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. 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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