Microsatellite Instability-High, Malignant Insulinoma With Brain Metastasis

Insulinomas are the most common type of functional pancreatic neuroendocrine tumor. Although insulinomas usually are noninvasive or benign, 10% are deemed invasive or malignant. The pathologic mechanisms that lead to the malignant phenotype are not well elucidated. In this case report, we present a patient with stage 4 malignant insulinoma with metastasis to the liver, bone, and brain. Genetic analysis of the tumor showed that the tumor was mismatch-repair deficient and had a high rate of microsatellite instability. There was loss of MLH1- and PMS2-encoded protein expression, and MLH1 and MEN1 variants were identified. Notably, the liver metastasis showed considerable tumor heterogeneity (well differentiated) compared with the brain metastasis (poorly differentiated).