Contribution of Nuclear Morphometry by Confocal Laser Scanning Microscopy to the Diagnosis of Malignant Bile Duct Strictures

Papaxoinis, Kostis; Patsouris, Efstratios; Athanassiadou, Pauline; Nicolopoulou-Stamati, P.

doi:10.1159/000325114

Cited by 9 publications

(3 citation statements)

References 24 publications

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“…1,2 Most 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.…”

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confidence: 99%

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

Hacıhasanoğlu¹,

Memiş²,

Pehlivanoğlu³

et al. 2018

Archives of Pathology &Amp; Laboratory Medicine

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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...

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

Hacıhasanoğlu¹,

Memiş²,

Pehlivanoğlu³

et al. 2018

Archives of Pathology &Amp; Laboratory Medicine

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“…1 Additionally, the high frequency of deceptively benign-appearing carcinomas in this site accounts for a significant number of false-negative results. 2 As a result of these factors cytological diagnosis of malignancy on bile duct brushing is notoriously limited with low sensitivity rates (6-64%; mean 42%) and negative predictive value, [3][4][5][6][7][8][9][10][11][12] despite high test specificity (98-100%). 2,13,14 Because of newly improved imaging modalities bile duct brushings are steadily increasing and cytologic abnormalities are being identified in these samples even before a mass is visible.…”

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Cytologic predictors of malignancy in bile duct brushings: a multi-reviewer analysis of 60 cases

et al. 2017

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Diagnosing malignancy in bile duct brushings is highly challenging. Seven reviewers of variable backgrounds and levels of participation in bile duct brushing sign out blindly reviewed 60 specimens (30 malignant with histologic confirmation and 30 benign (15 stented) with resection or ≥18 months of uneventful follow-up), testing the utility of 14 malignant characteristics. Eleven characteristics were statistically significantly associated with malignancy including 3-dimensional clusters (63% in malignant vs 3% in benign, odds ratio 50, P=0.0003), pleomorphism (62 vs 3, odds ratio 48, P=0.0004), 2-cell population (60% vs 3, odds ratio 44, P=0.0005), chromatin pattern (hypo/hyperchromasia) changes (70% vs 7%, odds ratio 33, P<0.0001), high nuclear-to-cytoplasmic ratio (48 vs 3%, odds ratio 27, P=0.0023), cytoplasmic vacuoles (43 vs 3%, odds ratio 22, P=0.0042), nuclear irregularity (70 vs 10%, odds ratio 21, P<0.0001), cellular discohesion (38 vs 3%, odds ratio 18, P=0.0082), hypercellularity (23% vs 0), nuclear molding (20% vs 0) and prominent nucleoli (21% vs 0). Necrosis and infiltrating inflammation were not helpful in identifying malignancy ('neutrophil cannibalism' was noted in 43% malignant); 21/30 (70%) malignant brushings had ≥3 malignant characteristics, while 23 (77%) benign brushings had none. Of 20 brushings with ≥4 characteristics, 1(5%) proved benign and showed detachment atypia, a close malignant mimicker in brushings. Identification of 3 characteristics maximized the combined sensitivity (70%), specificity (97%) and accuracy (83%), but sensitivity dropped as number of characteristics increased. Identification of 3/11 characteristics (3-dimensional clusters, pleomorphism, high nuclear-to-cytoplasmic ratio, nuclear irregularity, hypercellularity, discohesion, chromatin changes, vacuoles, prominent nucleoli, molding and 2-cell population) improves pathologists' overall performance greatly.

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“…Pancreaticobiliary strictures are difficult to diagnose accurately because of limitations of current diagnostic methods and characteristics of malignancies [2, 8, 9] such as most of them grow along the bile duct wall [3, 6, 10–14]. The flexible probe-based confocal laser endomicroscopy (pCLE) has overcome many of the challenges met when evaluating the biliary tree [5].…”

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A Review on the Use of Confocal Laser Endomicroscopy in the Bile Duct

Smith

Kline

Gaidhane

et al. 2012

Gastroenterology Research and Practice

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Background. Current methods to diagnose malignant biliary strictures are of low sensitivity. Probe-based confocal laser endomicroscopy (pCLE) is a new approach that can be used to evaluate in vivo histopathology of the GI tract. This paper is of studies evidencing pCLE's application in the diagnosis of indeterminate biliary strictures. Methods. This paper examined peer-reviewed studies conducted between January 2000 and November 2011. A PubMed search for relevant articles was performed using the following keywords:“pCLE”, “confocal”, “endomicroscopy”, “probe-based confocal laser endomicroscopy”, “and “bile duct”. Further individual review was done to assess the screened articles' relevance to the topic. Results. After individual review, 6 studies were included; with a cumulative sample size of 165, with 75 subjects identified as having a malignancy. These studies included tertiary care centers in Germany, France, and USA, including one multicenter trial. 3 studies assessed pCLE's specificity (range 67%–88%) ,sensitivity (range 83%–98), and accuracy (range 81%–86%). Conclusion. Confocal endomicroscopy is a novel and promising modality for the biliary tree. Further studies need to be conducted both to establish its usefulness for the diagnosis of indeterminate biliary strictures and to understand the histological meaning of the imaging patterns that are observed.

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Contribution of Nuclear Morphometry by Confocal Laser Scanning Microscopy to the Diagnosis of Malignant Bile Duct Strictures

Cited by 9 publications

References 24 publications

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

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

Cytologic predictors of malignancy in bile duct brushings: a multi-reviewer analysis of 60 cases

A Review on the Use of Confocal Laser Endomicroscopy in the Bile Duct

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