Key Facts

Cutaneous SCC is a malignant tumour of epidermal keratinocytes with genuine metastatic potential. It is the second most common skin cancer and the most common skin cancer to cause death after melanoma. Early detection and complete excision are key.

Epidemiology

• ~50,000 new cases/year in UK
• M:F ratio ~2:1
• Incidence increases with age; peak >70 years
• Most common on sun-exposed sites: head/neck, dorsum of hands, forearms
• Incidence rising ~3–4% per year
• Second commonest cause of skin cancer death (after melanoma)

Aetiology

• UV radiation: cumulative UVB exposure — strongest risk factor
• Immunosuppression: organ transplant recipients (65–250× risk), chronic immunosuppressive therapy
• Pre-malignant lesions: actinic keratoses (5–10% progress to SCC), Bowen's disease
• Chronic inflammation/scarring: Marjolin's ulcer (SCC in chronic wound/burn scar)
• HPV: types 16, 18 — particularly periungual and genital SCC
• Arsenic, tar, industrial carcinogens: occupational exposure
• Xeroderma pigmentosum: defective DNA repair → markedly increased skin cancer risk

Pathophysiology

• UV-induced mutations in p53 tumour suppressor gene → loss of cell cycle control
• Field cancerisation: widespread UV-damaged epidermis predisposes to multiple lesions
• Progression from dysplasia → in situ → invasive carcinoma
• Tumour thickness, depth of invasion, and perineural invasion determine metastatic risk

Well-Differentiated SCC

• Firm, flesh-coloured or erythematous, keratinised nodule or plaque
• Central keratin horn or crust
• On sun-exposed skin — scalp, face, ears, dorsal hands

Poorly Differentiated SCC

• Fleshy, friable, rapidly growing nodule
• May ulcerate with necrosis
• Higher metastatic potential

Bowen's Disease (SCC In Situ)

• Well-demarcated, erythematous, scaly plaque
• Slowly enlarging; usually on lower legs in women
• ~3–5% progress to invasive SCC

Keratoacanthoma

• Rapidly growing dome-shaped nodule with central keratin plug
• May regress spontaneously but treat as SCC
• Crateriform architecture

Special Sites

• Lip SCC: lower lip most common; higher metastatic rate (~10–15%)
• Ear SCC: higher recurrence and metastatic rate
• Marjolin's ulcer: SCC in chronic wound — aggressive, high metastatic potential

Red Flags

• Rapid growth
• Pain, paraesthesia (perineural invasion)
• Regional lymphadenopathy (metastasis)
• Non-healing ulcer in a chronic wound or scar
• Immunosuppressed patient with new or changing lesion

Bedside

• Clinical examination: full skin survey, regional lymph node palpation
• Dermoscopy: white structureless areas, keratin, hairpin vessels, polymorphous vessels

Biopsy

• Excision biopsy: preferred for small lesions — diagnostic and therapeutic
• Incisional/punch biopsy: for larger lesions to determine grade and depth before definitive surgery
• Histology: degree of differentiation, depth of invasion, perineural/lymphovascular invasion, Clark level

Imaging

• USS regional lymph nodes: if lymphadenopathy or high-risk features
• CT/MRI: for deep invasion, perineural spread, or staging of metastatic disease
• Sentinel lymph node biopsy: considered for high-risk SCC (not yet standard in UK)

Special Tests

• Fine needle aspiration: palpable lymph nodes
• PET-CT: if distant metastasis suspected

Non-Pharmacological

• Sun protection: SPF 30+, protective clothing, UV avoidance — lifelong
• Patient education: self-examination, prompt reporting of new/changing lesions
• Surveillance: regular dermatology follow-up for high-risk patients (transplant recipients)

Surgical (Mainstay)

• Wide local excision: first-line treatment
  • Low-risk: ≥4 mm peripheral margin
  • High-risk (poorly differentiated, >2 cm, perineural, ear, lip): ≥6 mm margin
• Mohs micrographic surgery: for high-risk sites (periorbital, nose, lip, ear), recurrent SCC, or where tissue conservation is critical
• Curettage and cautery: only for small, well-differentiated, low-risk SCC on trunk/limbs

Pharmacological

• Topical 5-fluorouracil (5-FU) 5%: for Bowen's disease — apply BD for 3–4 weeks
• Topical imiquimod 5%: for Bowen's disease — 5 nights/week for 6 weeks (unlicensed)
• Cemiplimab (anti-PD-1): NICE TA592 — for locally advanced or metastatic SCC not amenable to surgery/radiotherapy

Radiotherapy

• Adjuvant: positive/close margins, perineural invasion
• Primary: inoperable tumours, elderly/unfit for surgery

Referral Criteria

• NICE NG12: 2-week wait referral for suspected skin cancer
• MDT discussion for high-risk SCC
• Oncology referral for metastatic disease

• Overall 5-year survival: >90% for localised disease
• Metastatic rate: 2–5% overall; up to 10–15% for high-risk sites (lip, ear) and immunosuppressed patients
• Lymph node metastasis: 5-year survival drops to ~25–35%
• Recurrence: 3–8% after adequate excision; higher for morphoeic, perineural, or incompletely excised
• Transplant recipients: poorer outcomes, higher recurrence and metastasis rates
• Key prognostic factors: tumour thickness (>4 mm), differentiation, perineural invasion, immunosuppression

SCC Risk Stratification

Pre-Malignant to Malignant Progression