near-doubling of the risk if tanning bed use begins before age 24.11

Pathophysiology

BASAL CELL CARCINOMA

BCC develops from basal keratinocytes of the epidermis, hair follicles, and eccrine sweat ducts. BCC requires surrounding stroma for support during growth; therefore, the risk of metastasis by blood or lymphatics is less than 1%.

BCC has two common histologic patterns: nodular (60% to 80%) and superficial (20%). Approximately 15% of BCCs exhibit a micronodular pattern, and less than 10% have morpheaform or sclerosing, desmoplastic, or infiltrative changes.12 A mixed pattern, containing two or more histologic patterns, occurs in more than 40% of cases.13

CUTANEOUS SQUAMOUS CELL CARCINOMA

Actinic keratosis is the principal precursor to CSCC. Actinic keratosis and CSCC represent the same disease process at different stages of development, with neoplastic transformation of epidermal keratinocytes commonly triggered by ultraviolet radiation.14 CSCC spreads by local infiltration and expansion, and may follow tissue planes and conduits, such as nerves and vessels. The average risk of nodal metastasis in CSCC is approximately 3%.15 The risk of metastasis increases in patients who are immunosuppressed.16

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