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    Gastrointestinal Carcinoid Tumors Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Cellular and Pathologic Classification of Gastrointestinal Carcinoid Tumors

    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

    CCK = cholecystokinin; D = somatostatin-producing; EC = enterochromaffin; ECL = enterochromaffin-like; G = Gastrin cell; GIP = gastric inhibitory polypeptide; L = enteroendocrine; M = motilin; N = neurotensin; PP = pancreatic polypeptide; S = secretin.
    a Adapted from [1,2,3]
    Cell Type Location Secretory Product
    G cell Gastric antrum and duodenum Gastrin
    ECL cell Gastric fundus and body Histamine
    D cell Stomach, duodenum, jejunum, colon, and rectum Somatostatin
    EC cell Stomach, duodenum, jejunum, ileum, colon, and rectum Serotonin, motilin, and substance P
    CCK cell Duodenum and jejunum Cholecystokinin
    GIP cell Duodenum and jejunum Gastric inhibitory polypeptide
    M cell Duodenum and jejunum Motilin
    S cell Duodenum and jejunum Secretin
    PP cell Duodenum Pancreatic polypeptide
    L cell Jejunum, ileum, colon, and rectum Polypeptide YY
    N cell Jejunum and ileum Neurotensin

    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.
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