Pancreatic non-functioning neuroendocrine tumor and ,lynch syndrome: a new tumor association

Abstract

Background: Lynch Syndrome (LS) is a autosomal dominant inheritance caused by a mutation in one of the deoxyribonucleic acid mismatch repair genes. Mutations occur most frequently in the MLH1 and MSH2 genes, followed by MSH6 and then finally PMS2. Colorectal carcinoma (CRC) is the most commonly associated neoplasm. But other neoplasm had been associated: endometrium, gastric, ovarian, breast, small intestine, renal, skin, brain and pancreatic adenocarcinoma. However pancreatic neuroendocrine tumor (PNET), were suggested to be associated but with no confirmation to date. Methods: We present a 65 years old woman affected by LS. She had a CRC 20 year ago. Twelve years later had another one in the right colon. At age of 58 an endometrial cancer was resected. A genetic study was performed and discover a MLH1 MMR gene mutation. She had also a low grade ductal carcinoma of breast at the age of 63 with the same gene mutation. A gastroscopy found a duodenal adenocarcinoma. Results: A pancreaticoduodenectomy was performed. Histology reported a duodenal adenocarcinoma T1N0, two PNET, one G1 and another G2. IHC confirmed the lack of expression of MLH1 and PMS2 in all tumor except in the small PNET. Polymerase chain reaction showed instability only in CRC, duodenal and skin tumors. Conclusion: The association of pancreatic NE tumors and LS is now confirmed and its due to the mutation of the MLH1 and PMS2 nuclear proteins. A gastroscopy with duodenal study should be added in the follow-up of theses patients.