Basal Cell Carcinoma

Basal cell carcinoma is a slow-growing malignant tumor of the basal layer of the epidermis and the most common human cancer. It makes up about 75% of skin cancers, with an incidence of 1000 to 2000 per 100,000 people a year in fair-skinned populations. Peak age is 50 to 70 years, and it is increasingly seen in younger adults and women.

Biology: dysregulated hedgehog signaling, most often through loss-of-function mutations in PTCH1 (and gain of function in SMO), driven by ultraviolet damage. Risk factors are intermittent sun exposure, fair skin, sunburns in childhood, immunosuppression, arsenic, previous radiotherapy, and Gorlin syndrome (germline PTCH1 mutation, with multiple early tumors, jaw cysts, palmar pits and medulloblastoma risk).

Histological subtypes

• Low risk: nodular and superficial
• High risk: infiltrative, morpheaform (sclerosing), micronodular and basosquamous (metatypical)

Metastasis is rare (under 0.1%), but tumors destroy local tissue, especially on the central face, eyelids, nose and ears (the H-zone). Recurrence is about 5% at 5 years after standard excision, and higher for high-risk subtypes and recurrent tumors. Complications: local destruction of cartilage, bone and orbit, perineural invasion and multiple new primaries (about 40% within 3 years).

• Nodular: a pearly translucent papule with rolled borders and telangiectasia, which later ulcerates ("rodent ulcer")
• Superficial: a slow-growing erythematous scaly patch, usually on the trunk
• Morpheaform: a flat, scar-like indurated plaque with indistinct margins
• Pigmented: brown to blue-black lesion mimicking melanoma
• A sore that bleeds and does not heal for over 4 weeks
• Red flags: size over 2 cm, location on the nose, eyelid, ear or lip, recurrence, perineural pain or numbness, rapid growth and immunosuppression

1. Clinical assessment with dermoscopy: arborizing vessels, blue-gray ovoid nests, leaf-like areas, ulceration and absence of a pigment network.
2. Biopsy (punch or shave deep enough to show subtype and depth) for any lesion considered for non-excisional therapy, or if the diagnosis is uncertain.
3. Imaging (MRI or CT) only for tumors suspected of invading bone, orbit or nerve, or for large and recurrent tumors.
4. Gorlin syndrome evaluation in patients with multiple tumors before age 30: dental panoramic radiograph for jaw cysts, family history, and PTCH1 testing.

Differentials: squamous cell carcinoma, melanoma, actinic keratosis, Bowen disease, seborrheic keratosis, sebaceous hyperplasia, nevus and dermatofibroma.

Choice depends on risk, site, patient factors and cosmetic goals.

1. Surgical excision (standard): 4 mm clinical margins for low-risk tumors under 2 cm, and 5 to 10 mm for high-risk tumors. Local anesthesia with lidocaine 1% with adrenaline 1:100,000 (maximum 7 mg/kg of lidocaine). Complication: wound infection, bleeding, scarring.
2. Mohs micrographic surgery for tumors on the face, ears, hands and genitals, for high-risk subtypes, recurrent tumors and tumors over 2 cm. Cure is over 98% for primary tumors.
3. Curettage and electrodesiccation for small, low-risk nodular tumors on the trunk and limbs.
4. Superficial tumors only:
   • Imiquimod 5% cream applied 5 nights a week for 6 weeks (expect local inflammation).
   • Fluorouracil 5% cream twice daily for 3 to 6 weeks.
   • Photodynamic therapy: methyl aminolevulinate 160 mg/g cream under occlusion for 3 hours, then red light 37 J/cm2, repeated 1 week later.
   • Cryotherapy with two freeze-thaw cycles of about 30 seconds each, for small low-risk lesions.
5. Radiotherapy for elderly patients, inoperable tumors or adjuvant therapy after incomplete excision: 50 to 55 Gy in 20 fractions, or 60 to 66 Gy in 30 to 33 fractions. Avoid in young patients and in Gorlin syndrome.
6. Locally advanced or metastatic disease:
   • Vismodegib 150 mg orally once daily until progression or intolerance.
   • Sonidegib 200 mg orally once daily.
   • Adverse effects: muscle cramps, alopecia, taste loss, weight loss and raised creatine kinase. These drugs are teratogenic: women of childbearing age need effective contraception during and for 24 months after treatment, and men must use condoms during and for 3 months after, with no blood donation for 24 months.
   • Cemiplimab 350 mg IV every 3 weeks after hedgehog inhibitor failure or intolerance.
7. Chemoprevention: nicotinamide 500 mg orally twice daily reduces new lesions in high-risk patients. Sunscreen SPF 30 or higher, protective clothing and avoidance of tanning.

Follow-up: skin examination every 6 to 12 months for life, or every 3 to 6 months in high-risk patients, with full-body examination and counseling on self-examination.