Squamous cell carcinoma

Overview

•Malignant tumour of keratinocytes arising on squamous epithelium-lined sites - most commonly sun-damaged skin

•Second most common skin cancer in the UK after BCC - but overtakes BCC to become the most common skin cancer in immunosuppressed patients (e.g. solid organ transplant recipients)

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Solid organ transplant recipients (particularly renal transplant) are 65-250 times more likely to develop SCC than the general population - due to long-term immunosuppression impairing immune surveillance of malignant keratinocytes. SCCs in transplant recipients arise earlier, grow faster, and metastasise more readily.

Risk Factors

Solid organ transplant (renal most cited) - highest risk group

Cumulative UV/sun exposure

Fair skin, age >60, male sex

Actinic keratosis (precursor lesion)

HPV (types 16/18 for mucosal SCC; types 5/8 cutaneous in immunosuppressed)

Chronic wounds/burn scars (Marjolin's ulcer)

Smoking - lip and oral cavity SCC

Presentation

•Chronically sun-exposed sites - face, scalp, dorsum of hands, forearms, lower lip

•Indurated, keratinised nodule or plaque - often with central ulceration or keratin-filled crater; may bleed or crust

•Ulceration with raised, everted edges - distinguishes SCC from BCC (BCC has pearly, rolled edge)

•Cutaneous horn - hard conical keratin projection; SCC underlies ~20%

•Perineural invasion - numbness, pain, or tingling at site; marks high-risk lesion

•Regional lymphadenopathy - suggests nodal metastasis

•Marjolin's ulcer - SCC in chronic wound, burn scar, or area of chronic inflammation; more aggressive with higher metastatic rate

Investigations

🥇 First-line

•clinical examination + dermoscopy

🏆 Gold standard

•excisional biopsy with histopathology - confirms diagnosis, depth, margin status, and high-risk features

•If nodal involvement suspected: ultrasound of draining lymph nodes; CT/MRI for locally advanced or perineural disease

Management

•All suspected SCCs - refer via two-week-wait pathway

🥇 First-line

•surgical excision with 4-6 mm margins for low-risk SCC

•Mohs micrographic surgery - high-risk or cosmetically critical sites (nose, eyelid, lip, ear); highest cure rates

🥈 Second-line

•radiotherapy - when surgery not feasible, or adjuvant post-excision for positive margins/perineural invasion/nodal disease

🥉 Third-line

•cemiplimab (anti-PD-1) for locally advanced/metastatic SCC not amenable to surgery or radiotherapy; cisplatin-based chemotherapy as alternative for metastatic disease

•Transplant recipients: consider reduction of immunosuppression where safe; switching from ciclosporin to sirolimus (mTOR inhibitor with anti-tumour properties) reduces SCC incidence

Complications

•Regional lymph node metastasis - ~2-5% of cutaneous SCCs overall; up to 20% from high-risk sites

•Perineural invasion - worse prognosis

•Second primary SCC - 30-50% risk of further SCC within five years (field cancerisation)

•Distant metastasis (lung, liver, bone) - uncommon in cutaneous SCC, more frequent in mucosal SCC