Basal cell carcinoma is the most common human malignancy, arising from basal keratinocytes with strong links to UV exposure and PTCH1/HH pathway dysregulation. It grows slowly with rare metastasis but can cause significant local destruction. Subtypes include nodular, superficial, infiltrative/morpheaform, and pigmented. Diagnosis is clinical with biopsy confirmation. First-line treatment is surgical (standard excision or Mohs micrographic surgery). Topicals, photodynamic therapy, and radiation are options for select low-risk cases; systemic hedgehog inhibitors are used for advanced disease.
Epidemiology and Risk Factors
- Very common in fair-skinned individuals; incidence increases with age and cumulative UV.
- Risks: UV (intermittent and chronic), indoor tanning, ionizing radiation, arsenic, immunosuppression (transplant), genetic syndromes (Gorlin syndrome/PTCH1, xeroderma pigmentosum).
- Occurs in all skin types but underdiagnosed in darker skin; often presents later and more aggressive.
Clinical Features
- Nodular: pearly papule/nodule with telangiectasias; may ulcerate (“rodent ulcer”).
- Superficial: erythematous scaly patch/plaque with thin rolled border, often on trunk.
- Morpheaform/infiltrative: scar-like, indurated plaque with ill-defined borders; more aggressive.
- Pigmented: increased melanin; mimic melanoma in skin of color.
- High-risk locations: H-zone of face (periorbital, nose, lips, ears), hands/feet, genitalia; recurrent tumors; aggressive histology.
Diagnosis
- Clinical dermoscopy: arborizing vessels, shiny white structures, blue-gray ovoid nests, leaf-like areas (subtype-dependent).
- Biopsy: shave or punch for histopathology; guides risk stratification.
Risk Stratification (typical factors)
- Low-risk: primary, small (<2 cm trunk/extremities; <1 cm face), well-defined, nodular/superficial histology, immunocompetent.
- High-risk: location in H-zone/critical sites, size thresholds, recurrent, aggressive histology (infiltrative, micronodular, basosquamous), perineural invasion, immunosuppression.
Management
- Surgical
- Standard excision with 4–5 mm margins for low-risk BCC; wider for high-risk.
- Mohs micrographic surgery (MMS): tissue-sparing with highest cure rates; preferred for high-risk sites, recurrent tumors, aggressive subtypes, or ill-defined borders.
- Destructive/field therapies (low-risk, superficial)
- Curettage and electrodessication (C&E): effective for small, low-risk lesions on trunk/extremities.
- Topicals for superficial BCC: imiquimod 5% (5×/week for 6 weeks) or 5-fluorouracil 5% (qd–bid for 6 weeks); cosmetic areas when surgery undesirable.
- Photodynamic therapy (PDT) with aminolevulinic acid or methyl aminolevulinate: good cosmesis; recurrence higher than surgery.
- Radiation therapy
- For nonsurgical candidates, adjuvant for positive margins/perineural invasion, or challenging sites; consider long-term skin changes.
- Systemic therapy
- Hedgehog pathway inhibitors (HHIs): vismodegib, sonidegib for locally advanced/metastatic BCC or multiple in Gorlin syndrome; AEs: muscle cramps, dysgeusia, alopecia, weight loss; teratogenic.
- PD-1 inhibitor (cemiplimab) may be used after HHI failure/intolerance in advanced BCC.
- Follow-up and Prevention
- Skin checks every 6–12 months; earlier after high-risk lesions.
- Field cancerization: treat actinic keratoses (5-FU, imiquimod, PDT) and counsel on sun protection.
- Photoprotection, avoid tanning beds; nicotinamide 500 mg bid may reduce new NMSC in high-risk patients.
References (recent guidelines and key reviews)
- NCCN and AAD BCC guidelines, 2022–2024.
- Comparative outcomes of MMS vs standard excision, 2021–2024.
- Trials of HHIs and cemiplimab in advanced BCC, 2021–2024.