Cancer Health Center

A variety of neuroendocrine cells normally populate the gastrointestinal (GI) mucosa and submucosa. The type, location, and secretory products of GI neuroendocrine cells are well defined and are summarized in Table 1 below. As previously noted, individual carcinoid tumors have specific histologic and immunohistochemical features based on their anatomic location and neuroendocrine cell type. However, all carcinoids share common pathologic features that characterize them as well-differentiated neuroendocrine tumors (NETs).[1]

Table 1. Gastrointestinal Neuroendocrine Cellsa

Updated in 2000, the World Health Organization (WHO) classification of GI NETs is clinically and prognostically useful for patients with newly diagnosed NETs of the GI tract because it accounts for specific biological behavior according to location and tumor differentiation.[4,5]

This classification distinguishes between the following:

• Well-differentiated, mostly benign tumors with an excellent prognosis.
• Well-differentiated carcinomas with a low malignant potential and a favorable prognosis.
• Poorly differentiated carcinomas (small cell and fewer large cell), which are highly malignant and carry a poor prognosis.

In this classification, the term carcinoid (or typical carcinoid) is used only for well-differentiated NETs of the GI tract, excluding the pancreas; the term malignant carcinoid (or atypical carcinoid) is used for the corresponding well-differentiated NETs at the same GI tract locations.[6,7] Despite some uncertainty surrounding the role of cell proliferation indices in the prognosis of NETs, it is clear that poorly differentiated carcinomas are highly aggressive and require a special therapeutic approach.[7,8,9] In a second step, the WHO classification subdivides GI NETs on the basis of localization and biology to achieve a prognostically relevant classification of the tumors.[5,6,7,9] In this subclassification, GI anatomical locations included the following:

• Stomach (four different types).
• Duodenum (and proximal jejunum) (five different types).
• Ileum (including the distal jejunum).
• Appendix.
• Colon-rectum.

(Refer to the Site-Specific Clinical Features section in the General Information About Gastrointestinal Carcinoid Tumors section of this summary for more information about a clinicopathologic correlation of cell types and anatomical location.)

In addition, in the WHO classification scheme, GI NETs have been grouped with pancreatic NETS (islet cell tumors) and labeled as gastroenteropancreatic NETs (GEP-NETs). However, because of differences in chromosomal alteration patterns and molecular genetics between GI NETs and pancreatic NETs, some investigators have suggested that this GEP-NET grouping requires reassessment.[7,9,10]