Response of immunotherapy and targeted therapy in mixed neuroendocrine non-neuroendocrine neoplasms of the gallbladder: a case report

Neuroendocrine neoplasms (NENs) of the gallbladder (GB) are rare, accounting for approximately 0.5% of all NENs. Neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare two-part tumor with a poor prognosis. Currently, there is no clear treatment strategy or management guideline. A 77-year-old male was admitted to Xuanwu Hospital after a physical examination revealed ten days of thickening of the gallbladder floor detected during a physical examination. Laboratory examinations raised suspicion of malignant tumors, and subsequent pathological diagnosis confirmed MiNENs of the gallbladder (GB-MiNENs) following surgical resection. Eleven months after discharge, follow-up CT revealed multiple intrahepatic masses indicating liver metastasis. After that, the patient initiated systemic therapy with sintilimab with surufatinib and achieved stable disease. However, treatment was interrupted because of COVID-19 infection after three cycles. A reexamination via abdominal CT revealed an increase in liver lesion size. Therefore, treatment with sintilimab resumed accordingly, and treatment with surufatinib resumed once the infection improved. After seven cycles of treatment, the patient was readmitted due to heart failure caused by COVID-19 infection and unfortunately died seven months later following liver metastasis treatment completion. The exploratory treatment of this case provides some reference value for the treatment of GB-MiNEN patients who have metastasized to the liver after laparoscopic radical cholecystectomy.