Aggressive Forms of Gastric Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type I

Abstract

In recent classifications of gastric endocrine tumors, tumors arising in patients with multiple endocrine neoplasia type 1 (MEN-1) are regarded to be regulated by the concomitant hypergastrinemia resulting from to pancreatic or, most commonly, duodenal gastrinomas and to have a benign behavior. In this article, we report on two cases of MEN-1 gastric neuroendocrine tumors having a fatal course. Case 1 was a young male with hyperparathyroidism and Zollinger-Ellison syndrome and with florid development of multiple gastric carcinoids and multiple duodenal gastrinomas. Metastases occurred in the liver, of exclusive gastric origin, in periduodenal lymph nodes, of exclusive duodenal origin, and in perigastric lymph nodes, of mixed origin. The patient died 48 months after diagnosis. Case 2 was an adult female patient with hyperparathyroidism, adrenocortical disorders, and gastric tumors but no hypergastrinemia. The patient died 3 months after tumor diagnosis. At autopsy, the stomach showed multiple benign carcinoids and two independent neuroendocrine carcinomas not reported before in MEN-1 and massively metastatizing to lymph nodes, liver, and peritoneum. Multiple islet cell tumors mostly producing pancreatic polypeptide were found, whereas gastrinomas were seen in neither the pancreas nor the duodenum. Allelic losses at the MEN-1 gene locus in chromosome 11q13, the mechanism responsible for tumor development in MEN-1 syndrome, were demonstrated in the carcinoid tumors of case 1 and in the neuroendocrine carcinoma of case 2. We conclude that gastric neuroendocrine tumors in patients with MEN-1 may have a poor outcome, they have the same genetic mechanism as MEN-1 tumors in other organs, and they may be independent of the trophic effect of hypergastrinemia.

Genetic alterations in poorly differentiated endocrine carcinomas of the gastrointestinal tract

“…14,38 Nonetheless, recent reports of frequent 18q LOH in midgut carcinoids indicate that a novel putative tumor suppressor gene (distinct from DCC or DPC4) that is located on 18q may play an important role in the pathogenesis of midgut endocrine tumors. 15,16 In an attempt to evaluate whether the pathogenesis of PDECs is more consistent with that of WDECs, as suggested by some studies, [5][6][7][8] or with that of classical nonendocrine adenocarcinomas (i.e., CRCs), as suggested by other reports, 3,4 we compared the gastric subset of PDECs with a series of gastric WDECs and also compared the colorectal subset of PDECs with a series of CRCs.…”

Classification and pathology of gastroenteropancreatic neuroendocrine neoplasms

“…Occasionally they harbour an adenocarcinoma component. Hormones cannot be demonstrated and there is no relationships to chronic atrophic gastritis, but in exceptional cases are associated with MEN1 (Bordi et al 1997). At the time of diagnosis most of the tumours are already in an advanced stage (tumour diameter more than 4 cm) and show extensive metastasis (Bordi et al 1997).…”

CONSENSUS: Guidelines for Diagnosis and Therapy of MEN Type 1 and Type 2

“…The tumors are usually multiple, smaller than 1.5 cm, and associated with proliferation of extratumoral ECL cells, from which the tumors (gastric carcinoids ϭ ECLomas) are presumed to originate (48). Compared with other MEN1-related tumors, little is known about their malignant potential (49). Foregut carcinoids in MEN1 rarely hypersecrete hormones.…”