Recurrent gastric amphicrine tumor with neuroendocrine and pancreatic acinar cell differentiation and somatic MEN1 inactivation arisen during immunotherapy

Amphicrine neoplasms (ANs) are poorly understood epithelial malignancies composed of cells with co-existing exocrine-neuroendocrine features. Here, we report a recurrent mucin-producing gastric amphicrine tumor co-expressing neuroendocrine (chromogranin-A, synaptophysin, and CD56) and pancreatic acinar cell (BCL10 and trypsin) markers, arisen in a 64-year-old woman during adjuvant immunotherapy for melanoma. Ki-67 was < 2%. The gastric background context was atrophic gastritis. Next-generation sequencing showed MEN1 mutation (p.P71fs*42) coupled with loss of heterozygosity. The key lessons were as follows: (1) gastric ANs can show the co-existence of exocrine mucin-producing elements with neuroendocrine and pancreatic acinar differentiation; (2) they may represent a new entity arising in the context of atrophic gastritis and during immunotherapy; (3) they should be considered in the diagnostic workup of gastric neuroendocrine tumors; and (4) their molecular profile can show striking similarities with well-differentiated neuroendocrine tumors. These findings may be of help to improve the knowledge and the biological taxonomy of ANs.