Context: Although somewhat uncommon, neuroendocrine tumors of the gastrointestinal tract and pancreas have come under scrutiny in recent times. With advances in imaging techniques, more of these tumors are being removed and sent for pathologic evaluation. It is important for the diagnostic pathologist to be aware of recent developments in this field.
Objective: This overview focuses on nomenclature/terminology, classification, practical issues related to recent developments in immunohistochemical markers that aid diagnosis and may relate to prognosis, and molecular advances.
Data sources: Currently available literature and personal experience in the field of neuroendocrine pathology.
Conclusions: The preferred terminology is neuroendocrine/tumor/carcinoma and it is recommended that the World Health Organization classification be used, taking note of the site variations that may occur. A large number of immunohistochemical markers are available but a core panel that is relevant to the site should be used. Cytokeratin 19 positivity is an independent marker of aggressive behavior in pancreatic neuroendocrine tumors. Gastrointestinal neuroendocrine tumors arise via the CpG island methylator phenotype pathway, whereas their pancreatic counterparts arise as a result of chromosomal instability. The MEN1 gene is implicated in both syndromic and sporadic forms of these tumors.