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GROSS PATHOLOGY: Glucagonomas are usually solitary, well-circumscribed, large solid tumors with an average size of 5 to 10 cms (range 0.5 to 35 cm). Rare cases may be cystic or have infiltrative appearance. The most common location is the tail of pancreas.

In glucagon cell hyperplasia and neoplasia, there is no large solitary mass, but instead there is diffuse involvement of pancreas by variably-sized whitish-grey nodules.

MICROSCOPIC FEATURES: Histologic features of glucagonomas are similar to and indistinguishable from other PanNETs. They are almost always well-differentiated and composed of uniform cells arranged in densely packed anastomosing trabeculae separated by scant fibrovascular stroma. Some cases have abundant sclerotic stroma which may have areas of calcification (see next three images).

Even though most cases are malignant, mitotic activity and nuclear atypia are not common and do not appear to have a bearing on the prognosis. There are no poorly-differentiated glucagonomas; however, Grade 3 tumors have been described.

In glucagon cell hyperplasia and neoplasia, there are normal pancreatic islets, hypertrophic islets with glucagon cell hyperplasia, and glucagon microadenomas. Some cases contain one dominant tumor nodule amongst many microadenomas. Stromal calcification may be present.

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