Introduction:
Basal Cell Carcinoma (BCC) is the most common cancer in humans worldwide, with more than 800,000 new cases annually in the US alone, where its incidence has been rising at about 10% per year. It is most common in fair-skinned individuals with a significant lifetime history of intense, intermittent sun exposure. Most BCCs begin as a pink or translucent bump on the skin. There are numerous treatments available for BCCs, and the overwhelming majority of patients are cured. If left untreated, BCC can be disfiguring and destroy tissue locally, but metastasis is extremely uncommon. Among those rare patients who develop metastatic disease, fewer than 10% survive more than 5 years. Most deaths from BCC are due to direct extension of the malignancy into a vital structure in patients who remain untreated for several years (rather than metastatic disease). 
What Causes Basal Cell Carcinoma?
Basal Cell Carcinoma is a cancer of immature skin cells thought to be associated with the hair follicle, and most BCCs have mutations occurring in a series of genes (named hedgehog, patched, and smoothened) that control the growth of these cells. In most cases, mutations in these genes are the result of DNA damage resulting from sunlight exposure or artificial ultraviolet light (from tanning booths). Some have attributed the steadily increasing incidence of Basal Cell Carcinoma to increased sun exposure and declining protective ozone.
Who Gets Basal Cell Carcinoma?
While BCC can occur at any age, most cases occur after the age of 40. Although BCC is seen in people of all races and ethnicities, it is most often found in light-skinned individuals. There are a number of risk factors for the development of basal cell carcinoma. Those with red or blond hair, blue or green eyes, freckling in childhood, a family history of skin cancer, and those who sunburn easily are at particularly high risk. Whereas squamous cell carcinoma risk appears to be directly related to cumulative sun exposure, the risk of BCC appears to be affected by the timing, pattern, and amount of sun exposure. Those with a history of recreational sun exposure or blistering sunburns during childhood and adolescence, and those with a history of intense, intermittent sun exposure are at higher risk. The use of indoor tanning beds also is associated with increased risk.
People who have been diagnosed with one nonmelanoma skin cancer (BCC or squamous cell carcinoma) are at increased risk of developing additional skin tumors in the future. Less common risk factors include exposure to ionizing radiation or arsenic intake (arsenic can be present in well water in certain areas). Patients with compromised immune systems (including those on immune suppressing drugs after organ transplants) have an increased incidence of basal cell carcinoma (though their incidence of squamous cell carcinoma is more dramatically increased).
Certain genetic syndromes put patients at high risk for developing BCCs. These include Basal Cell Nevus Syndrome (Gorlin syndrome), Xeroderma Pigmentosum, and Bazex Syndrome.
The Types of Basal Cell Carcinoma and their Symptoms:
Basal Cell Carcinoma is categorized according to its clinical and microscopic presentation:
- Nodular BCC is the most common subtype. There may be a single semi-translucent to pink (pearly) bump, or multiple bumps forming
around a central depression. The area may be crusted or ulcerated. Larger lesions form a classic “rolled border” at the edge. Small blood vessels (telangiectasias) are sometimes visible within the lesion. The tumor is usually painless, and bleeds easily when traumatized. Gradual enlargement is common. The face and ears are by far the most common locations, though any body part may be involved.
around a central depression. The area may be crusted or ulcerated. Larger lesions form a classic “rolled border” at the edge. Small blood vessels (telangiectasias) are sometimes visible within the lesion. The tumor is usually painless, and bleeds easily when traumatized. Gradual enlargement is common. The face and ears are by far the most common locations, though any body part may be involved.
- Superficial BCC is the second most common subtype. This form is
most commonly seen on the trunk, but can also be seen on the head, neck, or extremities. The usual appearance is of a dry, flat, scaly, red plaque. They enlarge slowly and may be confused with psoriasis or eczema, but can eventually grow to 10-15cm in diameter.
most commonly seen on the trunk, but can also be seen on the head, neck, or extremities. The usual appearance is of a dry, flat, scaly, red plaque. They enlarge slowly and may be confused with psoriasis or eczema, but can eventually grow to 10-15cm in diameter.
- Micronodular BCC clinically resembles the classic nodular form, but has smaller nodules of tumor cells under the microscope, and may behave more aggressively.
- Morpheaform (or sclerosing) BCC is a less common subtype, which may resemble a scar. This subtype also may behave more aggressively.
- Infiltrative BCC is a more aggressive subtype, and most frequently occurs on the head and neck of older patients. The clinical presentation is not distinctive (it can appear nodular or morpheaform).
- Pigmented BCCs have many features in common
with nodular tumors, but also contain brown or black pigmentation. This type is more commonly seen in Latino or Asian patients who develop BCC.
with nodular tumors, but also contain brown or black pigmentation. This type is more commonly seen in Latino or Asian patients who develop BCC.
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- Fibroepithelioma of Pinkus is a rare variant that typically occurs on the trunk or extremities, but can also be seen in the genital area.
How is Basal Cell Carcinoma Diagnosed?
A skin biopsy is usually required to confirm the diagnosis and determine the subtype. Usually, a small shave biopsy in which a thin area is removed from the surface of the lesion after local anesthesia is adequate.
How is Basal Cell Cancer Treated?
Each BCC lesion must be evaluated individually to determine a treatment strategy, taking into account several patient factors and tumor characteristics. Surgical treatment to remove the tumor is the recommended treatment in the majority of cases, though selected BCCs are amenable to topical treatments. Few head-to-head studies are available to allow for accurate comparisons between treatment options.
Surgical options include:
- Electrodessication and Curettage involves using a sharp instrument called a curette to scrape out the tumor, followed by cauterizing the base and margins of the area. The wound is left to heal on its own. This approach is most often used on superficial and nodular tumors of the trunk and extremities, and is not recommended for recurrent or high-risk lesions. When performed by an experienced physician on appropriately selected tumors, cure rates exceed 95%.- Excisional Surgery of the tumor and a surrounding margin is another common treatment. Typically, the lesion is removed with a 3-4mm margin, and the resulting wound is closed with sutures. Cure rates exceed 95%.- Mohs Micrographic Surgery offers the highest cure rates (more than 99% for primary tumors) and best preservation of normal tissue. It is indicated for tumors at certain sites (such as the central face, eyelids, nose, or ears) where tissue-sparing is important, and for recurrent, large, or other high-risk tumors. The Mohs technique allows for rapid, in-office examination by the surgeon of frozen section specimens to assess whether microscopic tumor remains, and if so, to map out its exact location in the skin. If additional tumor is present along any part of the margin, additional “stages” are performed in which the process of tissue removal and microscopic examination is repeated until the tumor has been completely removed. The resulting wound is then usually closed with sutures, and a flap or skin graft is sometimes required.- Cryosurgery (freezing the tumor with liquid nitrogen) is used less frequently because of higher recurrence rates and sometimes inferior cosmetic results.
Selected tumors may also be treated with topical medications:
- Fluorouracil cream (a chemotherapy agent) is perhaps useful in some superficial BCCs, though recurrence rates may be high.- Imiquimod cream (an immune-response modifier) applied 5 times per week for 6 weeks is useful in selected superficial BCCs, with cure rates of about 80%. It was approved by the U.S. Food and Drug Administration in 2004 for the treatment of primary, small, superficial BCCs on the trunk and extremities. Long-term cure rates are unknown.
Additional therapeutic options include:
- X-ray treatment is occasionally used for elderly patients who cannot tolerate surgery. Because problematic radiation-induced skin changes can occur years after X-ray treatment, it is not recommended for younger or middle-aged patients.
- Photodynamic therapy (PDT) involves the use of specific wavelengths of light following application of sensitizing chemicals. It appears to be effective for superficial tumors.- Injections of interferon alfa-2b into tumors appears to cure about 80% of small BCCs
Is Basal Cell Carcinoma Associated with Other Cancers?
As stated above, patients who have had a basal cell carcinoma are at substantially increased risk to develop additional skin cancers (squamous cell carcinoma, melanoma, and additional BCCs) during their lifetime.
One large study that followed 37,674 patients diagnosed with BCC in Denmark for up to 14 years found that these patients were also at somewhat increased risk for cancers of the lip, salivary glands, larynx, lung, breast, testicle, and kidney, as well as non-Hodgkin lymphoma. The degree of increased risk for some of these cancers was greatest for those whose first BCC occurred before the age of 60. It remains controversial whether these results represent a true association, or whether the higher rates of cancer observed are due to more careful surveillance or to shared (confounding) risk factors.
Can Basal Cell Cancer be Prevented?
The best way to lower the risk of basal cell carcinoma is to decrease skin exposure to ultraviolet radiation by avoiding peak hours of sunlight, using sunscreen, and wearing UV-protective clothing and hats. Given the epidemiologic data, these interventions may be most important during childhood and adolescence. No prospective, randomized trials have shown an effect of the use of sunscreen on the incidence of BCC (they have revealed reductions in squamous cell carcinomas), but these trials have been plagued by methodological difficulties.
Certain populations at much higher risk (such as organ transplant recipients) may benefit from the use of prescription oral vitamin A derivatives (such as acitretin).
(Nothing in this Knol should be construed as individual medical advice. Patients should consult with their own physician regarding the diagnosis and treatment of Basal Cell Carcinoma. Not all of the medications discussed are FDA-approved for the treatment of BCC, and some side-effects and contra-indications have not been listed.)