Cytologic analysis
A tissue diagnosis is usually obtained by brush cytology or bile duct
biopsy during ERCP. In the setting of primary sclerosing cholangitis, interpretation
of cytology can be challenging due to reactive changes by inflammation
[68]. The sensitivity and specificity for conventional brush cytology
are reported to be 37% to 63% and 89% to 100%, respectively [69–71]. The
limitations of conventional cytology relate to the typically desmoplastic
structure of this cancer and limited access to the biliary system. To improve
diagnostic accuracy for the diagnosis of cholangiocarcinoma, new advanced
cytologic techniques have been introduced, including digital image analysis
and fluorescence in situ hybridization (FISH). Both techniques identify
aneuploidy. In digital image analysis, DNA content relative to normal
ploidy is quantitated. A comparison of digital image analysis with cytology
in patients with suspicious biliary strictures demonstrated a sensitivity of
39.3% with digital image analysis compared with 17.9% by cytology. The
specificity was 77.3% with digital image analysis compared with 97.7%
with cytology [72]. Evaluation of digital image analysis in patients who
had primary sclerosing cholangitis, 20% of whom had cholangiocarcinomas,
demonstrated a sensitivity and specificity of 43% and 87%, respectively.
In patients who had primary sclerosing cholangitis with negative
cytology, a sensitivity and specificity of 14% and 88% were described
[73]. FISH allows the detection of chromosomal amplifications by fluorescence
and is interpreted as positive if five or more cells display gains of
two or more chromosomes (polysomy) [73]. In patients who had primary
sclerosing cholangitis, polysomy detected by FISH had a sensitivity of
47%, a specificity of 100%, a positive predictive value of 100%, and a negative
predictive value of 88% in the detection of cholangiocarcinomas. In
the setting of neither positive nor suspicious cytology, the sensitivity was
20% and the specificity 100%; the positive predictive value was reported
to be 100% and the negative predictive value 88% [74]. FISH remarkably
increases the yield of brush cytology for the diagnosis of cholangiocarcinoma
without compromising specificity.