Colocalization of pancreatic polypeptide and insulin in secretory granules of a pancreatic endocrine neoplasm.

A 45-year-old woman presented with clinical symptoms of hypoglycemia of 4 months duration. Laboratory testing confirmed hyperinsulinemia; mild hypercalcemia and hypergastrine-mia were also documented. At the time of operation, 3 pancreatic endocrine neoplasms were found, and a diagnosis of multiple endocrine neoplasia type I was made. Immunohistochem-istry and immunoelectron microscopy showed all the tumors to be plurihormonal, each containing three or more of the following: insulin, glucagon, somatostatin, pancreatic polypep-tide, gastrin, and serotonin. Electron microscopy of 2 tumors revealed numerous atypical granules. In 1 tumor, pancreatic polypeptide and insulin were colocalized in secretory granules by dual-staining immunoelectron microscopy. To our knowledge, this combination of hormones has not been described previously in pancreatic endocrine neoplasms and suggests that such neoplasms, like mature pancreatic endocrine cells, may originate from pluripotential common precursor cells.