Skin cancer is the most common type of cancer in the United States, with basal cell carcinoma (BCC) comprising most cases.1-3 The incidence of skin cancer has been increasing over time.1 Millions of BCCs and squamous cell carcinomas are diagnosed each year, with BCCs making up 70% of these nonmelanoma cases.1,4
Typically occurring in non-Hispanic white individuals aged >65 years,4 BCC is more frequently encountered in men than women, which is often attributed to increased occupational exposure to the sun.1,4 The condition tends to occur on the head and neck, hands, and other areas of the body that have increased sun exposure.4 Environmental and genetic factors contribute to the development of BCC, with exposure to ultraviolet (UV) light being the most important risk factor.3,4 Other risk factors include living near the equator, personal or family history of skin cancer, use of tanning beds, therapeutic exposure to psoralen plus ultraviolet light (PUVA) for cutaneous disorders, arsenic, immune-suppressing drugs, photosensitizing drugs such as tetracyclines or diuretics, and inherited syndromes that cause skin cancer such as xeroderma pigmentosum.2,4
The pathophysiology of BCC formation is largely associated with UV-induced mutation that results in uncontrolled growth of precursor cells in the epidermis.2,4 The epidermis is the outermost layer of the skin, and the basal cells found in its bottom layer are responsible for the generation of new skin cells. As new skin cells form, they push the older, more superficial skin cells toward the surface, allowing the oldest cells to die and slough off. When basal cell DNA becomes mutated, typically by UV light, the cell can multiply at an uncontrolled rate and form a tumor.2,4 Some genetic conditions, such as Gorlin syndrome, can increase the risk for BCC through germline mutations in key signaling pathways.4
Although clinical appearance varies, the classic description of BCC is that of a pink, pearly papule with central depression. Other characteristic features include waxy papules; erosion or ulceration; bleeding with or without trauma; oozing or crusting in areas; raised borders; translucency; telangiectasias; slow growth; and areas that are blue, brown, or black.5
Several clinical variants of BCC include nodular, superficial, morpheaform, and pigmented.3,4 Nodular BCC is the most common subtype and resembles a pearly, pink papule that is translucent with overlying telangiectasia, with or without a central ulceration.3,4 Superficial BCC appears as erythematous, scaly macules and plaques.3 Morpheaform BCC is infiltrative and appears as scar-like plaques with large subclinical extensions under the skin. Pigmented BCC is typically a colored variant of the nodular subtype and can be confused for melanoma.
Histologically, BCC is grouped into 4 major subtypes: superficial, fibroepithelial, nodular, and infiltrative.3,6 The nodular subtype is most common and appears as basaloid cells with scant cytoplasm and hyperchromatic nuclei, peripheral palisading, peripheral clefting, and mucinous alteration of surrounding stroma.3 The superficial subtype depicts nests of subdermal basaloid cells that are connected to the epidermis, without infiltration into the reticular dermis.3 The infiltrative subtype portrays thin bundles of basaloid cells that infiltrate into the collagen fibers of the dermis.The fibroepithelial subtype reveals trabeculated and elongated branches of basaloid cells that extend into the dermis.The presence of myxoid stroma and peripheral clefting is the most helpful feature for distinguishing BCC from other basaloid tumors.6
As there are many subtypes of BCC, it can often resemble other skin conditions; therefore, the differential diagnosis is broad. The nodular variants of BCC can resemble dermal nevi, epidermal inclusion cysts, sebaceous hyperplasia, molluscum contagiosum, or keratoacanthomas.7 Superficial BCCs may resemble nummular eczema, benign lichenoid keratosis, actinic keratosis, and amelanocytic melanoma. Morpheaform BCCs can resemble scars due to trauma or localized scleroderma. The broad differential diagnosis emphasizes the importance of biopsy for suspected BCCs.
The definitive diagnosis of BCC is made with a skin biopsy. Typically, a shave biopsy is sufficient and requires less instrumentation.8 Occasionally, an excisional or punch biopsy may be needed when a more aggressive or invasive pattern is suspected.8 The sample is then examined histologically, looking for the aforementioned findings, such as basaloid cells with large hyperchromatic nuclei, scant cytoplasm, large nuclear-to-cytoplasmic ratio, and cleft formation.3 BCC rarely metastasizes and is generally not staged.4
The goal of treatment for BCC is to remove the tumor while preserving tissue, function, and physical appearance. Several therapies exist for BCC: surgical therapy, topical treatments, radiation therapy, photodynamic therapy, systemic retinoids, and hedgehog pathway inhibitors.4 In most cases, surgery is recommended as it has the highest cure rate and is the most effective treatment method.9 Surgical modalities include electrodesiccation and curettage, excisional surgery, Mohs micrographic surgery, and cryosurgery. Of all the surgical modalities, Mohs micrographic surgery has the lowest recurrence rate.9 Topical treatments that interfere with the growth of BCC and induce tumor cell death include 5-fluorouracil 5%, interferon, and imiquimod. These treatments are reserved for BCCs that are superficial and nonrecurring or for patients who cannot undergo surgery. Radiation therapy is reserved for patients who have lesions that are extensive or advanced or who are not surgical candidates.4
The patient in this case underwent biopsy of the suspicious lesion, which revealed BCC. He was treated with Mohs micrographic surgery, which allowed for tissue preservation and clear margins. To prevent subsequent lesions, his physician advised avoidance of UV sun exposure, especially during the middle of the day, and instructed the patient to wear sun-protective clothing such as long sleeves and hats.10 The patient was also instructed to wear sunscreen with a sun protection factor of 30 or higher and UVA and UVB protection when spending time outdoors.10
Click to the next page for Case 2.