Gastric and rectal carcinoids

A changing terminology

The term ”carcinoid” was proposed in 1907 by Siegfried Oberndorfer, for slow-growing tumors in the small bowel, because he considered them to be ”cancer-like” rather than cancerous. In subsequent years this name was applied to tumors of the diffuse endocrine system in the digestive and bronchial mucosae. The term has even been restricted to serotonin-producing tumors resulting in a carcinoid syndrome. The appellation ”carcinoid” is still currently used to denote those tumors that have developed from the disseminated endocrine cells. However, without any accompanying qualification, the term ”carcinoid” is not informative about the management of the lesion; furthermore it is worrying that it carries a connotation that the lesion should always have benign clinical and biological behavior. Therefore, the first step in the history of classification of ”carcinoids” was their designation as tumors of the disseminated endocrine system hosted in the digestive and bronchial mucosae, which are based on enterochromaffin and enterochromaffin-like (ECL) cells. The secretion of serotonin by enterochromaffin cells was confirmed in 1953 and the term ”carcinoid” designated only tumors that had developed from EC cells and produced serotonin and multiple peptides in the rectum and ileum. A further extension of the terminology included tumors of ECL cells which have a potential for secreting histamine.

”Carcinoids” and ”pancreatic endocrine tumors” warrant classification into two distinct categories. Pancreatic endocrine tumors originate in the islets of Langerhans within the pancreas and may secrete hormones, such as insulin or gastrin or peptides (vasoactive intestinal peptide [VIP], calcitonin, or pancreatic polypeptide) or remain nonsecretory. Carcinoid tumors may produce serotonin (5-hydroxytryptamine [5-HT]), a biogenic amine that causes a specific syndrome including flushing, diarrhea, and asthma. They are also further classified, depending on the point of origin in the disseminated endocrine system, as carcinoid tumor of the foregut (lung, thymus, stomach, and duodenum), midgut (distal ileum and proximal colon), or hindgut (distal colon and rectum).

In 2000, the World Health Organization (WHO) considered that the term ”carcinoid” does not cover the entire spectrum of neoplasms of the disseminated neuroendocrine cell system. Therefore, the WHO classification [1] uses instead of ”carcinoid” the general term ”neuroendocrine tumor” (NET). A uniform classification for the diagnosis of neuroendocrine tumors within the gastroenteropancreatic tract (GEP-NETs) was then proposed. Topographically, the NET tumors are localized in the foregut (bronchial tree, esophagus, stomach, duodenum), the midgut (jejunum, ileum, proximal colon), or the hindgut (distal colon). The basic classification of the neuroendocrine tumor is based on the mitotic count and the Ki-67 index; it is stratified into three categories or grades (G1, G2, and G3) that can be applied across all sites within the gastrointestinal tract: well differentiated neuroendocrine tumors with benign or uncertain behavior; well differentiated neuroendocrine carcinomas with low-grade malignancy; and poorly differentiated neuroendocrine carcinomas. A consensus proposal for the TNM staging of gastrointestinal neuroendocrine tumours was put forward by 62 experts of the European Neuroendocrine Tumor Society (ENETS) in Frascati, in November 2005. It was again proposed to replace the term ‘carcinoid tumor’ by the terms ‘neuroendocrine tumor’ and ‘neuroendocrine carcinoma’ when appropriate [2] [3]. This new presentation is now adopted in publications that aim at classification [4] [5] [6] [7].

NETs are considered to be rare, but over the last 50 years their incidence has been increasing in most countries. The use of endoscopy and improvements in histopathologic methods during this period accounts for a large part, but not for all, the variation. In the US, between 1973 and 2004 the age-adjusted (US population in 2000) annual incidence of NETs increased from 1.09 / 100 000 to 5.25 / 100 000, according to the Surveillance Epidemiology and End Results (SEER) registries [8].

As a matter of fact this new classification is not universally accepted and the term ”carcinoid” is still used worldwide in clinical practice as an equivalent to NET [9). In the present issue of Endoscopy, one paper deals with the classification of gastric carcinoids [10] and another concerns the endoscopic treatment of rectal carcinoids [11].

References

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• 2 Rindi G, Klöppel G, Couvelard A. et al . TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system.  Virchows Arch. 2007;  451 757-762
• 3 Rindi G, Klöppel G, Alhman H. et al . European Neuroendocrine Tumor Society (ENETS). TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system.  Virchows Arch. 2006;  449 395-401
• 4 Modlin I M, Oberg K, Chung D C. et al . Gastroenteropancreatic neuroendocrine tumours.  Lancet Oncol. 2008;  9 61-72
• 5 Gustafsson B I, Kidd M, Modlin I M. Neuroendocrine tumors of the diffuse neuroendocrine system.  Curr Opin Oncol. 2008;  20 1-12
• 6 Massironi S, Sciola V, Spampatti M P. et al . Gastric carcinoids: between underestimation and overtreatment.  World J Gastroenterol. 2009;  15 2177-2183
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• 8 Yao J C, 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
• 9 Chetty R. Requiem for the term ”carcinoid tumour” in the gastrointestinal tract?.  Can J Gastroenterol. 2008;  22 357-358
• 10 Scherübl H, Cadiot G, Jensen R T. et al . Neuroendocrine tumors of the stomach (gastric carcinoids) are on the rise: small tumors, small problems?.  Endoscopy. 2010;  42 664-671
• 11 Lee D S, Jeon S W, Park S Y. et al . Feasibility of endoscopic submucosal dissection for rectal carcinoid tumors: comparison with endoscopic mucosal resection.  Endoscopy. 2010;  42 647-651
• 12 Borch K, Ahrén B, Ahlman H. et al . Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type.  Ann Surg. 2005;  242 64-73
• 13 Soga J. Early-stage carcinoids of the gastrointestinal tract: an analysis of 1914 reported cases.  Cancer. 2005;  103 1587-1595
• 14 Landry C S, Brock G, Scoggins C R. et al . A proposed staging system for gastric carcinoid tumors based on an analysis of 1,543 patients.  Ann Surg Oncol. 2009;  16 51-60
• 15 Modlin I M, Latich I, Zikusoka M. et al . Gastrointestinal carcinoids: the evolution of diagnostic strategies.  J Clin Gastroenterol. 2006;  40 572-582
• 16 Modlin I M, Pavel M, Kidd M. et al . Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours.  Aliment Pharmacol Ther. 2010;  31 169-188
• 17 Kwaan M R, Goldberg J E, Bleday R. Rectal carcinoid tumors: review of results after endoscopic and surgical therapy.  Arch Surg. 2008;  143 471-475
• 18 Landry C S, Brock G, Scoggins C R. et al . A proposed staging system for rectal carcinoid tumors based on an analysis of 4701 patients.  Surgery. 2008;  144 460-466
• 19 Fujishiro M. Perspective on the practical indications of endoscopic submucosal dissection of gastrointestinal neoplasms.  World J Gastroenterol. 2008;  14 4289-4295