Most NETs of the small and large intestines occur sporadically, while others may occur within the background of an inherited neoplasia syndrome such as multiple endocrine neoplasia type 1 (MEN1) or neurofibromatosis type 1 (NF1) (e.g., gastrin-producing G-cell tumors and somatostatin-producing D-cell tumors of the duodenum, respectively). Tumor multifocality is the rule within the background of neuroendocrine cell hyperplasia, but multifocality is found in approximately one-third of patients with small enterochromaffin cell tumors in the absence of proliferative or genetic factors; clonality studies suggest that most of these neoplasms are separate primary lesions.[10,11] Gastric carcinoids may be associated with chronic atrophic gastritis.
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 Endocrine and Neuroendocrine Neoplasias 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]