Cytology of Bile Duct Brushings: Streaming Ahead with Time
AbstractEndoscopic retrograde brush cytology of the biliary duct is an established tool for evaluation of obstructive biliary strictures or screening of primary sclerosing cholangitis (PSC) patients for dysplasia. It is a simple, minimally invasive procedure that can be performed during a therapeutic ERCP. Most authors have reported a sensitivity of 30-60% and a specificity of 90-100%. A positive result can be a reliable indicator of malignant neoplasm. However, there is no standardized reporting terminology designed specifically for bile duct brushings. Majority of bile duct brushings yield either benign ductal epithelium, reactive atypia of ductal epithelium or suspicious/positive for malignancy. Diagnosing malignancy in bile duct brushings is based on a constellation of cytologic features, and consideration of the overall picture- clinical presentation, radiology/endoscopy findings, etc. Different studies have highlighted various key features for diagnosing malignancy in bile duct brushings. Features most consistently associated with a malignant category are- loss of honeycomb architecture, 3D clusters, high n:c ratio, anisonucleosis (≥1:4 variation), irregular nuclear outlines, coarse clumped chromatin, and single malignant cells in the background. The utility of biliary brush cytology has been expanded by using FISH, immunocytochemistry, and Next-generation sequencing.
Osnes M, Serck-Hanssen A, Myren J. Endoscopic retrograde brush cytology (ERBC) of the biliary and pancreatic ducts. Scand J Gastroenterol. 1975;10(8):829-31.
Pitman MB, Layfield LJ. The Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology: Definitions, Criteria and Explanatory Notes. Springer International Publishing; 2015.
Layfield LJ, Zhang T, Esebua M. Diagnostic sensitivity and risk of malignancy for bile duct brushings categorized by the Papanicolaou Society of Cytopathology System for reporting pancreaticobiliary cytopathology. Diagnostic Cytopathology. 2022; 50:24–27.
Kurzawinski TR, Deery A, Dooley JS, et al. A prospective study of biliary cytology in 100 patients with bile duct strictures. Hepatology 1993; 18:1399–1403.
Fogel EL, Sherman S. How to improve the accuracy of diagnosis of malignant biliary strictures. Endoscopy 1999; 31:758–760.
Brugge WR, De Witt J, Klapman JB, Ashfaq R, Shidham V, Chhieng D, Kwon R, Baloch Z, Zarka M, Staerkel G. Techniques for cytologic sampling of pancreatic and bile duct lesions: The Papanicolaou Society of Cytopathology Guidelines. Cytojournal. 2014 Jun 2;11(Suppl 1):2. doi: 10.4103/1742-6413.133311. PMID: 25191516; PMCID: PMC4153336.
Ferrari Junior AP, Lichtenstein DR, Slivka A, et al. Brush cytology during ERCP for the diagnosis of biliary and pancreatic malignancies. Gastrointest Endosc 1994;40 (Part 1):140–145.
Fogel EL, deBellis M, McHenry L, et al. Effectiveness of a new long cytology brush in the evaluation of malignant biliary obstruction: A prospective study. Gastrointest Endosc 2006; 63:71–77.
Bardales RH, Stanley MW, Simpson DD, Baker SJ, Steele CT, et al. Diagnostic value of brush cytology in the diagnosis of duodenal, biliary, and ampullary neoplasms. Am J Clin Path. 1998. 109(5): 540-548.
Mantoo S. Bile duct brush cytology—challenges, limitations and ancillary studies. J Immun Virol. 2017;2(1). doi:10.19080/JOJIV.2017.02.555578.
Chadwick BE, Layfield LJ, Witt BL, Schmidt RL, Cox RN, et al. Significance of atypia in pancreatic and bile duct brushings: follow-up analysis of the categories atypical and suspicious for malignancy. Diagn Cytopath, 2014. 42(4): 285-291.
Selvaggi SM. Biliary brush cytology. Cytopathology 2004; 15: 74– 79.
Layfield LJ, Wax TD, Lee JG, Cotton PB. Accuracy and morphologic aspects of pancreatic and biliary duct brushings. Acta Cytol 1995; 39:11–8.
Avadhani, V., Hacihasanoglu, E., Memis, B. et al. Cytologic predictors of malignancy in bile duct brushings: a multi-reviewer analysis of 60 cases. Mod Path, 2017. 30, 1273–1286. https://doi.org/10.1038/modpathol.2017.51.
Cohen MB, Wittchow RJ, Johlin FC, Bottles K, Raab SS. Brush cytology of the extrahepatic biliary tract: comparison of cytologic features of adenocarcinoma and benign biliary strictures. Mod Pathol. 1995;8(5):498-502.
Renshaw AA, Madge R, Jiroutek M, Granter SR. Bile duct brushing cytology: statistical analysis of proposed diagnostic criteria. Am J Clin Pathol. 1998;110(5):635-640.
Stoos-Veić T, Bilić B, Kaić G, Ostović KT, Babić Z, Kujundzić M: Biliary brush cytology for the diagnosis of malignancy: a single center experience. Coll Antropol 2010; 34: 139–143.
Mehmood S, Loya A, Yusuf MA. Biliary Brush Cytology Revisited. Acta Cytologica 2016; 60:167–172. DOI: 10.1159/000446149.
De la Sancha C, Cramer H, Wu HH, Layfield LJ. Bile duct brushing cytology: a large, single institutional retrospective review with an emphasis on sensitivity, specificity and positive predictive value. Mod Pathol. 2019;32(supplement 1–138):345.
Ferrari AP Jr., Lichtenstein DR, Slivka A, Chang C, CarrLocke DI. Brush cytology during ERCP for the diagnosis of biliary and pancreatic malignancies. Gastrointest Endosc 1994; 40: 140– 145.
Lee JG, Leung JW, Baillie J, Layfield LJ, Cotton PB. Benign, dysplastic or malignant-making sense of endoscopic bile duct brush cytology: Results in 149 consecutive patients. Am J Gastroenterol 1995; 90: 722– 726.
Govil H, Reddy V, Kluskens L, et al. Brush cytology of the biliary tract: Retrospective study of 278 cases with histopathologic correlation. Diagn Cytopathol 2002; 26: 273– 277.
Nakajima T, Tajima Y, Sugano I et al. Multivariate statistical analysis of bile cytology. Acta Cytol 1994; 38:51–55.
Dudley JC, Zheng Z, McDonald T, Le LP, Dias-Santagata D, et al. Next-generation sequencing and fluorescence in situ hybridization have comparable performance characteristics in the analysis of pancreaticobiliary brushings for malignancy. 2016. J Mol Diagn 18(1): 124-130.
Kocjan G, Nisbet-Smith A. Bile duct brushings cytology: Potential pitfalls in diagnosis. Diagn Cytopathol 1997; 16: 358– 363.
Mahmoudi N, Enns R, Amar J, Ali JA, Lam E, Telford J: Biliary brush cytology: factors associated with positive yields on biliary brush cytology. World J Gastroenterol 2008; 14:569–573.
Layfield LJ, Cramer H. Primary sclerosing cholangitis as a cause of false positive bile duct brushing cytology: report of two cases. Diagn Cytopathol. 2005 Feb;32(2):119-24. doi: 10.1002/dc.20192. PMID: 15637668.
Barr Fritcher EG, Caudill JL, Blue JE et al. Identification of malignant cytologic criteria in pancreatobiliary brushings with corresponding positive fluorescence in situ hybridization results. Am J Clin Pathol 2011; 136:442–449.
Logrono R, Kurtycz D, Molina C, et al. Analysis of false negative diagnoses on endoscopic brush cytology of biliary and pancreatic duct strictures. Arch Pathol Lab Med 2000; 124:387–392.
Nanda A, Brown JM, Berger SH, et al. Triple modality testing by endoscopic retrograde cholangiopancreatography for the diagnosis of cholangiocarcinoma. Ther Adv Gastroenterol 2015; 8:56–65.
Stewart CJR, Burke GM. Value of p53 immunostaining in pancreaticobiliary brush cytology specimens. Diagn Cytopathol 2000; 23:308–13.
Chen L, Huang K, Himmelfarb EA, et al. Diagnostic value of maspin in distinguishing adenocarcinoma from benign biliary epithelium on endoscopic bile duct biopsy. Hum Pathol 2015; 46:1647–1654.
Layfield L, Ehya H, Filler AC, Hruban RH, Jhala N, et al. Utilization of Ancillary studies in the cytologic diagnosis of biliary and pancreatic lesions: the Papanicolaou society of cytology guidelines of pancreatobiliary cytology. Diagn Cytopath. 2014. 42(4): 351-362.
Brand RE, Adai AT, Centeno BA, Lee LS, Rateb G, Vignesh S, et al. A microRNA-based test improves endoscopic ultrasound-guided cytologic diagnosis of pancreatic cancer. Clin Gastroenterol Hepatol. 2014;12(10):1717–23.
Barr Fritcher EG, Voss JS, Brankley SM et al. An optimized set of fluorescence in situ hybridization probes for detection of pancreatobiliary tract cancer in cytology brush samples. Gastroenterology 2015; 149:1813–1824 e1811.
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