Neuroendocrine Tumors

Abstract

Abstract: Neuroendocrine (NE) tumors include a morphologically and functionally diverse family of neoplasms that can arise in virtually all tissues and organs. Although early studies suggested a neural crest origin for all NE tumors, the term NE simply describes a shared phenotype notable for the expression of multiple genes encoding a wide spectrum of neural and NE traits. NE tumors can be subdivided into epithelial and neural types with both types expressing a set of common NE markers, including synaptophysin. Epithelial NE tumors are further defined on the basis of expression of cytokeratins (CK), with variable expression of neurofilaments (NF), while neural NE tumors, such as neuroblastomas and paragangliomas, are negative for CKs but are positive for NFs. Epithelial NE tumors exhibit a broad range of cytologic and histologic features, ranging from those that have a well-defined nesting or ribbonlike growth pattern with low mitotic rates to those that have a small- or large-cell morphology with high mitotic rates and diffuse growth patterns. There is general agreement that the generic term carcinoid as proposed in the 1980 World Health Organization classification has become increasingly more inappropriate to describe the full range of low- and intermediate-grade neoplasms with NE features. The value of the term NE, modified by the inclusion of the grade of the neoplasm, lies in the fact that it defines a particular phenotype that may respond to specific forms of targeted therapy. Additional studies, including gene expression profiling, will be essential for further classifying tumors with NE phenotypes and for elucidating their interrelationships.