In patients undergoing hepatic resection for combined hepatocellular cholangiocarcinoma (cHCC), the microvascular invasion 3-tiered grading (MiVI-TTG) scheme shows a higher prognostic value and is a better treatment option than the 2-tiered microvascular invasion grading scheme, according to a recent study.

cHCC, a rare subtype of cholangiocarcinoma disease, accounts for only 0.4% to 14.2% of primary liver carcinomas (PLC), the researchers noted. Prior studies have indicated that patients with cHCC suffered dismal prognoses with high recurrence and poor survival rates even after undergoing hepatic resection, the study authors added.

The findings were published in the journal Cancer Medicine.

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MiVI is defined as tumor cell nests in the portal vein, hepatic vein, or capsular tumor vessel lined by endothelium, viewable only under the microscope, the researchers noted.

Microvascular invasion (MiVI) demonstrates aggressive biological behaviors of the tumor with a commendable predictive value for diagnosis in PLC, as reported previously, the authors said. Nevertheless, the research on MiVI in patients with cHCC is still limited and requires further exploration, they added.

The 2-tiered grading scheme, though accepted globally, neglects the significant effect of the number and distance of MiVI on the prognosis, the investigators noted. Furthermore, a 3-tiered MiVI-TTG for the diagnosis of hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and cHCC has been proposed by the Liver Cancer Pathology Group of China, they continued.

This study assessed and compared the prognostic value of MiVI-TTG with the 2-tiered MiVI scheme in patients who have undergone hepatic resection for cHCC. The study also aimed to explore the risk factors for MiVI in cHCC. 

This study included 208 patients with cHCC who had undergone hepatic liver resection between January 2014 and December 2018. The patients were divided into 3 groups based on the MiVI-TTG as M0 (38.9%), M1 (36.5%), and M2 (24.5%) group. 

Study results indicated that cHCC patients with severe MiVI status have a poor prognosis associated with significantly worse recurrence-free survival (RFS) and overall survival (OS) rates. Additionally, MiVI-TTG demonstrated high prognostic value in predicting the OS and RFS compared to the 2-tiered MiVI scheme.

Multiple studies have reported the risk factors of MiVI, including the presence of macrovascular invasion along with portal hypertension, incomplete tumor capsule, and alpha-fetoprotein score of greater than or equal to 400, the investigators noted. The authors highlighted that multivariable logistic regression analysis in their study showed an AFP score of greater than or equal to 400 and was regarded as the independent risk factor for MiVI-positive and the presence of satellite nodules for M2.

“MiVI-TTG has a greater prognostic value in predicting OS and RFS than the traditional 2-tiered MiVI pathological scheme, with a larger c-index, tdAUC, and net benefit rate in patients with cHCC,” the authors concluded.


Wu Y, Liu H, Chen Y, et al. Prognostic significance of three-tiered pathological classification for microvascular invasion in patients with combined hepatocellular-cholangiocarcinoma following hepatic resection. Cancer Med. Published online November 10, 2022. doi:10.1002/cam4.5328doi:10.1002/cam4.5328