Mixed Adenoneuroendocrine Carcinomas (MANECs) of the Gastrointestinal Tract: An Update

Abstract

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 of the gut. It is now well known that there is a wide spectrum of combinations of exocrine and neuroendocrine components, ranging from adenomas or carcinomas with interspersed neuroendocrine cells at one extreme to classical neuroendocrine tumors with a focal exocrine component at the other. In addition, both exocrine and neuroendocrine components can have different morphological features ranging, for the former, from adenomas to adenocarcinomas with different degrees of differentiation and, for the latter, from well differentiated to poorly differentiated neuroendocrine tumors. However, although this range of combinations of neuroendocrine and exocrine components is frequently observed in routine practice, mixed exocrine-neuroendocrine carcinomas, now renamed as mixed adenoneuroendocrine carcinomas (MANECs), are rare; these are, by definition, neoplasms in which each component represents at least 30% of the lesion. Gastrointestinal MANECs can be stratified in different prognostic categories according to the grade of malignancy of each component. The present paper is an overview of the main clinicopathological, morphological, immunohistochemical and molecular features of this specific rare tumor type.

Mixed adenoneuroendocrine carcinoma of the gastric stump following Billroth II gastrectomy: case report and review of the literature

“…This subtype often involves the whole stomach with a pattern of linitis plastica. 6,9,10 There is no optimal management strategy to date, because of the rarity of this pathological condition. 6 The most aggressive component should be taken into account when treatment options are considered.…”

“…6 A wide spectrum of possible combinations of exocrine and neuroendocrine components has been recognized, ranging from adenomas or carcinomas with interspersed neuroendocrine cells to typical NET with a focal exocrine component. 6,7 Both the exocrine and the neuroendocrine components may present different morphological characteristics. For the former, these range from adenomas to adenocarcinomas with varying degrees of differentiation, while for the latter, these range from well to poorly differentiated NET.…”

“…In the stomach, their distribution is equal in the antrum and in the body. 6 This group also includes poorly cohesive neuroendocrine carcinoma, in which there are noncohesive signet ring cells mixed with neuroendocrine cells. This subtype often involves the whole stomach with a pattern of linitis plastica.…”

“…Mixed exocrine-neuroendocrine neoplasms can be grouped into different prognostic categories according to the grade of malignancy of each component. 6,7 They are classified as follows: There are approximately 60 reported cases in the literature, throughout the gastrointestinal tract. They are more prevalent in men in their fifth to sixth decades of life.…”

Multiple neuro-endocrine tumours complicating chronic atrophic gastritis: the cloak that hides the dagger

“…These tumours, known as mixed adeno-neuroendocrine carcinomas (MANECs), tend to behave according to their epithelial component and are likely to be more aggressive neoplasms than pure neuroendocrine tumours arising on a basis of CAG. Nevertheless biopsies may miss one or other of the components and thus may not be reflective of the behaviour of such tumours [12,13] . It should also be remembered that CAG itself also predisposes to pure epithelial tumours, namely adenomas and adenocarcinomas, in the stomach and the natural history and treatment of the latter will be very different to that of small neuro-endocrine tumours of the stomach [14][15][16] .…”