Somatic Mosaic AXIN2-associated Colonic Polyposis Predominantly Involving the Proximal Colon: A Case Report

Colonic adenomatous polyposis is most commonly caused by germline pathogenic variants in the APC gene; however, recent genetic studies have identified patients without APC mutations. AXIN2-associated colonic polyposis is a rare condition related to dysregulation of the Wnt/β-catenin signaling pathway. Most reported cases have involved germline AXIN2 variants, whereas somatic mosaic AXIN2 alterations remain poorly documented. We report a rare case of somatic mosaic AXIN2-associated colonic polyposis predominantly involving the proximal colon. A 77-year-old asymptomatic man was referred for colonoscopic surveillance after previous polypectomy. Colonoscopy revealed multiple adenomatous polyps from the cecum to the proximal ascending colon, with some lesions up to 10 mm in size, while only a few small polyps were observed in the transverse and descending colon and none in the sigmoid colon or rectum. The patient underwent intensive endoscopic management, including endoscopic submucosal dissection for extensive adenomatous mucosa in the cecum, followed by repeated endoscopic resections and close surveillance. Histopathological examination confirmed low-grade tubular adenomas. Because of multiple adenomas, genetic testing was performed after genetic counseling. No pathogenic variants were detected in peripheral blood. Analysis of independently resected colonic polyps consistently identified the same heterozygous frameshift mutation in AXIN2 with loss of heterozygosity, whereas no AXIN2 abnormalities were detected in normal colonic mucosa, leading to a definitive diagnosis of somatic mosaic AXIN2-associated colonic polyposis. This case highlights a previously unreported mechanism of AXIN2-driven colonic polyposis through somatic mosaicism and suggests that intensive endoscopic treatment with close surveillance may be an effective management strategy in selected patients.