The Role of Fluorescence In Situ Hybridization in Pancreatobiliary Brushing Cytology: A Large Retrospective Review with Histologic Correlation

Abstract

(1) Background: Although the specificity of brush cytology for the detection of malignant pancreaticobiliary strictures is high, its sensitivity is low. Fluorescence in situ hybridization (FISH) can be used to detect chromosomal aneuploidy in biliary brushing specimens, and when used as an adjunct to routine cytology, it significantly improves diagnostic sensitivity. (2) Methods: We searched our laboratory information system to identify all bile duct brush cytology cases with follow-up surgical pathology between January 2001 and September 2019. Cytologic diagnoses were classified as negative, atypical, suspicious, or malignant. Correlated surgical pathological diagnoses were classified as benign or malignant. FISH test results were obtained for a subset of cytology cases with concurrent FISH testing, and the sensitivity, specificity, positive predictive value, and negative predictive value in identifying malignancy for cytology alone, FISH alone, and combined cytology and FISH were calculated. (3) Results: A total of 1017 brushing cytology cases with histologic correlation were identified. A total of 193 FISH tests were performed concurrently with cytological specimens. Malignant diagnoses were identified in 623 of 1017 patients, while 394 patients had benign strictures. The sensitivity, specificity, positive predictive, and negative predictive rate were 65%, 78%, 83%, and 49% for cytology alone; 72%, 67%, 63%, and 68% for FISH alone; and 85%, 42%, 60%, and 74% for combined cytology and FISH, respectively. Among FISH-positive cases, the risk of malignancy for polysomy was 82% and 32% for trisomy. (4) Conclusions: FISH improves the sensitivity and negative predictive rate of bile duct brush cytology. The combination of cytology and FISH has increased the sensitivity from 65% to 85% and the negative predictive rate from 49% to 74% when compared to cytology alone. A patient with a polysomy FISH result had a significantly higher risk of malignancy than a patient with a trisomy 7 result (82% vs. 32%, p < 0.00001).

Diagnostic Performance of Bile Duct Brush Cytology with Risk of Malignancy of Standardized Categories in the Wake of World Health Organization Reporting System for Pancreaticobiliary Cytopathology: An Updated Systematic Review and Meta-Analysis

“…The flow diagram of the study selection process is shown in Figure 1, as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [15]. Thirteen studies were included after exclusions per the criteria [10,11,[16][17][18][19][20][21][22][23][24][25][26]. Among the studies analyzed, 4,398 bile duct brushings were included, consisting of 2,589 samples classified as clinically malignant and 1,809 as clinically benign.…”

“…Numerous studies have utilized alternative approaches for sample acquisition, processing, and additional techniques in conjunction with BDC samples to enhance sensitivity. These include increasing the passes of endoscopic brush, liquid-based cytology processing, combination of BDC and tumor markers like CA-19.9 and CA-125, intraductal forceps biopsy, DNA image cytometry, fluorescent in situ hybridization, polymerase chain reaction-based mutation profiling, next-generation sequencing, microRNA expression analysis [8,16,18,20,[30][31][32][33][34][35][36][37][38]. The majority of the studies incorporated in the present meta-analysis have employed liquid-based cytology, either as a stand-alone method or in conjunction with conventional smears, for diagnostic assessment.…”

“…Seven studies were deemed to have a high risk of patient selection bias due to their consideration of the number of brushing samples as the unit of analysis instead of individual patients [10,[21][22][23][24][25][26]. Two studies uniformly regarded resection histopathology as the reference standard method for all cases [16,22]. Three studies considered a clinical follow-up period of >1 year, while one study specified a minimum follow-up duration of at least 10 months, leading to a low risk of flow and timing bias [11,[18][19][20].…”

Endoscopic diagnosis and treatment for proximal biliary obstruction of tumor origin (literature review)

“…Цитологическое исследование имеет значительную специфичность (90-100%), но малую чувствительность (20-40%) [5]. Флуоресцентная гибридизация in situ (FISH), по данным ряда авторов, значительно улучшила чувствительность по сравнению с изолированной браш-биопсией (85% по сравнению с 65%) и отрицательную прогностическую ценность (74% по сравнению с 49%) [6]. Щипцовая внутрипротоковая биопсия обеспечивает более полный образец ткани и включает субэпителиальную строму, но является более сложной для выполнения.…”