Perfusion beyond Margin in Hepatocellular Carcinoma: A Contrast-enhanced US Feature Related to Tumor Invasiveness and Prognosis.

Background Previous studies on imaging of hepatocellular carcinoma (HCC) have shown inconsistency in the growth of tumor vascularity and gross morphologic features. Contrast-enhanced US (CEUS) is one of the few methods that can depict both features simultaneously, making it valuable for assessing this inconsistency and its potential clinical influence. Purpose To evaluate and establish a new CEUS feature representing inconsistency between vascularity and gross morphologic features (perfusion beyond margin [PBM]) and analyze its underlying biologic mechanisms and prognostic influence. Materials and Methods This multicenter retrospective study included patients with HCC from January 2015 to August 2023. Three radiologists (5-8 years of experience) measured tumor diameter using gray-scale US and CEUS. Mathematic, prognostic, and bioinformatics analyses were used to quantify the PBM diagnostic standard. Prognostic analysis included recurrence-free survival after laparoscopic hepatectomy and local tumor progression-free survival after thermal ablation. Bioinformatics analysis included pathologic and immunohistochemical evaluation and RNA sequencing. Results This study included 1076 patients (mean age ± SD, 60 years ± 10.5; 854 men, 1166 HCCs). PBM was defined as the tumor diameter on arterial phase exceeding that at gray-scale US by 5 mm. PBM was associated with worse recurrence-free survival (hazard ratio [HR], 1.76 [95% CI: 1.05, 2.94]; P = .03); worse local tumor progression-free survival (HR, 2.40 [95% CI: 1.84, 3.13]; P < .001); and higher rates of microvascular invasion (52.2% [12 of 23] vs 25.0% [29 of 116]; P = .02), cytokeratin-7 positivity (26.2% [11 of 42] vs 11.3% [14 of 124]; P = .04), and cytokeratin-19 positivity (26.9% [seven of 26] vs 8.8% [13 of 148]; P = .02) compared with the non-PBM group. PBM occurrence was related to upregulation of genes for angiogenesis (VEGA, PIGF), epithelial-mesenchymal transition (TGFB1, MMP2), and immunosuppressive tumor microenvironment (CD163). PBM was more common in patients with cirrhosis (26.8% [236 of 880]; P = .04; odds ratio, 1.41), recurrent tumors (28.4% [161 of 567]; P = .02; odds ratio, 1.38), and tumors greater than 3 cm (30.8% [92 of 298]; P = .01; odds ratio, 1.46). Conclusion Perfusion beyond margin, a new imaging feature, was identified through contrast-enhanced US in patients with hepatocellular carcinoma; it was associated with greater invasive potential and poorer prognosis. © RSNA, 2026 Supplemental material is available for this article. See also the editorial by Shafaat and Reis in this issue.