Mixed Neuroendocrine-Non-Neuroendocrine Carcinoma (MiNEN) in Gallbladder: A Rare Case Report with Successful Neoadjuvant Therapy

Abstract

Introduction: Mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs) of the gallbladder are exceptionally rare and diagnostically challenging tumors characterized by the coexistence of both neuroendocrine and non-neuroendocrine components, each comprising at least 30% of the tumor. Their clinical presentation often mimics benign gallbladder conditions, leading to delayed diagnosis and poor prognosis. This report aims to highlight a rare case of gallbladder MiNEN and review its diagnostic, therapeutic, and pathological features. Case Report: A 54-year-old male presented with upper abdominal discomfort and intermittent vomiting. Imaging revealed a hypodense gallbladder mass infiltrating liver segments 4B and 5. PET-CT confirmed metabolic activity consistent with malignancy. Biopsy showed a tumor composed of 20% moderately differentiated adenocarcinoma (CK7, CK19, AE1/AE3 positive) and 80% high-grade small cell neuroendocrine carcinoma (chromogranin, synaptophysin positive) with a Ki-67 index >70%. Following four cycles of neoadjuvant cisplatin and etoposide chemotherapy, imaging showed marked tumor reduction and complete metabolic response. The patient subsequently underwent radical cholecystectomy with liver wedge resection and lymphadenectomy. Final pathology revealed minimal residual adenocarcinoma and no residual neuroendocrine carcinoma. Surgical margins and lymph nodes were free of disease (ypT3N0). Discussion: Gallbladder MiNENs are rare, often presenting with non-specific symptoms. Accurate preoperative diagnosis remains difficult, with histopathology and immunohistochemistry being essential. The neuroendocrine component often dictates tumor aggressiveness and response to therapy. In this case, neoadjuvant chemotherapy achieved tumor downstaging and enabled complete surgical resection. The negative TTF-1 and CDX2 helped confirm the primary biliary origin. Radical resection remains the mainstay of treatment, while the role of chemotherapy and somatostatin analogues continues to evolve. Conclusion: This case highlights the diagnostic complexity and therapeutic potential in managing gallbladder MiNENs. Early multimodal treatment, including neoadjuvant chemotherapy and radical surgery, may offer favorable outcomes. Greater clinical awareness and reporting of such cases are essential to develop standardized diagnostic and treatment protocols.