Appendiceal lesions in serrated polyposis patients are easily overlooked but only seldomly lead to colorectal cancer

Abstract

Background Serrated polyposis syndrome (SPS) is the most prevalent colonic polyposis syndrome and is associated with an increased colorectal cancer risk. A recent study in resected appendices of SPS patients reported that 6/23 (26.1 %) of identified serrated polyps had histological dysplasia. We evaluated the prevalence and clinical relevance of appendiceal lesions in a large SPS cohort.

Methods Prospective data from 2007 to 2020 for a cohort of 199 SPS patients were analyzed. Data were retrieved from endoscopy and pathology reports. Patients who underwent (pre)clearance colonoscopies, surveillance colonoscopies, or colorectal surgery including the appendix were separately evaluated for the presence of appendiceal lesions. The primary outcome was the prevalence of adenocarcinomas and serrated polyps/adenomas with advanced histology in the surgery group.

Results 171 patients were included, of whom 110 received endoscopic surveillance and 34 underwent surgery. Appendiceal lesion prevalence in the surgery group was 14 /34 (41.2 %, 95 %CI 24.7 %–59.3 %); none were advanced on histology. Detection rates in the (pre)clearance group were 1 /171 (0.6 %, 95 %CI 0.01 %–3.2 %) for advanced and 3 /171 (1.8 %, 95 %CI 0.04 %–5.0 %) for nonadvanced appendiceal lesions, all of which were sessile serrated lesions. During 522 patient-years of surveillance, no advanced appendiceal lesions were detected at endoscopy, and in 1 /110 patients (0.9 %, 95 %CI 0.02 %–5.0 %) was a nonadvanced lesion detected.

Conclusion Appendiceal lesions are common in SPS patients. The discrepancy between the endoscopic detection rate of appendiceal lesions and the reported prevalence in surgically resected appendices suggests a substantial miss-rate of appendiceal lesions during colonoscopy. Advanced appendiceal lesions are however rare and no appendiceal adenocarcinomas occurred, implying limited clinical relevance of these lesions.

• References

• 1 IJspeert JEG, Bevan R, Senore C. et al. Detection rate of serrated polyps and serrated polyposis syndrome in colorectal cancer screening cohorts: a European overview. Gut 2017; 66: 1225-1232
• 2 Bleijenberg AG, IJspeert JE, Hazewinkel Y. et al. The long-term outcomes and natural disease course of serrated polyposis syndrome: over 10 years of prospective follow-up in a specialized center. Gastrointest Endosc 2020; 92: 1098-1107.e1
• 3 Carballal S, Rodríguez-Alcalde D, Moreira L. et al. Colorectal cancer risk factors in patients with serrated polyposis syndrome: a large multicentre study. Gut 2016; 65: 1829-1837
• 4 van Leerdam ME, Roos VH, van Hooft JE. et al. Endoscopic management of polyposis syndromes: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2019; 51: 877-895
• 5 Bettington M, Brown IS, Rosty C. Serrated lesions of the appendix in serrated polyposis patients. Pathology 2016; 48: 30-34
• 6 McKay O, Shahidi N, Gupta S. et al. Is it time to consider prophylactic appendectomy in patients with serrated polyposis syndrome undergoing surveillance?. Gut 2021; 70: 231-233
• 7 van Herwaarden YJ, Madani A, van der Post RS. et al. Incidental diagnosis of serrated polyp in the appendix warrants colonoscopy to screen for colorectal neoplasia. Br J Surg 2021; 108: e373-e374
• 8 Arnau-Collell C, Soares de Lima Y, Diaz-Gay M. et al. Colorectal cancer genetic variants are also associated with serrated polyposis syndrome susceptibility. J Med Genet 2020; 57: 677-682
• 9 IJspeert JEG, Rana SA, Atkinson NS. et al. Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis. Gut 2017; 66: 278-284
• 10 MacPhail ME, Thygesen SB, Patel N. et al. Endoscopic control of polyp burden and expansion of surveillance intervals in serrated polyposis syndrome. Gastrointest Endosc 2019; 90: 96-100
• 11 Rodríguez-Alcalde D, Carballal S, Moreira L. et al. High incidence of advanced colorectal neoplasia during endoscopic surveillance in serrated polyposis syndrome. Endoscopy 2019; 51: 142-151
• 12 Rosty C, Brosens LAA, Dekker E. et al. Serrated polyposis. Arends MJ, Carneiro F, Lax SF. et al. WHO classification of tumours: Genetic tumour syndromes of the digestive system. Lyon: IARC; 2019: 24-26
• 13 Nagtegaal ID, Arends MJ, Odze RD. et al. WHO Classification of Tumours of the Digestive System. Lyon: IARC; 2019
• 14 Wolff M, Ahmed N. Epithelial neoplasms of the vermiform appendix (exclusive of carcinoid). II. Cystadenomas, papillary adenomas, and adenomatous polyps of the appendix. Cancer 1976; 37: 2511-2522
• 15 Collins DC. 71,000 human appendix specimens. A final report, summarizing forty years' study. Am J Proctol 1963; 14: 265-281
• 16 Rodríguez-Alcalde D, Castillo-López G, López-Vicente J. et al. Long-term incidence of advanced colorectal neoplasia in patients with serrated polyposis syndrome: experience in a single academic centre. Cancers (Basel) 2021; 13: 1066
• 17 Younes M, Katikaneni PR, Lechago J. Association between mucosal hyperplasia of the appendix and adenocarcinoma of the colon. Histopathology 1995; 26: 33-37
• 18 Pai RK, Hartman DJ, Gonzalo DH. et al. Serrated lesions of the appendix frequently harbor KRAS mutations and not BRAF mutations indicating a distinctly different serrated neoplastic pathway in the appendix. Hum Pathol 2014; 45: 227-235
• 19 Chezar K, Minoo P. Appendiceal sessile serrated lesions are distinct from their right-sided colonic counterparts and may be precursors for appendiceal mucinous neoplasms. Hum Pathol 2022; 122: 40-49
• 20 Li F, Lu Y, Hou F. et al. Significance of the entire appendiceal evaluation in the diagnosis of serrated lesions, low-grade appendiceal mucinous neoplasm, and appendiceal diverticulosis disease. Front Oncol 2021; 11: 812794
• 21 Schmidt A, Beyna T, Schumacher B. et al. Colonoscopic full-thickness resection using an over-the-scope device: a prospective multicentre study in various indications. Gut 2018; 67: 1280-1289
• 22 Zwager LW, Bastiaansen BAJ, Bronzwaer MES. et al. Endoscopic full-thickness resection (eFTR) of colorectal lesions: results from the Dutch colorectal eFTR registry. Endoscopy 2020; 52: 1014-1023