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Abstract
Cutaneous squamous cell carcinoma (SCC) is among the most common cancers in humans, and many patients with SCC will develop multiple tumors within their lifetime. The field cancerization concept, originally proposed over 60 years ago, hypothesized that multiple primary cancers may arise simultaneously and coexist with subclinical precursor lesions within a defined field. Genetic sequencing of SCC and precursor lesions has identified what may be the earliest clonal proliferations in SCC development and confirmed that field cancerization in the skin is mediated by ultraviolet radiation. For patients with multiple SCCs and severe actinic damage, treatment of precursor lesions within a cancerized field can decrease the risk of subsequent cancer development. Sunblock is an effective intervention for field cancerization, even in patients with established disease. There is now direct evidence that field therapy with topical 5-fluorouracil is effective in reducing the incidence of subsequent SCC, and there is indirect evidence suggesting that topical imiquimod, topical ingenol mebutate, and photodynamic therapy are similarly effective. There is limited direct evidence to show that systemic acitretin or nicotinamide can decrease incident SCC in patients with field cancerization. In this review, an approach to the management of patients with multiple SCCs and field cancerization is presented along with the rationale to support field-directed therapy.
Highlights
Cutaneous squamous cell carcinoma (SCC) is the second most common malignancy in humans; up to 1 million SCC tumors are treated annually in the United States[1]
The classic presentation of SCC is a solitary lesion, some patients present with multiple lesions that may be admixed with premalignant lesions known as actinic keratoses (Figure 2)
The superiority of Mohs micrographic surgery over standard excision for these high-risk tumors has been documented in retrospective studies[12], and the Mohs technique is currently recommended for SCC with high-risk features or in anatomically sensitive locations[13]
Summary
Cutaneous squamous cell carcinoma (SCC) is the second most common malignancy in humans; up to 1 million SCC tumors are treated annually in the United States[1]. NOTCH1 mutations are present in clinically and histologically normal skin adjacent to SCC and appear to arise by contiguous growth of a clonal precursor[38] Based on these data, a mechanistic model of field cancer emerges, in which initial exposure to UV radiation causes sporadic somatic mutations and subsequent UV exposure induces clonal expansion of these mutants and inhibits immune surveillance of these malignant precursors (Figure 3). In a 24-month trial of organ transplant recipients at high risk of SCC, patients provided with SPF 50 broad-spectrum sunblock developed fewer SCCs (eight in the control group versus zero in the sunblock group) and exhibited a significant regression of existing AK47 This suggests that rigorous sun protection will have significant and long-lasting benefits in both prevention and management of field cancerization. Organ transplant recipients often require more frequent monitoring, earlier initiation of multi-modal field therapy, and potentially modification of their immunosuppression regimen in collaboration with their transplant team
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