|
| A) | Melanoma | ||
| B) | Kaposi sarcoma | ||
| C) | Basal cell carcinoma | ||
| D) | Merkel cell carcinoma |
A wide variety of tumors and lesions arise in the skin, and most are benign. However, it is important to evaluate all suspicious lesions to distinguish benign tumors from nonmelanomas and melanomas. Skin cancers primarily comprise melanoma and two types of nonmelanomas—basal cell carcinoma and squamous cell carcinoma. Basal cell carcinoma is far more common, accounting for approximately 70% to 80% of nonmelanoma skin cancers, while squamous cell carcinoma accounts for nearly 20% [7,8].
| A) | White men. | ||
| B) | Black women. | ||
| C) | Hispanic women. | ||
| D) | Asian/Pacific Islander men. |
As is true for the White population, basal cell carcinoma is the most common skin cancer among the Hispanic and Asian populations [27,28]. In fact, among Hispanic individuals, basal cell carcinoma is six times more likely than squamous cell carcinoma [28]. In contrast, squamous cell carcinoma is the most common skin cancer in the Black population [25,28]. Melanoma is the third most common skin cancer among all racial/ethnic populations [25,28]. The highest rate of melanoma is found among non-Hispanic White men and the lowest is among Black women [29,202]. Although melanoma is predominant among White men compared with White women, the incidence of melanoma in men and women is similar in Black, Hispanic, and Asian/Pacific Islander populations [29,202]. The clinical features of skin cancers (i.e., appearance and anatomic site) also vary according to race/ethnicity, as will be discussed later.
| A) | The overall survival rate for most skin cancers is 80%. | ||
| B) | The mortality rate for melanoma is highest for Black men. | ||
| C) | Basal cell and squamous cell carcinomas are increasing among younger individuals. | ||
| D) | Basal cell carcinomas are associated with more deaths than squamous cell carcinomas. |
As noted, the incidence of all types of skin cancers in adults has been increasing over the past few decades. In 1930, the likelihood of melanoma was 1 in 5,000 Americans; by 2013–2015, that rate increased to 1 in 27 for men and 1 in 40 for women [36,222]. Overall, the rate of skin cancers has increased 3% to 8% per year since the 1960s [37]. In addition, the incidence of pediatric melanoma increased at a rate of 2% to 2.9% per year since the 1970s [38]. As discussed, the most recent data show melanoma rates may be leveling off or even decreasing [1]. The demographics of other skin cancers are also changing. Both basal cell and squamous cell carcinoma are occurring in an increasing percentage of people younger than 40 years of age, and one study found a disproportionate increase in basal cell carcinoma among women in that age-group [39,201]. These two types of skin cancer have nearly tripled in frequency among women younger than 40 years of age since the 1970s [9,40].
When detected and treated early, most skin cancers are associated with an overall survival rate of 97.7% [41]. Squamous cell carcinoma is associated with the greatest number of deaths attributed to nonmelanomas, and a 2013 study estimated that squamous cell carcinoma was responsible for 3,900 to 8,800 deaths in the United States in 2012 [42]. Previous estimates for annual nonmelanoma deaths have been closer to 2,000. As noted, of the three most common skin cancers, melanoma accounts for the most skin cancer-related deaths, and an estimated 7,650 people will die of the disease in 2022 [1]. Mortality rates associated with melanoma vary according to demographic factors; the rate is higher for men than for women (3.9 vs. 1.6 per 100,000), is highest for White men (4.5 per 100,000), and is lowest for Asian/Pacific Islander men and women (0.4 and 0.3 per 100,000, respectively) (Figure 4) [43].
Since the 1970s, the relative five-year survival rate for melanoma has increased significantly, from approximately 82% (1975–1977) to 94% (2008–2014), with a 10-year survival rate of greater than 92% [1,41]. However, this rate is lower among racial/ethnic minority populations; for example, the five-year survival rate rose from 57% to 66% for the Black population during the same time period [1,43]. This disparity in survival is primarily the result of melanoma being diagnosed at later stages in Black individuals [24,134].
| A) | Tanning devices confer minimal risk of skin cancers. | ||
| B) | Melanomas have a greater association with sun exposure than nonmelanomas. | ||
| C) | The risks of the different types of skin cancers vary according to patterns of sun exposure. | ||
| D) | The 10 states with the greatest number of melanoma cases all have high rates of year-round sun exposure. |
In the United States, the incidence of basal cell carcinoma has increased in states with a higher UV index (an estimate of the amount of UV radiation reaching the surface of the earth), with a greater difference for squamous cell carcinoma [46]. The risk of melanoma, however, was not found to differ with variations in the UV index, with only a few of the states with the highest numbers of melanoma cases associated with higher rates of sun exposure year-round (Table 1) [1,46,47]. These findings may be explained by many factors, including exposure to the sun in other locations (e.g., during vacation), changes in residence, frequency of exposure, and genetic susceptibility to the effects of UV radiation [48]. The findings also point to the need for enhanced awareness and attention to sun protection regardless of the geographic location of residence.
Both the epidermis and the underlying dermis are susceptible to damage from UV exposure. UV-A rays penetrate to the dermis, where they alter structural and matrix proteins, leading to the aged appearance associated with chronic sun exposure. UV-B rays are readily absorbed in the outer epidermal layer and are the primary cause of sunburn. UV-B rays are more carcinogenic than UV-A rays, and UV-B rays are thought to act as tumor initiators, while UV-A rays act as tumor promoters [32]. An early target of UV radiation is thought to be the p53 suppressor gene, which is often mutated in skin cancers [49].
The exposure to UV rays from the sun has increased as the protection afforded by the atmosphere has decreased because of the depletion of the ozone layer—individuals born between 1960 and 1980 have experienced the greatest increases in lifetime UV dose due to atmospheric ozone depletion [50]. Cloud cover protects only 20% to 40% of UV rays, glass blocks UV-B rays but only half of UV-A rays, and certain clothing provides little protection (e.g., a white t-shirt, particularly when wet, offers very little protection) [17,242]. Sunscreen provides a chemical or physical barrier to UV rays, but only when applied correctly [17].
Although UV exposure is the primary factor in the development of nonmelanomas, data are conflicting about the pattern of exposure (i.e., cumulative exposure versus intense, intermittent exposure). Exposure to UV radiation begins in early childhood, and 23% of lifetime exposure is reached by the age of 18 years (Table 2) [51,52]. The greatest accumulation occurs between the ages of 41 and 59 years, which would account for the increase in rates of skin cancers with advancing age [36,51].
The risk of basal cell carcinoma has been found to be higher with episodic acute overexposure to the sun (sunburn) than with a similar degree of continuous exposure [53,54]. In contrast, chronic (cumulative) exposure to the sun has been associated with a higher risk of squamous cell carcinoma [54,55]. The findings of a study of Asian individuals demonstrated that lifetime sun exposure was primarily associated with higher risk of squamous cell carcinoma among women, while early-age sun exposure was associated with a greater risk among men [56].
The pattern of exposure associated with melanoma has been debated, with some researchers finding a higher risk with episodic overexposure to the sun and other investigators finding a higher risk with chronic exposure [57,58,59,60,61,62]. One study found that the exposure pattern depends on the anatomic site; melanomas on the head and neck were associated with chronic exposure, and melanomas on the trunk were related to episodic exposure [63]. A meta-analysis of 57 studies published before 2002 supported a relationship between sunburn history and an increased risk for melanoma (relative risk: 2.03); the analysis also demonstrated an inverse relationship between continuous exposure and high risk [64]. Studies have shown that the risk of melanoma is doubled for an individual who had one blistering sunburn in childhood or adolescence or five or more sunburns at any age [6,65,66]. Additionally, a cohort study published in 2014 noted that individuals experiencing five or more blistering sunburns between 15 to 20 years of age have an 80% increased risk of developing melanoma and a 64% increased risk of developing non-melanoma skin cancer in their lifetimes [6,227].
Through widespread education and legislation regarding the dangers of indoor tanning, exposure to artificial UV radiation has decreased in recent years, but nearly 8 million adults still tan each year. Among adults, the rates of indoor tanning declined from 5.5% in 2010 to 3.5% in 2015 [69]. Among women, the prevalence decreased from 8.6% in 2010 to 5.2% in 2015, and the rates were 2.2% in 2010 and 1.6% in 2015 among men [69]. The national Youth Risk Behavior Survey also indicates a continued decrease among adolescents, with 15.6% indicating that they used indoor tanning in 2009, compared with 7.3% in 2015 [67,68]. The highest rates of indoor tanning are among White women 18 to 21 years of age (20.4%). Among White adults who reported indoor tanning, 40.8% reported at least one sunburn in the past 12 months, compared with 33.9% of non-indoor tanners [69].
The high use of devices with known carcinogenicity has led to much research on the association between indoor tanning and skin cancers. More than 419,000 cases of skin cancer are diagnosed annually due to indoor tanning, including 245,000 basal cell carcinomas, 168,000 squamous cell carcinomas, and 6,200 melanomas [2]. Studies have shown an increased risk for basal cell (29%) and squamous cell carcinoma (83%) associated with use of a tanning device; people who first use a tanning device before 35 years of age have a 75% increased risk for developing melanoma [2,70]. The direct cost of medical care for indoor tanning-related skin cancers is $343.1 million annually in the United States.
| A) | Location on the lip | ||
| B) | Location in existing scar | ||
| C) | Increasing depth of invasion | ||
| D) | Tumor larger than 2 cm with poor cell differentiation |
Squamous cell carcinoma, which originates in keratinizing epidermal cells, differs from basal cell carcinoma because of its potential to grow rapidly and invade fatty tissues beneath the skin and to metastasize. The risk of metastasis for squamous cell carcinoma varies widely, with an average rate of 2% to 6% [7,75,76]. However, the rate of metastasis is 11% to 15% for lesions on the lip and is nearly 30% for tumors larger than 2 cm with poor cell differentiation [32]. Other risk factors associated with metastasis include increasing depth of invasion, location in old scars or areas of chronic radiation dermatitis, and the presence of a compromised immune system [32].
| A) | History | ||
| B) | Review of symptoms | ||
| C) | Physical examination | ||
| D) | Evaluation of the clinical features of the lesion |
The primary challenges in diagnosing skin cancers are to distinguish between benign and malignant lesions and to identify lesions with malignant potential. The first steps in diagnosing skin cancers involve obtaining a history and physical examination and evaluating the clinical features of the lesion. Symptomatology does not play a large role in the detection and diagnosis of skin cancers, as early stage lesions are usually asymptomatic. Preliminary diagnoses for nonmelanomas can be based on the clinical appearance of the lesion, but biopsy should be performed to determine a definitive diagnosis.
| A) | back. | ||
| B) | trunk. | ||
| C) | hands. | ||
| D) | head and neck. |
The most common sites for basal cell carcinomas are the head and neck (85% of cases) and the trunk [8,33]. The clinical features and most common anatomic sites of basal cell carcinoma are similar across all racial/ethnic populations. One difference is the prevalence of pigmentation in the lesion; pigmentation is present in more than half of basal cell carcinomas in individuals of color, compared with approximately 5% in the White population [28]. Among the Asian population, basal cell carcinomas often appear brown to glossy black and have a black, pearly appearance [28].
| A) | are usually blue or black. | ||
| B) | have well-defined borders. | ||
| C) | occur most often on the feet. | ||
| D) | usually do not have telangiectasia on the surface. |
Squamous cell carcinoma usually presents as an ulcerated erythematous nodule, scaling patch, or superficial erosion on the skin or lower lip, but the clinical features of this nonmelanoma vary widely (Table 5) [7,9,32,33,76]. These lesions may also appear as a verrucous papule or plaque. Color also varies, and lesions may be reddish-brown, pink, or flesh-colored. Squamous cell carcinomas typically present as exophytic tumors, ranging in size from a few millimeters to centimeters. Larger lesions may appear crusted, erythematous, or eroded (Image 4). In contrast to basal cell carcinoma, overlying telangiectasias are uncommon. The margins may be ill-defined, and the lesion may be fixated to underlying structures [9,32].
| A) | Cryosurgery | ||
| B) | Laser therapy | ||
| C) | Photodynamic therapy | ||
| D) | Mohs micrographic surgery |
TREATMENT OPTIONS FOR BASAL CELL AND SQUAMOUS CELL CARCINOMAS
| Treatment Option | Type of Tumors | Comments | 5-Year Cure Rate | ||
|---|---|---|---|---|---|
| Electrodesiccation and curettage | Low-risk tumors | A commonly used technique | >92% | ||
| Surgical excision | High-risk basal cell carcinoma, standard treatment for squamous cell carcinoma | A commonly used technique; offers good histologic control | >90% | ||
| Mohs micrographic surgery | Large, ill-defined tumors, hard-to-treat locations (head, neck, hands, feet), recurrent lesions | Offers best histologic control; saves greatest amount of healthy tissue; high cost | 95% to 99% | ||
| Radiation therapy | Lesions near eye, nose, ear | An option for patients who are not good candidates for surgery | >90% | ||
| Photodynamic therapy | Superficial basal cell carcinoma, large, extensive lesions, or multiple lesions | Excellent cosmetic outcome, with minimal damage to normal tissue | Not available | ||
| Topical fluorouracil (5-FU) | Superficial basal cell carcinoma, multiple lesions, difficult treatment sites | Nonvisible dermal involvement may persist; local skin reaction | Not available | ||
| Topical 5% imiquimod cream | Superficial basal cell carcinoma | Local skin reaction | Not available | ||
| Cryotherapy | Low-risk tumors | Specialized equipment and skills; long healing time | 92.5% | ||
| Laser surgery | Treatment secondary to failed topical medications | Risk of scarring and pigment loss greater than with other techniques | Not available | ||
| Hedgehog pathway inhibitors | Treatment of metastatic or locally advanced basal cell carcinoma | New class of treatment; long-term efficacy unknown. Should be considered in those not responding to surgery or radiation. | Not available | ||
| PD-1 inhibitors (checkpoint inhibitors) | Treatment of metastatic or locally advanced carcinomas |
| Not available |
| A) | Cryotherapy | ||
| B) | Laser treatment | ||
| C) | Topical treatment | ||
| D) | Electrodessication and curettage |
A systematic review of the literature has shown that surgery or radiation therapy is the most effective treatment for basal cell carcinomas, with surgery associated with the lowest rates of failure [102,232]. Guidelines developed by the National Comprehensive Cancer Network (NCCN) recommend electrodessication and curettage for low-risk lesions, defined as lesions less than 1.5 cm in diameter and of less aggressive subtypes, as well as lesions in more favorable locations [103]. However, the technique cannot be used in a hair-bearing area, as tumor that extends into follicular structures may not be adequately removed [103]. Traditional surgical excision, superficial therapies (where radiation and surgery are contraindicated), and radiation therapy (typically reserved for those older than 60 years of age) are other options [103].
| A) | High-risk lesion | ||
| B) | Preservation of cosmesis | ||
| C) | A patient younger than 60 years of age | ||
| D) | None of the above |
As with basal cell carcinomas, radiation therapy may be used for patients who are not surgical candidates, when it is critical to preserve function or cosmesis, or as an adjunct to surgery for high-risk tumors, and should not be routinely used for patients younger than 60 years of age [84].
| A) | Recommended follow-up is once annually. | ||
| B) | The risk of a second nonmelanoma is about 15%. | ||
| C) | The risk of subsequent nonmelanoma is not increased. | ||
| D) | The size of the primary lesion is a major risk factor for recurrence. |
As noted, appropriate treatment of basal cell and squamous cell carcinomas can lead to high cure rates. However, a second nonmelanoma will develop in approximately 60% of individuals within 10 years after treatment of a first skin cancer, and the risk for cutaneous melanoma is also increased [107,108,109]. An estimated 30% to 50% of patients will develop a recurrent cutaneous squamous cell carcinoma within five years after treatment (70% to 80% of these recurrences develop within two years) [84,110]. A primary risk factor for recurrence of either basal cell or squamous cell carcinomas is size, in accordance to location, as follows [84,103]:
20 mm or more: Trunk, extremities
10 mm or more: Cheeks, forehead, scalp, neck
Any, not dependent on size: So-called mask areas of the face
Poorly defined borders, immunosuppression, and site of previous radiation therapy are other risk factors for recurrence of both types of nonmelanomas; site of chronic inflammatory process, neurologic symptoms, rapid tumor growth, moderate or poor differentiation, and thickness increase the risk of recurrent squamous cell carcinomas [84].
The NCCN recommends a history and physical examination, including a complete skin examination, every 6 to 12 months for 2 years after treatment and then, if appropriate, a reduced follow-up schedule for basal cell carcinoma; follow-up after treatment for squamous cell carcinoma is based on the extent of disease (Table 7) [84,103]. Follow-up for all patients should include extensive education on sun protection and self-examination [84,103].
| A) | immunosuppression. | ||
| B) | excessive sun exposure. | ||
| C) | persistently changing mole. | ||
| D) | family history of melanoma. |
The factors associated with an increased risk of melanoma, in decreasing order of importance, include [100,235]:
A persistently changed or changing mole
Adulthood (compared with childhood)
Irregular varieties of pigmented lesions, including dysplastic nevi and lentigo maligna
A congenital mole
White race
A personal or family history of melanoma
Immunosuppression
Sun sensitivity
Excessive sun exposure
| A) | Large size | ||
| B) | Asymmetry | ||
| C) | Uniform color | ||
| D) | Irregular border |
ABCDE RULE FOR DISTINGUISHING BENIGN TUMORS FROM MELANOMAS
| Criteria | Benign Tumors | Melanoma |
|---|---|---|
| A: Asymmetry | Symmetric | Asymmetric |
| B: Border | Clear-cut, distinct border | Irregular border |
| C: Color | Uniform light or dark pigment | Pigment variegation |
| D: Diameter | <6 mm (usually) | ≥6 mm |
| E: Evolving | No change over time | Change in size, shape, surface, shades of color, or symptoms |
| A) | shave. | ||
| B) | punch. | ||
| C) | full-thickness excision. | ||
| D) | full-thickness incisional. |
When melanoma is suspected, full-thickness excision should be done when possible [25,76]. An excisional biopsy allows for the determination of the thickness of the melanoma, an important clinical and prognostic factor [131,132].
| A) | Chemotherapy and immunotherapy | ||
| B) | Radiation therapy | ||
| C) | Cytotoxic chemotherapy alone | ||
| D) | Surgical resection |
Metastatic melanoma (stage IV) can be cured in certain patients depending primarily on the site(s) of metastases [132] The prognosis for patients with distant disease has significantly improved due to the development of effective systemic therapies [132]. If disease is limited (resectable), surgical resection is the preferred option, and nivolumab, pembrolizumab, or high-dose ipilimumab may be used after excision [132]. Immunotherapy with either interferon alfa-2b or interleukin-2 (IL-2) has led to response rates of 10% to 20% in appropriately selected patients, and complete responses achieved with immunotherapy seem to be more durable than those obtained with chemotherapy [148]. However, the toxicity associated with immunotherapy can be severe. Cytotoxic therapy may be considered on a case-by-case basis but is typically not preferred [132].
| A) | Skin examination every three years after treatment of stage 0 disease | ||
| B) | History and physical examination every two years after treatment for stage IA disease | ||
| C) | History and physical examination annually for three years after treatment for stage IIA disease and then every two years thereafter | ||
| D) | History and physical examination every three to six months for two years after treatment for stage III disease, followed by follow-up at increasingly longer intervals over subsequent years |
NATIONAL COMPREHENSIVE CANCER NETWORK RECOMMENDATIONS FOR FOLLOW-UP AFTER TREATMENT FOR MELANOMA
| Clinical/Pathologic Stage | Follow-Up |
|---|---|
| Stage 0 (in situ) | Skin examination and surveillance annually for life |
| Stage IA–IIA | History and physical exam (with emphasis on lymph nodes and skin) every 6 to 12 months for five years, then annually as clinically indicated. Routine laboratory testing or imaging studies to screen for asymptomatic recurrent or metastatic disease is not recommended. |
| Stage IIB–IV | History and physical exam (with emphasis on lymph nodes and skin) every 3 to 6 months for two years, then every 3 to 12 months for three years, then annually as clinically indicated. Chest x-ray and other imaging studies may be considered to screen for recurrent/metastatic disease every 3 to 12 months. Routine laboratory testing or imaging studies to screen for asymptomatic recurrent or metastatic disease is not recommended after three to five years. |
| A) | The U.S. Preventive Services Task Force recommends melanoma screening for the general population. | ||
| B) | The American Cancer Society recommends skin cancer screening annually beginning at 20 years of age. | ||
| C) | The Skin Cancer Foundation recommends annual skin cancer screening by a dermatologist. | ||
| D) | The American Academy of Dermatology recommends a skin examination by a dermatologist every two years. |
Another barrier to screening is the lack of scientific evidence to support the practice [122]. In general, there is insufficient evidence to recommend periodic screening for melanoma in the general adult population. This was the conclusion of the U.S. Preventive Services Task Force (USPSTF) when it updated its statement in 2016 [170,171]. The Task Force noted that there was "fair" evidence that screening by clinicians was "moderately accurate" in detecting melanoma, but that there was insufficient evidence to determine that screening reduces the morbidity or mortality rates associated with skin cancer [170]. Potential harms of detection and early treatment were noted to be misdiagnosis, overdiagnosis, and harm related to biopsy and treatment [170]. This same conclusion has been drawn by many other organizations, including the American Academy of Family Physicians and the NCI [172,173]. The HINTS study indicates that routine screening through total-body skin exam for melanomas and nonmelanomas is also not recommended, as there is inadequate evidence to suggest that population-wide screening would be effective [241].
Other professional organizations have set forth recommendations that primarily target individuals at high risk for melanoma. The American Academy of Dermatology suggests an annual skin examination by a dermatologist, especially for adults who have known risk factors, such as a history of substantial sun exposure or a family history of skin cancer [177]. The Academy also offers the Melanoma/Skin Cancer Screening Program, which provides free skin examinations by volunteer dermatologists [177]. The Skin Cancer Foundation also recommends annual screening by a dermatologist [174]. The American Cancer Society has set forth definitive screening recommendations: skin examination by a physician as part of a cancer check-up every three years for individuals 20 to 39 years of age and annually beginning at 40 years of age [178]. The American Cancer Society, American Academy of Dermatology, Skin Cancer Foundation, and the NCI recommend that individuals perform self-examinations, usually at four-to eight-week intervals [172,174,177,178].
| A) | Sunscreen should be mainly used in the summer. | ||
| B) | Sunscreen is good for blocking only ultraviolet B rays. | ||
| C) | Sunscreen is not needed in addition to make-up that has sun protection factor (SPF). | ||
| D) | Sunscreen should be applied 30 minutes before exposure to sun and reapplied frequently. |
POINTS OF EMPHASIS FOR PATIENT EDUCATION ON PREVENTION OF SKIN CANCERS
| Use of Sunscreen | |||||||||
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| Other Protection from UV Rays | |||||||||
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| Self-Examination | |||||||||
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Learn how to:
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| Other | |||||||||
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| A) | Seeking shade | ||
| B) | Using sunscreen | ||
| C) | Wearing long pants | ||
| D) | Wearing a long-sleeved shirt |
