Abstract
BACKGROUND: Gastric neuroendocrine tumors (carcinoid) associated with Zollinger Ellison Syndrome (ZES) induced hypergastrinemia in Multiple Endocrine Neoplasia type 1 (MEN1) occur in 15-50% of patients and are generally thought to be benign. Here we present a case of metastatic grade 3 gastric neuroendocrine tumor in MEN1. CASE: A 41-year male with history of MEN1 syndrome manifested by hyperparathyroidism, pancreatic neuroendocrine tumors, and Zollinger-Ellison Syndrome had been followed for 10 years. The patient had undergone yearly surveillance including CT, MRI, upper GI endoscopy (EGD) and (68)Ga-DOTATATE, which had identified multiple small foci in the pancreas and duodenum. However, only MRI revealed a T2 hypointense 2.6 cm mildly enhancing mass along the lesser curvature of the stomach that was not visible on CT, MRI, EGD or (68)Ga-DOTATATE within the 2 years prior. Gastrin levels remained <500 pg/mL during this time. EGD within 3 months prior to diagnosis demonstrated near complete suppression of acid (on omeprazole 120mg BID) confirmed with an acid output of 0 mEq/hr and no visible masses within the enlarged gastric folds. A follow-up (68)Ga-DOTATATE scan identified an intraluminal mass on the medial aspect of the gastric wall (17.55 SUV). On review, the tumor was not able to be visualized on prior scans due to the diffuse ZES-induced hypertrophic gastric mucosa and poorly distended stomach. In addition, (18)F-FDG-PET/CT scan demonstrated a faint but discrete photopenic defect associated with known mass in the gastric wall. The patient underwent surgical resection of a 3.5cm mass. Pathology demonstrated strong and diffusely positive synaptophysin and chromogranin A with Ki-67 labelling index (MIB-1) >20% and mitotic count >20 per 10 high powered fields. At the time of diagnosis, this lesion was histologically classified as well to moderately differentiated, high grade neuroendocrine carcinoma (Grade 3), large cell type. Loss of heterozygosity for the MEN1 gene at 11q13 was confirmed in the tumor. Monitoring with serial scans demonstrated right hepatic lobe metastasis by 1-year post-surgery. CONCLUSION: Previous reports of MEN1/ZES gastric carcinoid are associated with high gastrin levels, long disease duration, and are typically grade 1 or 2[i]. Special attention to identification of gastric mucosal nodules with well-controlled ZES is required as these lesions may rarely become malignant. Endnotes (i) Berna MJ, et al. A prospective study of gastric carcinoids and enterochromaffin-like cell changes in multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: identification of risk factors. JCEM. 2008; 93(5):1582-91.