[Gastrointestinal mixed adenoneuroendocrine carcinomas. An attempt at classification of mixed cancers]

Mixed adenoneuroendocrine carcinomas (MANECs) are a challenge for the diagnostics and the concept of a histogenetic tumor typing. They are classified into three malignant subgroups: high grade malignant MANECs combine an adenoma or adenocarcinoma with a small cell or large cell neuroendocrine carcinoma, intermediate grade malignant MANECs consist of a neuroendocrine tumor (NET grade 1 or 2), often a globlet cell carcinoid and a poorly differentiated adenocarcinoma or diffuse carcinoma of signet ring cell type. The prototype of a low grade malignant MANEC is the globlet cell carcinoid. Molecular analysis indicates a common clonal origin of the different components in MANECs. The prognosis is determined by the most aggressive tumor component. The pathogenesis of MANECs is apparently a sequence of increasing malignant transformation which leads either from an adenoma/adenocarcinoma to a small or large cell neuroendocrine carcinoma or from a neuroendocrine tumor (NET), often a globlet cell carcinoid to a poorly differentiated adenocarcinoma or a diffuse carcinoma of signet ring cell type.