Basal cell carcinoma (BCC) is the most common type of skin cancer in the United States, with an estimated 3.6 million new cases diagnosed annually.1-3 The exact number of new BCC cases is unclear as nonmelanoma skin cancers (most commonly BCC and squamous cell carcinoma) are not reported in cancer registries.2

Although BCC rarely leads to metastases or death, it is commonly locally destructive, and disfigurement can result if treatment is delayed. Timely identification of risk factors, diagnosis, and treatment are essential components of care.

Presentation and Diagnosis of BCC

BCC is a slow-growing malignancy and almost exclusively appears on sun-exposed areas of the body, including the face, shoulders, and trunk.1,4 It rarely appears on mucous membranes, palms, or soles. BCC lesions typically appear as a papule with a distinct pearly appearance or a flat macule, patch, or thin plaque that is pink-to-red in color.4 Dermoscopic features of these lesions include white streaks, irregular vascularity (telangiectasias), and translucency.2,5,6 These primary lesions may ulcerate and crust over, giving the borders of the lesion a rolled appearance often called a rodent ulcer.4 Bleeding with minor trauma is a common finding in BCC lesions.4

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Figure 1. Photographs showing nodular (top), superficial (middle), and ulcerated (bottom) basal cell carcinoma. Source: National Cancer Institute/Kelly Nelson, MD.

Biopsy is the only way to definitively diagnose BCC, and treatment should be delayed until biopsy confirmation is obtained.4 Biopsy methods include excisional, shave, and punch, with shave biopsies being the most common.7 When examined microscopically, BCC samples show aggregates of basaloid keratinocytes.4

Epidemiology of BCC

BCC is more common in White populations, and an inverse relationship between BCC incidence and darker skin pigment is found.8 Similar incidence rates are found in Europe, Canada, and Asia, while Australia has the highest incidence of BCC worldwide.8 BCC tends to be pigmented in people of color, leading to misdiagnosis.9 Skin cancer in patients of color is often diagnosed in its later stages when it is more difficult to treat.10

The incidence of BCC is on the rise and increased by 145% between 1976-1984 and 2000-2010.7 BCC incidence is higher in men than women.11

UV radiation exposure, childhood sunburns, age older than 50 years, fair skin tone, blonde or red hair, light eye color, history of skin cancer, environmental exposure, and genetics are all known risk factors for the development of BCC.1,8,11,12

Table. Risk Factors for BCC1,8,11,12

Family history of skin cancer
Blond or red hair color
UV exposure
Higher number of extremity moles
Higher susceptibility to sunburn as a child/adolescent
Higher lifetime number of severe/blistering sunburns
Genetic factors
Environmental exposure
UV Exposure

Research suggests that BCC risk is associated with timing, intensity, and pattern of UV radiation exposure. In one study, a strong positive relationship between BCC and number of sunburn incidents was found.13 Sun exposure that was measured in hours spent at the beach showed a positive linear relationship with development of BCC, while chronic sun exposure measured in hours of outdoor work was closely linked to the development of squamous cell carcinoma.13

Of the 3 types of UV rays, UV-B rays can directly damage DNA of skin cells and are most closely linked to the development of skin cancer.14 The most important preventative strategy for BCC is to avoid overexposure to UV rays by wearing protective clothing, avoiding sunlight during peak UV hours, and using sunscreen.

UV exposure from tanning bed use is also a risk factor for BCC. Data from a meta-analysis on tanning bed use suggest that BCC is more strongly linked to intense, intermittent UV exposure than overall cumulative UV exposure.15 The relative risk for BCC among tanning bed users was 1.29 (95% CI, 1.08-1.53). Of the 12 studies analyzed, 8 controlled for skin type or sun sensitivity, and 5 controlled for outdoor UV exposure to rule out these confounding variables.

Environmental Exposure and Genetic Risk Factors

Other risk factors for BCC include exposure to ionizing radiation or arsenic (via contaminated water, food, or medications), chronic immunosuppression (HIV infection or immunosuppressive medication following solid organ transplant), use of photosensitizing drugs, and genetic predisposition.12

MC1R gene polymorphisms have been linked to BCC risk and somatic PTCH1 gene mutations are found in 70% to 75% of BCCs.8 Somatic inactivating mutations in the TP53 gene are also frequently found in BCCs.8 Genetic syndromes associated with an increased risk of BCC include xeroderma pigmentosum, basal cell nevus syndrome (also known as Gorlin syndrome), multiple hereditary infundibulocystic, Bazex-Dupre-Christol syndrome, and Rombo syndrome.1,8

Treatment of BCC

Surgical treatment — excision, Mohs surgery, or curettage and electrodesiccation — is the most effective option for most cases of BCC, according to the American Academy of Dermatology management guidelines.7 In some cases, cryotherapy, radiation, or topical therapy may be considered.7

BCC generally has a good prognosis and high cure rate. However, for the small subset of patients with metastatic BCC, improving tolerance to targeted Hedgehog (HH) inhibitors (vismodegib, sonidegib) and optimizing second-line treatment with immune checkpoint inhibitors (eg, cemiplimab) are important.16 Topical chemotherapy agents (aminolevulinic acid hydrochloride, fluorouracil, and imiquimod) also may be used.16

Conclusion

BCC is a growing health concern worldwide, with cases increasing over the last several decades. Although UV exposure has long been known to be directly related to the development of skin cancer, research has demonstrated that different types of sun exposure, such as chronic vs intense intermittent, are linked to different types of skin carcinomas. This warrants more explicit and accessible patient education regarding the importance of sun protection in childhood, as every sunburn exponentially increases the risk of skin cancer, and even short episodes of UV exposure can cause malignancy.

While most patients are aware that chronic sun exposure is directly related to skin cancer growth, many patients would benefit from emphasis on sunburn prevention and sun safety even with sporadic exposure. These findings also necessitate provider urgency in encouraging patients to take extra precautions for sun protection when prescribing photosensitivity-increasing medications.

McKenzie Lane, PA-C, is a student in the Physician Assistant Program at Augusta University. Lisa Daitch, MPAS, PA-C, is an associate professor in the Physician Assistant Department of Augusta University, in Augusta, Georgia.

References

  1. Cameron MC, Lee E, Hibler BP, et al. Basal cell carcinoma: epidemiology; pathophysiology; clinical and histological subtypes; and disease associations. J Am Acad Dermatol. 2019;80(2):303-317. doi:10.1016/j.jaad.2018.03.060
  2. Our new approach to a challenging skin cancer statistic. The Skin Cancer Foundation; April 1, 2021. Accessed January 23, 2023. https://www.skincancer.org/blog/our-new-approach-to-a-challenging-skin-cancer-statistic
  3. Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the US Population, 2012. JAMA Dermatol. 2015;151(10):1081-1086. doi:10.1001/jamadermatol.2015.1187
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  6. Reiter O, Mimouni I, Dusza S, Halpern AC, Leshem YA, Marghoob AA. Dermoscopic features of basal cell carcinoma and its subtypes: a systematic review. J Am Acad Dermatol. 2021;85(3):653-664. doi:10.1016/j.jaad.2019.11.008
  7. Work Group; Invited Reviewers; Kim JYS, Kozlow JH, Mittal B, Moyer J, Olencki T, Rodgers P. Guidelines of care for the management of basal cell carcinoma. J Am Acad Dermatol. 2018;78(3):540-559. doi:10.1016/j.jaad.2017.10.006
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  12. Kim DP, Kus KJB, Ruiz E. Basal cell carcinoma review. Hematol Oncol Clin North Am. 2019;33(1):13-24. doi:10.1016/j.hoc.2018.09.004
  13. Zanetti R, Rosso S, Martinez C, et al. Comparison of risk patterns in carcinoma and melanoma of the skin in men: a multi-centre case-case-control study. Br J Cancer. 2006;94(5):743-751. doi:10.1038/sj.bjc.6602982
  14. Stoebner PE, Poosti R, Djoukelfit K, Martinez J, Meunier L. Decreased human epidermal antigen-presenting cell activity after ultraviolet A exposure: dose-response effects and protection by sunscreens. Br J Dermatol. 2007;156(6):1315-1320. doi:10.1111/j.1365-2133.2007.07895.x
  15. Wehner MR, Shive ML, Chren MM, Han J, Qureshi AA, Linos E. Indoor tanning and non-melanoma skin cancer: systematic review and meta-analysis. BMJ. 2012;345:e5909. doi:10.1136/bmj.e5909
  16. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Basal cell skin cancer. Version 2.2022. Accessed February 16, 2023. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1416

This article originally appeared on Clinical Advisor

Topics:

Basal Cell Carcinoma Skin Cancer