Pancreatic neuroendocrine tumors (PNETs) Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms with an incidence of 1 per 100,000 individuals per year and comprising just 1-2% of all pancreatic tumors (170). Pancreatic neuroendocrine tumors can present at any age but are most common during the 4th to 6th decades of life with no sex predilection (170). Although most tumors are sporadic there is an association with hereditary endocrinopathies such as multiple endocrine neoplasia type I (MEN I), von Hippel-Lindau syndrome, neurofibromatosis and tuberous sclerosis. PNETs can be broadly divided into functional and nonfunctional tumors. Functional neuroendocrine

tumors Inhibitors,research,lifescience,medical are tumors which produce a variety of clinical syndromes due to an excess in hormones and include insulinoma, gastrinoma, glucagonoma, VIPoma, and somatostatinoma (171). The non-functional PNETs may also produce hormones but generally do not have symptoms due to the hormone production. These Inhibitors,research,lifescience,medical tumors are classified according to the WHO classification into well differentiated endocrine tumor, well differentiated endocrine carcinoma and poorly differentiated endocrine carcinoma based on size, mitotic count, Ki-67 proliferation index, angioinvasion and metastasis. PNETs are diffusely positive for synaptophysin consistently while chromogranin A

may show Inhibitors,research,lifescience,medical a more focal ABT-888 supplier staining pattern of variable intensity (170). They also express CD56, CD57, PDG 9.5 and NSE (172,173), as well a CK8 and 18. In differentiating PNETs from neuroendocrine tumors from other primary sites, CDX-2 Inhibitors,research,lifescience,medical may also be helpful as it has been reported to be positive in 20-30% of PNET cases (83,84). Other markers shown to be positive in pancreatic endocrine tumors include trypsin, chymotrypsin and lipase (174,175). Pancreatoblastoma Pancreatoblastoma is the most common pancreatic neoplasm of childhood. Most cases occur in children less than 10 years of age (176), and there is a slight male predominance and association with

Inhibitors,research,lifescience,medical Beckwith-Weidemann syndrome (177). These tumors are generally large, and may arise in either the head or the tail of the pancreas as well-circumscribed and lobulated masses. Histologically, the tumor has a lobular appearance with well-defined islands of small epithelial new cells separated by fibrous bands with a geographic pattern of lighter and darker staining cells due to the different cell types present. The tumor cells in the darker staining areas are small with centrally placed nuclei and prominent nucleoli with scant cytoplasm, while cells in the lighter areas have abundant eosinophilic cytoplasm and may be spindled in shape with a whorling pattern. The presence of occasional squamoid nests is characteristic for this lesion (178).