Basal cell carcinoma (BCC) arises from keratinocyte progenitor cells and usually first appears as a tiny papule, growing slowly into a plaque or nodule over years.1–5 These lesions are not normally aggressive but in rare cases can result in advanced and metastatic tumors if neglected for several years.1-3,5,6 The development of BCC is driven by somatic mutations induced by exposure to UV-B rays resulting in constitutive activation of the Hedgehog (Hh) signaling pathway.1–5 The Hh pathway is responsible for regulating the development of sebaceous glands and hair follicles and controlling populations of cutaneous skin cells.2 Aberrations in the Hh pathway alone are sufficient to cause BCC but mutations can also occur in PIK23C, STK19, ERBB2, LATS1, N-RAS, H-RAS, K-RAS, PPC6C, RB1, MYCN, PTPN14, and FBXWJ genes.1,2
Certain genetic diseases such as xeroderma pigmentosum, Bazex-Dupré-Christol syndrome, nevoid basal cell carcinoma syndrome, multiple hereditary infundibulocystic syndrome, and Rombo syndrome can increase the risk of developing BCC.1,2,5 Since UV-B exposure is involved in the development of BCC, most cases are found on sun-exposed skin such as the face and neck.3,5
Basal cell carcinoma is the most common form of skin cancer in light-skinned populations with an average lifetime risk of 30%.1 The highest number of cases are seen in Australia, the United States, and European countries; 2 million cases of BCC are diagnosed annually in the US alone.1,6 The incidence of BCC is higher in older men.1,5 Besides UV-B exposure, other risk factors include genodermatoses, arsenic consumption, immunosuppression, exposure to ionizing radiation, family history of BCC, older age, and fair skin pigmentation.1–3,5,7 The risk of developing BCC increases by 100% between the ages of 40 and 70 years.2 Darker pigmentation helps protect individuals from BCC and lowers the risk; Black patients are 19 times less likely to develop BCC than are White patients.2
Diagnosis of BCC is made through clinical inspection with dermoscopy and histopathologic examination of skin biopsy.1,3,7 The differential diagnosis for BCC should include trichoepithelioma, trichoblastoma, sebaceous hyperplasia, and other adnexal lesions with sweat gland and follicular differentiation. In addition, some types of squamous cell carcinoma, melanoma, morphea plaques, and inflammatory dermatoses such as eczema and psoriasis may also mimic BCC.1,5
More than 26 clinical subtypes of BCC exist with the most common types being nodular, superficial, morphoeic, fibroepithelial, infiltrative, infundibulocystic, and ulcerated.1–3,5 On dermoscopy, BCC has an absent pigment network, erosions, ulcerations, superficial and arborizing telangiectasias, spoke-wheel areas, ovoid nests and globules, and leaf-like areas.1,3,8 Aggressive cases may have more scar-like areas.1
Nodular BCC (nBCC) is the most prevalent subtype and is commonly found on the head and neck of patients.1–3 Nodular BCC presents with a red or pearly papule, nodule, or plaque, telangiectasias, and rolled borders, and on dermoscopy normally has features of focused, branching vessels, occasionally with bluish-grey clods.1-3 On microscopic examination, nBCC may present with nodules of basaloid keratinocytes, mucoid stroma with rounded spindle cells, and peripheral palisading.2,3,5
Superficial BCC (sBCC) is the second most common subtype of BCC and usually appears on the lower extremities and trunk as a scaly, well-circumscribed erythematous plaque.1–3 Appearance with dermoscopy can show short, fine telangiectasias; focused, linear vessels around the border; structureless hyper- and/or hypopigmentation; and radial lines in pigmented cases.1,3,7,8 Superficial BCC appears histologically with multiple foci of basaloid keratinocyte tumors attached to the epidermis with lichenoid infiltrate and myxoid stroma.2,3
Fibroepithelial BCCs are mostly found as skin-colored, erythematous plaques or pedunculated papulonodules on the trunk.2,3 The fibroepithelial BCC basaloid keratinocytes follow a reticular pattern histologically with spindle stroma.2 Infundibulocystic BCCs also tend to favor the head and neck and present as well-demarcated pearly papules with infundibulum-like cystic structures and a tumor of basaloid cells seen with histology.2,5 All subtypes may include
Most subtypes of BCC can be removed through surgical techniques with a minimal margin of 4 mm to reduce the risk for recurrence.1,3,5–7 Mohs micrographic surgery is recommended for BCC lesions with a high risk for recurrence.3,5,7 Destructive techniques can be employed for small, low-risk BCC lesions not located on the face and include curettage and electrodessication, cryotherapy, and laser ablation.1,3,5–7 Low-risk BCCs can be treated with topical therapies or photodynamic therapy (PDT) if surgery is contraindicated, such as for logistical issues, comorbidities, and age. Topical therapies include 5% imiquimod cream and 5% fluorouracil.1,3,5–7 Locally advanced BCC (laBCC) and metastatic BCC (mBCC) may require more aggressive treatments such as radiotherapy and medical therapy.1,3–5,7 Vismodegib and sonidegib are approved by the US Food and Drug Administration (FDA) for the management of sBCC treatment and both work by inhibiting the Hh pathway.1,3–5,7 Side effects from these medications include hair loss, change in taste, fatigue, weight loss, and muscle spasms.1,4 Platinum-based chemotherapies are a last-line treatment for rare mBCCs with a response rate typically of 20% to 30% after a 2- to 3-month duration.1,3
Our patient was diagnosed with nBCC via a shave biopsy and was treated successfully with Mohs micrographic surgery.
Click to the next page for Case 2.