The antral mucosa as a new site for endocrine tumors in multiple endocrineneoplasia type 1 and Zollinger-Ellison syndromes

Carcinoid tumors were identified in the antro-pyloric mucosa of four patien ts with multiple endocrine neoplasia type 1 (MEN-1)/Zollinger-Ellison syndr ome, accounting for 8.7% of 46 patients with this condition examined by end oscopy and histology. In contrast, no tumors were found in the antral biops ies from 124 cases of sporadic Zollinger-Ellison syndrome (P < 0.001), indi cating a prominent role for the MEN-1 gene defects in tumor development. Im munohistochemically the tumors did not express the hormones produced by ant ral endocrine cells (gastrin, somatostatin, serotonin). In contrast, two of them were diffusely immunoreactive for the isoform 2 of the vesicular mono amine transporter (VMAT-2), a marker specific for the gastric nonantral ent erochromaffin-like (ECL) cells. In one of these patients a second antral VM AT-2-positive carcinoid was seen 21 months after the first diagnosis. The o ther two antral carcinoids were unreactive for VMAT-2. Multiple ECL cell tu mors were found in the gastric body-fundus mucosa of the two patients with VMAT-2-positive, but not in those with VMAT-2-negative, antral carcinoids. In one case, the former tumors were diagnosed 22 months after the detection of the antral tumor. We conclude that the antral mucosa is an additional t issue that may harbor endocrine tumors in MEN-1 syndrome. These tumors did not express the phenotype of normal antral endocrine cells and, in at least two cases, were identified as ectopic ECL cell carcinoids.