Epidermolysis bullosa-associated cSCC

Background — RDEB

• Recessive dystrophic epidermolysis bullosa is a genodermatosis caused by biallelic loss-of-function mutations of COL7A1 encoding type VII collagen — the principal anchoring fibril component of the dermo-epidermal junction.
• Patients suffer recurrent skin and mucosal blistering from minor trauma, leading to scarring, mitten-deformities of hands and feet, oesophageal strictures, ocular scarring and chronic anaemia.
• The severe generalised RDEB phenotype carries the highest cSCC risk; intermediate generalised and inversa RDEB have lower but still substantial risk.
• Refer all RDEB patients to one of the UK national EB services (Birmingham Children's, Great Ormond Street, St Thomas' Hospital).

cSCC risk

• Cumulative SCC incidence in severe generalised RDEB (Fine et al., NEJM Reg.) — 7.5% by age 20, 76% by age 35, 88% by age 45.
• Cumulative SCC mortality — 39% by age 35, 70% by age 45, 87% by age 55.
• Mean number of SCCs per patient — 2 to 3 simultaneously; cumulative 5–10 over a lifetime.
• SCC arises within chronically eroded / scarred skin — typically dorsa of hands, feet, lower limbs, sacrum.
• Pathogenic mechanism — chronic inflammation, defective epithelial-mesenchymal interaction, repeated wound healing, type VII collagen loss in tumour stroma.

Clinical features

• Non-healing ulcer, exophytic mass, induration or hyperkeratotic plaque within previously eroded RDEB skin.
• Pain disproportionate to the patient's chronic baseline.
• Often multifocal at presentation; new SCCs continue to appear.
• Histology — typically well- or moderately-differentiated SCC; verrucous variant in some.
• Multiple deep biopsies recommended — superficial sampling may show only chronic inflammation.

Management

• Multidisciplinary EB-centre management — dermatology, plastic surgery, oncology, palliative care, anaesthesia.
• Wide local excision with at least 1 cm margins, preserving function as far as possible.
• Mohs micrographic surgery may be appropriate for selected lesions in functionally critical sites.
• Imaging staging — MRI of the affected limb; CT chest/abdomen/pelvis.
• Sentinel lymph node biopsy and selective lymphadenectomy considered for high-risk lesions.
• Anaesthesia — challenging because of mucosal fragility, oral / pharyngeal scarring, and tissue handling.
• Adjuvant radiotherapy for incomplete margins or extensive disease (radiotherapy planning needs careful consideration of EB skin tolerance).
• Cemiplimab (NICE TA802) for advanced / metastatic SCC; small case series and clinical trial data show meaningful response in EB-cSCC.
• Rigosertib, anti-EGFR therapy and combination immunotherapy under investigation.
• Beremagene geperpavec (Vyjuvek) gene therapy approved in some jurisdictions for RDEB skin healing — emerging role in cSCC prevention.

Prognosis

Aggressive — metastatic risk substantially exceeds conventional cSCC; 5-year overall survival 25–40%. SCC remains the leading cause of death in severe RDEB. Long-term oncology surveillance, patient self-monitoring, and optimised wound care to reduce chronic inflammation are key supportive measures. Early biopsy of any non-healing wound or change in chronic ulcer is essential.