Basal Cell Carcinoma

Basal Cell Carcinoma (BCC)

Definition

• Most common type of skin cancer, arising from basal cells in the epidermis.
• Slow-growing, rarely metastasizes, but can be locally invasive and disfiguring.

Risk Factors

• UV exposure (chronic sunlight)
• Fair skin, light hair, blue/green eyes
• Genetic syndromes (e.g., Gorlin syndrome / Basal Cell Nevus Syndrome)
• Immunosuppression

Pathophysiology / Molecular Targets

• Hedgehog (HH) pathway activation is central:
  • PTCH1 mutation → constitutive activation of SMO → GLI transcription factors → cell proliferation
• Hedgehog pathway inhibitors target this molecular driver.

Clinical Features

• Pearly papule with telangiectasia
• Non-healing ulcer or nodule, sometimes with rolled borders
• Can occur anywhere on sun-exposed skin (face, neck, trunk)

Diagnosis

• Biopsy: shave, punch, or excisional
• Histopathology confirms BCC subtype (nodular, superficial, morpheaform, infiltrative)

Treatment

1. Surgical
   • Excision (standard)
   • Mohs micrographic surgery (for high-risk or facial lesions)
2. Topical / Local
   • 5-Fluorouracil (5-FU) cream – superficial BCC
   • Imiquimod cream – immune-mediated clearance
3. Systemic Therapy (Advanced / Metastatic BCC)
   • Hedgehog pathway inhibitors (HPIs):
     • Vismodegib (Erivedge®) – 150 mg PO daily
     • Sonidegib (Odomzo®) – 200 mg PO daily
   • Indicated for locally advanced or metastatic BCC not amenable to surgery or radiation

Key Toxicities (Hedgehog Inhibitors)

• Muscle spasms / cramps
• Alopecia
• Dysgeusia / taste changes
• Weight loss, fatigue, nausea
• Teratogenicity → avoid in pregnancy; contraception required
• Hepatotoxicity / electrolyte changes → monitor LFTs and electrolytes

Pharmacist Pearls

• Counsel patients on muscle cramps, taste changes, and hair loss before starting HPIs.
• Drug interactions: both are CYP3A4 substrates → avoid strong inhibitors/inducers.
• Pregnancy prevention required during and 2 months after therapy.
• Monitor for adverse events and adherence, as therapy is oral and chronic.

Summary:

• BCC = slow-growing skin cancer, usually treated surgically.
• Advanced cases → Hedgehog inhibitors (vismodegib, sonidegib).
• Key pharmacist role: counsel on toxicity, adherence, and teratogenicity.