Histologic patterns of venous invasion in distal extrahepatic bile duct carcinoma correlate with prognosis

Venous invasion (VI) is a well-established prognostic factor in distal extrahepatic bile duct carcinomas (DBDCs), yet its histologic features have not yet been systematically evaluated. We retrospectively analyzed hematoxylin and eosin-stained slides from 325 surgically resected DBDCs to assess VI and to classify the patterns of VI as destructive, biliary intraepithelial neoplasia (BilIN)-like, or conventional. VI was identified in 101 (31.1%) DBDCs and was associated with larger tumor size (P = 0.014), higher T and N categories (all, Ps < 0.001), poorer differentiation (P = 0.015), sclerosing macroscopic type (P = 0.001), and perineural (P = 0.002) and lymphovascular (P < 0.001) invasions. Among DBDCs with VI, the BilIN-like pattern of VI was most common (61, 60.4%), followed by the destructive (46, 45.5%), and conventional (39, 38.6%) patterns. Of the DBDCs with VI, 36 (35.6%) showed multiple VI patterns. The destructive pattern was associated with higher T category (P = 0.001) and duodenal invasion (P = 0.010). The patients with DBDCs with destructive VI pattern had shorter recurrence-free survival (RFS) (P < 0.001) than those with non-destructive VI pattern. The destructive pattern remained as a poor prognostic factor of RFS (P = 0.007) in multivariable analysis. VI in DBDC displays distinct histologic patterns, and specifically the destructive VI pattern associated with aggressive clinicopathologic features and poorer outcomes. Recognition of VI patterns may enhance prognostic assessment and guide postoperative management in patients with resected DBDC.