Evaluating Diagnostic Clarity: The Comparative Efficacy of BlueStain in Serous Effusion Cytology under the International System for Reporting Serous Fluid Cytopathology Reporting Framework.

Serous effusion cytology is a pivotal diagnostic and staging tool in clinical pathology, valued for its simplicity and cost-effectiveness. Staining techniques such as Giemsa and Papanicolaou are foundational, yet the search for rapid and efficient alternatives continues. Our study assesses the efficacy of an in-house-developed BlueStain, a toluidine blue variant, within the International System for Reporting Serous Fluid Cytopathology (TIS), aiming to optimize diagnostic clarity and resource use. MATERIALS AND METHODS: This section provides details on the cohort of 237 patients with serous effusions, the ethical approval process, sample collection, and staining procedures with BlueStain, Papanicolaou, and Giemsa. It also describes the microscopic evaluation criteria, scoring system, and statistical methods used to compare the stains. RESULTS: BlueStain demonstrated notable performance, particularly in identifying malignant cells, presenting a competitive alternative to the Papanicolaou stain, which, despite higher quality indices in other categories, requires more resources and time. The study revealed that BlueStain might offer a valuable balance between quality and efficiency, especially in cases where rapid diagnostic turnaround is essential. CONCLUSIONS: Our findings suggest that BlueStain is a viable staining method in the context of serous effusions, capable of providing detailed cytomorphological analysis. While traditional stains hold their place for their established diagnostic clarity, BlueStain offers a rapid and resource-optimized alternative. The absence of definitive diagnostic criteria in the atypical category and the inherent sample heterogeneity underscores the necessity for adaptable staining methods like BlueStain. The study highlights the potential trade-offs between detail and practicality in staining techniques, advocating for further research into innovative methods that do not compromise diagnostic precision for cost and time efficiency.

A Novel Validated Real-World Dataset for the Diagnosis of Multiclass Serous Effusion Cytology according to the International System and Ground-Truth Validation Data.

INTRODUCTION: The application of artificial intelligence (AI) algorithms in serous fluid cytology is lacking due to the deficiency in standardized publicly available datasets. Here, we develop a novel public serous effusion cytology dataset. Furthermore, we apply AI algorithms on it to test its diagnostic utility and safety in clinical practice. METHODS: The work is divided into three phases. Phase 1 entails building the dataset based on the multitiered evidence-based classification system proposed by the International System (TIS) of serous fluid cytology along with ground-truth tissue diagnosis for malignancy. To ensure reliable results of future AI research on this dataset, we carefully consider all the steps of the preparation and staining from a real-world cytopathology perspective. In phase 2, we pay special consideration to the image acquisition pipeline to ensure image integrity. Then we utilize the power of transfer learning using the convolutional layers of the VGG16 deep learning model for feature extraction. Finally, in phase 3, we apply the random forest classifier on the constructed dataset. RESULTS: The dataset comprises 3,731 images distributed among the four TIS diagnostic categories. The model achieves 74% accuracy in this multiclass classification problem. Using a one-versus-all classifier, the fallout rate for images that are misclassified as negative for malignancy despite being a higher risk diagnosis is 0.13. Most of these misclassified images (77%) belong to the atypia of undetermined significance category in concordance with real-life statistics. CONCLUSION: This is the first and largest publicly available serous fluid cytology dataset based on a standardized diagnostic system. It is also the first dataset to include various types of effusions and pericardial fluid specimens. In addition, it is the first dataset to include the diagnostically challenging atypical categories. AI algorithms applied on this novel dataset show reliable results that can be incorporated into actual clinical practice with minimal risk of missing a diagnosis of malignancy. This work provides a foundation for researchers to develop and test further AI algorithms for the diagnosis of serous effusions.

Optimal Volume Assessment for Serous Fluid Cytology.

OBJECTIVE: This study aimed to investigate the optimal volume of serous fluid needed for accurate diagnosis using The International System for Reporting Serous Fluid Cytopathology (TIS), as well as to provide information on the distribution of serous effusion cases in the TIS categories (ND: non-diagnostic, NFM: negative for malignancy, AUS: atypia of undetermined significance, SFM: suspicious for malignancy, MAL: malignant) and relevant epidemiological data. METHODS: A retrospective analysis of 2340 serous effusion cases (pleural, peritoneal, and pericardial) from two hospitals between 2018 and 2020 was conducted. TIS categories were assigned to each case, and for 1181 cases, these were correlated with the volume of the analyzed fluid. RESULTS: Our study found statistically significant differences in volume distributions between certain TIS categories. Statistically lower volumes were observed in NFM compared to MAL, in UNCERTAIN (ND, AUS, SFM) compared to both MAL and NFM, and in NOT MAL (ND, NFM, AUS, SFM) compared to MAL. However, these differences were not substantial enough to hold any clinical relevance. CONCLUSIONS: This study suggests that while fluid volume may slightly influence the TIS category, it does not impact the diagnostic accuracy of serous effusion cytology. Therefore, the ideal serous effusion specimen volume can be defined solely by practical parameters.

Diagnostic accuracy of International System for Reporting Serous Fluid Cytopathology: A systematic review and meta-analysis in malignancy diagnosis.

This study conducts the first meta-analysis to assess the aggregated risk of malignancy associated with each category of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) for reporting serous effusion cytology, while also evaluating diagnostic accuracy. PubMed/MEDLINE and Embase were systematically searched using the keywords "(pleural, peritoneal, and pericardial effusions) AND (serous effusion cytology) OR (International System for Reporting Serous Fluid Cytopathology)". Articles underwent risk of bias assessment using the QUADAS-2 tool. After excluding inadequate samples, a meta-analysis determined sensitivity and specificity for different cutoff points, including "atypical considered positive," "suspicious of malignancy considered positive," and "malignant considered positive." Summary receiver operating characteristic curves assessed diagnostic accuracy, and the diagnostic odds ratio was pooled. Sixteen retrospective cross-sectional studies, totaling 19,128 cases, were included. Sensitivity and specificity for the "atypical and higher risk categories" considered positive were 77% (95% confidence interval [CI], 68%-84%) and 95% (95% CI, 93%-97%) respectively. For the "suspicious for malignancy and higher risk categories" considered positive, sensitivity and specificity were 57% (95% CI, 49%-65%) and 100% (95% CI, 99%-100%) respectively. Sensitivity and specificity for the "malignant" category considered positive for malignancy were 70% (95% CI, 60%-77%) and 99% (95% CI, 98%-99%), respectively. The pooled area under the curve ranged from 85% to 89.5% for each cutoff. This meta-analysis underscores the ISRSFC's accuracy in reporting serous fluid cytology. It emphasizes the diagnostic importance of the "suspicious" and "malignant" categories in identifying malignancy, and the role of the "benign" category in ruling out malignancy.

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

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.

Clinical presentation and cytopathologic features of malignant pericardial cytology: a single institution analysis spanning a 29-year period.

INTRODUCTION: Pericardial effusion can be a consequence of various diseased states, including infection, autoimmune disease, renal failure, myocardial disease, and neoplasms. Although multiple case reports of malignancy-associated pericardial effusion have been published, few database analyses are available in these published reports. In this study, we retrospectively reviewed 1022 cytology cases and assessed malignancy-associated pericardial effusion. MATERIALS AND METHODS: We reviewed our cytology reports for pericardial effusion cases from January 1, 1983 to July 31, 2013. These cases were classified as benign, atypical, malignant, and nondiagnostic. The malignant cases were further characterized based on either immunohistochemical staining results or patients' history. RESULTS: We identified 1022 cases and grouped them as follows: 824 benign (80.6%), 38 atypical (3.7%), 158 malignant (15.4%), and 2 unsatisfactory (0.1%). Malignant cases included 131 adenocarcinoma (82.9%), 12 lymphoma (7.9%), 6 poorly differentiated carcinoma (3.8%), 4 mesothelioma (2.5%), 2 squamous cell carcinoma (1.3%), 1 melanoma (0.6%), 1 sarcoma (0.6%), and 1 small cell carcinoma (0.6%). Of these 131 adenocarcinomas, 83 cases had clinical history and/or immunohistochemical study available for further classification, which included 44 lung, 18 breast, 7 esophagogastric adenocarcinomas, 6 adenocarcinomas of unknown primary sites, 5 ovarian, and 2 rectal adenocarcinomas. The clinical presentation, prognosis, and cytopathologic features for malignant pericardial effusions are summarized. CONCLUSIONS: In this study, 15.4% of pericardial effusion cases were caused by metastatic malignancy, with lung adenocarcinoma being the most common primary site, followed by breast and lymphoma. Relatively young patients are affected, with average age being 56 years. Prognosis is poor for patients with malignant pericardial effusion. However, targeted therapy showed improved survival.