Liver and Gallbladder Pathology in Small Duct Primary Sclerosing Cholangitis: Is There a Risk for Neoplasia?
TT Wu, S Shah, JJ Poterucha, SC Abraham. Mayo Clinic, Rochester; MD Anderson Cancer Center, Houston
Background: The elevated risk for cholangiocarcinoma (CCA) in primary sclerosing cholangitis (PSC) is well known. Small duct PSC (i.e., biochemical and histologic evidence of PSC but normal cholangiography) forms a minor subgroup with a favorable prognosis. In particular, it is thought that small duct PSC never develops CCA outside of radiologic progression to large duct PSC. However, due to the small number of cases requiring transplant, neither the biliary nor gallbladder pathology of small duct PSC has been well characterized.
Design: We investigated the presence of metaplastic and dysplastic lesions of bile ducts and gallbladder mucosa in patients with end-stage small duct PSC who underwent liver transplant (n=8) and concomitant cholecystectomy (n=5). Extensive sections of biliary mucosa were taken (mean 14/case) and evaluated for the following: intestinal metaplasia, mucinous metaplasia, pyloric metaplasia, and dysplasia (low or high grade, papillary or flat). Small duct PSC was compared to 2 previously-characterized control groups (100 liver explants with PSC and 164 with cirrhosis from alcohol or hepatitis C).
Results: Bile duct metaplasia was found in 6 (75%) small duct PSC. Low grade dysplasia involved intrahepatic bile ducts of 3 (38%) patients, one with extensive papillary dysplasia, one with extensive flat dysplasia and one with several (7) dysplastic ducts. There was no hilar dysplasia, high grade dysplasia or CCA. None of the accompanying gallbladders had lymphoplasmacytic chronic cholecystitis. Comparison to controls is shown in Table 1.
Conclusions: Low grade biliary lesions (metaplasia and low grade dysplasia) in small duct PSC are similar to large duct PSC in frequency, but without progression to high grade dysplasia or CCA. Since most PSC-associated CCAs involve the hilum, the lack of hilar bile duct dysplasia in small duct PSC might play a protective role.
|Small duct PSC (8)||PSC (100)||Alcohol/hepatitis C cirrhosis (164)|
|Intestinal metaplasia||3 (38%)||26 (26%) (ns)||8 (5%) (p=0.009)|
|Pyloric metaplasia||4 (50%)||73 (73%) (ns)||3 (2%) (p<0.001)|
|Mucinous metaplasia||7 (88%)||77 (77%) (ns)||152 (93%) (ns)|
|Biliary dysplasia (any)||3 (38%)||50 (50%) (ns)||85 (52%) (ns)|
|High grade dysplasia||0 (0%)||26 (26%) (ns)||8 (5%) (ns)|
|CCA or gallbladder carcinoma||0 (0%)||34 (34%) (p=0.05)||6 (4%) (ns)|
|Lymphoplasmacytic cholecystitis||0 of 5 (0%)||35 of 72 (49%) (p=0.06)||--|