Dysplastic Biliary Lesions in Primary Sclerosing Cholangitis Harbor Cytogenetic Abnormalities Similar to Cholangiocarcinoma.
Sarah E Kerr, Emily G Barr Fritcher, Michael B Campion, Benjamin R Kipp, Jesse S Voss, Susan C Abraham, Kevin C Halling, Jason T Lewis. Mayo Clinic, Rochester, MN; The University of Texas MD Anderson Cancer Center, Houston
Background: Grading criteria for biliary dysplasia (biliary intraepithelial neoplasia, BilIN) have been recently described. This literature suggests a dysplasia-carcinoma sequence in which dysplasia is associated with concurrent or future cholangiocarcinoma (CCA), especially in primary sclerosing cholangitis (PSC). If so, cytogenetic abnormalities similar to those seen in CCA may be present in BilIN.
Design: Nine PSC liver explants in which a previous multi-section gross protocol had identified BilIN grade 3 were selected. One or two formalin fixed, paraffin embedded blocks from each patient represented the following lesions of interest: normal/reactive (N/R) biliary epithelium, intestinal metaplasia without dysplasia (IM), BilIN 1-2 (low grade dysplasia), BilIN 3 (high grade dysplasia), and CCA. Areas of interest were chosen by consensus of two pathologists and circled on H&E stained slides as a template for UroVysion® fluorescence in situ hybridization (FISH probes to 9p21 and centromeres 3, 7, and 17). A cytotechnologist scored 50 consecutive well-visualized epithelial cells per lesion.
Results: Mean (range) % of cells with abnormality on a per lesion basis.
|HISTOLOGY||Lesions Counted||Hemiz. 9p21 Loss||Homoz. 9p21 Loss||Homoz. 9p21 Loss Only*||Single Locus Gain||Polysomy|
|N/R||7||14 (4-28)||3 (0-6)||3 (0-6)||5 (0-16)||0 (0-2)|
|IM||4||20 (6-26)||3 (2-4)||3 (2-24)||11 (0-36)||0 (0-0)|
|BilIN 1-2||11||32 (0-14)||15 (0-100)||5 (0-14)||5 (0-12)||15 (0-86)|
|BilIN 3||10||33 (0-56)||35 (0-100)||14 (0-62)||21 (2-38)||34 (0-70)|
|CCA||1||0 (0)||100 (100)||16 (16)||22 (22)||62 (62)|