Most appendiceal carcinoids are serotonin-producing EC-cell tumors similar to carcinoids that occur in the jejunum and ileum; less commonly, appendiceal carcinoids are L-cell tumors similar to those in the colon. The biologic behavior of both cell types is strikingly different in the appendix compared with tumors of the ileum and nonappendiceal colon. Most appendiceal carcinoids have a benign clinical course and do not metastasize, perhaps because growth in the appendix produces obstruction, appendicitis, and subsequent surgical removal.[5,36] Although appendiceal carcinoids occur in patients of all ages, patients with these tumors tend to be much younger than patients diagnosed with other appendiceal neoplasms or carcinoids at other sites. Appendiceal carcinoids are reportedly more common in female patients.[3,5] However, age and gender patterns may be spurious, reflecting the younger age range of patients who typically undergo appendectomy for inflammatory appendicitis, and the larger number of incidental appendectomies performed in women during pelvic operations.
Most colorectal carcinoids occur in the rectum; fewer arise in the cecum. In the cecum, argentaffinic EC-cell carcinoids are most common, become increasingly less common in the more distal colon, and are uncommon in the rectum. Rectal carcinoids account for approximately one-fourth of GI carcinoids and fewer than 1% of all rectal cancers.[3,31] Most rectal carcinoids have L-cell differentiation. The mean age of patients at diagnosis for colonic carcinoids is 66 years and for rectal carcinoids, 56.2 years. Although there is no specific gender predilection for colorectal carcinoids, rectal carcinoids are more common in the black population.[3,37] Abdominal pain and weight loss are typical symptoms of colonic carcinoids, but more than 50% of patients with rectal carcinoids are asymptomatic, and the tumors are discovered at routine rectal examination or screening endoscopy. Symptoms of rectal carcinoids include bleeding, pain, and constipation. Metastatic disease from colonic carcinoids may produce carcinoid syndrome, whereas metastatic disease from rectal carcinoids is not associated with carcinoid syndrome.[5,38]
Diagnostics: Biochemical Markers, Imaging, and Approach
Biochemical investigations in the diagnosis of GI carcinoids include the use of 24-hour urinary 5-hydroxyindoleacetic acid (5-HIAA) collection, which has a specificity of approximately 88%, although the sensitivity is reported to be as low as 35%.[39,40,41] A time-consuming test, 5-HIAA requires dietary avoidance of serotonin-rich foods, such as bananas, tomatoes, and eggplant. Measurement of plasma chromogranin A (CgA), first described in a study of adrenal gland secretions in 1967 as one of the soluble protein fractions (also including CgB and CgC) of chromaffin granules, is also useful. Although plasma levels of CgA are very sensitive markers of carcinoids, they are nonspecific because they are also elevated in other types of NETs, such as pancreatic and small cell lung carcinomas.[44,45,46] Plasma CgA appears to be a better biochemical marker of carcinoids than does urinary 5-HIAA. Numerous investigations have revealed an association between plasma CgA levels and disease severity. However, false-positive plasma levels of CgA may occur in patients on proton pump inhibitors, reported to occur even with short-term, low-dose treatment.[48,49] Many other biochemical markers are associated with NETs—including substance P, neurotensin, bradykinin, human chorionic gonadotropin, neuropeptide L, and pancreatic polypeptide—but none match the specificity or predictive value of 5-HIAA or CgA.