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. 2025 Oct 30.
doi: 10.1001/jama.2025.18749. Online ahead of print.

Keratinocyte Carcinoma: A Review

Affiliations

Keratinocyte Carcinoma: A Review

Mackenzie R Wehner. JAMA. .

Abstract

Importance: Keratinocyte carcinomas are skin cancers that arise from keratinocytes and are composed of basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (cSCCs). Keratinocyte carcinomas are common in North America, Australia, New Zealand, and Europe. Approximately 5.4 million keratinocyte carcinomas are diagnosed in the US annually.

Observations: Keratinocyte carcinomas are primarily located on the head and neck (40%-64% of BCCs; 35%-45% of cSCCs). BCC typically presents as a pink, smooth, raised lesion or a pink to red, flat lesion. cSCC typically presents as a red, scaly, flat lesion (in situ tumors) or a red, firm, raised lesion with scale or erosion (invasive tumors). UV light exposure is the primary cause, and lighter skin pigmentation and skin phototype (eg, skin that more easily burns) are the primary risk factors. Other risk factors include older age, male sex, indoor tanning, history of precancerous lesions (actinic keratoses), history of keratinocyte carcinomas, and immunosuppression (eg, organ transplant). In-office surgical excision or curettage and electrodessication (in which the tumor is scraped away using a curette and the wound base is cauterized) is typically performed by a dermatologist for keratinocyte carcinomas with lower risk of recurrence, including those that are nonrecurrent and have well-defined borders, small size, and location on the trunk and extremities. After surgical excision, approximately 3% of BCCs and 5% of cSCCs recur; after curettage and electrodessication, approximately 6% of BCCs and 2% of cSCCs recur. For keratinocyte carcinomas at higher risk of recurrence, in-office Mohs surgery (a technique in which a dermatologist with specialized training removes the tumor in stages and evaluates the entire surgical margin pathologically using a microscope after each stage to ensure complete tumor excision) is typically used. After Mohs surgery, approximately 4% of BCCs and 3% of cSCCs recur. Patients diagnosed with keratinocyte carcinoma are at high risk of additional keratinocyte carcinomas (approximately 40% within 5 years). Evidence-based prevention of keratinocyte carcinoma involves use of sunscreen. In a randomized clinical trial, use of daily sunscreen decreased cSCC risk (rate ratio, 0.62; 95% CI, 0.38-0.99; 1587 cSCCs per 100 000 person-years in controls vs 953 per 100 000 person-years in sunscreen group).

Conclusions and relevance: Keratinocyte carcinoma, composed of BCC and cSCC, is the most common cancer in the US, with an estimated 5.4 million diagnoses annually. Most keratinocyte carcinomas are effectively treated with in-office surgical procedures. Patients with keratinocyte carcinoma are recommended to undergo a skin examination at least annually due to their high risk of developing additional skin cancers.

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