Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Mar 22;17(7):1074.
doi: 10.3390/cancers17071074.

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

Daniela Sambataro  1   2 , Sandro Bellavia  3 , Paolo Di Mattia  2   4 , Danilo Centonze  4 , Carmela Emmanuele  3 , Annalisa Bonasera  1 , Giuseppe Caputo  1 , Andrea Maria Onofrio Quattrocchi  1 , Ernesto Vinci  1 , Vittorio Gebbia  2 , Maria Rosaria Valerio  5
Affiliations
Review

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

Daniela Sambataro et al. Cancers (Basel). .

Abstract

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.

Keywords: MINEN; biopsy; hepatocellular; liver; neuroendocrine.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
PRISMA 2020 flow diagram.
Figure 2
Figure 2
Distribution of sex, histology, hepatitis, and cirrhosis in cases reported in the literature.
Figure 3
Figure 3
Treatment and median overall survival. LT: local treatment (PTPE: percutaneous transhepatic portal vein embolization; RFA: radiofrequency thermoablation; TACE: transarterial); ST: systemic treatment.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Rossi R.E., Massironi S. The Increasing Incidence of Neuroendocrine Neoplasms Worldwide: Current Knowledge and Open Issues. J. Clin. Med. 2022;11:3794. doi: 10.3390/jcm11133794. - DOI - PMC - PubMed
    1. Elpek G.O. Mixed neuroendocrine–nonneuroendocrine neoplasms of the gastrointestinal system: An update. World J. Gastroenterol. 2022;28:794–810. doi: 10.3748/wjg.v28.i8.794. - DOI - PMC - PubMed
    1. Frizziero M., Chakrabarty B., Nagy B., Lamarca A., Hubner R.A., Valle J.W., McNamara M.G. Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: A Systematic Review of a Controversial and Underestimated Diagnosis. J. Clin. Med. 2020;9:273. doi: 10.3390/jcm9010273. - DOI - PMC - PubMed
    1. Cattaneo L., Centonze G., Sabella G., Lagano V., Angerilli V., Pardo C., Bertani E., Spada F., Prinzi N., Pusceddu S., et al. Digestive MiNENs: Could histological classification and molecular characterization drive clinical outcome and therapeutic approach? Crit. Rev. Oncol. Hematol. 2023;188:104044. doi: 10.1016/j.critrevonc.2023.104044. - DOI - PubMed
    1. Xu B., Zhang F., Wu R., Peng Y., Mao Z., Tong S. Incidence, survival, and prognostic factors for patients with gastrointestinal mixed neuroendocrine non-neuroendocrine neoplasms: A SEER population-based study. J. Cancer Res. Clin. Oncol. 2023;149:15657–15669. doi: 10.1007/s00432-023-05356-z. - DOI - PMC - PubMed

LinkOut - more resources