Pancreatic neuroendocrine neoplasms: current paradigms and diagnostic challenges

Pancreatic neuroendocrine neoplasms (PanNENs) are broadly divided into well-differentiated pancreatic neuroendocrine tumors (PanNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). Grading is based on the mitotic count and Ki-67 proliferation index. PanNETs demonstrate typical neuroendocrine morphology, including nested and trabecular growth patterns, and "salt-and-pepper" coarse, clumped chromatin, whereas PanNECs can look like any poorly differentiated carcinoma. Differentiation of PanNETs from PanNECs and other hypercellular pancreatic neoplasms may sometimes be challenging but is crucial for patient management. Immunohistochemistry will demonstrate positivity for neuroendocrine markers. The advent of sequencing technology has elucidated critical signaling pathways potentially involved in the development of PanNENs, while also highlighting potential predispositions due to previously known and newly identified germline mutations.