Most common human cancer; slow-growing locally invasive tumor of basal keratinocytes driven by UV-induced PTCH/Hedgehog mutations.
Also known as: BCC, basal cell carcinoma, rodent ulcer, nodular BCC, morpheaform BCC
Overview
The most common cutaneous malignancy, arising from basal keratinocytes of the epidermis and hair follicle. Slow-growing, locally invasive, and rarely metastatic.
Epidemiology
Most common cancer in humans worldwide. ~4 million US cases annually. Lifetime risk ~30% in fair-skinned individuals. Male > female (2:1). Median age at diagnosis ~70, but incidence rising in younger adults.
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Personal history of skin cancer (40% develop second BCC within 5 years)
Pathophysiology
UV radiation induces mutations in PTCH1 (most common, ~70%), SMO, and SUFU components of the Hedgehog signaling pathway → constitutive Hedgehog activation → GLI transcription factor activation → uncontrolled basaloid proliferation. p53 mutations also common. Slow growth and intact stromal interactions limit metastatic potential (<0.05%).
Clinical presentation
Symptoms
Often asymptomatic; patient notices 'pimple' or 'sore that won't heal' for months to years
Occasional bleeding with minor trauma; rarely painful unless ulcerated/infected
Signs / physical exam
Nodular BCC (most common, ~60%): pearly translucent papule or nodule with rolled border, arborizing telangiectasias, and central depression or ulceration ('rodent ulcer')
Superficial BCC (~30%): erythematous scaly slightly elevated patch with thread-like rolled border; trunk/extremities; can mimic eczema/psoriasis
Pigmented BCC: nodular BCC with brown/blue-gray pigment; common in skin of color
CT/MRI only for advanced or recurrent tumors with suspected perineural invasion or deep tissue involvement
Routine imaging not indicated for typical primary BCC
Diagnostic algorithm
Subtype
Appearance
Preferred Treatment
Nodular (60%)
Pearly papule, rolled border, telangiectasias, central ulcer
Surgical excision 4 mm margin; Mohs if H-zone
Superficial (30%)
Erythematous scaly patch with thread-like rolled border
Imiquimod, 5-FU, ED&C, or excision
Pigmented
Nodular BCC with brown/blue-gray pigment
Excision; Mohs if H-zone
Morpheaform / infiltrative
Ill-defined scar-like indurated plaque
Mohs preferred — subclinical extension common
Basosquamous (aggressive)
Variable; mixed BCC + SCC histology
Mohs ± radiation; consider systemic for advanced
Locally advanced / metastatic
Deep invasion or unresectable
Vismodegib / sonidegib; cemiplimab if HPi-resistant
Basal cell carcinoma subtypes and preferred treatment.
Treatment
First-line
Surgical excision with 4 mm margins for low-risk primary BCC (cure rate ~95%)
Mohs micrographic surgery (preferred for high-risk BCC): face (especially H-zone — central face, periocular, periauricular, perinasal), morpheaform/infiltrative subtypes, recurrent tumors, large tumors (>2 cm), positive margins after standard excision — cure rate ~99% for primary, ~95% for recurrent
Electrodessication and curettage (ED&C) for low-risk superficial or small nodular BCC on trunk/extremities (NOT on terminal hair-bearing skin or face — high recurrence)
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