Herein, we report a rare case of CPUE with localized lesions, including multiple carcinomas, in the right side of the colon. In contrast to the recommended total proctocolectomy for CPUE cases with over 100 adenomatous polyps, we opted for a right hemicolectomy with regional lymph node dissection, resulting in long-term survival. Despite a comprehensive search for germline variants in genes associated with polyposis diseases, including APC and MUTYH, no causative germline variant was identified.

While a definitive consensus on the trend in the lesion distribution in CPUE remains elusive, several reports have suggested that lesions are more frequently found on the right side in CPUE cases with a small number of lesions [10]. However, CPUE cases with > 100 lesions distributed in a local area of the colon or rectum have not been reported, other than the present case. With respect to FAP cases with APC pathogenic variants, a search of the PubMed database revealed two prior reports of typical FAP cases involving localized lesions. In one case, a complication of ulcerative colitis was reported, and the right side of the colon was covered by innumerable small adenomatous polyps; conversely, ulcerative colitis was observed on the left side of the colon [11]. This patient underwent total abdominal colectomy as a curative treatment for both FAP and ulcerative colitis. In the other case, numerous right-sided polyps were detected, sparing the left side of the colon [12]. In this case, laparoscopic subtotal colectomy was performed, while laparoscopic pancreatoduodenectomy was conducted simultaneously for ampullary cancer. In our case, the patient had > 100 colon adenomas and was diagnosed with CPUE after germline multigene panel testing. Although the condition in our case may have been caused by a variant in a gene that was not included in our multigene panel, to the best of our knowledge, this is the first reported case of localized polyposis lesions in CPUE with > 100 lesions.

According to guidelines [3], the management of CPUE cases with > 100 adenomatous polyps should follow that of FAP; as such, the standard treatment is total proctocolectomy. However, no strong evidence is available to support this treatment approach. Total proctocolectomy is associated with a decreased quality of life [13]. Given that our patient was older, the detrimental impact on quality of life was expected to be even greater. Accounting for the localization of the polyps and adenocarcinomas, we opted to perform segmental resection and regional lymph node dissection of the diseased colon, assuming strict endoscopic surveillance after the surgery. In attenuated FAP cases, endoscopic polypectomy followed by endoscopic surveillance is considered a standard treatment [14]. Therefore, we deemed that our strategy, with strict endoscopic surveillance, would be a feasible approach in our case. Postoperatively, periodic surveillance with colonoscopy for > 5 years revealed no evidence of polyposis or cancer recurrence in the remaining colon or rectum. Even in cases of CPUE with > 100 lesions, curative resection might be achieved by resecting the diseased bowel (with lymph node dissection in cases with adenocarcinomas) instead of performing total proctocolectomy when the lesion is localized, as in the present case.

In addition to FAP and MUTYH-associated polyposis, colorectal adenomatous polyposis can be caused by other hereditary diseases, including polymerase proofreading-associated polyposis [15], NTLH1 tumor syndrome [16], and MBD4-associated neoplasia syndrome [17]. Pathogenic biallelic germline variants in one of the four mismatch repair genes (MLH1, MSH2, MSH6, or PMS2) can cause colorectal adenomatous polyposis in childhood [18]. In our case, we performed germline multigene panel testing to detect genes associated with these diseases with blood samples; however, no pathogenic variants suggestive of these diseases were found in the germline. Pathogenic biallelic germline variants in MSH3 are also associated with colorectal polyposis, namely, MSH3-associated polyposis [19]. In the present case, we identified a heterozygous variant in MSH3. Although it was expected to be silent, we tried to annotate the variant; in the tissue immunostaining, the expression of MSH3 was the same in the normal mucosa, adenomas, and carcinomas, suggesting that the MSH3 variant in our case was unlikely to have contributed to the development of polyposis or carcinogenesis. Germline loss-of-function variants in AXIN2 are also reported to be associated with colonic polyposis and colorectal cancers [20]. We added the mRNA sequence of AXIN2 using blood samples, and the function of AXIN2 was deemed to be normal. In addition to germline variants related to adenomatous polyposis, loss-of-function of RNF43 can cause serrated polyposis syndrome [21]. In the present case, serrated changes were observed in part of the polyps. However, no obvious variants in the RNF43 gene sequence were detected. Overall, no pathogenic variants were detected in the present case, and we diagnosed the patient with CPUE. The sporadicity and localization of the lesions indicated the possibility of the involvement of somatic variants, such as APC mosaicism [22]. In our case, the variant frequency threshold was lowered to 0.5% for APC to investigate the possibility of mosaic, but no variants were detected as possible causes from blood samples. Mosaicism might be detected by genetic searches in adenomas and surrounding normal mucosa. In addition to genetic factors, colorectal polyposis has been associated with cancer treatment in childhood or adulthood [23, 24]; however, no such history was found in our patient.

Herein, we reported the first CPUE case with numerous adenomas and multiple adenocarcinomas, all located in the right side of the colon. The diagnosis of CPUE was made after a germline multigene panel testing was conducted on a blood sample to detect polyposis-associated germline variants. However, no pathogenic variant was detected. The sporadicity of the case and localization of the lesions raised the possibility of the involvement of somatic variants. Given that CPUE cases may encompass some undiagnosed hereditary diseases, it is generally accepted that the standard treatment for CPUE cases with numerous adenomas is total proctocolectomy. However, in this specific case, considering the patient’s general condition and distribution of the lesions, we opted to perform right hemicolectomy and regional lymph node dissection as a curative treatment. This approach resulted in a long-term recurrence-free survival for the patient. Therefore, in cases with localized lesions, segmental colectomy might be an option for curative treatment.