This study is, to the best of our knowledge, the largest single center study on colorectal juvenile polyps in adults in the Asia-Pacific area to date. Colorectal juvenile polyps are rare in adults. The incidence of juvenile polyps in Danish adults ranges from 1:65000 to 1:400005. Based on our study, the average age of onset in adults was 43.2 years. The ratio of males to females was 1.6:1. These findings were in line with those of previous reports that showed that the average age was between 25.5 and 48.9 years5, 11, and the male:female ratio was 0.8-1.4:18.
The clinical manifestations of juvenile polyps are similar to those of other types of polyps, including abdominal pain, rectal bleeding, prolapse, and diarrhea. Juvenile polyps can occur in any part of the colon, but most in this study were located in the rectum and sigmoid colon (68.2%), which is similar to the distribution of juvenile polyps in children12 and in previous studies in adults5. A total of 98.1% (101/103) of the patients had a single juvenile polyp, which was similar to the 94.9% reported by other researchers5. In children, 42%-75.9% had a single polyp 12, 13. A total of 83.2% of the polyps were Paris 0-Isp/Ip according to the Paris endoscopic classification14, 15 in our study, which is similar to previous reports16.
The size of juvenile polyps ranged from sessile nodules of a few millimeters to pedunculated lesions of up to several centimeters, as determined by endoscopy. Large polyps may be multilobulated, while small polyps are usually round and smooth. Erosion and granulation tissue hyperplasia are often observed on the surface of polyps17. Sometimes, there are small yellow particles around juvenile polyps, which are referred to as CSM18.
Histopathology is the gold standard for diagnosing juvenile polyps since the clinical symptoms and endoscopic features are not entirely typical. This condition mainly manifests as mucinous gland hyperplasia and mucous cysts of different sizes in fibrous tissues. Juvenile polyps are composed of differentiated glandular ducts. The glandular cavity is dilated to varying degrees. This is usually accompanied by interstitial hyperplasia and the infiltration of large numbers of inflammatory cells in the stroma, such as lymphocytes, plasma cells, neutrophils and eosinophils. These characteristics distinguish juvenile polyps from juvenile polyposis and Peutz-Jeghers syndrome.
Juvenile polyps are a type of hamartoma. It is generally believed that the risk is minimal8, 19, 20, while the potential of solitary or sporadic juvenile polyps to develop into cancer is not clear. Only a few cases of carcinogenesis from solitary or sporadic juvenile polyps have been described in the literature. Intramucosal carcinoma arising within a solitary juvenile polyp was regarded as ‘a wolf in sheep’s clothing’16, 21. Other researchers10, 22, 23 have reported three cases of signet ring cell carcinoma in juvenile polyps. In our study, one juvenile polyp with focal carcinogenesis and 7 with low-grade intraepithelial neoplasia were identified. They were all single polyps. Neither neoplasia nor carcinogenesis was associated with the number of polyps in adults, as reported in children13 .
The polyp with focal carcinogenesis showed a higher Ki-67 and p53 expression level than the 7 polyps with low-grade intraepithelial neoplasia. These 7 polyps showed a higher Ki-67 than simple polyps. As previously reported, the expression of p53 and Ki-67 may be used as prognostic factors for adenomas. A high cell proliferation suggests more aggressive behavior. Greater expression of p53 and higher expression of Ki-67 were found in adenomas with high-grade dysplasia24, 25. Other studies showed that higher cyclooxygenase-2 (COX-2) indicated a higher potential for carcinogenesis. Colorectal juvenile polyps, hamartomatous polyposis, adenoma and adenocarcinoma groups showed no difference in the expression of COX-2, which was higher than that in the normal mucosa26.
Based on the results of the immunohistochemical markers mentioned above, we hypothesized that juvenile polyps may follow a ‘low-grade intraepithelial neoplasia to high-grade intraepithelial neoplasia to carcinoma’ pathway. In a study involving 213 pediatric patients, the researchers also found adenomatous changes, suggesting the same progression13. Based on these findings, the risk of carcinogenesis and route of cancerization are independent of age and the number of polyps. On the basis of previous studies and our research, we believe that even sporadic juvenile polyps might carry an inherent potential for malignancy.
CSM was first identified in 199827 and was described as specific mucosal morphologic changes adjacent to colorectal neoplasms. CSM is characterized by a pale yellow-speckled pattern of colorectal mucosa on endoscopy. Histologically, CSM is caused by a large accumulation of lipid-filled macrophages in the lamina propria. The prevalence of CSM was 30.7% (225/733) in patients with adenomas. CSM-related adenoma was mainly found in the distal colon (93.3%). Adenomas with CSM, compared to those without CSM, presented more high-grade dysplasia and carcinoma, higher expression of Ki-67, COX2 protein and survivin, and lower expression of caspase-3, which indicated the carcinogenetic progression of colorectal adenomas28, 29. Hence, CSM is generally considered a tumor marker in colorectal adenomas. In contrast, since the levels of Ki-67 or p53 do not increase in juvenile polyps with CSM in children, CSM was not regarded as a marker for subsequent malignancy30, 31. In our study, there was no difference in the incidence of neoplasia or tumorigenesis between polyps with or without CSM. Hence, CSM was not identified as a tumorigenesis marker of colorectal juvenile polyps as it has been in children.
Endoscopic polypectomy is the main therapy for colorectal juvenile polyps. Thermal biopsies, loop snare techniques, EMR, and even endoscopic submucosal dissection (ESD) have been proven to be safe and effective for sporadic, semipedunculated or sessile large juvenile polyps. However, for multiple or diffuse juvenile polyps, very large polyps, or polyps with suspicious malignant transformation, colectomy may be a beneficial32, 33. Patients with more complete removal of juvenile polyps and improved compliance with follow-up had a reduced risk of carcinogenesis.