Are we ready to develop a tiered scheme for the effusion cytology? A comprehensive review and analysis of the literature

Abstract

Background: Cytology is widely utilized in the initial evaluation of fluid accumulation in the body cavities. The aim of this study was to determine the accuracy of cytology in distinguishing between benign and malignant (MAL) effusions. Methods:A comprehensive and systematic review of the literature was conducted to evaluate the accuracy of serous effusion cytology (SEC) against tissue biopsy/resection histology, imaging, or clinical follow-up as the reference test. Risk of publication bias and level of heterogeneity in the included studies was assessed. Meta-regression was performed to assess the effect of various variables on the accuracy of SEC. Results: Eighty studies met the inclusion criteria for meta-analysis comprising of 34 941 samples; of which 52 (0.2%), 22 202 (72.7%), 194 (0.6%), 711 (2.3%), and 6507 (21.3%) could be reclassified as nondiagnostic (ND), negative for malignancy (NFM), atypical (atypia of uncertain significance-AUS), suspicious for malignancy (SFM), and malignant (MAL), respectively. On follow-up, the mean risk of malignancy for ND, NFM, AUS, SFM, MAL was 17.4%, 20.7%, 65.9%, 81.8%, and 98.9%, respectively. A total of 73 studies were included in estimating the diagnostic accuracy of SEC. The bivariate mixed-effect model estimated the SEC sensitivity, specificity, diagnostic odds ratio, positive likelihood ratio, and negative likelihood ratio as 73.1%, 99.9%, 7850.6%, 2112.2%, and 0.27%, respectively. Conclusion: Serous effusion cytology shows high specificity and moderate sensitivity in the evaluation of serous effusions. A tiered classification scheme can improve the consistency of terminology for reporting SEC results, thus improving communication between the pathologists and clinical team, and quality of patient care. K E Y W O R D S analysis, classification scheme, comprehensive review, risk of malignancy, serous effusion cytology 1 | INTRODUCTION Serous effusion cytology (SEC) has been widely utilized in the initial evaluation of the etiology of fluid accumulation in the body cavities. Serous fluid can form in body cavities due to various inflammatory, infectious, and benign or malignant neoplasms. Malignancy is the underlying cause of serous effusion in 10% to 61% cases. 1,2 A majority of malignant effusions are caused by metastasis from adenocarcinoma of lung, breast, gastrointestinal, and female genital tract. 2,3 Malignant mesothelioma caninitially present as a serous effusion in up to 10% to 53% cases. 4-8

The utilization and utility of immunostains in body fluid cytology

“…It is difficult to compare the 2 studies, however, because the patient populations may differ significantly, as could the diagnostic style of the cytopathologists working at different institutions in different periods. The rate of indeterminate diagnoses found in their study appears high by today's standards, while that found in our study is identical with the 2.9% indeterminate (0.6% ATY and 2.3% SUS) diagnoses found in a recent review compiling data on 34,941 specimens from 80 published studies . We can also infer that the IHC use on pleural effusions increased significantly (6‐fold) in the 20 years ensuing the publication of the study from the University of Iowa, a conclusion also supported by other studies …”

“…Although the total number of cases included in our study was relatively high, as we analyzed a consecutive series of over 4000 cases from pleural, peritoneal, and pericardial effusions as well as from pelvic and peritoneal washing specimens, the percentage of malignant cases was relatively low at 13.5%. The range of malignancy rates in BFC reported in the literature varies from 10% to 61%; with an average of 21.3%, which is closer to our rate of POS diagnoses. The relatively lower malignancy rate found in our study reflects our institution's patient population, and especially the fact that it has large solid organ transplantation programs, in which patients with end‐stage heart, renal, or liver disease are more likely to have benign transudative effusions.…”

The value of a tiered cytology diagnostic reporting system in assessing the risk of malignancy in indeterminate serous effusions

“…There are limited data in the literature on the ROM for serous effusion specimens and the clinical effect of an indeterminate (ie, AUS vs SFM) diagnosis. A meta‐analysis of 73 studies reported a mean ROM for the AUS and SFM categories of 65.9% and 81.8%, respectively 19 . Another recently published single‐institution study reported an ROM of 50% and 83.3% for AUS and SFM cases, respectively 20 .…”

Role of CD68 immunohistochemistry in categorizing benign nonmesothelial cell population and refining “atypical” category in serous fluid cytology

“…This system was proposed in February 2019, and an online survey has been conducted to help the authors in addressing the perceived problem areas in serous fluid cytology 3 . Although a meta‐analysis study of the literature on serous fluid cytology performed by Farahani et al showed high specificity and moderate sensitivity of the ISRSFC tier classification, no clear cytological criteria or systematic approach guidelines for gray zone tiers had been introduced 12 . Like in any other classification system in cytology, atypical and suspicious groups should be considered as the last resort.…”