Combined Neuroendocrine Carcinoma and Hepatocellular Carcinoma of the Liver: Systematic Literature Review Suggests Implementing Biological Characterization to Optimize Therapeutic Strategy

Background: Mixed neuroendocrine–non-neuroendocrine tumors (MINEN) of the liver are exceptionally rare, with limited data available regarding their clinical behavior, pathogenesis, and optimal management. The coexistence of hepatocellular carcinoma (HCC) and neuroendocrine carcinoma (NEC) within the liver presents diagnostic and therapeutic challenges. Methods: A systematic literature search was conducted on PubMed, identifying cases of primary mixed HCC and NEC in the liver. The search adhered to PRISMA guidelines, and relevant studies were critically analyzed. A total of 45 documented cases were reviewed, focusing on patient demographics, clinical characteristics, treatment strategies, and outcomes. Results: Most patients (90%) were male, with a median age of 66.5 years. Hepatitis B or C infection was present in 74% of cases, and liver cirrhosis was reported in 38%. The combined type was the most frequently observed histological pattern (65%). Treatment modalities varied, including transarterial chemoembolization (TACE), radiofrequency ablation (RFA), surgery, and systemic therapies. The median overall survival was 10 months, highlighting the aggressive nature of these tumors. Conclusions: Given the rarity and poor prognosis of hepatic MINEN tumors, multidisciplinary management is essential. Advanced molecular profiling may offer insights into tumor biology and potential therapeutic targets. Future research should explore novel systemic therapies, including immune checkpoint inhibitors, to improve patient outcomes.