Question: This 41-year-old Asian man received laparoscopic proximal gastrectomy and distal esophagectomy in March 2020 to remove a gastroesophageal junction adenocarcinoma of stage pT2N1. Adjuvant chemotherapy with tegafur/gimeracil/oteracil (TS-1) was administered. Follow-up computer tomography revealed no evidence of recurrence in February 2022. He had no epigastric discomfort, odynophagia, or dysphagia. However, an esophagogastroduodenoscopy revealed a grape-like polypoid lesion measuring 1 cm in dimension near the anastomotic site (38 cm level) in June 2022 (Figure A, white light image; Figure B, narrow band image). An esophageal polypectomy was performed, and representative photomicrographs of histologic sections were shown (Figure C; H&E; 10x objective). What is the diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Esophageal squamous papilloma is a benign lesion with prevalence ranging from 0.01–0.45%.1Mosca S. Manes G. Monaco R. et al.Squamous papilloma of the esophagus: long-term follow up.J Gastroenterol Hepatol. 2001; 16: 857-861Crossref PubMed Scopus (71) Google Scholar, 2Sablich R. Benedetti G. Bignucolo S. et al.Squamous cell papilloma of the esophagus. Report on 35 endoscopic cases.Endoscopy. 1988; 20: 5-7Crossref PubMed Scopus (34) Google Scholar, 3Talamini G. Capelli P. Zamboni G. et al.Alcohol, smoking and papillomavirus infection as risk factors for esophageal squamous-cell papilloma and esophageal squamous-cell carcinoma in Italy.Int J Cancer. 2000; 86: 874-878Crossref PubMed Scopus (72) Google Scholar It is usually found incidentally as an asymptomatic lesion characterized endoscopically by wart-like, polypoid growth with surface vessel crossing under narrow-band imaging.4Wong M.W. Bair M.J. Shih S.C. et al.Using typical endoscopic features to diagnose esophageal squamous papilloma.World J Gastroenterol. 2016; 22: 2349-2356Crossref PubMed Scopus (11) Google Scholar The lesion is usually solitary and small (2 mm–8 mm), but cases of widespread esophageal squamous papilloma have been reported.4Wong M.W. Bair M.J. Shih S.C. et al.Using typical endoscopic features to diagnose esophageal squamous papilloma.World J Gastroenterol. 2016; 22: 2349-2356Crossref PubMed Scopus (11) Google Scholar, 5Shimamoto Y. Shichijo S. Ishihara R. Sudden appearance of widespread esophageal squamous papilloma with reflux esophagitis.Clin Gastroenterol Hepatol. 2021; 19: e27Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar, 6Franzin G. Musola R. Zamboni G. et al.Squamous papillomas of the esophagus.Gastrointest Endosc. 1983; 29: 104-106Abstract Full Text PDF PubMed Scopus (32) Google Scholar It is usually found in the distal esophagus in Western countries but in the middle esophagus in Asian countries.4Wong M.W. Bair M.J. Shih S.C. et al.Using typical endoscopic features to diagnose esophageal squamous papilloma.World J Gastroenterol. 2016; 22: 2349-2356Crossref PubMed Scopus (11) Google Scholar,7Ekin N. Bestas R. Cetin A. Clinicopathological characteristics of patients with oesophageal squamous papilloma in Turkey and comparison with the literature data: the largest case series ever reported from Turkey.Int J Clin Pract. 2021; 75e14420Crossref Scopus (1) Google Scholar,8d'Huart M.C. Chevaux J.B. Bressenot A.M. et al.Prevalence of esophageal squamous papilloma (ESP) and associated cancer in northeastern France.Endosc Int Open. 2015; 3: E101-E106Crossref PubMed Google Scholar Histologically, it is characterized by papillary fronds composed of fibrovascular cores covered by nondysplastic squamous epithelium.9Odze R. Antonioli D. Shocket D. et al.Esophageal squamous papillomas. A clinicopathologic study of 38 lesions and analysis for human papillomavirus by the polymerase chain reaction.Am J Surg Pathol. 1993; 17: 803-812Crossref PubMed Scopus (94) Google Scholar Although the etiology of esophageal squamous papilloma is uncertain, mucosal irritation and human papillomavirus infection have been proposed.4Wong M.W. Bair M.J. Shih S.C. et al.Using typical endoscopic features to diagnose esophageal squamous papilloma.World J Gastroenterol. 2016; 22: 2349-2356Crossref PubMed Scopus (11) Google Scholar,9Odze R. Antonioli D. Shocket D. et al.Esophageal squamous papillomas. A clinicopathologic study of 38 lesions and analysis for human papillomavirus by the polymerase chain reaction.Am J Surg Pathol. 1993; 17: 803-812Crossref PubMed Scopus (94) Google Scholar Differential diagnosis from squamous cell carcinoma, especially verrucous carcinoma, is important. It is generally treated with endoscopic resection, and recurrence after complete resection is uncommon.10Abeid M. Labib S. Neizamy E. Esophageal squamous papilloma.Gastrointest Endosc. 2011; 73: 1035Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar