Goblet cell carcinoids and other mixed neuroendocrine/nonneuroendocrine neoplasms

Abstract

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.

Neuroendocrine Tumors of the Pancreas

“…Mixed neuroendocrine/non-neuroendocrine tumors have also been described, lending credence to this theory [48]. Nonetheless, ␤-cell turnover remains under intense investigation; however, conclusive data for mechanisms of adult ␤-cell regeneration (stem cells versus cell replication versus transdifferentiation) are still missing [49].…”

Digestive System Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms

“…They usually include a well-differentiated NET associated with an adenoma or adenocarcinoma component, with an intermediate grade of malignancy [4,6] . MiNEN with a PDNEC component are exceptional, like "pure" PDNEC from these primary sites.…”

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Towards a Standardized Approach to the Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors and Their Prognostic Stratification

“…Gastrointestinal and pancreatic adenocarcinomas with mixed differentiation present a special challenge in the classification [17]. In most of these neoplasms, the cells staining for synaptophysin and chromogranin A represent a minor component of the total tumor cell population.…”