Advances in the cytologic diagnosis of gastroenteropancreatic neuroendocrine neoplasms.

Two-thirds of neuroendocrine neoplasms arising in the human body originate from the gastrointestinal system or pancreas. Gastroenteropancreatic neuroendocrine neoplasms are heterogeneous, comprising both well differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The clinical presentation, molecular characteristics, and behavior are distinct for NETs and NECs. Fine-needle aspiration is an important modality for the primary diagnosis and staging of these neoplasms and can provide information of prognostic and therapeutic significance. Our evolving understanding of neuroendocrine neoplasm biology has led to several iterations of classification. In this review, new concepts and issues most relevant to cytology diagnosis of gastroenteropancreatic neuroendocrine neoplasms are discussed, such as newer detection methods that aid in diagnosis and staging, recent changes in World Health Organization classification, practical issues related to grading these neoplasms on cytology, guidelines for diagnostic reporting, and panels of immunohistochemical stains for the diagnosis of metastasis. The current understanding of genetic and epigenetic events related to tumor development and potential applications for cytology also are presented as they relate to prognostication and recent therapeutic advances.