Goblet cell carcinoids and other mixed neuroendocrine/nonneuroendocrine neoplasms

Within the spectrum of neuroendocrine tumors arising in different organs, intermediate and controversial entities exist displaying a coexistence of neuroendocrine and nonneuroendocrine cell populations, and that are grouped under terms such as 'goblet cell carcinoid', 'mixed endocrine-exocrine carcinoma', 'combined carcinomas', or 'adenocarcinoma with neuroendocrine differentiation'. These tumors may display variable amounts of the two components, potentially ranging from 1 to 99%, and variable structural patterns, ranging from single scattered neuroendocrine cells to a well-defined neuroendocrine tumor cell component organized in typical organoid, trabecular, or solid growth patterns. Although variably included in the site-specific World Health Organization classification schemes, clear definitions and diagnostic features are still missing, as well as a definite knowledge of their biological properties and histogenesis. In the present report, the main characteristics of tumors showing mixed neuroendocrine and nonneuroendocrine features will be described, using morphological patterns and site of origin as schematic guidelines. Moreover, molecular and clinical aspects, which might help to understand their possible histogenesis and biological behavior, will be reviewed.