S6317 Poorly Differentiated Adenocarcinoma With Neuroendocrine Differentiation of the Esophagogastric Junction: A Rare Case With Diagnostic and Management Challenges

Introduction: Cancers of the esophagogastric junction (EGJ) present diagnostic and therapeutic challenges due to their complex anatomical location and variable histology. Poorly differentiated adenocarcinoma with neuroendocrine differentiation (PD-ADC-NED) is a rare and aggressive tumor subtype, often misdiagnosed unless IHC staining is done. These mixed tumors may resemble or overlap with MiNENs (Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms) and carry unique prognostic and management implications, particularly in elderly patients. Case Description/Methods: A 92-year-old Asian man presents for evaluation of dysphagia, abdominal distention, and melena. Laboratory results were compatible with anemia HB 7.4 and an elevated carcinoembryonic antigen 45.1. Cross-sectional imaging was performed, showing multiple hepatic masses highly suspicious for metastatic disease and positive retroperitoneal lymphadenopathy. Esophagogastroduodenoscopy (EGD) revealed a large 5 cm mass at cardia with biopsies confirming poorly differentiated adenocarcinoma. Further immunohistochemistry (IHC) analysis demonstrated positive staining for synaptophysin, AE1/AE3, CDx2, p53, indicating neuroendocrine differentiation; but negative staining for chromogranin, S100 and CD56. The Ki-67 proliferation index exceeded 70%, consistent with a high-grade tumor. Additionally a strongly positive IHC was found for MLH1, PMS2 and MSH6 in 100% cells at the cardia area. Given the patient’s advanced age, a multidisciplinary team recommended supportive care focused on chemotherapy and symptom control. Discussion: Existing literature indicates that adenocarcinoma and neuroendocrine tumors require markedly different treatment approaches. Therefore, therapy should be tailored based on the predominant and most biologically aggressive component. PD-ADC-NED of the EGJ is rare and often underrecognized; its dual histology introduces diagnostic complexity and necessitates a tailored management strategy. Given its aggressive behavior and the lack of standardized guidelines, a multidisciplinary approach is essential—balancing therapeutic efficacy with patient age, performance status, and personal treatment preferences. This case contributes to the limited but growing body of literature on EGJ tumors with neuroendocrine features. It underscores the urgent need for further research into standardized diagnostic criteria and therapeutic guidelines for PD-ADC-NED.