Gastrointestinal Carcinoid Tumors Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Cellular and Pathologic Classification of Gastrointestinal Carcinoid Tumors
Table 1. Gastrointestinal Neuroendocrine Cellsa continued...
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. 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.
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.
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- Solcia E, Kloppel G, Sobin LH, et al.: Histological Typing of Endocrine Tumours. 2nd ed. New York, NY: Springer, 2000 .
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- 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.
- Zikusoka MN, Kidd M, Eick G, et al.: The molecular genetics of gastroenteropancreatic neuroendocrine tumors. Cancer 104 (11): 2292-309, 2005.