Characterization of Cholangiocarcinomas With Tubulocystic Morphology Associated With Biliary Adenofibroma or Biliary Adenofibroma-Like Lesions.

Hepatic biliary adenofibroma (BAF) is a benign neoplasm composed of tubuloglandular and microcystic structures within a fibrous stroma, resembling von Meyenburg complexes or ductal plate malformation (DPM). Intrahepatic cholangiocarcinoma (iCCA) with a DPM pattern (iCCA-DPM) is an established variant of iCCA, whereas adenofibroma-like tubulocystic carcinoma (AL-TCC) is a newly proposed iCCA variant associated with BAF-type lesions. We hypothesize that BAF, AL-TCC, and iCCA-DPM form a tumorigenic spectrum. Ten cases of surgically resected iCCAs with BAF (n = 1) or BAF-like (n = 9) lesions compatible with AL-TCC were analyzed and compared with 7 iCCA-DPM and 26 unspecified small duct iCCA (SD-iCCA). The AL-TCC cohort (6 women and 4 men) had a median age of 62 years. Tumors were often multifocal (70%), averaging 5.5 cm in size, with frequent lymphovascular invasion (40%), but no perineural invasion. Comparisons between AL-TCC and iCCA-DPM revealed no significant differences in age, sex, tumor size, focality, lymphovascular invasion, perineural invasion, or outcomes. When AL-TCC and iCCA-DPM were grouped together (n = 17) and compared with other unspecified SD-iCCA, the combined AL-TCC/iCCA-DPM cohort showed a stronger association with von Meyenburg complexes, biliary cysts, and/or bile duct adenomas (7/17 [41%] vs 0/26, P < .001), less perineural invasion (P = .027), more frequent ARID1A loss (11/17 [65%] vs 3/26 [12%], P < .001), and better patient outcomes (P = .036). Kaplan-Meier analysis revealed that ARID1A loss significantly improved patient survival (P = .046). In summary, AL-TCC with BAF or BAF-like lesions shares clinicopathologic and histogenetic characteristics with iCCA-DPM, suggesting that they are related and likely represent a continuum of tumorigenesis, distinct from other SD-iCCA.