I ndividuals with 10 or more adenomatous colon polyps and unremarkable germline genetic testing have carried many labels over the years, but more recently, they have been referred to as having colonic polyposis of unknown etiology (CPUE). Recent efforts have shown that CPUE is likely the most common polyposis syndrome. Analysis of screening programs focused on patients with positive stool screening tests (fecal occult blood or fecal immunochemical testing) have reported that 2.0% to 3.2% of patients have 10 or more colorectal adenomas on their initial colonoscopy and the great majority of these patients will not have a detected inherited cause. [1][2][3] This is 2 to 3 times as high as the reported rates of serrated polyposis syndrome, which is often labeled the most common polyposis syndrome, in similar cohorts. [4][5][6] In addition, this is an underestimate of the true prevalence of CPUE, as it does not incorporate the cumulative colonic adenoma count in patients with continued production and resection of colon adenomas over time.Although the name CPUE emphasizes that multiple polyps are found in the colon, individuals meeting this clinical criteria are increasingly being reported to also be at risk for important extracolonic manifestations. Therefore, we applaud Hajj Ali et al 7 for their manuscript investigating extracolonic manifestations in the largest-to-date, single-center cohort of patients with CPUE. Their findings bring up several aspects of CPUE that deserve further exploration and discussion.First, we know that CPUE is severely under-recognized by clinicians. Even within a specialized national colorectal cancer screening program, only 8% of these patients were recognized and referred for genetic counseling. 2 Hajj Ali and colleagues highlight the importance of appropriately identifying and diagnosing these individuals with CPUE to allow for extracolonic surveillance. The authors report a high rate of gastric adenomas (8.3%), duodenal adenomas (33.3%), and ampullary adenomas (8.3%) in patients with 10 to 19 colorectal adenomas, although this is in a cohort of only 12 patients. They also note in a larger cohort of 67 patients with 20 to 99 colorectal adenomas that gastric adenomas were found in 1.4%, duodenal adenomas in 10.1%, and ampullary adenomas in 1.4%. Although there was only 1 patient with advanced-stage duodenal polyposis and no cancers were noted, it is still likely beneficial to have identified and resected the gastroduodenal neoplasia in these individuals with CPUE.Second, the authors are also the first to our knowledge to show that clinically significant thyroid nodules are common in CPUE with 20 to 99 colorectal adenomas. Although there were no thyroid malignancies encountered, this finding deserves further investigation and confirmation, as thyroid screening may be another avenue to improve the care of CPUE patients. This is especially relevant as other adenomatous polyposis syndromes, such as familial adenomatous polyposis, have been associated with an increased risk of thyroid cancer ...
