Joe Biden’s Basal Cell Carcinoma

Last month, President Biden had a skin lesion removed from his chest. White House physician Kevin O’Connor, DO, is now reporting that the biopsy results of the lesion confirmed that the growth was a basal cell carcinoma (BCC). The lesion had been detected as part of his “comprehensive health assessment.” The lesion was biopsied and then “treated presumptively with electrodessication and curettage (EDC) at the time of the biopsy.” All the cancerous tissue was successfully removed, the wound is healing well, and no further treatment is necessary for the president. He will, however, undergo continued dermatological surveillance.

In January, First Lady Jill Biden, EdD, also was diagnosed with two BCCs: One was under her right eye and the other on the left side of her chest. Like the president, Dr. Biden’s lesions were found during a routine skin cancer screening. She underwent Mohs surgery to remove the lesions, and O’Connell reported that “all cancerous tissue was successfully removed and the margins were clear of any residual cancer cells.”

Basal Cell Carcinoma

Nonmelanoma skin cancer is the most common cancer in the U.S. BCC is the more common type, accounting for about three-quarters of nonmelanoma skin cancers. It is estimated to affect close to one in five Americans. The incidence of BCC is increasing worldwide at an annual rate of close to 10%.

BCC is rarely fatal, but it can cause significant local destruction, disfigurement, and morbidity if not recognized or adequately treated.

BCC occurs most commonly on sun-damaged skin of the head, neck, trunk, and extremities. It rarely occurs on the mucous membranes or on the palms and soles. Men have had a higher rate than women, although this difference is becoming less significant with changes in lifestyles, such as tanning beds and smoking.

Risk factors for nonmelanoma skin cancer include:

• Sun and ultraviolet (UV) radiation exposure (including tanning beds). Epidemiological evidence suggests that cumulative exposure to UV radiation and the sensitivity of an individual’s skin to UV radiation are risk factors for skin cancer. Skin cancers are more common in the southern latitudes of the Northern hemisphere.
• History of sunburns. People who have had sunburns are predisposed to the development of BCC.
• Light complexion and eye color. Individuals with a light complexion (fair skin that freckles and burns easily), light-colored eyes (blue, green, or other light-colored eyes), and light-colored hair (red or blond) who have had substantial exposure to sunlight.
• Family history or personal history of BCC, squamous cell carcinoma (SCC), actinic keratosis, familial dysplastic nevus syndrome, or atypical nevi.
• Immune suppression. Organ transplant recipients receiving immunosuppressive drugs and individuals with immunosuppressive diseases are at an elevated risk of developing skin cancers, particularly SCC.
• Increasing age (associated with increased cumulative sun exposure). White individuals over age 65 have the highest incidence of BCC.

Pathophysiology

Researchers believe that there are two main pathways of pathogenesis in BCC: UV radiation-induced carcinogenesis and genetic mutations. UV radiation causes direct and indirect DNA damage. It also causes dose-dependent suppression of the immune system of the skin.

As for genetic mutations, in almost 90% of cases, alterations in genes that cause hyperactivation of the hedgehog (HH) protein family are linked with BCC. HH is a signaling pathway that is frequently used during development for intercellular communication. HH is important for the organogenesis of almost all organs in mammals, as well as in regeneration and homeostasis. After embryogenesis, it continues to function in regulation of cell growth and differentiation.

The most important mutation in BCC involves the PTCH1 gene. Its role in BCC was discovered by researchers studying the inherited nevoid BCC syndrome, also known as Gorlin syndrome. It was also found in patients with xeroderma pigmentosum. PTCH1 encodes a protein acting as a transmembrane receptor for the HH protein family, an important component of the HH signaling pathway.

The second most important mutation in BCC is in the gene TP53, which encodes a protein called tumor protein p53 that acts as a tumor suppressor. It regulates cell division by keeping cells from growing and proliferating in an uncontrolled way.

Clinical Features and Subtypes

BCC derives from the BC layer and outer root sheath of the hair follicles, which contain immature pluripotent epithelial cells.

Although several different subtypes of BCC are described in the literature, they basically fall into one of three main subtypes: nodular, superficial, and infiltrative.

Nodular BCC is the most common subtype (50%-80% of all BCCs). It presents as a pink, pearly papule with rolled borders and overlying telangiectasias. It can ulcerate and bleed. It is slow growing and occurs most commonly on the face and neck. They may also contain a variable amount of melanin pigment. Histologically, there is a characteristic palisading of cells around the edge of islands of blue tumor cells. A cleft between the collagen and the palisaded cells is common.

Superficial BCC presents as a thin, pink plaque, papule or macule. It also has a pink, pearly border. Superficial BCC is most commonly seen on the chest, back, or extremities. Histologically, superficial BCC shows a palisaded border of blue basal cells budding from the epidermis.

Infiltrative BCC is further divided into infiltrative, micronodular, and morpheaform subtypes. Morpheaform BCC presents as a firm, scar-like plaque. The infiltrative types of BCC show small islands of blue tumor cells diving between collagen bundles. The morpheaform subtype has a sclerotic stroma, which correlates with the scar-like clinical appearance.

Treatment

“There is a wide range of approaches for treating [BCC] of the skin, including surgical excision with margin evaluation, radiation therapy [RT], cryosurgery, electrodesiccation and curettage, photodynamic or laser-beam light exposure, and topical therapies. Each of these approaches is useful in specific clinical situations. Depending on case selection, these approaches have recurrence-free rates ranging from 85% to 95%,” according to the National Cancer Institute.

Mohs surgery has the best long-term cure rate of all the treatment modalities for BCC. During Mohs surgery, one layer of tissue at the site of a visible cancer is removed at a time and checked under a microscope for the presence of cancer. This process is repeated until all cancerous tissue has been removed. This type of surgery removes as little normal tissue as possible.

EDC involves removal of a skin lesion with a spoon-shaped curette. Afterwards, the area is cauterized with a high-frequency electric current through a needle-shaped electrode. This sequence may be repeated one or two times during the procedure.

RT is particularly useful in the management of patients with primary lesions that would otherwise require difficult or extensive surgery (e.g., lesions on the nose or ears). It eliminates the need for skin grafting when surgery would result in an extensive defect. Cosmetic results are generally good, with a small amount of hypopigmentation or telangiectasia in the treatment port.

Cryosurgery may be considered for patients with small, clinically well-defined primary tumors. It is infrequently used for the management of BCC, but cryosurgery may be useful for patients with medical conditions that preclude other types of surgery.

Photodynamic therapy with photosensitizers is used in the management of a wide spectrum of superficial epithelial tumors. A topical photosensitizing agent, such as 5-aminolevulinic acid or methyl aminolevulinate, is applied to the tumor, followed by exposure to a specific wavelength of light related to the absorption characteristics of the photosensitizer. Upon light activation, the photosensitizer reacts with oxygen in the tissue to form singlet oxygen species, resulting in local cell destruction.

Topical 5-FU, as a 5% cream, may be useful in specific limited circumstances. The FDA approved this treatment for superficial BCCs in patients for whom conventional methods are impractical, such as individuals with multiple lesions or difficult treatment sites.

Treatment options for metastatic BCC of the skin (or locally advanced disease untreatable by local modalities) include HH pathway inhibitors and chemotherapy. HH pathway inhibitors include vismodegib and sonidegib. They are inhibitors of Smoothened, a transmembrane protein involved in the HH pathway, and are approved for the treatment of adults with metastatic BCC, patients with locally advanced BCC that has recurred after surgery, and patients who are not candidates for surgery or RT.

Michele R. Berman, MD, is a pediatrician-turned-medical journalist. She trained at Johns Hopkins, Washington University in St. Louis, and St. Louis Children’s Hospital. Her mission is both journalistic and educational: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.