S4347 Histologic Resolution of Esophageal Leukoplakia: A Case Challenging Surveillance Paradigms

Introduction: Esophageal leukoplakia, characterized by a granular layer with orthokeratosis/hyperorthokeratosis, is a rare premalignant condition associated with increased risk of esophageal squamous cell carcinoma. We present a case of esophageal leukoplakia that showed histologic resolution during surveillance, raising important questions regarding disease progression and surveillance strategies. Case Description/Methods: A 56-year-old woman with a smoking history presented with dysphagia and weight loss. Initial esophagogastroduodenoscopy (EGD) revealed eosinophilic esophagitis with an eosinophil count of 40 per HPF; she was started on proton pump inhibitor therapy. Two years later, persistent symptoms prompted repeat EGD, which showed multiple concentric rings and fibrotic mucosa. Biopsies demonstrated esophageal leukoplakia with acute esophagitis and rare eosinophils. A few months later, surveillance EGD revealed sloughed whitish plaques; biopsies showed epidermoid metaplasia and active esophagitis without dysplasia or eosinophilic esophagitis. She was enrolled in 6-month surveillance. Subsequent EGDs showed chronic inflammation with rare intraepithelial eosinophils, without leukoplakia or dysplasia. Endoscopically, the mucosa remained fibrotic and sloughed in appearance. The most recent biopsy showed benign squamous epithelium with mild inflammation and fungal organisms, which were treated. The patient remained adherent to twice-daily proton pump inhibitor therapy throughout. Discussion: This case underscores the diagnostic and clinical challenges in managing esophageal leukoplakia. Despite its known premalignant potential, our patient demonstrated histologic regression, though endoscopic abnormalities persisted. Preliminary genetic studies suggest that leukoplakia may represent an early precursor to squamous dysplasia. However, most SCCs arise de novo or directly from dysplastic epithelium, often bypassing identifiable leukoplakia stages. The natural history of esophageal leukoplakia may therefore parallel that of Barrett’s esophagus, where histologic improvement does not eliminate long-term malignant risk. Accordingly, we emphasize the need for ongoing endoscopic surveillance even in the setting of apparent histologic resolution.