Choledochal cysts: a clinicopathologic study of 36 cases with emphasis on the morphologic and the immunohistochemical features of premalignant and malignant alterations.

Choledochal cysts (CDCs) are believed to represent a risk factor for the development of neoplasia. However, the frequency and morphology of neoplastic changes have not been systematically studied, especially in North America. Our aims were to study the frequency and morphology of preneoplastic/neoplastic changes of CDCs. Thirty-six cysts were subjected to clinicopathological analyses. Metaplasia was found in 14 of 35, of which 9 had biliary intraepithelial neoplasia (BilIN). Of the 14 with metaplasia, 13 showed pyloric gland; 5, intestinal; and 2, squamous. BilINs included 6 BilIN-1, 2 BilIN-2, and 2 BilIN-3. Carcinoma was identified in 5 cases of which 3 were associated with metaplasia and BilIN. Only 1 of 18 cases without metaplasia had BilIN, and none had carcinoma (P = .0008). There was a trend toward more BilIN and carcinoma with intestinal rather than with pyloric gland metaplasia. All cases with metaplasia or/and BilIN were negative for MUC1. All cases with intestinal metaplasia were positive for CK20, CDX2, and MUC2, whereas cases with pyloric gland were positive for MUC6. MUC1, CEA, and B72.3 were positive only in carcinoma. There was a trend toward increasing p53 and Ki-67 from metaplasia to BilIN to carcinoma. Four of 5 patients with carcinoma died, and one was alive with disease. All others were free of disease except for one who developed new cysts. CDCs are associated with a high rate of BilIN (28.5%) and carcinoma (14.3%). CDCs show a sequence of tumor progression from metaplasia to BilIN and carcinoma.