Mixed neuroendocrine-non-neuroendocrine neoplasms of the digestive system: A mini-review

Figure 1 Classification of mixed neuroendocrine neoplasms. Mixed neuroendocrine-non-neuroendocrine neoplasms are specific mixed neuroendocrine tumors, which show an intimate mixture of neuroendocrine and non-neuroendocrine cells and are both derived from a common precursor cell. MiNEN: Mixed neuroendocrine-non-neuroendocrine neoplasms.

Figure 2 Conceptual framework for mixed neuroendocrine-non-neuroendocrine neoplasm of the digestive system. The tumor must include one neuroendocrine component and one non-neuroendocrine component. In the digestive system both components must have metastatic potential, excluding benign non-neuroendocrine neoplasms such as adenomas or squamous papillomas. NET: Neuroendocrine tumors; NEC: Neuroendocrine carcinomas.

Figure 3 Evolution of the terminology of mixed neuroendocrine-non-neuroendocrine neoplasm. The terminology has been broadened to include other non-neuroendocrine epithelial components beyond adenocarcinoma as well as including indolent or benign tumors such as neuroendocrine tumors. NE: Neuroendocrine; NEC: Neuroendocrine carcinoma; NET: Neuroendocrine tumor; MEEC: Mixed exocrine-endocrine carcinoma; MANEC: Mixed adenoneuroendocrine carcinoma; MiNEN: Mixed neuroendocrine-non-neuroendocrine neoplasm.

Figure 4 Histopathology of a mixed neuroendocrine-non-neuroendocrine neoplasm of colon. A: Hematoxylin and eosin (H&E) stain of mixed neuroendocrine-non-neuroendocrine neoplasm. On the right side is a well-differentiated invasive adenocarcinoma. On the left side is a poorly differentiated neuroendocrine carcinoma (20 ×, H&E); B: The adenocarcinoma component is positive for cytokeratin 20, but the neuroendocrine component is negative (20 ×); C: Positive synaptophysin staining in the neuroendocrine component but negative staining in the adenocarcinoma component (20 ×); D: Positive CDX2 staining in both adenocarcinoma and neuroendocrine carcinoma components (20 ×); E: Merging area of adenocarcinoma and neuroendocrine carcinoma components (20 ×); F: Positive synaptophysin staining of neuroendocrine cells in the merged area (20 ×).

Figure 5 Sample pathology report. MiNEN: Mixed neuroendocrine-non-neuroendocrine neoplasm.