Paradoxical Development of Reactive Squamous Atypia and Aggressive, Invasive Squamous Cell Carcinoma Following 5-Fluorouracil for Field Cancerization with Concurrent Immunomodulation.

Abstract

5-fluorouracil (5FU) is a widely prescribed therapy for field cancerization. However, the emergence of cutaneous squamous cell carcinoma (cSCC) after 5FU treatment is poorly described. We report five patients with eruptive cSCCs of varying severity following 5FU treatment for field cancerization from four university hospitals between March 2019 and May 2021. We examined the indications for treatment, immunosuppression status, onset of cSCCs, staging, and outcomes. Patients (3F, 2M; median age 74), were treated with 5FU for field cancerization. Four patients, including two solid-organ transplant recipients, were on immunomodulating therapy. Eruptive cSCCs developed within 3 weeks to 3 months of 5FU treatment, mostly within the treated area. Staging revealed a spectrum of BWH T2b in two patients and BWH T1 in three. Eruptive cSCCs are a poorly characterized adverse event of topical 5FU treatment. High-risk T stage cSCCs, not yet reported and distinct from eruptive squamous atypia, may also develop despite low grade background disease. Inflammation and immunomodulation could contribute to pathogenesis.