Primary Hepatic Neuroendocrine Tumors: A Stepwise Decision-Making Framework for Diagnosis and Surgical Management

Primary hepatic neuroendocrine tumors (PHNETs) are exceptionally rare, posing significant challenges in diagnosis and management. To address these challenges, this study establishes an actionable, surgeon-facing decision framework that transforms clinical evidence into a stepwise management algorithm. By synthesizing evidence from the Surveillance, Epidemiology, and End Results (SEER) program (n = 446) and clinical series, we propose a structured pathway that explicitly links diagnostic confirmation, biological characteristics, and therapeutic strategy. The framework first necessitates the definitive exclusion of extrahepatic primary lesions through functional imaging (eg, PET-CT) and origin-specific markers to confirm the diagnosis. Subsequent operative decision-making is guided by biological assessment; higher tumor grades (G3: HR 2.94; G4: HR 3.04) are strong independent predictors of poorer survival, warranting a shift toward systemic control for high-grade disease. For localized disease, surgical resection remains the cornerstone of management, offering 5-year survival rates of 60-80%, whereas liver transplantation is prioritized as a viable curative strategy for unresectable, liver-confined G1/G2 tumors (5-year survival 70-80%). In advanced or multifocal stages, locoregional approaches provide effective palliation. This structured decision framework enables practicing surgeons to determine the optimal intervention-whether resection, transplantation, or palliation-based on individualized tumor grade, burden, and distribution, thereby optimizing long-term outcomes for this rare malignancy.