Individual carcinoid tumors have specific histologic and immunohistochemical features based on their anatomic location and endocrine cell type. However, all carcinoids share common pathologic features that characterize them as well-differentiated NETs. In the gastric or intestinal wall, carcinoids may occur as firm white, yellow, or gray nodules and may be intramural masses or may protrude into the lumen as polypoid nodules; the overlying gastric or intestinal mucosa may be intact or have focal ulceration.
Neuroendocrine cells have uniform nuclei and abundant granular or faintly staining (clear) cytoplasm, and are present as solid or small trabecular clusters, or are dispersed among other cells, which may make them difficult to recognize in sections stained with hematoxylin and eosin; immunostaining enables their exact identification. At the ultrastructural level, neuroendocrine cells contain cytoplasmic membrane-bound dense-cored secretory granules (diameter >80 nm) and may also contain small clear vesicles (diameter 40–80 nm) that correspond to the synaptic vesicles of neurons.
Occasionally, GI carcinoids occur in association with inherited syndromes, such as MEN1 and NF1.[13,14,15]
MEN1 is caused by alterations of the MEN1 gene located at chromosomal region 11q13. (Refer to the PDQ summary on Genetics of Medullary Thyroid Cancer for more information.) Most carcinoids associated with MEN1 appear to be of foregut origin. NF1 is an autosomal dominant genetic disorder caused by alteration of the NF1 gene at chromosome 17q11. Carcinoids in patients with NF1 appear to arise primarily in the periampullary region.[5,17,18]
In sporadic GI carcinoids, numerous chromosomal imbalances have been found by comparative genome hybridization analysis. Gains involving chromosomes 5, 14, 17 (especially 17q), and 19 and losses involving chromosomes 11 (especially 11q) and 18 appear to be the most common.[19,20]
The most frequently reported mutated gene in GI carcinoids is β-catenin (CTNNB1). In one study, β-catenin exon 3 mutations were found in 27 (37.5%) of 72 cases.
However, no consistent genetic markers for GI carcinoid prognosis have yet been identified. (Refer to the Cellular and Pathologic Classification of Gastrointestinal Carcinoid Tumors section of this summary for more information.)
Carcinoid syndrome, which occurs in fewer than 20% of patients with carcinoid tumors, is caused by the release of metabolically undegraded vasoactive amines into the systemic circulation. It is associated with flushing, abdominal pain and diarrhea, bronchoconstriction, and carcinoid heart disease.[22,23] Because vasoactive amines are efficiently metabolized by the liver, carcinoid syndrome rarely occurs in the absence of hepatic metastases. Exceptions include circumstances in which venous blood draining from a tumor enters directly into the systemic circulation (e.g., primary pulmonary or ovarian carcinoids, pelvic or retroperitoneal involvement by metastatic or locally invasive small bowel carcinoids, or extensive bone metastases).