Mixed adenoma–well-differentiated neuroendocrine tumor of the major duodenal papilla: Case report with review of literature

Introduction: Mixed adenoma–well-differentiated neuroendocrine tumor (MANET) is a recently introduced tumor entity, composed of an adenoma and a well-differentiated neuroendocrine tumor. It occurs infrequently in the colorectum, is very rare in the duodenum, and no case arising from the major duodenal papilla has been reported to date. Case Report: We describe an extremely rare case of MANET arising from the major duodenal papilla in a woman in her 80s. The patient underwent endoscopic examination for abnormal liver function tests, which revealed a hypervascular, elevated lesion at the major duodenal papilla. Because ampullary carcinoma was suspected, subtotal stomach-preserving pancreaticoduodenectomy was performed. The 30 × 6 mm whitish tumor centered on the major papilla was histologically composed of three components: a pure adenomatous component, a pure neuroendocrine tumor component, and a mixed adenomatous-neuroendocrine component. The adenomatous component was predominantly high-grade, and the neuroendocrine component corresponded to grade 2. “Budding-off” and “ductuloinsular complex” patterns were frequently observed in the mixed component. Immunohistochemically, the neuroendocrine component was positive for serotonin and CDX2 in addition to neuroendocrine markers. Six months after surgery, the patient developed multiple metachronous liver metastases derived from the neuroendocrine component, and several metastatic foci were histologically diagnosed as grade 3 neuroendocrine tumor. Conclusion: Although rare, considering the possibility of MANET in the major duodenal papilla is essential to avoid misdiagnosis as neuroendocrine carcinoma or adenocarcinoma. In this paper, we summarize the clinicopathological features of MANET based on a review of literature and discuss issues requiring further investigation.