Dual Biological Aggressiveness in Gastric MiNEN With Squamous Differentiation: A Case of Rapid Postoperative Peritoneal Dissemination

BACKGROUND/AIM: Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare epithelial malignancies characterized by the coexistence of neuroendocrine and non-neuroendocrine components, each accounting for at least 30% of the tumor. Gastric MiNENs with squamous differentiation are extremely rare. Herein, we report a rare case of gastric MiNEN with focal squamous differentiation, highlighting its aggressive clinical course, early peritoneal dissemination within three months after curative resection, and pathological heterogeneity. CASE REPORT: An 89-year-old man presented with melena and dysphagia. Computed tomography and upper gastrointestinal endoscopy revealed an advanced tumor in the gastric cardia, and biopsy revealed poorly differentiated adenocarcinoma. The patient underwent laparoscopic proximal gastrectomy with lymphadenectomy. Histopathological examination revealed that the tumor was composed of a high-grade neuroendocrine carcinoma and an adenocarcinoma, including poorly differentiated and signet-ring cell carcinoma components. The Ki-67 labeling index exceeded 90% in hotspot areas. Focal squamous differentiation, suggested by p40 positivity, accounted for approximately 5% of the tumor. Despite curative-intent surgery, the patient showed early postoperative recurrence with malignant ascites and peritoneal dissemination within approximately three months after surgery. Systemic chemotherapy was not administered due to the patient's advanced age and limited performance status. Therefore, the best supportive care was provided. CONCLUSION: This case highlights the heterogeneity of the components and metastatic patterns of gastric MiNENs with focal squamous differentiation. The clinical features of this case suggest that both high-grade neuroendocrine carcinoma and biologically aggressive adenocarcinoma may contribute to early recurrence of gastric MiNENs.