Epidemiological, clinical and endoscopic characteristics of colorectal neuroendocrine neoplasms: a population-based study in the Netherlands

Abstract

Background and study aims Neuroendocrine neoplasms (NEN) account for a small number of colorectal neoplasms. Endoscopic detection is essential for diagnosis, treatment and follow-up. Little is known about incidence of NENs in colonoscopy populations or the relationship between clinical, endoscopic and histopathologic features. We evaluated epidemiology, endoscopic and clinical characteristics of colorectal NENs in a population-based cohort.

Patients and methods Medical records of NEN cases were cross-linked with the national pathology database from January 2001 to December 2015, in South Limburg County, the Netherlands, covering four endoscopy units. Senior pathologists reviewed and classified NENs using World Health Organization 5th edition (2019) guidelines.

Results The number of colorectal NEN diagnoses was stable over time with 0.6 NEN per 1,000 patients. A total of NENs were detected in 85 patients: 65 neuroendocrine tumors (NETs) and 20 poorly differentiated neuroendocrine carcinomas (NECs). Rectal NETs were usually small sessile/submucosal lesions with yellowish (lipoma-like) color. Colonic NETs were larger sessile/submucosal lesions with darker color compared to background. Colorectal NECs presented as large, dark-colored lesions with ulcerated/necrotizing areas.

Conclusions Our population-based data point to a stable and low incidence of 0.6 NEN per 1,000 patients in the Netherlands. Rectal NETs mainly present as small sessile yellowish lesions. Colonic NETs present as larger and darker lesions than background mucosa and NECs as darker lesions than background with ulceration/necrosis. Standardized endoscopic characterization of colorectal NENs is necessary to improve recognition of these lesions and provide a basis for evidence-based treatment and surveillance recommendations.

Publication History

Received: 09 July 2021

Accepted after revision: 08 March 2022

Accepted Manuscript online:
10 March 2022

Article published online:
15 July 2022

• References

• 1 Rindi G, Klimstra DS, Abedi-Ardekani B. et al. A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Mod Pathol 2018; 31: 1770-1786
• 2 Bosman FT, Carneiro F, Hruban RH. et al. WHO classification of tumours of the digestive system. 4th ed. Lyon: IARC Press; 2010
• 3 Caplin M, Sundin A, Nillson O. et al. ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: colorectal neuroendocrine neoplasms. Neuroendocrinology 2012; 95: 88-97
• 4 Ramage JK, De Herder WW, Delle Fave G. et al. ENETS Consensus Guidelines Update for Colorectal Neuroendocrine Neoplasms. Neuroendocrinology 2016; 103: 139-143
• 5 Leoncini E, Boffetta P, Shafir M. et al. Increased incidence trend of low-grade and high-grade neuroendocrine neoplasms. Endocrine 2017; 58: 368-379
• 6 Yao JC, Hassan M, Phan A. et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008; 26: 3063-3072
• 7 Fraenkel M, Kim M, Faggiano A. et al. Incidence of gastroenteropancreatic neuroendocrine tumours: a systematic review of the literature. Endocr Relat Cancer 2014; 21: R153-R163
• 8 Chung TP, Hunt SR. Carcinoid and neuroendocrine tumors of the colon and rectum. Clin Colon Rectal Surg 2006; 19: 45-48
• 9 Scherübl H. Rectal carcinoids are on the rise: early detection by screening endoscopy. Endoscopy 2009; 41: 162-165
• 10 Scherubl H, Kloppel G. Rectal carcinoids on the rise – update. Zeitschrift fur Gastroenterologie 2009; 47: 365-371
• 11 Basuroy R, OʼDonnell CM, Srirajaskanthan R. et al. Ileocolonic neuroendocrine tumours identified in the English bowel cancer screening programme. Colorectal Dis 2018; 20: O85-O91
• 12 Derikx LA, Vierdag WM, Kievit W. et al. Is the prevalence of colonic neuroendocrine tumors increased in patients with inflammatory bowel disease?. J Int Cancer 2016; 139: 535-542
• 13 Hofland J, Kaltsas G, de Herder WW. Advances in the Diagnosis and management of well-differentiated neuroendocrine neoplasms. Endocr Rev 2020; 41: 371-403
• 14 Concors SJ, Sinnamon AJ, Folkert IW. et al. Predictors of metastases in rectal neuroendocrine tumors: results of a national cohort study. Dis Colon Rectum 2018; 61: 1372-1379
• 15 Shimizu T, Tanaka S, Haruma K. et al. Growth characteristics of rectal carcinoid tumors. Oncology 2000; 59: 229-237
• 16 Shim KN, Yang SK, Myung SJ. et al. Atypical endoscopic features of rectal carcinoids. Endoscopy 2004; 36: 313-316
• 17 Eggenberger JC. Carcinoid and other neuroendocrine tumors of the colon and rectum. Clin Colon Rectal Surg 2011; 24: 129-134
• 18 Nagtegaal ID, Odze RD, Klimstra D. et al. The 2019 WHO classification of tumours of the digestive system. Histopathology 2020; 76: 182-188
• 19 Jung YS, Yun KE, Chang Y. et al. Risk factors associated with rectal neuroendocrine tumors: a cross-sectional study. Cancer Epidemiol Biomarkers Prev 2014; 23: 1406-1413
• 20 OʼToole D, Kianmanesh R, Caplin M. ENETS 2016 Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Tumors: An Update. Neuroendocrinology 2016; 103: 117-118
• 21 Update on the Paris classification of superficial neoplastic lesions in the digestive tract. Endoscopy 2005; 37: 570-578
• 22 Bisschops R, Hassan C, Bhandari P. et al. BASIC (BLI Adenoma Serrated International Classification) classification for colorectal polyp characterization with blue light imaging. Endoscopy 2018; 50: 211-220
• 23 Patrun J, Okreša L, Iveković H. et al. Diagnostic accuracy of NICE classification system for optical recognition of predictive morphology of colorectal polyps. Gastroenterol Res Pract 2018; 2018: 7531368
• 24 Taghavi S, Jayarajan SN, Powers BD. et al. Examining rectal carcinoids in the era of screening colonoscopy: a surveillance, epidemiology, and end results analysis. Dis Colon Rectum 2013; 56: 952-959
• 25 Korse CM, Taal BG, van Velthuysen ML. et al. Incidence and survival of neuroendocrine tumours in the Netherlands according to histological grade: experience of two decades of cancer registry. Europ J Cancer 2013; 49: 1975-1983
• 26 Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet 2014; 383: 1490-1502
• 27 Anthony LB, Strosberg JR, Klimstra DS. et al. The NANETS consensus guidelines for the diagnosis and management of gastrointestinal neuroendocrine tumors (nets): well-differentiated nets of the distal colon and rectum. Pancreas 2010; 39: 767-774
• 28 Kuiper T, van Oijen MGH, van Velthuysen MF. et al. Endoscopically removed rectal NETs: a nationwide cohort study. International journal of colorectal disease 2021; 36: 535-541
• 29 Konishi T, Watanabe T, Kishimoto J. et al. Prognosis and risk factors of metastasis in colorectal carcinoids: results of a nationwide registry over 15 years. Gut 2007; 56: 863-868
• 30 Madani A, Thomassen I, van Gestel Y. et al. Peritoneal metastases from gastroenteropancreatic neuroendocrine tumors: incidence, risk factors and prognosis. Ann Surg Oncol 2017; 24: 2199-2205
• 31 Hotz HG, Bojarski C, Buhr HJ. Neuroendocrine colorectal tumors. Surgical and endoscopic treatment. Chirurg 2011; 82: 607-611
• 32 Hrabe J. Neuroendocrine tumors of the appendix, colon, and rectum. Surg Oncol Clin N Am 2020; 29: 267-279
• 33 Vecchio R, Ferrara M, Mosca F. et al. Lipomas of the large bowel. Eur J Surg 1996; 162: 915-919
• 34 Law YY, Patel R, Cusick M. et al. A case of colonic intussusception and obstruction secondary to giant colonic lipoma. J Surg Case Rep 2020; 2020: rjaa429
• 35 Hsu-Heng Y. Colonic lipoma. Video J Encyclop GI Endosc 2014; 1: 661-662
• 36 Ford MM. Neuroendocrine tumors of the colon and rectum. Dis Colon Rectum 2017; 60: 1018-1020
• 37 Arnold R. Endocrine tumours of the gastrointestinal tract. Introduction: definition, historical aspects, classification, staging, prognosis and therapeutic options. Best Pract Res Clin Gastroenterol 2005; 19: 491-505
• 38 Ramage JK, Valle JW, Nieveen van Dijkum EJM. et al. Colorectal Neuroendocrine neoplasms: areas of unmet need. Neuroendocrinology 2019; 108: 45-53
• 39 Gao W, Liu SM, Lu HZ. et al. Analysis of clinicopathological features of intestinal neuroendocrine neoplasms. Zhonghua zhong liu za zhi [Chinese J Oncol] 2012; 34: 450-456
• 40 Wang AY, Ahmad NA. Rectal carcinoids. Curr Opin Gastroenterol 2006; 22: 529-535