Prevalence and risk factors for gallbladder neoplasia in patients with primary sclerosing cholangitis: Evidence for a metaplasia-dysplasia-carcinoma sequence

Primary sclerosing cholangitis (PSC) carries an increased risk (10% to 20%) of hepatobiliary malignancy, especially cholangiocarcinoma (CC). Dysplasia, adenomas, and carcinomas of the gallbladder have been described in PSC but are less common than bile duct carcinomas. However, the prevalence and risk factors for gallbladder neoplasia among patients with PSC undergoing orthotopic liver transplantation (OLT) have not been well studied. We evaluated 72 gallbladders from 100 consecutive liver explants for PSC, including 66 cholecystectomies performed at the time of OLT and 6 performed before OLT. All specimens were totally embedded for histologic examination. We evaluated the following histologic features: presence of diffuse lymphoplasmacytic chronic cholecystitis, pyloric metaplasia, intestinal metaplasia, dysplasia (low-grade or high-grade), and adenocarcinoma. Gallbladder dysplasia and adenocarcinoma were correlated with several clinicopathologic parameters using Fisher exact test and t test, including: (1) sex, (2) age, (3) PSC duration, (4) inflammatory bowel disease (IBD) at time of OLT, and (5) concomitant bile duct dysplasia or carcinoma. Lymphoplasmacytic chronic cholecystitis was present in 35 (49%), pyloric metaplasia in 69 (96%), intestinal metaplasia in 36 (50%), dysplasia in 27 (37%; low-grade in 12 and high-grade in 15), and adenocarcinoma in 10 (14%; 2 with lamina propria invasion and 8 with invasion into muscularis or adventitia). Gallbladder carcinoma was associated with intrahepatic bile duct dysplasia (P=0.001), CC (P=0.023), and IBD (P=0.03). Gallbladder dysplasia was associated with hilar/intrahepatic bile duct dysplasia (P=0.0006), CC (P=0.028), IBD (P=0.0014), and older age at OLT (P=0.007). Neither gallbladder carcinoma nor dysplasia had a significant association with sex or PSC duration. These results indicate that complete histologic evaluation of gallbladders in patients undergoing transplantation for PSC yields high frequencies of inflammatory, metaplastic, and neoplastic changes. The strong correlation between gallbladder dysplasia/adenocarcinoma and bile duct dysplasia/CC supports the concept of a neoplastic "field effect" along the intrahepatic and extrahepatic biliary tract in PSC.