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Cancer Health Center

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

Table 1. Gastrointestinal Neuroendocrine Cellsa continued...

(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]

Because there were no proven molecular and genetic alterations with clinical and prognostic relevance, only traditional morphologic and histopathologic criteria were used in the classification. In addition to the level of differentiation, these criteria include the following:

  • Size of the tumor.
  • Presence or absence of angioinvasion.
  • Proliferative activity (as measured by a Ki-67 index).[5,6]

Traditional cytologic and histopathologic assessment of growth patterns and cellular features of well-differentiated NETs are often of little help in predicting their functional behavior and degree of malignancy. In general, typical carcinoids occurring in the stomach, the appendix, or the rectum have an excellent prognosis.[6] In contrast, poorly differentiated NETs that are composed of cells displaying severe nuclear atypia, a high mitotic index, and few secretory granules are invariably high-grade malignancies.[7]

Diagnostic markers that help to identify GI NETs include the following:

  • Cytosolic and cell-membrane markers such as neuron-specific enolase, protein gene product 9.5, histidine carboxylase, vesicular monamine transporter 2 (VMAT2), and neural-cell adhesion molecule CD56 (high sensitivity and low specificity).
  • Small vesicle-associated markers such as synaptophysin and synaptic vesicle protein 2 (high sensitivity and high specificity).
  • Large secretory granule-associated markers such as chromogranins A, B, and C and CD57 (low sensitivity and high specificity).
  • Somatostatin receptors.
  • Specific peptide hormone markers such as serotonin, somatostatin, and gastrin.[7,8]

Hormones that are highly specific for certain GI NETs are serotonin and substance P for ileal and appendiceal NETs, and VMAT2 for ECLomas.[7]


  1. Levy AD, Sobin LH: From the archives of the AFIP: Gastrointestinal carcinoids: imaging features with clinicopathologic comparison. Radiographics 27 (1): 237-57, 2007 Jan-Feb.
  2. Hemminki K, Li X: Incidence trends and risk factors of carcinoid tumors: a nationwide epidemiologic study from Sweden. Cancer 92 (8): 2204-10, 2001.
  3. Burke AP, Thomas RM, Elsayed AM, et al.: Carcinoids of the jejunum and ileum: an immunohistochemical and clinicopathologic study of 167 cases. Cancer 79 (6): 1086-93, 1997.
  4. Capella C, Heitz PU, Höfler H, et al.: Revised classification of neuroendocrine tumours of the lung, pancreas and gut. Virchows Arch 425 (6): 547-60, 1995.
  5. Solcia E, Kloppel G, Sobin LH, et al.: Histological Typing of Endocrine Tumours. 2nd ed. New York, NY: Springer, 2000 .
  6. Arnold R: Endocrine tumours of the gastrointestinal tract. Introduction: definition, historical aspects, classification, staging, prognosis and therapeutic options. Best Pract Res Clin Gastroenterol 19 (4): 491-505, 2005.
  7. Klöppel G: Tumour biology and histopathology of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab 21 (1): 15-31, 2007.
  8. Williams GT: Endocrine tumours of the gastrointestinal tract-selected topics. Histopathology 50 (1): 30-41, 2007.
  9. Klöppel G, Perren A, Heitz PU: The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification. Ann N Y Acad Sci 1014: 13-27, 2004.
  10. Zikusoka MN, Kidd M, Eick G, et al.: The molecular genetics of gastroenteropancreatic neuroendocrine tumors. Cancer 104 (11): 2292-309, 2005.

This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http:// cancer .gov or call 1-800-4-CANCER.

WebMD Public Information from the National Cancer Institute

Last Updated: May 28, 2015
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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