Insulinoma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Parminder Dhingra, M.D. [2]

Overview

On microscopic histopathological analysis, solid or gyriform patterns, usually without glands are characteristic findings of insulinoma. Insulinoma may occur as part of other genetic syndromes such as multiple endocrine neoplasia type 1 and von Hippel-Lindau syndrome.

Pathophysiology

An insulinoma is a tumor of the pancreas that is derived from beta cells and secretes insulin. It is a rare form of a neuroendocrine tumor. Most insulinomas are benign in that they grow exclusively at their origin within the pancreas, but a minority metastasize. Insulinomas are one of the functional pancreatic neuroendocrine tumor ("functional" because it increases production of insulin). Beta cells secrete insulin in response to increases in blood glucose. The resulting increase in insulin acts to lower blood glucose back to normal levels at which point further secretion of insulin is stopped. In contrast, the secretion of insulin by insulinomas is not properly regulated by glucose and the tumors will continue to secrete insulin causing glucose levels to fall further than normal.

Genetics

Insulinoma can occur in association with inherited syndrome, such as multiple endocrine neoplasia type 1, von Hippel-Lindau syndrome or sporadic.^[1]
Multiple endocrine neoplasia type 1 is an autosomal dominant disorder caused by alterations of the MEN1 gene located at chromosomal region 11q13.

Microscopic Pathology

On microscopic histopathological analysis characteristic findings of insulinoma are:

Solid or gyriform patterns, usually without glands

Histopathology of pancreatic endocrine tumor (insulinoma). H&E stain^[2]
Histopathology of pancreatic endocrine tumor (insulinoma)^[2]
Histopathology of pancreatic endocrine tumor (insulinoma). Chromogranin A immunostain^[2]
Histopathology of pancreatic endocrine tumor (insulinoma). Insulin immunostain^[2]