Elsevier

The Lancet

Volume 375, Issue 9715, 20–26 February 2010, Pages 673-685
The Lancet

Seminar
Non-melanoma skin cancer

https://doi.org/10.1016/S0140-6736(09)61196-XGet rights and content

Summary

The rising incidence and morbidity of non-melanoma skin cancers has generated great interest in unravelling of their pathogenesis and in the search for new non-invasive treatments. Whereas the role of cumulative sun exposure in pathogenesis of squamous-cell carcinoma seems clear, the relation between sun-exposure patterns and subtypes of basal-cell carcinoma remains undetermined. Several complex genotypic, phenotypic, and environmental factors contribute to pathogenesis of non-melanoma skin cancers. Unlike basal-cell carcinoma, squamous-cell carcinomas can arise from precursor lesions. Diagnosis of non-melanoma skin cancer is made clinically and confirmed by histological testing. Prognosis depends on lesion and host characteristics, which also dictate choice of treatment. Prevention strategies aim at reduction of sun exposure, but are of unproven benefit, especially for basal-cell carcinoma. Surgical excision with predetermined margins is the mainstay of treatment for squamous-cell carcinoma and for most basal-cell carcinomas. Of the new non-invasive treatments, only photodynamic therapy and topical imiquimod have become established treatments for specific subtypes of basal-cell carcinoma, and the search for more effective and tissue-salvaging therapies continues.

Introduction

The term non-melanoma skin cancers (or keratinocyte carcinomas) encompasses cutaneous lymphomas, adnexal tumours, Merkel-cell carcinomas, and other rare primary cutaneous neoplasms, but is mainly used to define basal-cell carcinomas and squamous-cell carcinomas. Grouping of these two carcinomas under a common umbrella term poses challenges, because clear differences exist in their aetiopathogenesis, clinical course, and management strategies. Non-melanoma skin cancers are the most common human cancers, and despite growing public awareness of the harmful effects of sun exposure, incidence continues to rise.1, 2 A 3–8% yearly increase in incidence of non-melanoma skin cancer has been reported since 1960 worldwide.3, 4 Incidence of basal-cell carcinoma alone is increasing by 10% per year worldwide, suggesting that prevalence of this tumour will soon equal that of all other cancers combined.5 Furthermore, an estimated 40–50% of patients with a primary carcinoma will develop at least one or more further basal-cell carcinomas within 5 years. The estimated incidence of non-melanoma skin cancer in the USA is more than 1 000 000 cases per year, of which roughly 20–30% are of squamous-cell carcinoma.6

Section snippets

Epidemiology

Unfortunately, because of variation between registries in data capture, recording, and processing for skin-cancer registration, accurate figures for incidence of non-melanoma skin cancer in the UK are difficult to obtain.7 More than 76 000 new cases of non-melanoma skin cancer were registered in the UK in 2005, but the actual incidence is estimated to be at least 100 000 cases per year.8 Results of a Welsh study9 showed that the crude incidence of non-melanoma skin cancer increased from 173·5

Pathogenesis

UVB radiation causes direct damage to DNA and RNA by inducing covalent bond formation between adjacent pyrimidines, leading to generation of mutagenic photoproducts such as cyclopyrimidine dimers (TT) and pyrimidine-pyrimidine (6-4) adducts.25 UVA is less mutagenic than is UVB, and causes indirect DNA damage via a photo-oxidative-stress-mediated mechanism, resulting in formation of reactive oxygen species, which interact with lipids, proteins, and DNA to generate intermediates that combine with

Diagnosis

Early basal-cell carcinomas are usually small, translucent, or pearly, with raised telangiectatic edges. Roughly 80% of all basal-cell carcinomas occur on the head and neck, and clinical diagnosis is fairly straightforward.72 In addition to the classic rodent ulcer with an indurated edge and ulcerated centre, nodular or cystic, superficial, morphoeic, and pigmented basal-cell carcinomas are other common subtypes (figure 3). 10–40% of basal-cell carcinomas contain a mixed pattern of two or more

Prognosis and staging

Non-melanoma skin cancers, especially basal-cell carcinomas, have low metastatic potential and are associated with low mortality. The likelihood of metastases and recurrence of squamous-cell and basal-cell carcinoma depends on several prognostic indicators (table 4).86, 89, 90, 91 These indicators draw attention to the importance of a detailed pathological description, since individual lesion and host characteristics have to be taken into account when determining the prognosis of non-melanoma

Management

The British Association of Dermatologists has issued guidelines for management of non-melanoma skin cancers.86, 98 Interventions for management of basal-cell carcinomas in immunocompetent patients and prevention of non-melanoma skin cancers in high-risk groups have been systematically reviewed.99, 100 Routine use of sunscreen might prevent squamous-cell carcinoma, but is of unproven benefit in basal-cell carcinoma.101 Several government and charitable organisations have launched prevention

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