VEGF‐Positive Mass‐Forming Intrahepatic Cholangiocarcinoma: New Subtype Based on Radiological and Molecular Pathological Analysis

AIM: Among mass-forming (MF) type intrahepatic cholangiocarcinoma (ICC), approximately 20%-30% are hypervascular on imaging and are associated with improved prognosis. However, the molecular background based on gene expression of this entity remains unclear. METHODS: We retrospectively analyzed 109 patients with MF-type ICC resected at the National Cancer Center Hospital, Japan. Preoperative dynamic computed tomography (CT) images were available for 48 cases. Based on the late-arterial-phase enhancement area (EA) and the relative enhancement ratio (RER), 17 were classified as hypervascular ICC (H-ICC, EA ≥ 50%), 21 as hypovascular ICC (h-ICC, EA < 50%, RER ≥ 1), and 10 as nonvascular ICC (N-ICC, EA < 50%, RER < 1). We compared group-wise arterial vessel density (AVD), then profiled angiogenesis genes to identify a suitable immunohistochemical marker. RESULTS: The H-ICC group had a better prognosis than h-ICC (P = 0.024) and N-ICC (P = 0.002). H-ICC also had a higher AVD than other groups (P < 0.001). Among the angiogenesis-related genes, vascular endothelial growth factor A (VEGFA) exhibited the strongest correlation with EA (P = 0.012), and H-ICC exhibited higher VEGF positivity than other groups (P = 0.022). The survival and immunostaining profiles of h-ICC closely resembled those of N-ICC. ROC analysis revealed that a VEGF staining positivity of 70% was the optimal cut-off for identifying H-ICC. CONCLUSIONS: H-ICC is characterized by hyperenhancement occupying ≥ 50% of the tumor area on dynamic CT, high AVD, and elevated VEGFA expression. These findings support a distinct clinicopathological subset identifiable by LAP enhancement and VEGF immunostaining.