Somatic Mosaic <i>AXIN2</i>-associated Colonic Polyposis Predominantly Involving the Proximal Colon: A Case Report.
This case highlights the potential for somatic mosaic AXIN2 mutations to cause colonic polyposis, suggesting a need for careful genetic evaluation in similar cases.
Where it sits
this study against the rest of the hmg (human menopausal gonadotropin) corpusSummary and findings
This case report describes a 77-year-old asymptomatic man with somatic mosaic AXIN2-associated colonic polyposis, predominantly in the proximal colon. Multiple adenomatous polyps were found, with some lesions measuring up to 10 mm. Genetic testing revealed a heterozygous frameshift mutation in AXIN2 in the resected polyps, confirming the diagnosis.
Abstract
Colonic adenomatous polyposis is most commonly caused by germline pathogenic variants in the <i>APC</i> gene; however, recent genetic studies have identified patients without <i>APC</i> mutations. <i>AXIN2</i>-associated colonic polyposis is a rare condition related to dysregulation of the Wnt/β-catenin signaling pathway. Most reported cases have involved germline <i>AXIN2</i> variants, whereas somatic mosaic <i>AXIN2</i> alterations remain poorly documented. We report a rare case of somatic mosaic <i>AXIN2</i>-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 <i>AXIN2</i> with loss of heterozygosity, whereas no <i>AXIN2</i> abnormalities were detected in normal colonic mucosa, leading to a definitive diagnosis of somatic mosaic <i>AXIN2</i>-associated colonic polyposis. This case highlights a previously unreported mechanism of <i>AXIN2</i>-driven colonic polyposis through somatic mosaicism and suggests that intensive endoscopic treatment with close surveillance may be an effective management strategy in selected patients.
Background
Colonic adenomatous polyposis is typically linked to germline pathogenic variants in the APC gene, but some patients lack these mutations. AXIN2-associated colonic polyposis is a rare condition that involves dysregulation of the Wnt/β-catenin signaling pathway. This study is significant as it documents a rare case of somatic mosaic AXIN2 alterations, which are poorly understood compared to germline variants.
Methods
This case report details a 77-year-old asymptomatic man who underwent colonoscopic surveillance after a previous polypectomy. The colonoscopy identified multiple adenomatous polyps, and genetic testing was performed after genetic counseling. Histopathological examination was conducted on the resected polyps.
Results
The colonoscopy revealed multiple adenomatous polyps, with some lesions measuring up to 10 mm. Histopathological analysis confirmed low-grade tubular adenomas. Genetic testing found no pathogenic variants in peripheral blood, but a heterozygous frameshift mutation in AXIN2 was identified in the resected polyps.
Interpretation
This case adds to the understanding of AXIN2-associated colonic polyposis by highlighting somatic mosaicism as a potential mechanism. The findings suggest that intensive endoscopic management may be beneficial, although the clinical significance of the identified mutation and the effectiveness of the management strategy require further investigation. The limitations of a single case report and lack of broader data restrict the conclusions that can be drawn.
Key findings
- Multiple adenomatous polyps from the cecum to the proximal ascending colon, with some lesions up to 10 mm in size.
- Histopathological examination confirmed low-grade tubular adenomas.
- No pathogenic variants detected in peripheral blood.
- Heterozygous frameshift mutation in AXIN2 identified in independently resected colonic polyps.
Limitations
- Single case report limits generalizability.
- No statistical analysis performed.
- No control group for comparison.
- Lack of long-term follow-up data.