Multiple Endocrine Neoplasia Type 1 Associated with a New Mutation in Menin Gene and a Midgut Carcinoid Tumor: Report of a Case and Review of the Literature

Abstract

Purpose: Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant disorder that has a varied clinical presentation. Its classic features include hyperparathyroidism, pituitary adenomas and pancreatic neuroendocrine tumors. MEN-1 is typically only associated with foregut carcinoid tumors, such as those arising from the thymus, lung, stomach and duodenum. This vignette reports a rare case of a patient who had a classic presentation of MEN-1 and developed a metastatic carcinoid tumor of the ileum, a midgut tumor. This patient also was found to have an unpublished menin gene mutation. This patient had classic features of MEN-1: hyperparathyroidism, a pituitary adenoma and a pancreatic neuroendocrine tumor. He had been clinically well for three years after having a distal pancreatectomy and splenectomy for the pancreatic neuroendocrine tumor. Three years post-operatively, he experienced diarrhea, flushing and fatigue. Evaluation at our institution revealed a recurrent tumor in the remaining pancreas, a mass in the right lower quadrant and several small lesions in the liver. He underwent resection of the recurrent pancreatic tumor, ileal-mesenteric mass and liver lesions. The pathologic impression from positive immunostaining for serotonin and CDX2 in the ileal and liver tumors revealed that he had developed a primary midgut carcinoid tumor arising in the ileum with subsequent metastasis. Genetic testing revealed a new mutation of the MEN-1 gene -- S583P. This mutation involves a heterozygous cytosine to thymine point mutation in exon 10 of the menin gene. It has not been previously described in the literature. This case report describes an initial classic presentation of MEN-1, associated with a new MEN-1 mutation and a metastatic midgut carcinoid. Numerous MEN-1 gene mutations have been described, however, it is interesting to speculate whether this new mutation conferred an increased risk for developing the metastatic midgut carcinoid. Furthermore, this case report demonstrates that in a patient with MEN-1 and recurrent carcinoid symptoms, one can consider diagnosing a new tumor in an unlikely location.