S6460 Gastric MANET (Mixed Adenomas Well-Differentiated Neuroendocrine Tumor) or MiNEN (Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm)? A Dilemma

Introduction: Mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs) and mixed adenomas with well-differentiated neuroendocrine tumors (MANETs) are rare tumors containing both neuroendocrine (NE) and non-NE components. In MiNENs, the NE component may be a neuroendocrine tumor (NET) or carcinoma (NEC), and the non-NE component ranges from adenocarcinomas to benign lesions. The 2019 World Health Organization (WHO) classification redefined MiNENs to exclude combinations of NET with benign non-NE components, such as MANETs. We present a rare case of gastric tumor composed of tubular adenoma, gastric adenocarcinoma in situ, and a low-grade NET. Case Description/Methods: A 69-year-old woman presented with bloating and diarrhea 5 months after an outside esophagogastroduodenoscopy (EGD) revealed 2 gastric lesions, with biopsy showing tubular adenoma with low-grade dysplasia. Repeat EGD at our center identified an 11 mm pale, elevated, subepithelial lesion on the anterior wall of the upper gastric body. Histology showed intestinal-type adenoma with low- and high-grade dysplasia. Endoscopic ultrasound (EUS) revealed enlarged perigastric and peripancreatic lymph nodes, with biopsy confirming a well-differentiated grade 1 NET. Computed tomography (CT) of the abdomen and pelvis showed no evidence of distant metastasis. The patient underwent laparoscopic gastrectomy with D2 lymphadenectomy. Gross pathology revealed a 15 × 15 mm polypoid lesion on the lesser curvature. Histology confirmed a mixed tumor comprising NE and non-NE components, with 40% tubular adenoma exhibiting high-grade dysplasia, 10% gastric adenocarcinoma in situ, and 50% NET. Immunostaining of the NET component was positive for chromogranin A, synaptophysin, and CD56, with a Ki-67 index of 2.27%. The patient had no postoperative complications and remains in remission at 9-month follow-up. Discussion: MiNENs are aggressive tumors with poor prognosis and high recurrence, requiring intensive treatment, while MANETs are typically indolent and managed like pure adenomas. Distinguishing between them is critical. Our case does not meet World Health Organization criteria for MiNENs, which require both neuroendocrine (NE) and non-NE components to be invasive and ≥30% of tumor volume, nor does it align with MANETs due to atypical features such as the presence of adenocarcinoma in situ and rapid progression from low- to high-grade dysplasia. This highlights the need to refine the nomenclature and establish standardized management strategies for mixed tumors.