The grey zone between pure (neuro)endocrine and non-(neuro)endocrine tumours: a comment on concepts and classification of mixed exocrine–endocrine neoplasms

Abstract

Terms such as "mixed endocrine-exocrine carcinoma" (MEEC) and "adenocarcinoma with neuroendocrine (NE) differentiation" (ADC-NE) identify tumours belonging to the spectrum of neoplasms with divergent exocrine and (neuro)endocrine differentiation. These tumours display variable quantitative extent of the two components, potentially ranging from 1 to 99%, and variable structural patterns, ranging from single scattered NE cells to a well-defined NE tumour cell population organized in organoid, trabecular or solid growth patterns. In the present report, the grey zone of tumours/carcinomas with mixed NE and non-NE features is explored for various organs. From a practical point of view, MEECs differ from carcinomas with focal NE differentiation by (1) the extension of each component (more than 30%) and (2) the structural pattern of the NE component, either organoid for well-differentiated or solid/diffuse for poorly differentiated cases. In MEECs, the most aggressive cell population drives the clinical behaviour. Conversely, ADC-NE generally do not show a different clinical outcome, compared to the corresponding conventional forms, except for prostatic adenocarcinoma, in which NE cells are a negative prognostic factor. The recognition of MEECs may be of relevance for a targeted therapeutic strategy, foreseeing the use of biotherapies similar to those proposed for pure NE tumours.

Enteroendocrine precursors differentiate independently of Wnt and form serotonin expressing adenomas in response to active β-catenin

“…In the present work, the absence of serotonin-expressing neoplasms in the body of the stomach, a frequent site for the occurrence of neuroendocrine tumors in rodents and humans, was not surprising, because most enteroendocrine cells in this region of the stomach do not arise from Ngn3 ϩ cells (12). Although the tumors reported here show some similarity to carcinoids, many tumor cells did not stain for NE markers and may be related to ''mixed exocrine-endocrine carcinoma'' (MEEC), which contain significant endocrine and nonendocrine components (16).…”

Mixed Exocrine-Neuroendocrine Carcinoma of the Nasal Cavity: Clinico-Pathologic and Molecular Study of a Case and Review of the Literature

“…In the last 40 years, the systematic application of immunohistochemical techniques to the study of tumors has led to the recognition that neuroendocrine cells occur rather frequently in exocrine neoplasms [23][24][25] and, especially, in adenocarcinomas of the digestive system [7,26,27]. It is now well known that there is a wide spectrum of combination of exocrine and neuroendocrine components, ranging from adenomas or carcinomas with interspersed neuroendocrine cells at one extreme to classical neuroendocrine tumors with focal exocrine component at the other [7,26].…”

“…It is now well known that there is a wide spectrum of combination of exocrine and neuroendocrine components, ranging from adenomas or carcinomas with interspersed neuroendocrine cells at one extreme to classical neuroendocrine tumors with focal exocrine component at the other [7,26]. In addition, both exocrine and neuroendocrine components can show different morphological features ranging, for the former, from adenoma to adenocarcinoma with different degrees of differentiation and, for the latter, from well differentiated to poorly differentiated neuroendocrine tumors [7].…”

Composite neuroendocrine and adenomatous carcinoma of the papilla of Vater

“…At present 14 terms are used to define tumors with mixed exocrine-endocrine features. Volante et al [3] proposed classification based on the extension of each component and structural features of the NE component. Three separate patterns can be distinguished i.e.…”