SKIN CANCER AND IMMUNOSUPPRESSION IN LIVER TRANSPLANTATION: A COMPREHENSIVE REVIEW

INTRODUCTION

Cutaneous malignancies are the most frequent cancers after solid-organ transplantation. Among liver transplant recipients, cumulative incidence rises with time on immunosuppression and depends on regimen composition, UV exposure, and host factors.

EPIDEMIOLOGY & RISK

• Magnitude of risk: Organ transplant recipients (OTRs) have a several– to dozens-fold increased risk of non-melanoma skin cancer (NMSC), with SCC risk typically exceeding basal cell carcinoma (BCC).
• Time-dependent rise: Risk increases with years since transplantation and cumulative immunosuppressive exposure.
• Burden: SCC tends to be more aggressive in OTRs, with higher recurrence and metastasis rates than in immunocompetent patients.

MECHANISMS

• Immune surveillance impairment: Reduced tumor immunosurveillance allows UV- and virus-driven oncogenesis.
• Drug-specific effects: Azathioprine increases UVA photosensitivity and mutational signatures; CNIs promote oncogenic signaling; mTOR inhibitors may exert antitumor effects and are associated with reduced NMSC incidence in selected patients.
• Oncogenic viruses: HPV (cutaneous types) and Merkel cell polyomavirus can contribute to tumorigenesis in the setting of immunosuppression.

RISK FACTORS

COMMON SKIN CANCERS IN TRANSPLANT RECIPIENTS

• Squamous cell carcinoma (SCC): Most common and aggressive; frequent on sun-exposed, chronically damaged skin; can be multifocal.
• Basal cell carcinoma (BCC): Second most common; may present earlier and more frequently than in general population.
• Melanoma: Lower absolute incidence than NMSC but higher mortality; prompt recognition and standard oncologic principles apply.
• Other: Kaposi sarcoma, Merkel cell carcinoma, and adnexal tumors occur more often than in immunocompetent hosts.

SCREENING & PREVENTION

Dermatologic Surveillance

• Baseline full-body skin exam within the first post-transplant year; at least annually thereafter.
• Increase frequency (e.g., every 3–6 months) for high-risk patients or those with prior SCCs.

Photoprotection

• Broad-spectrum SPF ≥30 daily; reapply every 2 hours when outdoors.
• UPF clothing, wide-brim hats, UV-blocking sunglasses; seek shade 10am–4pm.
• Avoid tanning beds; counsel on vitamin D via diet/supplement if needed.

Chemoprevention & Regimen Optimization

• Nicotinamide (vitamin B3): May reduce actinic keratoses/NMSC in some populations; data in OTRs are evolving.
• Systemic retinoids (e.g., acitretin): Consider in patients with field cancerization or numerous SCCs; monitor lipids/LFTs and teratogenic risk.
• mTOR conversion or CNI minimization: In select cases with recurrent/aggressive SCC, consider switching from CNI to mTOR inhibitor, balancing rejection risk.
• Field therapy: Topical 5-FU, imiquimod, or photodynamic therapy for actinic keratoses/field disease.

DIAGNOSIS & STAGING

• Dermoscopic evaluation and biopsy of suspicious lesions (shave, punch, or excisional based on location/size).
• Use standard staging systems (e.g., AJCC for melanoma/SCC) and high-risk features (perineural invasion, depth, poor differentiation) to guide management.
• Consider nodal ultrasound or imaging for high-risk SCC or melanoma as per guidelines.

TREATMENT

• Excision/Mohs micrographic surgery: First-line for most NMSC; Mohs preferred for high-risk/anatomic sites.
• Topical/field therapies: 5-FU, imiquimod, photodynamic therapy for superficial disease and actinic fields.
• Radiation therapy: Consider for non-surgical candidates or adjuvant therapy in select SCCs.
• Systemic therapy: For advanced/metastatic disease—multidisciplinary discussion essential. Checkpoint inhibitors can be effective but may increase rejection risk; individualized risk–benefit analysis with hepatology/transplant team is mandatory.
• Immunosuppression optimization: Minimize CNI exposure, consider mTOR conversion when feasible.

SPECIAL CONSIDERATIONS

• Young recipients or those with genetic predisposition: Early and frequent dermatologic follow-up.
• Field cancerization: Combine field therapies with systemic chemoprevention and regimen review.
• Multidisciplinary care: Dermatology, transplant hepatology, oncology, and surgery coordination improves outcomes.

CONCLUSION

Skin cancer in liver transplant recipients reflects a complex interplay between UV exposure, viral co-factors, and immunosuppressive therapy. Preventive strategies, structured surveillance, and thoughtful immunosuppression tailoring can substantially mitigate risk and treatment burden.