Objectives To establish a diagnostic regimen based on gadoxetate acid disodium (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) integrated with tumor markers in differentiating combined hepatocellular-cholangiocarcinoma (cHCC-CCA) from mass-forming intrahepatic cholangiocarcinoma (iCCA) in high-risk patients. Materials and methods This multi-center study enrolled 137 patients with pathologically proven cHCC-CCAs (n = 52) and iCCAs (n = 85) who underwent Gd-EOB-DTPA enhanced MRI. The differences in clinical data and imaging features between cHCC-CCA and iCCA were compared. The diagnostic performance was evaluated using receiver operating characteristic (ROC) curves, and the area under the ROC curve (AUC) of all independent predictors was calculated and compared. Results Univariate and multivariable regression analysis revealed that progressive enhancement (OR = 0.283, p = 0.013), targetoid appearance on HBP (OR = 0.196, p = 0.001), and targetoid diffusion restriction (OR = 0.157, p < 0.001) were independent predictors o<Emphasis Type="Underline">f</Emphasis> iCCA. However, only elevated alpha-fetoprotein (AFP) (> 100 ng/mL) (OR = 3.416, p = 0.012) was an independent predictor of cHCC-CCA. Moreover, elevated AFP (> 100 ng/mL) with progressive enhancement (Z = 2.343, p = 0.019), elevated AFP (> 100 ng/mL) with targetoid appearance on HBP (Z = 2.402, p = 0.016), and elevated AFP (> 100 ng/mL) with targetoid diffusion restriction (Z = 3.196, p = 0.001) can significantly improve the AUC value in the diagnosis of cHCC-CCA. Among them, the AUC value of elevated AFP (> 100 ng/mL) with targetoid diffusion restriction was higher than elevated AFP (> 100 ng/mL) with progressive enhancement (Z = 2.092, p = 0.036). Conclusions A diagnostic regimen combining tumor markers and imaging features could help differentiation of cHCC-CCA from mass-forming iCCAs. When elevated AFP (> 100 ng/mL) in discordance with progressive enhancement, or targetoid diffusion restriction, or targetoid appearance on HBP, the lesion might be highly suspicious of cHCC-CCA. Key Points <Emphasis Type="BoldItalic">Question</Emphasis> Can contrast-enhanced MRI and tumor markers improve preoperative differentiation of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) from mass-forming intrahepatic cholangiocarcinoma (iCCA) with rim arterial phase hyperenhancement (APHE)? <Emphasis Type="BoldItalic">Findings</Emphasis> Elevated alpha-fetoprotein > 100 ng/mL in discordance with progressive enhancement, targetoid appearance on hepatobiliary phase (HBP), or targetoid diffusion restriction can improve differentiation of cHCC-CCA from iCCA. <Emphasis Type="BoldItalic">Clinical relevance</Emphasis> This diagnostic regimen improves preoperative accuracy in distinguishing cHCC-CCA from iCCA by integrating tumor marker with specific MRI imaging features, guiding appropriate treatment strategies while minimizing unnecessary biopsy. Graphical Abstract

Differentiating combined hepatocellular-cholangiocarcinoma from mass-forming intrahepatic cholangiocarcinoma with MRI and tumor markers: a multi-center study

期刊论文
发表日期：

2025年7月2日

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Xu He,
Fukun Shi,
Yingzhu Cui,
Jingjing Liu,
Jiacheng Zhang,
Qian Xu,
Jiameng Si,
Yihao Yan,
Junjie Shu,
Zhichao Feng,
Lan Zhang

摘要

Objectives

To establish a diagnostic regimen based on gadoxetate acid disodium (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) integrated with tumor markers in differentiating combined hepatocellular-cholangiocarcinoma (cHCC-CCA) from mass-forming intrahepatic cholangiocarcinoma (iCCA) in high-risk patients.

Materials and methods

This multi-center study enrolled 137 patients with pathologically proven cHCC-CCAs (n = 52) and iCCAs (n = 85) who underwent Gd-EOB-DTPA enhanced MRI. The differences in clinical data and imaging features between cHCC-CCA and iCCA were compared. The diagnostic performance was evaluated using receiver operating characteristic (ROC) curves, and the area under the ROC curve (AUC) of all independent predictors was calculated and compared.

Results

Univariate and multivariable regression analysis revealed that progressive enhancement (OR = 0.283, p = 0.013), targetoid appearance on HBP (OR = 0.196, p = 0.001), and targetoid diffusion restriction (OR = 0.157, p < 0.001) were independent predictors of iCCA. However, only elevated alpha-fetoprotein (AFP) (> 100 ng/mL) (OR = 3.416, p = 0.012) was an independent predictor of cHCC-CCA. Moreover, elevated AFP (> 100 ng/mL) with progressive enhancement (Z = 2.343, p = 0.019), elevated AFP (> 100 ng/mL) with targetoid appearance on HBP (Z = 2.402, p = 0.016), and elevated AFP (> 100 ng/mL) with targetoid diffusion restriction (Z = 3.196, p = 0.001) can significantly improve the AUC value in the diagnosis of cHCC-CCA. Among them, the AUC value of elevated AFP (> 100 ng/mL) with targetoid diffusion restriction was higher than elevated AFP (> 100 ng/mL) with progressive enhancement (Z = 2.092, p = 0.036).

Conclusions

A diagnostic regimen combining tumor markers and imaging features could help differentiation of cHCC-CCA from mass-forming iCCAs. When elevated AFP (> 100 ng/mL) in discordance with progressive enhancement, or targetoid diffusion restriction, or targetoid appearance on HBP, the lesion might be highly suspicious of cHCC-CCA.

Key Points

Question Can contrast-enhanced MRI and tumor markers improve preoperative differentiation of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) from mass-forming intrahepatic cholangiocarcinoma (iCCA) with rim arterial phase hyperenhancement (APHE)?

Findings Elevated alpha-fetoprotein > 100 ng/mL in discordance with progressive enhancement, targetoid appearance on hepatobiliary phase (HBP), or targetoid diffusion restriction can improve differentiation of cHCC-CCA from iCCA.

Clinical relevance This diagnostic regimen improves preoperative accuracy in distinguishing cHCC-CCA from iCCA by integrating tumor marker with specific MRI imaging features, guiding appropriate treatment strategies while minimizing unnecessary biopsy.

Graphical Abstract