Pancreatic
neuroendocrine tumors (
pNETs) are
neuroendocrine tumors primarily found in the pancreas and upper small intestine. There are ten different
pNETs: nine of these are associated with a specific functional syndrome, while one is not associated with a specific hormonal syndrome, and it is called non-functional. Up to 90% of
pNETs are classified as non-functional. Immunohistochemistry is essential to define the diagnosis. However, to have a correct and reliable diagnosis, the pathologist must have adequately collected and treated tissue samples, thus the surgeon himself should be aware of some fundamental notions about tissue collection and fixation. Although several common
biomarkers have been described to date,
Chromogranin A and
synaptophysin are currently considered the most specific immunohistochemical markers for NETs. Nearly 100% of
pNETs are positive for both
synaptophysin and
Chromogranin A. Therefore, CgA and
synaptophysin are effective for well-differentiated NETs but are less helpful in the diagnosis of poorly differentiated NECs, due to dedifferentiation, and then, degranulation of
tumor cells. The Neuronal Specific
Enolase (NSE) results to be an adequate marker in these cases. Considering the specific markers, many studies reported that endocrine
pancreatic neoplasms are able to produce many different
polypeptides and
amines. Through immunohistochemical techniques, it is possible to define the diagnosis of
pNET, which allows the clinicians to direct the patient to an effective therapeutic procedure. But to have a correct and reliable diagnosis, the tissue samples have to be adequately collected and treated.