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Simple Summary: Feline infectious peritonitis (FIP) is a severe and even fatal inflammatory disease of cats, caused by feline coronavirus (FCoV), and remains an important diagnostic challenge. This study validates the flow cytometry-based delta total nucleated cells (∆TNC) on the Sysmex XN-1000V® in effusion samples and introduces the FIP Effusion Index, a novel diagnostic method that integrates cellular and inflammatory markers of FIP in effusions. The FIP Effusion Index demonstrated improved diagnostic accuracy, achieving 96.3% sensitivity and 95.7% specificity for values of 5.06 or higher, and perfect specificity (100%) with 96.3% sensitivity at values of 7.54 or above. This combined approach outperforms traditional methods, providing a superior, rapid, and cost-effective tool for the accurate and timely FIP diagnosis. It offers considerable potential for enhancing the management of suspected FIP cases in clinical practice, with potential applications in both veterinary and human medicine for related coronavirus diseases. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led the medical and scientific community to explore the pathogenesis and clinical manifestations of coronaviruses. In felines, a widespread coronavirus known as feline coronavirus (FCoV) can lead to feline infectious peritonitis (FIP), a highly fatal disease characterised by severe systemic inflammation. Diagnosing FCoV remains challenging due to the limited accuracy of the available methods. The present study introduces the FIP Effusion Index, a novel diagnostic method that combines the albumin-to-globulin (ALB/GLOB) ratio with the delta total nucleated cell (∆TNC) count obtained via flow cytometry using the Sysmex XN-1000V® analyser in effusions. Samples from cats (n = 50) with suspected FIP were analysed for ∆TNC, with findings showing that a ∆TNC ≥ 2.1 is highly indicative of FIP and a ∆TNC ≥ 4.9 can be considered diagnostic. The FIP Effusion Index enhanced diagnostic precision in our group of samples, achieving 96.3% sensitivity and 95.7% specificity for values ≥ 5.06, and reaching perfect specificity (100%) with 96.3% sensitivity for values ≥ 7.54. This combined approach surpasses the accuracy of individual parameters, establishing the FIP Effusion Index as a superior diagnostic tool for FIP, with potential applications in both veterinary and human medicine for related coronavirus diseases. [ABSTRACT FROM AUTHOR]

Introduction: Morphology is routinely used for detecting malignant cells in body fluids, but it has limitations. Recently, flow cytometry (FCM) is used as an effective tool for studying non‐haematological malignancies. The main objective of this study is to standardize a simple and rapid FCM test for the detection of malignant epithelial cells in body fluids. Materials and Methods: Body fluids that had been processed for cytology/cytology and FCM were enrolled in this prospective study. We developed a fluorescent‐labelled, monoclonal antibody panel composed of cell surface markers for this FCM assay. We compared the results of cytology/cell block and FCM. Results: A total of 121 fluid samples were studied. Comparing the diagnostic performance of cytology/cell block and FCM, 52 (43%) cases were positive and 60 (49.5%) cases were negative for carcinoma cells by both techniques. Nine cases showed discordant results between the two techniques. Six cases were cytology+ but FCM‐ and three cases were FCM+ cytology‐. Clustered Epithelial Cell Adhesion Molecule (EpCAM)‐positive events with high scatter properties were definitive for positive diagnosis by FCM. We studied PD‐L1 expression in 13 cases by FCM. Six cases were reported as false negative by this FCM assay due to hypocellularity and lack of EpCAM expression in malignant cells. Conclusions: This FCM assay is simple, easier and cost‐effective yielding sensitive results with no inter‐observer variability. FCM would become a valuable tool to complement routine diagnostic cytology and reduces misdiagnosis. [ABSTRACT FROM AUTHOR]

Serous fluids offer crucial diagnostic insights, but inconsistent analysis hampers reporting quality, especially in indeterminate (ID) categories like atypia of undetermined significance (AUS) and suspicious for malignancy (SFM). The 2020 International System for reporting Serous Fluid Cytopathology (TIS) aims to standardize communication and reduce reporting disparities. This study evaluates TIS's role in AUS and SFM categories within our institution. A 4-year retrospective search of cytopathology reports from December 2015 to December 2019 for AUS and SFM diagnoses in pleural, ascitic, pericardial fluids, and peritoneal washings was performed and results reclassified using TIS definitions. The risk of malignancy (ROM) was calculated for existing and reclassified diagnoses. Over 4 years, we received 2998 serous fluid specimens. AUS constituted 2.3% (70 cases), while SFM constituted 0.5% (16 cases). Excluding repeats, 80 cases were TIS-reviewed. Sixteen cases of ID diagnoses were reclassified. Two cases of AUS were changed to negative for malignancy (NFM) and 12 to SFM. Two SFM cases were upgraded to malignancy. ROM shifted from 63% to 60% for AUS and 100% to 85% for SF (TIS's ROM range: AUS: 66% ± 10%; SFM: 82% ± 4.8%). This institution's ID diagnosis rate is low. AUS ROM is challenging but aligns with TIS, primarily favoring benign. All SFM diagnoses are highly suspicious but quantitatively inadequate for definitive malignancy, explaining the elevated ROM. AUS rate should gauge quality, not serve as a catch-all category. Algorithmic cytology with cell blocks and ancillary studies aids reclassification. TIS is user-friendly and is a consistent methodology for standardized reporting. Further studies are needed to evaluate ROM and define reproducible diagnostic criteria for each category for better system utilization. • Reclassified indeterminate diagnosis of serous fluids using the criteria published by The International System for Reporting Serous Fluid Cytopathology. • AUS rate should be a quality indicator for each institution and be monitored. • Cell block and immunostain/ancillary studies are helpful in reclassifying indeterminate diagnoses into definitive categories. [ABSTRACT FROM AUTHOR]

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led the medical and scientific community to explore the pathogenesis and clinical manifestations of coronaviruses. In felines, a widespread coronavirus known as feline coronavirus (FCoV) can lead to feline infectious peritonitis (FIP), a highly fatal disease characterised by severe systemic inflammation. Diagnosing FCoV remains challenging due to the limited accuracy of the available methods. The present study introduces the FIP Effusion Index, a novel diagnostic method that combines the albumin-to-globulin (ALB/GLOB) ratio with the delta total nucleated cell (∆TNC) count obtained via flow cytometry using the Sysmex XN-1000V® analyser in effusions. Samples from cats (n = 50) with suspected FIP were analysed for ∆TNC, with findings showing that a ∆TNC ≥ 2.1 is highly indicative of FIP and a ∆TNC ≥ 4.9 can be considered diagnostic. The FIP Effusion Index enhanced diagnostic precision in our group of samples, achieving 96.3% sensitivity and 95.7% specificity for values ≥ 5.06, and reaching perfect specificity (100%) with 96.3% sensitivity for values ≥ 7.54. This combined approach surpasses the accuracy of individual parameters, establishing the FIP Effusion Index as a superior diagnostic tool for FIP, with potential applications in both veterinary and human medicine for related coronavirus diseases.

From its onset and during its progression, lung cancer may affect various extrapulmonary structures. These include the serous membranes, the pleura and pericardium, and less frequently the central nervous system, with leptomeningeal involvement. In these cases, fluid accumulates in the serous membranes which may contain substances secreted by the tumor. Measuring the concentrations of these substances can provide useful information for elucidating the origin of the fluid accumulation, either in pleural and pericardial effusions or in cerebrospinal fluid. This paper describes the histological types of lung cancer that most frequently affect the serosa and leptomeninges. It also reviews the literature on tumor markers in different fluids and makes recommendations for their interpretation. [ABSTRACT FROM AUTHOR]

Background: To standardize the reporting pattern across various institutions, recently the international system for reporting serous fluid cytology (ISRSFC) was introduced. The objective of the present study was to classify serous fluids into various categories as per the ISRSFC, derive the risk of malignancy for each category and determine the diagnostic efficacy of fluid cytology when ISRSFC was applied. Methodology: Cross-sectional study involving 235 cases of serous effusion over a duration of two years. All the cases were reclassified as per ISRSFC into five categories. Descriptive statistics was derived. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was determined in 74 cases wherein final diagnosis was confirmed by clinical findings, radiology, or cell block. Results: Out of total 235 cases of fluid examined, distribution of cases in the diagnostic categories were as follows, 11 (4.6%) in nondiagnostic (ND), 208 (88.51%) in negative for malignancy (NFM), 5 (2.12%) in atypia of undetermined significance (AUS), 2 (0.85%) in suspicious for malignancy (SFM) and 9(3.82%) in malignant (MAL)category. Out of 208 cases of NFM, mesothelial cells were seen in only 8 (3.8%) cases. The risk of malignancy was 0% each in ND and NFM, 40% in AUS, 100% each in SFM and MAL. Sensitivity and specificity of fluid cytology was 100% and 96.6% respectively while PPV and NPV was 81.81% and 100 % respectively. Conclusion: ISRSFC is easy to apply and has high diagnostic efficacy. Most of the serous effusions fall in negative for malignancy category. Mesothelial cells are not important for specimen adequacy. [ABSTRACT FROM AUTHOR]

Serous fluids, encompassing pleural, pericardial, and peritoneal fluids, exhibit a wide spectrum of neoplastic and non-neoplastic conditions. Malignant effusions commonly result from metastasis, particularly from adenocarcinomas, and less frequently from primary malignant mesothelioma. Cytologic assessment of serous effusions remains an invaluable tool, especially with the expanding role of ancillary techniques available to resolve diagnostically challenging cases. The recently introduced International System for Reporting Serous Fluid Cytopathology (TIS) establishes a standardized reporting system with five distinct diagnostic categories: nondiagnostic (ND), negative for malignancy (NFM), atypia of undetermined significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). Understanding the distribution of malignancy in serous fluids by site of origin in effusion cytology is important, especially in patients with an unknown primary. Immunohistochemistry (IHC) combined with clinical and radiologic data plays a crucial role in confirming malignancy, establishing the primary site, determining the stage, predicting prognosis, monitoring recurrence, and influencing medical management. This review aims to provide an overview of TIS reporting system, emphasizing its malignant category. It provides updates on the distribution of malignancies in serous fluids and discusses valuable IHC panels based on differential diagnosis, addressing challenging cases within this context.

Background: To standardize the reporting pattern across various institutions, recently the international system for reporting serous fluid cytology (ISRSFC) was introduced. The objective of the present study was to classify serous fluids into various categories as per the ISRSFC, derive the risk of malignancy for each category and determine the diagnostic efficacy of fluid cytology when ISRSFC was applied. Methodology: Cross-sectional study involving 235 cases of serous effusion over a duration of two years. All the cases were reclassified as per ISRSFC into five categories. Descriptive statistics was derived. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was determined in 74 cases wherein final diagnosis was confirmed by clinical findings, radiology, or cell block. Results: Out of total 235 cases of fluid examined, distribution of cases in the diagnostic categories were as follows, 11 (4.6%) in nondiagnostic (ND), 208 (88.51%) in negative for malignancy (NFM), 5 (2.12%) in atypia of undetermined significance (AUS), 2 (0.85%) in suspicious for malignancy (SFM) and 9(3.82%) in malignant (MAL)category. Out of 208 cases of NFM, mesothelial cells were seen in only 8 (3.8%) cases. The risk of malignancy was 0% each in ND and NFM, 40% in AUS, 100% each in SFM and MAL. Sensitivity and specificity of fluid cytology was 100% and 96.6% respectively while PPV and NPV was 81.81% and 100 % respectively. Conclusion: ISRSFC is easy to apply and has high diagnostic efficacy. Most of the serous effusions fall in negative for malignancy category. Mesothelial cells are not important for specimen adequacy.

AIM: To describe a case of aqueous misdirection complicated by subsequent persistent choroidal effusions following implantation of a Preserflo MicroShunt (PMS) device to treat advanced closed angle glaucoma. METHODS: A 67-year-old caucasian female with advanced primary angle-closure glaucoma on four medications with an intraocular pressure (IOP) of 26 mm Hg was listed for a PMS insertion with mitomycin C (MMC). RESULTS: Past ocular history was significant for pseudophakia and previous yttrium aluminum garnet (YAG) peripheral iridotomy. Surgery was uneventful but on the first postoperative day, she developed aqueous misdirection complicated by subsequent development of persistent uveal effusions. Conventional treatment strategies including atropine drops, YAG hyaloidotomy and choroidal effusion drainage proved ineffective. A combination of oral steroids and pars plana vitrectomy (PPV) along with an irido-zonulo-hyloidectomy (IZH) proved efficacious. CONCLUSION: To the best of the author's knowledge, this is the first published case of aqueous misdirection complicated with the presence of significant, unresolving choroidal effusions, highlighting the possibility and sequelae of comorbid pathology in nanophthalmic eyes.

Effusions, characterized by abnormal fluid accumulations in body cavities, present difficulties in identifying the primary organs of metastatic tumors through cytopathologic investigation, particularly in cancer-related complications. This retrospective cross-sectional laboratory study aimed to investigate the role of thyroid transcription factor-1 (TTF-1) in distinguishing lung adenocarcinomas from non-pulmonary adenocarcinomas in effusions. The study was conducted at Almobarak Cytopathology Laboratory, a private cytopathology laboratory. H&E was used to confirm the histological diagnosis of 58 archived cell blocks. TTF-1 immunostaining patterns were then correlated with the histological diagnosis. Statistical analysis, including numerical and graphical data summaries, was conducted using the Chi-square test in SPSS 23. TTF-1 expression was observed in 20 (34.4%) cases, while 38 (65.5%) cases showed no TTF-1 reaction. Positive TTF-1 was found in pleural fluid in 61.1 % of lung adenocarcinomas, while negative TTF-1 was found in only 3.4%. TTF-1 was not detected in the majority of peritoneal fluid samples. There was a highly significant relationship between pleural fluid, TTF-1, and lung adenocarcinoma (p=0.000). The data provided further evidence that TTF-1 is a useful marker for distinguishing pulmonary adenocarcinomas from non-pulmonary adenocarcinoma tumors. [ABSTRACT FROM AUTHOR]

We sought to assess the utility of the International System for Serous Fluid Cytopathology (TIS) in the context of our department's routine practice. We examined 1028 archived effusion cytology (pleural, peritoneal, and pericardial) cases from 2018 to 2019, and re-classified them along the international system into the following diagnostic categories: nondiagnostic (ND), negative for malignancy (NFM), atypia cells of undetermined significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). The full distribution of the cases examined was as follows: ND 2.0%; NFM 66.1%; AUS 6.0%; SFM 4.7%; MAL 21.2%. Overall risk of malignancy for each category was calculated as: ND 30.0%; NFM 18.0%; AUS 61.9%; SFM 100%; MAL 94.4%. The overall performance attributes of TIS were as follows: sensitivity 57.1%; specificity 98.3%; positive predictive value 94.4%; negative predictive value 82.0%; diagnostic accuracy 84.5%. The new classification was simple and intuitive to use and our results appear to fall within the expected ranges of the new guidelines, with risk of malignancy and accuracy comparable to similar studies. The availability of a cell block allowed for refinement of the diagnosis in a majority of cases with equivocal cytology, though this was dependent on the cell yield. • We have undertaken one of the largest scale assessments of the International System for Serous Fluid Cytopathology (TIS) with over 1000 archival cases reviewed and re-categorized. • Being a relatively new system, we believe that our study assists in the validation of the TIS, as well as contributing to a still-developing consensus on parameters such as expected rates and risk of malignancy for each diagnostic category. • We are one of the first groups to compare our archival cell block results with the TIS, and demonstrate their predictive value, particularly in the more equivocal atypical and suspicious categories. [ABSTRACT FROM AUTHOR]

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Objectives: The diagnosis of lymphoma on cytologic preparations and core needle biopsies (CNBs) is often challenging due to limited material that precludes additional ancillary testing for accurate classification. We describe our institutional experience with patients who ultimately received a diagnosis of lymphoma using cytologic preparations and CNB material along with additional ancillary testing. Material and Methods: All patients whose cytology material (fluids, cytologic smears, and cell block) and CNB resulted in a diagnosis of lymphoma, atypical lymphoid population, or suspicious for lymphoma were retrieved. Diagnoses of lymphoma followed the established nomenclatures of the World Health Organization (WHO). For all cases, the ancillary test profiles were captured and summarized. Results: Of 389 cases identified, 17 (4.4%) were diagnosed as atypical lymphoid cells and 31 (7.9%) were suspicious for lymphoma resulting in an indeterminate rate of 12.3%. The rest of the malignant cases (341; 87.7%) were classified using 2017 WHO lymphoid classification system. Six low-grade and 26 high-grade B-cell lymphomas were not further classified because of limited tissue. B-cell lymphomas were the largest category (73.0%): Primarily diffuse large B-cell lymphoma (21.4%), followed by follicular lymphoma (17.5%) and chronic lymphocytic leukemia/small lymphocytic lymphoma (10.9%). A total of 140 cases (36.0%) had flow cytometry results, but 30 specimens (21.4%) were insufficient. Cytogenetic and molecular studies were performed for 78 cases (20.0%). Conclusion: Full classification of lymphomas is possible with combined cytologic preparations and CNB material and it is an attractive first sampling modality in the diagnostic process for this disease group. [ABSTRACT FROM AUTHOR]

Objectives: Signet-ring cells (SRCs) in effusion specimens represent a diagnostic challenge. In this study, a consecutive series of pleural and peritoneal effusions with benign SRCs are examined and compared with malignant SRCs. Material and Methods: We reviewed consecutive Wright-stained serous effusion slides and searched for cases with SRCs. Corresponding ThinPrep slides and clinical histories were reviewed. Cytology cases with known signet-ring adenocarcinoma were retrieved and reviewed. Results: Four hundred Wright-stained serous effusions were reviewed. Eighteen cases were identified with SRC-like cells. Thirteen patients had liver cirrhosis, three patients had end-stage renal disease, one patient had a history of pancreatic adenocarcinoma, and one patient had endometrioid carcinoma. For the latter two patients, the primary tumor showed no histologic findings of signet-ring features. In all cases, no SRCs were found on the corresponding ThinPrep slides. Five cytology cases with malignant SRCs were reviewed. Benign SRCs have a uniformly pale and markedly distended cytoplasm, and the nuclei are thin and curved. The malignant SRCs showed larger non-curved nuclei and bubbly mucin-containing cytoplasm. Conclusion: Mesothelial cells and histiocytes can mimic signet-ring adenocarcinoma cells on Wright-stained slides. Correlation with ThinPrep specimens is necessary before reporting, as the SRCs typically are not present in ThinPrep preparations. [ABSTRACT FROM AUTHOR]

Due to the remarkably wide morphologic spectrum of reactive mesothelial cells, some of the effusion fluids may be difficult to interpret with objective certainty by cytomorphology alone. Cytomorphology of well to moderately differentiated adenocarcinomas (responsible for the bulk of malignant effusions) may overlap with floridly reactive mesothelial cells. Even mesotheliomas including diffuse malignant epithelioid mesothelioma, are usually cytomorphologically bland without unequivocal features of malignancy. The intensity of challenge depends on the interpreter's training or experience level, institutional demographics of patients (such as type of prevalent diseases, predominant sex and age group), technical support, and quality of cytopreparatory processing. In general immunocytochemistry is valuable adjunct to facilitate objective interpretation with or without other ancillary techniques as indicated. An increasing number of immunomarkers is further refining the contribution of immunohistochemistry to this field. However, application of immunohistochemistry to effusion fluids is relatively challenging because of many variables. Multiple factors such as delay after specimen collection, specimen processing related factors including fixation and storage; ambient conditions under which paraffin blocks are archived (for retrospective testing); antigen retrieval method; duration of antigen retrieval step; antibody clone and dilution; and antibody application time are identical to application of immunohistochemistry in other areas. The significant challenge related to the potential compromization of the immunoreactivity pattern due to exposure to non-formalin fixatives / reagents is also applicable to effusion fluid specimens. The immunoreactivity results would be compared and corelated with cumulative metadata based on the reported studies performed and validated on formalin-fixed paraffin-embedded tissue sections. Deviating from such protocols may lead to suboptimal results, which is not uncommon in clinical practice with potential compromization of patient care and related liability. Because of this, it is critical to perform immunocytochemistry on formalin- fixed cell-block sections only. In addition, unless the interpretation criteria for immunohistochemical evaluation of effusion fluids are not modified specifically, it may not be productive in resolving some challenging cases. However, this aspect is not well elaborated in the literature. A basic and critical challenge is finding and locating the cells of interest in cell-block sections of effusion fluids. A unique approach is to choose a fundamental immunopanel which highlight the mesothelial and inflammatory cells in reactive effusion fluids to create the basic map. This allows detection of a 'second-foreign' population which can be immunocharacterized further with the help of subtractive coordinate immunoreactivity pattern (SCIP) approach elaborated here. [ABSTRACT FROM AUTHOR]

Background: Micronucleus (MN) is an extranuclear body within the cell formed due to failure of incorporation of whole chromosomes or their fragments during cell division. MN scoring can be done to identify malignant effusions. Aims: This study aimed to score micronuclei to distinguish malignant effusion from benign effusions and to correlate MN score with type of malignant effusion. Methods and Materials: A retrospective study was conducted on 30 malignant and 30 benign effusions. The number of micronucleated cells per 1,000 cells was counted in effusion smears stained with Papanicolaou stain under oil immersion (1,000×). Results: The mean MN score in malignant effusions was 3.77 with standard deviation (SD) of 2.13. The mean MN score in benign effusions was 0.50 with SD of 0.57. The difference in MN score between malignant and benign effusions is statistically significant (P < 0.001). A cut-off MN score of 6.5 was seen to distinguish malignant and benign effusions with 100% specificity and 100% sensitivity in this study. Conclusions: MN score is higher in malignant effusions when compared with benign effusions. This can be used to differentiate malignant effusions from benign effusions in low resource setting.

Introduction: In developing countries where talc may not be readily available, video-assisted thoracoscopic (VATS) iodopovidone pleurodesis offers an excellent alternative for the treatment of malignant pleural effusions (MPEs). Methods: This study analyzes a retrospective experience using VATS iodopovidone pleurodesis for malignant pleural effusions at a single cardiothoracic center in the capital of Colombia evaluating success according to LENT (Lactate, Eastern Cooperative Oncology Group-ECOG, Neutrophil- Lymphocyte ratio, Tumor type) scores. A total of 75 records of patients taken to VATS iodopovidone pleurodesis for MPEs were retrieved from our institutional database during a 5-year period from 2014- 2019. Of these, 45 had complete clinical history data necessary to analyze both LENT scores and postop follow-up imaging. Results: Of the 45 patients evaluated, 93.3% (42 patients) had either complete resolution of pleural effusions or partial resolution with an asymptomatic recovery within the first month post op. Chest pain was the most common postoperative complaint, which was present in 20% of patients. The mean postoperative ECOG score was 2±1.7. Patients with moderate to high-risk LENT scores had success rates of 96.7% and 92.3% respectively. Conclusion: Video-assisted thoracoscopic pleurodesis using Iodopovidone-iodine is an effective approach for MPEs. In developing countries where Iodopovidone iodine is readily available and affordable, patients may benefit from this agent with excellent results and minimal complications. [ABSTRACT FROM AUTHOR]

Ovarian carcinomas and carcinosarcomas often cause malignant effusions, an accumulation within serous cavities of fluid containing cancer cells. Few studies have focused on the molecular alterations and genetic mechanisms behind effusion formation. The present study investigated the mutation status of TP53, PIK3CA, KRAS, HRAS, NRAS and BRAF in effusion fluids from 103 patients with ovarian cancer. In addition, array Comparative Genomic Hybridization (aCGH) analysis was performed on 20 effusions from patients with high-grade serous carcinoma (10 cases positive for TP53 mutation and 10 with TP53 wild-type). TP53 mutations, two of which were novel: c.826_830delCCTGT and c.475_476GC>TT, were identified in 44% of the cases. Mutations in KRAS, HRAS, and PIK3CA were identified in two, two and four cases, respectively. None of the effusions analysed showed NRAS or BRAF mutations. The aCGH analysis revealed highly imbalanced genomes similar to those described in primary ovarian carcinomas. No specific profile was indicated to distinguish tumors with TP53 mutations from those without. The molecular profiling of cells found in effusion fluids from patients with ovarian cancer thus showed considerable molecular heterogeneity. TP53 seems to be the most frequently mutated gene in these cells and may serve a leading role in the metastatic process. [ABSTRACT FROM AUTHOR]

Background: Micronucleus (MN) is an extranuclear body within the cell formed due to failure of incorporation of whole chromosomes or their fragments during cell division. MN scoring can be done to identify malignant effusions. Aims: This study aimed to score micronuclei to distinguish malignant effusion from benign effusions and to correlate MN score with type of malignant effusion. Methods and Materials: A retrospective study was conducted on 30 malignant and 30 benign effusions. The number of micronucleated cells per 1,000 cells was counted in effusion smears stained with Papanicolaou stain under oil immersion (1,000×). Results: The mean MN score in malignant effusions was 3.77 with standard deviation (SD) of 2.13. The mean MN score in benign effusions was 0.50 with SD of 0.57. The difference in MN score between malignant and benign effusions is statistically significant (P < 0.001). A cut-off MN score of 6.5 was seen to distinguish malignant and benign effusions with 100% specificity and 100% sensitivity in this study. Conclusions: MN score is higher in malignant effusions when compared with benign effusions. This can be used to differentiate malignant effusions from benign effusions in low resource setting. [ABSTRACT FROM AUTHOR]

Introduction: The International Serous Fluid Cytopathology Reporting System (TIS) was developed to standardize communication among health professionals reporting analyses of serous fluid samples. The categories include non-diagnosis (ND), negative for malignancy (NFM), atypia of undetermined significance (AUS), suspected malignancy (SFM), and malignant (MAL). Each category was characterized by a risk of malignancy (ROM)., Methods: We performed a literature review to analyze studies related to TIS using several sources, including PubMed, followed by a search of relevant cytopathology journal websites (American Cancer Society, Diagnostic Cytopathology, Journal of the American Society of Cytopathology, and Acta Cytologica and Cytopathology). The search included articles published between January 2020 and December 2023, using the terms "international AND serous fluid system.", Results: We identified 257 articles, of which 20 addressed the inclusion and exclusion criteria. The overall ROMs for each category were 23.55% for ND, 16.46% for NFM, 50.78% for AUS, 91.34% for SFM, and 98.21% for MAL., Conclusion: Considering the TIS-recommended ROM rates, the ND category was between the suggested intervals, while the SFM category rate was bigger than expected. The other categories (NFM, AUS, and MAL) were below expected values. SFM and MAL had a stronger association with MAL results. New studies are needed to determine each category's ROM rate from TIS accurately., (© 2024 S. Karger AG, Basel.)

From its onset and during its progression, lung cancer may affect various extrapulmonary structures. These include the serous membranes, the pleura and pericardium, and less frequently the central nervous system, with leptomeningeal involvement. In these cases, fluid accumulates in the serous membranes which may contain substances secreted by the tumor. Measuring the concentrations of these substances can provide useful information for elucidating the origin of the fluid accumulation, either in pleural and pericardial effusions or in cerebrospinal fluid. This paper describes the histological types of lung cancer that most frequently affect the serosa and leptomeninges. It also reviews the literature on tumor markers in different fluids and makes recommendations for their interpretation.

The International System for the Reporting of Serous Fluid Cytopathology was initiated to provide a common language for cytopathology reports on body fluids. The International Academy of Cytology and the American Society of Cytopathology collaborated to provide evidence-based and expert-driven terminology for reporting serous fluids. Lead editors were selected and expert authors invited to form working groups for the diagnostic categories and special sections. Preliminary results of the collaboration include the 6 diagnostic terminology categories: non-diagnostic, negative for malignancy, atypia of undetermined significance, suspicious for malignancy, malignant-primary, and malignant-metastatic. Four special sections on ancillary testing, peritoneal washings, cytotechnical aspects, and quality assurance will appear in the final text. Initial results of an international survey indicate strong support for a uniform terminology for reporting serous fluids. This article outlines the initial findings of the collaboration as presented to the United States and Canadian Academy of Pathology at the 2019 annual meeting at the National Harbor, MD. [ABSTRACT FROM AUTHOR]

We live in the "era" of minimally invasive procedures, molecular testing, and personalized care. Effusions have a high sensitivity and will often yield diagnostic cytological material. The companion session presented by the American Society of Cytopathology at the 2019 United States and Canadian Academy of Pathology meeting outlined our current and future projected practices in characterizing, managing, and diagnosing serous cavity fluids. In this second part, the role of theranostics and the diagnosis of malignant mesothelioma, as was discussed at the meeting, have been highlighted. In theranostics, a vast amount of data has been reported regarding the epidermal growth factor receptor and related molecules. Some studies have also reported on HER2 immunohistochemistry and fluorescence in situ hybridization. This follows the most active areas of research in targeted therapy. Furthermore, during this session, malignant mesothelioma was extensively discussed. The cytologic diagnosis of malignant mesothelioma in effusion specimens has been controversial; however, a definitive diagnosis will be possible in many cases. Radiologic information should be sought, because the radiologist can often provide a definite or very likely diagnosis of malignancy. Microscopically, high cellularity and/or numerous balls of cells or papillary groups will favor the diagnosis of mesothelioma. It is important to exclude metastatic carcinoma with a broad-spectrum carcinoma marker, of which claudin-4 has been the best, because it will not cross react with mesothelioma. BAP1 and MTAP immunohistochemistry and CDKN2A fluorescence in situ hybridization are very useful adjunctive techniques for separating benign from malignant mesothelial proliferations. The use of 2 of these approaches together will produce a sensitivity of 80% to 90% for epithelial mesotheliomas in the pleura, although the sensitivity has been lower in the peritoneal cavity. [ABSTRACT FROM AUTHOR]

Epithelial cell adhesion molecule (EpCAM) has been used as diagnostic/prognostic marker and therapeutic target. The aim of the present study was to compare immunoreactivity of antibodies against distinct epitopes in the ectodomain of EpCAM for detection of carcinoma from different primary sites and of different histological types in effusions and peritoneal wash. Two antibodies against epitopes in the EGF-like domain I (clones Moc-31 and Ber-EP4) and one antibody against the epitope in the cysteine-poor region (158210) of EpCAM were used (all commercially available). Independently of the clone used, EpCAM overexpression was observed in almost all samples when all the adenocarcinoma samples were analyzed together. By using Moc-31, EpCAM overexpression was observed in all samples of adenocarcinoma. Absence of EpCAM overexpression was observed in a few adenocarcinoma samples at some sites of tumor origin, including ovary, breast and stomach, when Ber-EP4 and 158210 were used. Regarding carcinomas aside from adenocarcinomas, histological types, such as squamous cell, urothelial and small cell carcinoma showed different degrees of EpCAM expression according to the antibody used. In squamous cell carcinoma, overexpression was observed only with the clone 158210. It was concluded that, overall, most samples of metastatic carcinoma from effusions showed overexpression of EpCAM. However, there are significant variations in its detection according to the primary site, histological type of the carcinoma and depending on the antibody used. Thus, the use of more than one type of anti-EpCAM antibody would increase the chance of its detection in metastatic carcinoma effusion. [ABSTRACT FROM AUTHOR]

The cytomorphologic evaluation of serous cavity specimens can quickly determine the cause of an effusion as well as the presence or absence of a neoplastic process. Ancillary tests such as immunohistochemistry and fluorescence in situ hybridization are frequently used to help to definitively identify malignant cells, determine a site of origin, and distinguish between malignant and reactive mesothelial proliferations. In recent years, microRNAs (miRNAs) have been increasingly evaluated in cytologic specimens, including those from serous cavities. The examination of miRNA is attractive because of the stability of miRNA in such specimens and data suggesting that miRNA can provide prognostic and therapeutic information in addition to its role in diagnosis. Furthermore, miRNAs exist within extracellular exosomes, and this allows for their analysis in specimens that contain only rare malignant cells, degenerated cells, or obscuring components. This review discusses the technical aspects of specimen processing for miRNA analysis, recent studies of miRNA expression in malignant serous cavity specimens, and the potential importance of miRNA expression analysis for serous cavity specimens in the near future. MicroRNAs are powerful markers: stable, easily quantifiable, and informative. In effusions, microRNAs can be used as diagnostic tools for several cancer histotypes. [ABSTRACT FROM AUTHOR]

Prolonged pleural drainage is a common complication in patients after Fontan palliation and is associated with short- and long- term morbidities. Among many potential etiologies, prolonged drainage has an inflammatory component, but there are no descriptions of cytokines in Fontan pleural drainage to date. This study aimed to examine the inflammatory make-up of Fontan pleural drainage. This prospective age-range-matched cohort study recruited 25 patients undergoing Fontan procedure and 15 bi-ventricular patients undergoing cardiopulmonary bypass (CPB). Chest tube samples were taken on postoperative day (POD) 1–4, 7, and 10. Cytokines were measured using Bio-Plex Assays. Univariate comparisons were made in patient characteristics and cytokine levels. Median age was 3.7 y (IQR 2.8–3.9) for controls and 2.5 y (IQR 2.1–2.9) in Fontan patients (p = 0.02). Median drainage duration and daily volume was higher in Fontan patients (both p < 0.001). Inflammatory cytokines (IL-17A, IFN-y, MIP-1β, and TNF-α) were higher in Fontan patients than controls (all p < 0.02). There was an increase in pro-inflammatory cytokines (IL-8, MIP-1β, and TNF-α) from POD1 to the last chest tube day (LCD) in Fontan patients (all p < 0.0001) and a decrease in the anti-inflammatory cytokine IL-10 (p = 0.001). There was no difference in cytokine concentration from POD1 to LCD among controls. There was a significant association with the cytokine concentration of TNF-α on POD1 and duration of chest tube drainage (p < 0.05). Inflammatory cytokine levels in the pleural fluid of Fontan patients are higher compared to bi-ventricular controls and rise over time where controls do not. This suggests ongoing localized inflammation that is not a result of CPB alone and may be an important contributor to pleural drainage in patients after the Fontan procedure. [ABSTRACT FROM AUTHOR]

Objective To analyze the expression and clinical role of CHK1 and CHK2 in metastatic high-grade serous carcinoma (HGSC). Methods HGSC effusions (n = 335; 280 peritoneal, 55 pleural) were analyzed for protein expression of total CHK1 and its phosphorylated forms p-ser317 and p-ser296, as well as total CHK2 and its phosphorylated form p-thr68 using immunohistochemistry. Expression was analyzed for association with clinicopathologic parameters, including chemotherapy response, and survival. Results Carcinoma cells stained positive, predominantly at the nuclei, in the majority of cases (range 83–100% for the five antibodies), while expression in reactive mesothelial cells and tumor-associated macrophages was more variable. Total CHK1 (p = 0.037), p-CHK1ser317 (p = 0.001), p-CHK1ser296 (p = 0.002) and p-CHK2thr68 (p < 0.001) expression was significantly higher in post-chemotherapy disease recurrence compared to pre-chemotherapy effusions obtained at diagnosis. CHK1, p-CHK1ser296, p-CHK2thr68 and p-CHK1ser317 nuclear expression was positively related to expression of the checkpoint regulator WEE1, previously studied in this cohort (p = 0.003, p = 0.013, p = 0.001 and p = 0.01, respectively). Higher total CHK1 (p = 0.007), p-CHK1ser317 (p = 0.004), CHK2 (p = 0.01) and p-CHK2thr68 (p = 0.048) expression was significantly related to shorter overall survival in univariate analysis, and CHK1ser317 was an independent prognostic marker in multivariate analysis (p = 0.025). Higher p-CHK1ser317 (p = 0.03) and CHK2 (p = 0.034) expression was additionally associated with poor progression-free survival. Conclusions CHK1 and CHK2 and their activated forms are frequently expressed in HGSC effusions, with higher expression following exposure to chemotherapy, and their expression is related to survival. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the diagnostic role of PTEN and ARID1A in effusion cytology. Effusions (n = 279), consisting of 226 carcinomas (70 ovarian, 64 breast, 36 lung, and 15 uterine corpus carcinomas; 41 carcinomas of other origin) and 53 malignant mesotheliomas, were analyzed for PTEN and ARID1A expression using immunohistochemistry. PTEN was preserved in 166 (59%) tumors, partially lost in 38 (14%), and absent in 75 (27%), with lower expression in malignant mesotheliomas compared to carcinomas, though not significantly (p = 0.084). ARID1A was preserved in 243 (88%) tumors, partially lost in 18 (6%), and absent in 18 (6%). The majority of tumors with absent ARID1A were ovarian carcinomas, predominantly of clear cell or low-grade serous type. Reactive mesothelial cells in carcinoma specimens were uniformly positive for both proteins. ARID1A mutation analysis showed no mutations in eight analyzed specimens negative by immunohistochemistry. Loss of PTEN and ARID1A expression is highly specific for malignancy in effusion pathology. Loss of PTEN is not informative of organ of origin, whereas absence of ARID1A should raise suspicion of an ovarian primary. [ABSTRACT FROM AUTHOR]

Effusions are common among patients with disorders of the temporomandibular joint (TMJ), but publications are limited and results inconsistent about the correlation between them and important clinical variables, in particular severity of pain and degenerative disease. We organised a retrospective study of patients who presented for the evaluation and management of arthralgia of the TMJ and myofascial pain at the University of Michigan between 2011 and 2014. Inclusion criteria were: patients who had pain that was primarily arthrogenous, and coexisting myogenous pain, who had had initial non-surgical treatment, and arthroscopy of the TMJ with or without intramuscular injection of onabotulinumtoxinA (Botox, ® Allegan, Weston, Fl, USA). The primary outcome variables were pain at rest as measured by visual analogue score (VAS) and the presence of degenerative disease of the joint. The secondary outcome variables included the position of the disc and whether it was perforated, signs of synovitis, maximal interincisal opening (MIO), and duration of symptoms. We studied 47 patients (94 TMJ) who met the inclusion criteria. We found no significant differences in pain at rest before or after arthroscopy, between patients with and without effusions, or in maximal MIO or duration of symptoms between the two groups. There was, however, a significant relation between effusions and degenerative joint disease. Effusions were also associated with a lower probability of the disc being in a normal position and a higher probability of anterior disc displacement without reduction. [ABSTRACT FROM AUTHOR]

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As efusões são problemas clínicos frequentes e que ocorrem em consequência de uma enfermidade que culmine com diminuição da pressão coloidosmótica intravascular, elevação da pressão hidrostática local, aumento da permeabilidade vascular e/ou comprometimento da drenagem realizada pelos vasos linfáticos. Dessa maneira, a avaliação laboratorial desse fluido torna-se relevante para que, em conjunto com os sinais clínicos apresentados pelo paciente, possa ser firmado um possível diagnóstico e instituída ação terapêutica adequada. Assim sendo, a classificação de uma efusão em transudato ou exsudato torna-se um dos pontos críticos para a elucidação do diagnóstico e condução do caso clínico. Em Medicina Veterinária, o método tradicional de classificação de uma efusão é baseado na contagem celular e na concentração de proteínas do fluido. Contudo, diversos estudos evidenciam que tais parâmetros não são suficientes para a correta classificação de todas as efusões. Assim, o presente estudo foi conduzido com o objetivo de verificar a correlação de outros parâmetros bioquímicos com a diferenciação das efusões transudativas e exsudativas e, para tal, foram avaliadas as atividades de lacatato desidrogenase (LDH) das efusões, a relação de sua atividade fluido/soro, concentração de lactato das efusões, o gradiente de concentração de lactato do soro para o fluido e a concentração de proteínas das efusões. Os resultados obtidos permitiram observar que a atividade de LDH, a relação LDH efusão/soro, a concentração de lactato e o gradiente de concentração de lactato soro/efusão apresentam diferença estatisticamente significativa (PThe effusions are frequent clinical problems and can occur in consequence to an illness that culminates with decrease of the intravascular coloidosmotic pressure, increase of local hydrostatic pressure, increase of vascular permeability and/or compromising of the drainage accomplished by lymphatic vases. Therefore, the laboratorial evaluation of this fluid becomes relevant, jointly with clinical signs presented by patient; to become possible the diagnosis definition and institution of appropriate therapeutic. Thus, classification of effusion in exudate and transudate is one of major points to elucidation of diagnosis and conduction of clinical case. In veterinary medicine the traditional method of an effusion classification is based on cellular counting and protein concentration of the fluid, however, several studies evidence that such parameters are not enough for the correct classification of all kinds of effusions. Considering this, the present study aimed to verify the correlation of some biochemical parameters with the differentiation of transudatives and exudatives effusions. To perform this, the activities of lactate dehydrogenase (LDH) were appraised, as well as the relationship of their activities with fluid/serum; lactate and proteins concentration and fluid/serum gradients of concentration of these same substances. The results allowed to observe that the activity of LDH, relationship LDH and fluid/serum, lactate concentration and lactate fluid/serum gradient of concentration present statistically significant difference (P

Introduction: The diagnosis of mesothelioma in situ (MIS) is now accepted by the WHO as a pre-invasive neoplastic mesothelial proliferation and considered a diagnosis based on histologic evaluation only. Although the definition of MIS includes recurrent effusions, little is known about the cytologic features of such effusions. Since mesothelioma is usually diagnosed at an advanced stage and has a poor prognosis, early detection of a neoplastic mesothelial population in such effusions can potentially have a positive impact on the management of such a dire disease., Materials and Methods: We reviewed a total of 18 pleural effusions from nine patients with recurrent effusions. Of these, five patients had follow-up biopsies diagnosed as MIS and the remaining four cases had negative radiology and malignant cytology proven by molecular markers (BAP1, MTAP or CDKN2A deletion) and at least 1 year follow-up with no overt mass identified by radiology., Results: Initial effusions may mimic reactive mesothelial hyperplasia or exhibit atypia. As effusions recur, the cellularity and atypia increase and the mesothelial proliferation becomes morphologically indistinguishable from mesothelioma. Molecular alterations diagnostic of mesothelioma can be detected in these effusions, even in the initial-benign/reactive appearing ones. The cellularity and atypia detected in such effusions surpassed those noted on the biopsies, raising questions regarding the cause of such discrepancy., Conclusion: The diagnosis of MIS can be suspected based on malignant effusion cytology supported by molecular alterations. We propose that the proliferation of neoplastic mesothelial clones represent a clinically silent "liquid phase MIS stage" corresponding to in situ stage in other organs., (© 2023 Wiley Periodicals LLC.)

Aim: To describe a case of aqueous misdirection complicated by subsequent persistent choroidal effusions following implantation of a Preserflo MicroShunt (PMS) device to treat advanced closed angle glaucoma., Methods: A 67-year-old caucasian female with advanced primary angle-closure glaucoma on four medications with an intraocular pressure (IOP) of 26 mm Hg was listed for a PMS insertion with mitomycin C (MMC)., Results: Past ocular history was significant for pseudophakia and previous yttrium aluminum garnet (YAG) peripheral iridotomy. Surgery was uneventful but on the first postoperative day, she developed aqueous misdirection complicated by subsequent development of persistent uveal effusions. Conventional treatment strategies including atropine drops, YAG hyaloidotomy and choroidal effusion drainage proved ineffective. A combination of oral steroids and pars plana vitrectomy (PPV) along with an irido-zonulo-hyloidectomy (IZH) proved efficacious., Conclusion: To the best of the author's knowledge, this is the first published case of aqueous misdirection complicated with the presence of significant, unresolving choroidal effusions, highlighting the possibility and sequelae of comorbid pathology in nanophthalmic eyes., (International Journal of Ophthalmology Press.)

Background : New information is available on pleural diseases. The authors selected articles to make recommendations on diagnostic and treatment aspects of pleural diseases. Materials and Methods: Eleven articles published in the English language between 2004 and 2007 were chosen. The basis of selection of the articles was the impact on daily practice, change in prior thinking of a disease process or specific treatment modality, as well as proper design and execution of the study. 5-amino-laevulinic acid with fluorescent light combined with white light may allow further diagnostic yield in undiagnosed pleural disease. FDG-PET may allow prognostication of patients with pleural tumors. Utilizing ultrasound by trained Emergency Department physicians is a rapid and effective technique to evaluate non-traumatic pleural effusions in symptomatic patients. Serum osteopontin levels may distinguish patients exposed to asbestos with benign disease from those with pleural mesothelioma. Administration of streptokinase in patients with empyema does not need for surgical drainage, length of hospital stay, or mortality as compared to conventional treatment with chest tube drainage and intravenous antibiotics. Silver nitrate may be an alternative agent to talc for producing pleurodesis. Routine use of graded talc (50% particles greater than 25 microns) is recommended to reduce the morbidity associated with talc pleurodesis. Study design does not permit us to conclude that aspiration of spontaneous pneumothorax is as effective as chest tube drainage. Pleural catheter may prove to be an important palliative modality in treating debilitated patients or patients with trapped lung who show symptomatic improvement with drainage; however, at the present time, these catheters cannot be considered a first line treatment option for patients with malignant pleural effusion. One of the studies reviewed showed no significant difference in tract metastasis in patients with malignant mesothelioma undergoing an invasive pleural procedure with or without irradiation to the procedure site. However, the design of the trial does not allow us to make this conclusion at the present time.

The peritoneal fluid from six female health donkeys was evaluated. In each animal, it was carried out eight abdominocentesis with 40x12 needles, at 72-hour intervals. All animals presented clinical changes, and there was higher frequency of yellow-tinged fluid with turbidity aspect. Means, and respective standard deviations, for cytology and protein concentration were: erythrocytes, 24.7±11.7x10³/mm³; leukocytes, 15.8±6.79x10³/mm³; mesothelial cells, 3.85±1.30x10³/mm³; neutrophils, 10.9±4.51x10³/mm³; lymphocytes, 1.41±0.51x10³/mm³; macrophages, 0.98±0.55x10³/mm³; eosinophils, 2.48±1.36x10³/mm³, and total proteins, 1.97±0.31 g/dl.

Introduction: Malignant serous effusions are common in metastatic carcinomas. Although cytomorphology is recognized as the gold standard diagnostic method, it exhibits moderate sensitivity. This study aimed to assess the diagnostic value of immunophenotyping with a single epithelial marker, known as the epithelial cell adhesion molecule (EpCAM, CD326), in discriminating malignant metastatic carcinomas of serous fluids., Methods: This prospective study was conducted on suspicious or confirmed cases of malignant tumors from September 16, 2019, to June 21, 2020. Serous fluid samples were assessed via cytomorphology using the Wright-Papanicolaou method and the anti-EpCAM mouse monoclonal antibody (clone VU-1D9) flow cytometry. The EpCAM(+)/CD45(-) immunophenotype was defined as the metastatic involvement of carcinoma in the serous cavity., Results: A total of 118 samples (90 females and 28 males; mean age, 54.04 ± 16.14 years), collected from peritoneal and pleural fluids, were examined in this study. Five samples (4.24%) were positive in both EpCAM flow cytometry and cytology, while 102 samples (86.44%) were negative for both EpCAM flow cytometry and cytology, yielding an overall agreement of 92%, 84%, and 90.7% for the peritoneal, pleural, and total samples, respectively. Based on the Bayesian latent class model, the EpCAM flow cytometry showed sensitivity and specificity of 58.5% (95% CI: 0.3, 99.7) and 96.2% (95% CI: 47.8, 100), respectively. The corresponding values were 68.7% (95% CI: 0.3, 99.9) and 96.1% (95% CI: 47, 100) for cytology, respectively., Conclusion: The EpCAM flow cytometry and cytology showed comparable performance in detecting metastatic effusions. The EpCAM flow cytometry might have a diagnostic value in decreasing the false-negative rate of cytomorphology, while maintaining excellent specificity., (© 2023 S. Karger AG, Basel.)

Cell cannibalism is believed to be an indicator of high-grade aggressive cancers with increased metastatic potential. It denotes both anaplastic grade and invasiveness and is valuable in assessing tumor behavior. The present study was a 2-year retrospective and 1-year prospective study conducted in the Department of Pathology, Government Medical College, Jammu. PAP and MGG stained smears of effusions and urinary cytology were evaluated for cannibalism. Cannibalism was assessed by parameters like cellularity of cannibalism, diameter of cannibalistic cells, chromatin pattern and background of the smears. Of 350 cases evaluated, 260 (74.2%) were benign and 90 (25.8%) were malignant. Cannibalism was absent in all benign cases. Cannibalism was present in 14 ascitic fluids, 7 pleural fluids, 1 pericardial fluid and 3 cases of urine cytology. Comparison of distribution of cannibalism in effusions and urine did not yield statistically significant result (X² = 0.8678 and p >0.05). Comparison of other parameters between effusions and urine samples also did not yield significant results. We conclude that cytological parameters of cellular cannibalism are better observed in malignant effusions than in urine cytology but did not reach statistical significance. Cannibalism can be assessed morphologically in malignant body fluids and is an indicator of increased tumour growth. [ABSTRACT FROM AUTHOR]