Multidisciplinary treatment with durvalumab-containing regimens for mixed neuroendocrine-non-neuroendocrine neoplasm of the extrahepatic bile duct.

Abstract

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare tumors comprising both neuroendocrine and non-neuroendocrine components, with each component constituting at least 30% of the tumor. MiNEN of the extrahepatic bile duct is particularly uncommon and is often associated with a poor prognosis. We report the case of a 63-year-old male with jaundice, who was diagnosed with cholangiocarcinoma at the confluence of the cystic duct. Imaging and endoscopic cholangiography revealed perihilar-to-distal bile duct involvement, accompanied by bulky lymph node metastases. Endoscopic biliary drainage was performed, and biopsy revealed adenocarcinoma. The patient received four cycles of neoadjuvant chemotherapy with gemcitabine, cisplatin, and durvalumab. The tumor and lymph nodes decreased in size, enabling curative pancreatoduodenectomy. Pathological examination revealed adenocarcinoma with small-cell neuroendocrine components, confirming MiNEN. The therapeutic response was grade 2, and curative resection was achieved. Four months after surgery, the patient developed para-aortic lymph node recurrence, prompting chemotherapy resumption; however, he died 2 years after treatment initiation. MiNENs with neuroendocrine carcinoma components are associated with a poor prognosis. Despite the initial response to neoadjuvant chemotherapy and curative resection, early recurrence indicates tumor aggressiveness. Additional case reports and further research exploring optimal treatment strategies are required to improve outcomes.