Basal Cell Carcinoma – Diagnosis, Treatment and Prevention

What Is Basal Cell Carcinoma?

Basal cell carcinoma (BCC) is the most common and least dangerous skin cancer. It usually develops in sun-exposed areas and is a slow-growing tumor that does not often spread to surrounding tissues. This article discusses its diagnosis and treatment, risk factors and prevention.

Although precise Turkish statistics on basal cell carcinoma (BCC) are difficult to obtain, it is the most common skin cancer worldwide, and the situation is similar in Turkey. BCC is the most common skin cancer in the United States, with approximately 3.6 million new cases diagnosed annually. It very rarely metastasizes or causes death, but delayed treatment can allow local tissue destruction and skin deformity. Timely identification of risk factors, diagnosis and treatment are essential components of care.

BCC is a slow-growing tumor generally found on sun-exposed areas, particularly the face, shoulders and trunk. Typical lesions appear as a distinctly pearly papule or a flat pink-red macule, patch or thin plaque. Dermoscopic features include white lines, irregular blood vessels and translucency. The main tumor may ulcerate and crust over, giving the lesion’s edges a rounded appearance.

Symptoms of Basal Cell Carcinoma

Symptoms include:

• A slow-growing, shiny, firm skin nodule
• A flat, scaly, red skin lesion
• Bleeding sores that do not heal
• Redness and inflammation around the lesion

A biopsy is required for definitive BCC diagnosis, and treatment should be deferred until the diagnosis is confirmed. Microscopic examination for the pathology report shows clusters of basaloid keratinocytes in BCC samples.

BCC is more common in white people, with an inverse relationship between its frequency and dark skin pigmentation. Similar incidence rates (new cases per year) are seen in Europe, Canada and Asia, while Australia has the highest incidence worldwide. In people with darker skin, BCC tends to be pigmented, which can lead to misdiagnosis. Skin cancer in people with darker skin tends to be diagnosed at advanced stages, when treatment may be more difficult.

Other common skin cancers besides basal cell carcinoma (BCC) include:

• Squamous cell carcinoma: This skin cancer arises from squamous cells in the upper skin layers. It usually occurs in sun-exposed areas and may behave more aggressively than BCC.
• Melanoma: This skin cancer arises from cells called melanocytes and is the most aggressive skin cancer. It may appear as skin lesions or changing moles. It is treatable when detected early, but at advanced stages it can metastasize to other organs.

BCC can sometimes be confused with similar conditions or diseases:

• Seborrheic keratosis: These benign skin lesions are associated with aging and appear as raised brown or black spots. They are generally harmless and can be left untreated.
• Actinic keratosis: This skin condition develops in sun-exposed areas and features rough, crusted patches. It should be treated because it carries a risk of developing into squamous cell carcinoma.
• Dermatofibroma: A benign skin tumor appearing as firm, brown or reddish nodules. It usually requires no treatment but may be removed for cosmetic reasons or if it causes discomfort.
• Pigmented nevi (moles): These lesions are mostly benign and vary in color, shape and size. However, regular checks are important because of melanoma risk.

BCC Is Becoming More Common

BCC incidence is increasing, with a 145% rise between 1976-1984 and 2000-2010. Incidence is higher in men than women. UV radiation exposure, childhood sunburn, age over 50, fair skin, blond or red hair, light-colored eyes, a history of skin cancer, environmental exposure and genetic factors are known risk factors.

Basal Cell Carcinoma (BCC) and Its Causes

Known risk factors for basal cell carcinoma (BCC) include UV exposure, childhood sunburn, age over 50, fair skin, blond or red hair, light-colored eyes, a history of skin cancer, environmental exposure and genetic factors. The following list outlines BCC risk factors:

• A family history of skin cancer
• Blond or red hair
• UV exposure
• A greater number of moles
• High susceptibility to sunburn during childhood or adolescence
• A high number of severe or blistering sunburns over a lifetime
• Genetic factors
• Environmental exposure

Research shows that BCC risk is associated with the timing, intensity and duration of UV exposure. One study found a strong positive association between BCC and sunburn episodes. Sun exposure measured by hours spent at the beach showed a positive linear relationship with BCC development, while chronic exposure measured by outdoor work was closely associated with squamous cell carcinoma.

Of the 3 types of UV radiation, UV-B can directly damage skin-cell DNA and is most closely associated with skin cancer development. The most important BCC prevention strategy is to avoid excessive UV exposure by wearing protective clothing, avoiding sunlight during peak UV hours and using sunscreen.

Tanning-bed UV exposure is also a BCC risk factor. A meta-analysis of tanning-bed use found a stronger link between BCC and intense, intermittent UV exposure than total cumulative exposure. People using tanning beds have a BCC risk 1.29 times as high (95% CI, 1.08-1.53).

Environmental and Genetic Risk Factors

Other BCC risk factors include exposure to ionizing radiation or arsenic through contaminated water, food or medicines; chronic immunosuppression from HIV infection or immunosuppressive drugs after solid-organ transplantation; photosensitizing drugs; and genetic susceptibility.

MC1R gene polymorphisms are linked to BCC risk, and somatic PTCH1 mutations occur in 70-75% of BCCs. In addition, the TP53 gene frequently has somatic inactivating mutations in BCC. Genetic syndromes associated with BCC risk include xeroderma pigmentosum, basal cell nevus syndrome (also called Gorlin syndrome), multiple hereditary infundibulocystic, Bazex-Dupre-Christol syndrome and Rombo syndrome.

Can Basal Cell Carcinoma Risk Be Reduced? Prevention

Several prevention strategies can reduce basal cell carcinoma (BCC) risk. Important steps include:

1. Protect yourself from the sun and use sunscreen

2. Avoid tanning beds

3. Check your skin: people with many moles in particular should have an annual dermatology examination

4. Quit smoking: smoking may increase skin cancer risk. Quitting can reduce your BCC risk.

5. Nicotinamide supplements: some studies suggest that oral nicotinamide supplements (a form of vitamin B3) may help reduce basal cell carcinoma risk. A doctor’s prescription and recommendation are required to use them.

Reducing Skin Cancer Risk with Nicotinamide (Vitamin B3)

A systematic review and meta-analysis evaluating nicotinamide for skin cancer prevention was published in 2022. It found that nicotinamide is associated with a significant reduction in skin cancers of all types (high-strength evidence). It also significantly reduces basal cell carcinomas (BCCs) and squamous cell carcinomas. However, it may increase the risk of gastrointestinal side effects.

Nicotinamide is a form of vitamin B3 involved in many important processes, including energy production and cell repair. Recent research suggests that oral nicotinamide supplements may help prevent skin cancers such as basal cell carcinoma.

Nicotinamide may therefore be considered a supplement for reducing skin cancer risk, particularly in patients with a history of basal and squamous cell skin cancers or organ transplantation (weak recommendation; moderate-quality evidence). It is thought to prevent cancer by repairing DNA damage and reducing UV-induced immunosuppression.

Recommended nicotinamide supplement doses vary across studies. However, studies focusing on skin cancer prevention, particularly Chen 2015 and Chen 2016, recommend an oral dose of 500 mg twice daily. This is a commonly recommended dose for patients at risk of skin cancer.

Treatment of Basal Cell Carcinoma

Surgical removal of the tumor area—by excision, Mohs surgery or curettage and electrodesiccation—is the most effective option for most BCC cases. Cryotherapy (destruction by freezing), radiation or topical treatment may be considered in some circumstances.

BCC generally has a favorable course and a high cure rate. However, for a small subset of patients with metastatic BCC, targeted Hedgehog (HH) inhibitors (vismodegib, sonidegib) and second-line immune checkpoint inhibitors, such as cemiplimab, may be considered. Topical chemotherapy agents (aminolevulinic acid hydrochloride, fluorouracil and imiquimod) may also be used.

Conclusion

Basal cell carcinoma (BCC) is the most common skin cancer worldwide and is treatable when detected early. Attention to known risk factors and sun protection can reduce its risk. Regular skin checks and mole monitoring are also important for early diagnosis. Preventive strategies such as nicotinamide supplements and healthy lifestyle choices may help reduce BCC risk. Awareness and appropriate protective measures play a key role in addressing this common skin cancer.