Detailed Histological Assessment of Primary Sclerosing Cholangitis: Confirmation Utilizing Significance Analysis of Microarray (SAM) and Hierarchical Clustering Analysis (HCA)
Gonzalo Carrasco, Thomas D Schiano, Mohammad Raoufi, Stephen C Ward, Swan N Thung, Maria Isabel Fiel. Mount Sinai School of Medicine, New York, NY; Henry Ford Hospital, Detroit, MI
Background: The histological diagnosis of primary sclerosing cholangitis (PSC) is often difficult to make on needle biopsy. Definitive diagnosis of PSC can only be made by cholangiography and there may be histologic overlap with other liver conditions. Employing a detailed histological analysis and utilizing a powerful statistical system, we sought to identify specific features of PSC.
Design: Explants from 20 PSC and 10 primary biliary cirrhosis (PBC) & 10 HCV control cases were examined. Clinical parameters such as age at transplant, gross and microscopic features subdivided into abnormalities of vascular structures, various-sized bile ducts (BD), such as %BD loss, BD scars, atrophy and scalloping of the epithelium, periductal onion-skin fibrosis, cholestatic features and inflammatory changes were scored. Fibrosis was assessed using both the modified Knodell and PSC staging schemes. Twenty-five fields/case were analyzed for each of the 39 variables. Data were analyzed by contingence 2x2 tables, Fisher exact 2-tail test and T-test (significant if p<.05) where applicable and integrated by SAM (significant if q-value=0) and HCA.
Results: A total of 1800 scores were recorded. Specific features seen in PSC were BD scars, onion-skin fibrosis of both small and medium-sized BDs, >50% BD loss of both small and medium-sized BDs, bile infarcts, and fibrointimal hyperplasia of hepatic arteries; hepatolithiasis, cholangitis and cholestasis were all significant (p<.05). SAM integration and comparison between PSC and PBC/HCV show that PSC is typified by BD scars, medium-size BD loss and periductal onion-skin fibrosis even in the smallest BD radicles (q-value=0).
Unsupervised HCA correctly grouped PSC, PBC & HCV cases.
Conclusions: PSC patients were younger at time of transplant. A histologic diagnosis of PSC can be reliably made by the presence of BD scars, medium-sized BD loss and terminal BD onion-skin fibrosis and, by extrapolating from these findings, these features can be employed when evaluating liver needle biopsies. SAM allows the integration of quantitative clinical and qualitative histological variables for this assessment.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 257, Monday Morning