Basal cell carcinoma

Section: Skin and soft tissue Sub-section: Skin cancer Curriculum: Curriculum, page 52

Definition

• Locally invasive cancer of skin
• Arising from progenitor cells in the basal layer of the Epidermis
• No precursor lesion

Incidence

• Most common skin cancer
• BCC > SCC 4:1
• Lifetime risk in Caucasians ≈ 25% (1:4)
• M > F
• Rare < age 40

Classification

• Nodular/Nodulocystic 70%
• Superficial (Spreading) 20%
• Aggressive variants
  • Infiltrative/Morphoiec BCC
    • Usually found in mid facial sties
    • Waxy, scar like plaque with indistinct borders
    • Wide and deep subclinical extension
    • May infiltrate cutaneous nerves
  • Basosquamous
    • Mixed BCC and SCC features
    • Infiltrative growth pattern

Nodular/Nodulocystic

• Well defined nodular lesion with waxy appearance
• Noduloulcerated
  • Contains central ulcer (common)
• Pigmented
  • Within macrophages in stroma
• Cystic
  • Central degeneration of cells, can look like blue nevus
• Micronodular
  • More aggressive with higher recurrence rates

Superficial (Spreading)

• Can look like psoriasis, tinea, eczema
• Macular growth pattern
• Ill-defined margin and central non-healing crusting wound

Aetiology

• Risk Factors
  • UV (not as strong an association as SCC & Melanoma)
  • Radiotherapy
  • Arsenic
  • Immune suppression
• Genetic Risk Factors:
  • Gorlin Syndrome
    • Genetics
      • Autosomal Dominant
      • Germline pathogenic variants in the human homolog of the patched (PTCH1) gene which leads to activation of the hedgehog pathway
    • Clinical
      • Multiple BCCs usually < 30 yrs
      • Odontogenic keratocysts
      • Ovarian fibromas
      • Medulloblastoma
      • Other features include palmar and plantar pits, craniofacial and skeletal abnormalities, ocular abnormalities, and ectopic intracranial calcifications
    • Screening
      • Regular skin checks
  • Xeroderma Pigmentosum

Clinical Presentation

• No precursor lesion
  • SCC & melanoma can both have a precursor
• Most on Head & Neck – Forehead/face (90%)
  • Rare on back of hand (unlike SCC)
  • Slowly growing
    • Months – yrs
  • Tend to infiltrate locally but rare to metastasize

Nodular

• Pearly nodule with surface blood vessels or diffuse spreading
• Small, translucent / shiny (pearly) elevated nodules
• Central ulceration & raised / rolled pearly edges (umbilication)
• Telangiectatic vessels are commonly seen over the surface
  • Esp. infiltrating type: Ill-defined borders and telangiectasia
• Ulcerate early
  • May erode deeply (Rodent Ulcer) but almost never metastasizes

Superficial

• Pink / red, scaly patch
  • Often multiple
• Upper trunk, shoulders
• Bleed / ulcerate easily
• Difficult to distinguish from Bowen’s disease

High risk subtypes

• Sclerosing
  • Mid-face
  • Skin-colored / waxy
    • Scar-like
  • Perineural spread
• Micronodular
• Infiltrative
• Basosquamous

Pathology

• Abnormal growth of progenitor cells in the basal layer of the epidermis
  • Deepest layer of the epidermis
• Typical microscopic features of BCC
  • Clumps with “palisading nuclei” (lined up like a fence)

• Slow local invasion; rarely metastasize
  • Lymph Node Metastasis 0.4% (Basosquamous form most likely)
• If the tumour starts as a nodule, the centre may die
  • Results in a lesion with a rolled / elevated (but not inverted) edge
• Superficial BCC
  • Often extends (microscopically) beyond the clinical borders
• Infiltrating and Sclerosing BCCs
  • Exhibit islands of tumour extending into the tissue
  • ± Perineural invasion in 3% of pts
  • Finding correlates with highest recurrence rates and positive margins after excision
• Basosquamous type contains elements of both BCC & SCC
  • Can metastasize

Investigation and DDx

• Excision biopsy for diagnosis
• Differential Diagnosis
  • SCC
    • But BCCs usually have long hx and a more typical rolled edge
  • Keratoacanthoma
    • Usually a short history

Management

• Should divide into low risk BCC and high risk BCC

Low risk BCC

Definition

• <2cm in diameter
• Located on trunk or extremities (excluding genitalia and hands).
• Superficial or nodular type
• Lack of perineural invasion.

Treatment of low risk BCC

Surgical/first line therapy

• Excision with a macroscopic 2-3mm margin. This is gold standard. Adequate microscopic margin is 0.5mm
• If margins are positive - should have re-excision. If surgery not possible can consider radiation OR close clinical follow up.

Second line therapy

• Recommended for patients who wish to avoid surgery (unsatisfactory cosmetic result or difficulty with wound healing) and are low risk.
  • Options include:
    • Imiquimod 5% cream
      • 5 days per week for 6 weeks until erythema, crusting, and scab formation develops.
      • Stimulates the immune system by activating toll like receptor 7
    • Topical 5-Fluorouracil 5%
      • Twice daily for 6 weeks.
    • Photodynamic therapy

Other less commonly used options

• Cryosurgery
• Intralesional therapy with 5-FU and bleomycin.

High risk BCCs

Definition of high risk BCC

• Tumours >2cm
• Tumours on the head, neck, hands, feet, pre-tibia, and anogenital areas.
• Recurrent lesion.
• Lesions in sites of prior radiation therapy.
• Aggressive subtype.
• Perineural invasion
• Immunocompromised patient.

Treatment of high risk BCC

Surgical/first line therapy

• MOHS (mohs micrographic surgery)
  • Is essentially excision, frozen section with margin examination using formalin, followed by re-excision as required.
• Standard surgical excision with 4-6mm macroscopic margin- higher recurrence rate than MOHs.
• If margins are positive can re-excise OR consider radiation therapy.

Second line therapy

• Radiation therapy - good option for large tumours where surgery would be morbid or for patients who are not surgical candidates. Higher recurrence rate.

Treatments not recommended

• Topical therapies such as imiquimod and 5-FU

Systemic therapy for locally invasive or metastatic BCC

• Metastatic BCC is extremely rare and should be managed by experience MDT.
• Targeted treatment is sonic hedgehog inhibitors – visnodegib, and sonidigeb.
  • Inhibit SMO
  • Bad side effects - muscle spasm, alopecia, altered taste, nausea, fatigue. 30% will stop treatment.

Cryotherapy

• Freeze for 5-15 sec to create a 1-3mm rim of freeze beyond lesion, and then thaw over 20-40 sec
• Perform 2 cycles
• Depth of freeze is 1.5x lateral spread
• Longer freeze-thaw times destroy portions of dermis
• Erythema occurs immediately
• Freezing can cause separation at the dermoepidermal junction and produce a bulla, which usually resolve in a few days
• Avoid freezing areas where nerves lie superficially
• Superficial lesions crust in 7-10 days then falloff
• NB: Major issue is no tissue for histology and clearance margin uncertain

Topical Chemotherapy

• 5-Fluorouracil (Efudix)
  • Twice daily for 6 weeks.
  • Blocks incorporation of thymidine into DNA
• Imiquimod (Aldara)
  • 5 days per week for 6 weeks until erythema, crusting, and scab formation develops.
  • Stimulates the immune system by activating toll like receptor 7
    • Upregulates cytokines
  • Can be used for early superficial BCC (but not nodular BCC)

Radiotherapy

• Indications:
  • Difficult lesions in elderly only (may itself cause cancer)
  • BCC with neural involvement
• Avoided near cartilage (necrosis risk)
• 3000-5000 cGy in 6-20 fractions
• 200-500cGy/ session

Prognosis

• If untreated will cause invasion & massive ulceration
• 95% curable with excision
• Recurrence Risk Factors
  • Excision margin involved
    • 60% of margin +ve BCC don’t recur - Don’t always have to re-excise
    • Exception: Deep margins should be negative - difficult to monitor clinically
  • Immunosuppression
  • Prior radiotherapy
  • Site – Head & neck (especially lip & pinna)
  • Perineural involvement
  • ↑ Size

    • 1.5cm 10% at 5 yrs

    • 3cm 25% at 5 yrs

  • Depth of invasion
  • Aggressive variants - infiltrating, multifocal, sclerosing
    • 1/3 will develop a 2nd primary BCC within 5 years