Factors Impacting the Performance Characteristics of Bile Duct Brushings: A Clinico-Cytopathologic Analysis of 253 Patients

Abstract

Context.-Literature on factors impacting bile duct brushings (BDBs) performance characteristics remain limited.Objective.-To capture the current state of daily practice with BDB sign-out.Design.-Two hundred fifty-three of 444 BDBs signed out by more than 7 cytopathologists, with histopathologic and/or clinical follow-up of at least 18 months, were examined.Results. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of malignancy detection were 35%, 100%, 100%, 58%, and 66%, respectively. When atypical, suspicious, and malignant (ASM) categories were combined, sensitivity increased (58%), specificity and PPV dropped (97%), and accuracy increased (73%). Carcinoma type (bile-duct versus pancreatic-ductal) had no effect on accuracy (P ¼ .60) or diagnostic class (P ¼ .84), nor did time of performance (first 7.5 versus latter 7.5 years, P ¼ .13). Interestingly, ThinPrep þ cell block (n ¼ 41) had higher sensitivity (61%) and lower specificity (80%) than ThinPrep only (versus 51% and 100%, respectively). Sensitivity and specificity were higher (47% and 100%) in nonstented than stented specimens (59% and 97%). Relative risk of malignancy for ''suspicious'' (2.30) and ''atypical'' (2.28) categories was lower but not very different from that of ''malignant'' category (2.41).Conclusions.-Bile duct brushings had fairly low sensitivity but high specificity and PPV with no false positives. Sensitivity almost doubled and specificity dipped minimally when ASM categories were combined, highlighting the need for better classification criteria for atypical/suspicious cases. Higher specificity, PPV, NPV, and accuracy but lower sensitivity in stented BDBs suggest that they be called malignant only when evidence is overwhelmingly convincing. (Arch Pathol Lab Med. 2018;142:863-870; doi: 10.5858/ arpa.2017-0150-OA) T he diagnosis of malignancy in the biliary tree remains a clinical and pathologic challenge, with brush cytology being the most frequently used initial diagnostic test. Cytologic diagnosis is especially challenging, as tumors are often well differentiated and thus cytologically bland.Conversely, these well-differentiated examples are closely mimicked morphologically by reactive changes in patients with primary sclerosing cholangitis, nonspecific inflammation, cholelithiasis, and stents. 1,2Most studies on bile duct brushings (BDBs) agree that the sensitivity of this modality is fairly low, although the numbers vary substantially from 6% to 64%, [3][4][5][6][7][8][9][10][11][12][13][14][15][16] and the factors implicated in the test's inaccuracies are also significantly different. These variations are presumably related to case definition (identification) as well as the setting in which the studies were performed and the different methods of specimen processing used. 3,17,18 Consequently, the relative impact of different parameters on BDB interpretation by cytopathologists remains unclear and is yet to be fully unraveled.In this study, in order to capture the current s...

Effect of single operator cholangioscopy on accuracy of bile duct cytology

“…Additionally, logistic fit of clinically benign diagnosis is negatively correlated with these variables (results not shown).Site of malignancy, presence of a stent or calculus had no effect on cytological diagnosis. This is contrary to a study that reported lower sensitivity of cytological diagnosis in stented vs nonstented cases 14. This was explained to be due to the reluctance of cytopathologists in rendering a malignant diagnosis in context of anticipated reactive changes.…”

“…Other studies have also highlighted false-positive cytology in the setting of low-grade dysplasia, reactive papillary changes, postsurgical bile duct stenosis and primary sclerosing cholangitis. 5,10,14 Cytological criteria of malignancy are reported by Avadhani et al 15 One of the strengths of our study is that the endoscopists and cytopathologists were experienced and remained consistent during the entire period of the study. Our weakness is that fluorescence in situ hybridization (FISH) studies on cytology material was not performed in any of our cases.…”

“…The four cases of false‐positive cytology results occurred in the setting of primary sclerosing cholangitis (2 cases), primary biliary sclerosis (1 case) and one case in which the patient does not have evidence of malignancy but the cause of biliary stricture is not established. Other studies have also highlighted false‐positive cytology in the setting of low‐grade dysplasia, reactive papillary changes, postsurgical bile duct stenosis and primary sclerosing cholangitis 5,10,14 …”

Should uncertainty concerning the risk of malignancy be included in diagnostic (nongynecologic) cytopathology reports?

“…For bile duct brushing cytology, the known published ROM approaches 100% in the published literature; however, the various studies show a range of false‐positive results of 0% to 3% 35‐40 . The possible reasons for these false‐positive results include primary sclerosing cholangitis, 41 chronic pancreatitis, inflammatory conditions that mimic malignancy, or the presence of a bile duct stent that was unknown to the reporting cytologist or that the reporting cytologist did not consider when formulating the diagnosis 42 .…”

Bile duct involvement by hepatocellular carcinoma: A rare occurrence and poor prognostic indicator in bile duct brushing samples

“…Nonetheless, the majority of biliary tract tumors that are diagnosed on bile duct brushing samples (BDBs) or intraductal biopsy either are pancreatic (pancreatic ductal adenocarcinoma) or biliary (intrahepatic and extrahepatic cholangiocarcinoma) in origin . Other sources of positive results are intraductal papillary neoplasms of the bile duct, primary tumoral intraductal neoplasms of the intrahepatic and extrahepatic biliary tree, and metastatic nonpancreatobiliary tumors from the upper and lower gastrointestinal tract, and even the lung . In addition to metastases from distant sites, the biliary tract also may be involved by direct extension of hepatocellular carcinoma (HCC).…”