Pancreatic Endocrine Neoplasms, Part 2

Most pancreatic endocrine neoplasms are non-syndromic, that is they do not produce a clinical syndrome caused by excess hormone production by the tumor. A growing number of these are asymptomatic, discovered when a patient is imaged for a different indication. When the patients do have symptoms, the symptoms typically include abdominal pain, nausea and vomiting, weight loss, or rarely jaundice (a yellowing of the skin caused by blockage of the bile duct). The diagnosis can often be suggested on CT scan, as most pancreatic endocrine neoplasms have a rich blood supply (they are hypervascular), and, as a result, they “enhance” when contrast is used in CT scanning.

The treatment of choice is usually surgical removal. When removed, most pancreatic endocrine neoplasms can be seen to be well-demarcated, soft tan to reddish masses. This appearance is very different from the more common pancreatic cancer (ductal adenocarcinoma) of the pancreas, which forms firm, sometimes rock-hard, white to yellow poorly-defined infiltrative masses.

Pancreatic endocrine neoplasms also differ from pancreatic cancers (ductal adenocarcinomas) of the pancreas under the microscope. Microscopically, the cells of pancreatic endocrine neoplasms form small nests and trabeculae (ribbons). The cells themselves are uniform, usually round, and they often have a round centrally placed nucleus. If there is any question about the diagnosis pathologists can run special stains, called immunohistochemistry, for markers which are typically present in pancreatic endocrine neoplasms, including synaptophysin and chromogranin.

Two features are used to determine the prognosis for a patient with a surgically resected pancreatic endocrine neoplasm. First is the mitotic rate, how fast the cells in the tumor are dividing. This can be determined by the pathologist simply by counted the number of cells in a microscopic slide that appear to be dividing. The other way that a mitotic rate can be determined is with a special stain, called a “Ki-67.” Tumors with really high mitotic rates are often called “endocrine carcinomas,” “small cell carcinoma,” or “large cell carcinoma.” The second prognostic indicator is the stage of the tumor- how big is the tumor (the T stage) has it spread to lymph nodes (the N stage) or to other organs (the M stage)?

The 5-year survival rate for patients with a non-syndromic pancreatic endocrine neoplasm is 65%, and the ten-year survival rate is 45%. These tumors, although not as aggressive as pancreatic cancer (ductal adenocarcinoma of the pancreas), are nonetheless fully malignant tumors. A great deal of effort has therefore gone into developing new chemotherapies to treat pancreatic endocrine neoplasms. While a detailed discussion of these is beyond my expertise, there are some exciting agents on the horizon such as the mTOR inhibitor everolimus (see Curr Opin Oncol. 2010 Jul;22(4):381-6. PMID: 20473165). A multi-disciplinary approach to the treatment of patients with a pancreatic endocrine neoplasm is often needed.