Use of the ThinPrep® method in bile duct brushings: Analysis of morphologic parameters associated with malignancy and determination of interobserver reliability

Abstract

Recent work suggests the ThinPrep method can improve diagnostic sensitivity and accuracy in bile duct brushings. However, the proportion of atypical and suspicious diagnoses remains high. The aim of this study was to identify the most useful morphologic features in ThinPrep bile duct cytology and evaluate interobserver reliability. We evaluated 100 bile duct brushings prepared by ThinPrep, all with either histology or long term clinical follow-up (55 malignant, 45 benign). Morphologic features were evaluated by four experienced cytopathologists blind to clinical information and follow-up diagnoses. These features included cellularity, blood or diathesis, mitoses, inflammation, three-dimensional groups, discohesive atypical cells, macronucleoli, well-defined cytoplasmic borders, and nuclear features of malignancy (nuclear membrance irregularity, chromatin clumping). The data were analyzed by intraclass correlation (ICC) and stepwise multiple logistic regression. Reviewers showed unanimous agreement in 29% of cases, one degree of disagreement in 58% of cases, and full disagreement in 13% of cases. Of benign cases, 38% were thought to be diagnostic of malignancy by at least one of the four reviewers. Sensitivity for the morphologic parameters varied from 18 to 67%; the highest sensitivity was for discohesive atypical cells, well-defined cytoplasmic borders, nuclear features of malignancy, and cellularity (67, 62, 51 and 46%, respectively). Specificity of parameters varied from 16 to 100%; the highest specificity was for mitoses, three-dimensional groups, nuclear features of malignancy, and macronucleoli (100, 98, 93, and 93%, respectively). Interobserver reliability (ICC) was very good for specimen cellularity (0.72) and nuclear features of malignancy (0.60). In logistic regression analysis, only nuclear features of malignancy and increasing patient age separated benign from malignant. On ThinPrep bile duct brushings, nuclear features of malignancy are most useful in distinguishing benign from malignant, and interobserver reliability for this parameter is very good. Discohesive atypical cells show moderate sensitivity and specificity, while three dimensional clusters and macronucleoli are specific but not sensitive for malignancy, and are not significant in multivariate logistic regression models. The relatively high proportion of benign cases thought to be diagnostic of malignancy by at least one reviewer argues for a consensus approach to this diagnosis.

Identification of Malignant Cytologic Criteria in Pancreatobiliary Brushings With Corresponding Positive Fluorescence In Situ Hybridization Results

“…Cytologic criteria that were significantly different include depth of focus (PC, 25 Multiple logistic regression analysis revealed that abnormal single cells, irregular nuclear membranes, and enlarged nuclei were independently associated with malignancy. The only feature that was exclusively associated with malignancy in this study was the cell-within-cell architectural feature, but this feature was only rarely identified in malignant cases.…”

“…Likewise, in the present study, blinded review by 2 experienced cytopathologists increased the sensitivity of a positive diagnosis from 19% to 24%, but at the expense of Previous morphologic studies have been performed to evaluate diagnostic criteria for the detection of malignancy in pancreatobiliary brushings. [21][22][23][24][25] Investigators from Japan determined loss of honeycombing, enlarged nuclei, loss of polarity, bloody background, flat nuclei, and cell-within-cell arrangement to be the best criteria for diagnosis of malignancy in bile specimens based on multivariate statistics. 24 One of the first morphologic studies published on brushing specimens reported nuclear molding, chromatin clumping, and increased nuclear/cytoplasmic ratio (referred to as the Iowa criteria) to be most associated with malignancy by multiple logistic regression analysis.…”

FISHing for pancreatobiliary tract malignancy in endoscopic brushings enhances the sensitivity of routine cytology

“…To preserve the specificity of ERCP brushing cytology, pathologists are hesitant to categorize cases as positive for malignancy unless multiple cells with frankly malignant criteria are present. With the goal of improving the detection rate for malignancy in pancreatobiliary brushings, multiple studies have been published to identify the cytological criteria that are most associated with malignancy . Various combinations of morphological criteria were identified in these reports.…”

Comparison of diagnostic accuracy between CellprepPlus® and ThinPrep® liquid‐based preparations in effusion cytology

“…Many studies have compared liquid-based preparation methods, such as ThinPrepV R LBC, and the conventional smear, [3][4][5][6][7][8][9][10][11] and some reports have also examined CellprepPlusV R LBC. 12,13 However, to our knowledge, only one study has compared the accuracy and unsatisfactory rates in cytology between CellPrepV R LBC and ThinPrepV R LBC.…”