The location of these carcinoid tumors can be divided based on their embryologic derivation into find more carcinoids of the foregut (esophagus, stomach and duodenum), midgut (jejunum, ileum, appendix and ascending colon) and hindgut (transverse colon, descending colon, sigmoid and rectum) (71). Tumors from each different region of the gastrointestinal tract may secrete different hormones as

well. Foregut and midgut carcinoid often produce serotonin and substance P while hindgut carcinoids may produce glucagon like peptide, pancreatic polypeptide, and polypeptide YY (72-78). In spite of these differences, these tumors share similar morphologic features such as clusters/sheets/nests of neuroendocrine cells with round to Inhibitors,research,lifescience,medical ovoid nuclei, “salt and pepper” chromatin Inhibitors,research,lifescience,medical and moderate amounts of clear cytoplasm. All gastrointestinal neuroendocrine tumors are positive for the generic markers of neuroendocrine differentiation such as chromogranin A, synaptophysin and NSE, as well as PGP 9.5, and CD56 (79). Determining

the origin of the tumor may be challenging; however, immunohistochemical stains can be very helpful. Carcinoids Inhibitors,research,lifescience,medical from the foregut and midgut are generally positive for chromogranin A and CD56, while those from the hindgut are usually negative (73,80,81). Hindgut carcinoids on the other hand often express prostatic acid phosphatase (82). A less helpful marker is CDX-2, which although positive for most colorectal carcinomas has an immunoreactivity of about 40% in well differentiated carcinoids (83-87) but has a reported 80% expression rate in poorly differentiated carcinoids (80). Carcinoid tumors make up about a third of the neoplasms in the small intestine. They most often occur in the ileum and rarely in the duodenum and can be separated by their Inhibitors,research,lifescience,medical location:

duodenal and jejunoilieal carcinoids. Duodenal carcinoids, similar to any carcinoid in the gastrointestinal tract can be further divided by the type of cells which make up the tumor into gastrinomas (G-cell tumors), somatostatinomas (D-cell tumors) and a small percentage Inhibitors,research,lifescience,medical of the undefined type (88). Classification of neuroendocrine tumors is based on the degree of differentiation. Most carcinoids are well-differentiated carcinoid (50-75%), well-differentiated neuroendocrine Terminal deoxynucleotidyl transferase carcinoma and poorly differentiated neuroendocrine carcinoma (<1-3%) (88). Carcinoid tumors usually show a monotonous proliferation of small bland polygonal cells with round nuclei, “salt and pepper” chromatin and moderate amounts of cytoplasm in either a nested (type A), trabecular (type B) or acinar (type C) pattern. Distinction between benign and malignant carcinoid is based on the presence or absence of metastasis rather than just on histology. Colon and rectum Colorectal cancer (CRC) CRC is the third most common cancer diagnosed in the United States and third most common cause of cancer deaths. Risk for development of colorectal carcinoma increases significantly after the age of 40.