Glucagon expression in cystic pancreatic neuroendocrine neoplasms: an immunohistochemical analysis

Pancreatic neuroendocrine neoplasms (P-NENs) are usually solid and only rarely cystic. Glucagon expression and the association with multiple endocrine neoplasia type 1 (MEN1) seem to be common in cystic P-NENs. In this study, we analyzed 404 P-NENs to gain information about the relative frequency of grossly cystic P-NENs and their association with glucagon production by the tumor cells. Three hundred forty-six solitary P-NENs and 58 P-NENs (>1 cm in diameter) from 35 patients with an MEN1 syndrome were studied. Immunostaining was performed for the four pancreatic hormones; 5.5% (19/346) of the sporadic P-NENs showed unilocular or multilocular cystic changes that were macroscopically detectable. Sixty-three percent of the solitary cystic P-NENs (versus 7% of the solitary non-cystic P-NENs) expressed predominantly glucagon. In MEN1-associated P-NENs, the relative frequency of cystic tumors was 10.3%, and all of them expressed glucagon. None of the glucagon-positive cystic P-NENs were associated with a glucagonoma syndrome. Solitary non-MEN1-associated and MEN1-associated cystic P-NENs are predominantly non-syndromic glucagon-expressing tumors. However, cystic insulinomas may also occur. Cyst formation seems to be related to hormone production.