Insulinoma

Insulinoma is defined as a neuroendocrine tumor associated with clinical symptoms and biological alterations due to hyperinsulinism. It is a rare tumor but is the most frequent of functioning neuroendocrine tumors of the pancreas. Most insulinomas are small, circumscribed, and well-differentiated neoplasms. Their histological grade is usually G1. Some of them are associated with amyloid deposits in the stroma: this aspect is suggestive but not pathognomonic. Most, but not all, insulinomas express insulin and proinsulin detectable by immunohistochemistry. Insulinoma is the most frequent pancreatic tumor observed in the MEN-1 syndrome; some rare cases have also been described in neurofibromatosis type 1 and in tuberous sclerosis. In contrast, sporadic insulinomas exceptionally harbor mutations in MEN1 gene or in other genes known to be mutated in sporadic nonfunctioning pancreatic neuroendocrine tumors. Recently, a recurrent mutation in YY1 gene has been described in a significant proportion of sporadic insulinomas.