Chapter 41

Screening for Skin Cancer

Randy M. Gordon

Definition and Epidemiology

Although early detection and treatment of skin cancer can improve patient outcomes, evidence is insufficient to recommend for or against routine screening for early detection of skin cancer by a total-body skin examination (TBSE) during a routine office visit.¹ The U.S. Preventive Services Task Force (USPSTF) based this decision in part on poor and inconsistent research methodology in the literature. Nevertheless, one significant purpose of the skin cancer screening is to educate both the patient and the provider to identify the characteristic changes associated with skin cancer. The USPSTF agreed there is fair evidence that supports screening for skin cancer by clinicians to be moderately accurate in detecting melanoma. The USPSTF offered the following recommendations regarding skin cancer screening research: (1) standardizing skin cancer screening research methodology, (2) modeling studies based on the available indirect evidence, and (3) targeting high-risk patient populations for screening.¹

The American Cancer Society (ACS) recommends skin cancer screening every 3 years for people aged 20 to 40 and annually for people older than 40.² The American College of Preventive Medicine recommends a TBSE for patients at high risk for malignant melanoma (MM). The American College of Obstetricians and Gynecologists recommends screenings for females aged 13 years or older with a history of habitual exposure to sunlight, a family or personal history of skin cancer, or clinical evidence of precursor lesions (actinic keratosis).³ These cancers include nonmelanomatous skin cancers (NMSCs), such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), and melanomatous skin cancers, such as MM.

Researchers estimate that one in five Americans will develop skin cancer at least once in their lifetime.² The most recent research suggests that approximately 3.5 million cases of BCC or SCC are diagnosed each year. Although BCC is the most common form of skin cancer, MM is by far the most fatal. Based on reports from 2008 to 2012, the age-adjusted incidence rate of melanoma is 21.6 per 100,000 men and women per year according to the national Surveillance, Epidemiology, and End Results (SEER) database.⁴ Of the estimated 73,870 new cases of melanoma of the skin that occur annually, 9940 deaths are expected.⁴ Overall MM incidence rates are higher in women than in men before age 50. However, MM incidence rates in men versus women are twice as high by age 65, and nearly triple by age 80.² The differences in risk by age and sex primarily reflect differences in occupational and recreational sun exposure, which have changed over time. The rising incidence of skin cancer during the past several decades may also be attributed to increased sun exposure associated with societal and lifestyle shifts in the U.S. population and to depletion of the protective ozone layer.³

Ninety percent of all skin cancers are caused by the sun.⁵ Acute sunburns place the patient at increased risk, and the effects of sun damage are cumulative. Second-degree burns before the age of 18 years can double the incidence of NMSC and greatly increase the risk for MM.⁶ Fair-skinned men and women older than 65 years, patients with atypical moles, and those with more than 50 nevi constitute known groups at substantially increased risk for development of melanoma.² In addition, skin cancers appear to have a hereditary component. Xeroderma pigmentosum is the prototype syndrome of genetically determined increased skin cancer risk.³

Multiple risk factors exist for all types of skin cancer, including endogenous factors (phototype, skin and eye color, number of melanocytic nevi, presence of dysplastic nevi, and individual or family history of skin cancer), and exogenous factors (type and degree of cumulative sun exposure, history of sunburn, and sun protection behavior).²^–³^,⁵ Primary care providers should devote more time to screening patients with multiple risk factors. Providers must learn to identify high-risk patients for targeted assessment by incorporating patient risk assessment tools into their practice.³

Pathophysiology

The pathogenesis of skin cancer is multifactoral.³ Heavy sun exposure is a significant risk factor for MM.³ Ultraviolet radiation (UVR) in sunlight is the main causative agent in the development of MM and NMSC. UVR produces DNA damage, gene mutations, immunosuppression, oxidative stress, and inflammatory responses, all of which play a pivotal role in photoaging of the skin and skin cancer genesis. Researchers have suggested an association between skin cancer genesis and UVR-induced immunosuppression. UVR is a complete carcinogen in that it not only initiates tumorigenesis by inducing mutations in tumor suppressor genes, but also promotes tumor development. When UVR penetrates the skin, much of its energy is absorbed by the DNA of epidermal keratinocytes. Another major mechanism of carcinogenesis is UVR-induced free radical damage, and genetically determined ability to metabolize free radicals may also predispose patients to skin cancer.³ Repeated and unprotected exposure to ultraviolet light causes photoaging of the skin over time.

Normal skin aging begins by 30 to 35 of age and is characterized by thinning, atrophy, decreased elasticity, and fragility that lead to wrinkling. Skin that is photoaged from sun damage may be coarse with yellow discoloration (solar elastosis), irregularly pigmented, rough, or atrophic with deep wrinkling. Reactive hyperplasia of melanocytes results in persistent hyperpigmentation or hypopigmentation of the hands, forearms, legs, chest, and back.³ Chronic exposure disrupts the maturation of the outer layer of the epidermis, resulting in scaling, roughness, seborrheic keratoses, actinic keratoses, and NMSCs.⁶^–⁸ Tanning beds and sun lamps provide additional sources of ultraviolet light exposure and should be avoided.² The International Agency for Research on Cancer has classified indoor tanning devices as “carcinogenic to humans” based on an extensive review of scientific evidence.²

Clinical Presentation

Primary care providers must solicit a detailed patient history, including a social, family, and UVR-exposure history, to identify patients with the highest risk of developing skin cancer. Questions about the patient’s use of sunscreens, repeated sun exposure without protection, tendency to burn, outdoor employment, or family history of melanoma are beneficial to estimate the risk for NMSC and MM.³^,⁶ Patients scheduled for routine physical examinations should be queried about any changes in the appearance or size of skin lesions (Table 41-1). Warning signs for skin cancer include (1) an open sore that does not heal for 3 weeks; (2) a spot or sore that burns, itches, stings, crusts, or bleeds; and (3) any mole or spot that changes in size or texture, develops irregular borders, or appears pearly, translucent, or multicolored. Important clinical signs of cutaneous carcinoma include changes in size, shape, color, or texture of a mole or other skin lesion or the appearance of a new growth on the skin. Changes that occur over a few days are usually not cancer, but changes that progress over a month or more should be evaluated by a health care provider.³

TABLE 41-1

Signs Suggesting Malignant Transformation in Pigmented Lesions

Sign	Implication
CHANGE IN COLOR
Sudden darkening; brown, black	Increased number of tumor cells, the density of which varies within the lesion, creating irregular pigmentation
Spread of color into previously normal skin	Tumor cells migrating through epidermis at various speeds and in different directions (horizontal growth phase)
Red	Vasodilation and inflammation
White	Areas of regression or inflammation
Blue	Pigment deep in dermis; sign of increasing depth of tumor
CHANGE IN CHARACTERISTICS OF BORDER
Irregular outline	Malignant cells migrating horizontally at different rates
Satellite pigmentation	Cells migrating beyond confines of primary tumor
Development of depigmented halo	Destruction of melanocytes by possible immunologic reaction and inflammation
CHANGES IN SURFACE CHARACTERISTICS THAT SHOULD PROMPT EVALUATION FOR SKIN CANCER
Scaliness
Erosion
Oozing
Crusting
Bleeding
Ulceration
Elevation
Loss of normal skin lines
DEVELOPMENT OF SYMPTOMS THAT SHOULD PROMPT EVALUATION FOR SKIN CANCER
Pruritus
Tenderness
Pain