Carcinoma sequence inferred from increasing age at choledochal cyst excision

Choledochal cysts pose risk for biliary carcinoma, although age-related progression of biliary epithelial transformation remains uncharacterized. This study aimed to elucidate the carcinoma sequence within choledochal cysts across all patient ages to inform cancer risk and screening.

Patients treated either for choledochal cysts or biliary carcinoma at 1 institution (1988-2023) were analyzed. Choledochal cyst pathology was reviewed for biliary epithelial changes, whereas patients with biliary carcinoma were assessed for history of choledochal cysts. Descriptive statistics and logistic regression of age at epithelial change were performed.

Among 130 patients with choledochal cysts, median age at resection was 12 years, female patients predominated (73%), and Asian race was 2.5-fold increased. Patients commonly presented with biliary obstruction, pancreatitis, and type I choledochal cysts. Cyst pathology revealed chronic inflammation (56.1%) and progressive epithelial transformation (6.9%): 3 metaplasia, 1 hyperplasia, 3 dysplasia, and 3 synchronous biliary carcinoma. Logistic regression showed positive association between increasing age at excision and progressive epithelial transformation (P = .038). One 6-year-old patient with choledochal cysts developed metachronous biliary carcinoma at age 37 years. Among 886 nonampullary patients with biliary carcinoma, 8 (0.9%) had choledochal cysts: 7 synchronous and the same metachronous. Resection of choledochal cysts after age 17 years showed increased odds for epithelial transformation (odds ratio, 15.0; P = .0093). Cumulatively, median age (years) increased from premalignant biliary epithelial transformation (34 [16-35]), to biliary carcinoma with choledochal cysts (51 [37-78]), to biliary carcinoma without choledochal cysts (65 [56-72]; P < .001).

These data infer sequential epithelial transformation to biliary carcinoma correlating with increasing age at resection of choledochal cysts. Coupled with 1 case of metachronous biliary carcinoma, this study underscores the need to screen patients with previous excision of choledochal cysts for cancer beginning at age 30 years.