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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.

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BACKGROUND: Metastatic germ cell tumors (GCTs) involving body cavity effusions and cerebrospinal fluid (CSF) are rare. Diagnosis is challenging because of limited morphological and clinicopathological information in the literature. METHODS: A database search of our institution from 1990 to 2024 identified 27 cases of metastatic GCTs, comprising five pediatric and 22 adolescent and adult patients, in serous cavities or the CSF, including peritoneal (15), pleural (nine), CSF (two), and pericardial (one) fluid. RESULTS: The most common primary site was the testis (n = 10), followed by the ovaries (n = 7), mediastinum (n = 4), retroperitoneum (n = 3), pineal gland (n = 2), and sacrum/coccyx (n = 1). The primary tumors in 14 patients were mixed GCTs (six with a seminoma component), followed by immature teratomas (six), yolk sac tumors (three), embryonal carcinomas (two), pure seminomas (one), and postpubertal teratomas (one). The median interval between primary tumor diagnosis and diagnosis of fluid positivity was 7 months (range: 0-134 months). In nine cases, the malignant fluid was diagnosed simultaneously with or within 1 month of the primary tumor. GCT subtyping was performed on 23 of the 27 cytological specimens. Twenty-four patients (89%) also had metastases to other sites. Thirteen patients died of the disease (48%), with a median survival time of 4 months. CONCLUSIONS: Metastatic GCTs in serous effusions and CSF are often associated with disseminated disease and poor prognosis. Subtyping can be performed by cytomorphology combined with immunohistochemistry.

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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.

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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.

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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.

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The objective of this study was to investigate the relationship between serum tumor markers and serous effusion in systemic lupus erythematosus (SLE) patients, thereby contributing preliminary data on the utility of these tumor markers in diagnosing serous effusion. In this retrospective analysis, clinical data of SLE patients were extracted from electronic medical records. This included the levels of serum tumor markers, including pro-gastrin-releasing peptide, neuron-specific enolase (NSE), cytokeratin-19 fragments (CYFRA 21-1), various carbohydrate antigens (CA 153, CA 125, CA 19-9), along with carcinoembryonic antigen, and alpha-fetoprotein. Positivity of tumor markers was established based on serum levels surpassing the upper threshold of the respective reference ranges. This study included 149 eligible patients with SLE, of whom 38 (25.50%) had serous effusion, and the prevalence of pleural, pericardial, and peritoneal effusions was 11.41%, 14.77%, and 6.71%, respectively. The analysis revealed that patients with serous effusion had higher scores on the SLE Disease Activity Index 2000 (SLEDAI 2000) than those without serous effusion. Notably, this disparity remained significant when the serositis score was excluded from the SLEDAI 2000 calculation. The positivity rate and serum levels of CA 125 were higher in patients with serous effusion and pleural effusion. Patients with pericardial effusion demonstrated an elevated CYFRA 21-1 positivity rate and serum CA 125 and CYFRA 21-1 levels compared to patients without pericardial effusion. CA 125 and NSE were higher both in terms of positivity rate and serum levels for patients with peritoneal effusion. Through receiver operating characteristic curve analysis, a moderate relationship was discerned between the conjoined levels of CYFRA 21-1 and CA 125 and the occurrence of pericardial effusion. Additionally, CA 125, NSE, and their combination revealed the moderate diagnostic ability of peritoneal effusion. In summary, this study observed elevated serum levels of various tumor markers in SLE patients exhibiting serous effusion, which is likely attributable to lupus-induced inflammation. These findings suggest that serum tumor markers can be valuable in diagnosing pericardial and peritoneal effusions.

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BACKGROUND: The aim of this study was to analyze the effectiveness and safety of H101 in Chinese patients with malignant pleural effusion and ascites (MPE/MA) in the real world. METHODS: This multicenter, observational, real-world study recruited patients with MPE/MA caused by malignant tumor receiving H101-containing treatment between January 2020 and June 2022. Effectiveness was evaluated by overall remission rate (ORR), and safety was evaluated based on adverse events (AEs). Subgroup analysis was performed on patients grouped according to tumor type, the volume of MPE and MA, and dosage of H101. RESULTS: A total of 643 eligible patients were enrolled, and 467 received H101 monotherapy and 176 received H101 combined with chemotherapy. The ORR of total patients was60.3% with 388 case of PR. In the H101 monotherapy group, the decrease of MPE or MA was achieved in 282 (60.4%, PR) patients, 176 (37.7%, NC) patients showed no change in volume of MPE or MA, and nine (1.9%, PD) patients showed an increase, yielding an ORR of 60.4% (282/467). The ORR for the combination therapy group was 60.2% (106/176), with 106 cases of PR, 69 cases of NC and one case of PD. Subgroup analyses based on tumor type, volume of MPE and MA, and dosage of H101 all showed high ORR, approximately 60%. The main AEs associated with H101-containing regimens were fever, nausea and vomiting. No serious AEs occurred in both groups. CONCLUSION: Encouraging clinical benefits and manageable toxicity of H101 against MPE/MA were preliminarily observed in the real-world clinical setting, indicating that the H101-containing regimen is reliable, safe, and feasible, providing a novel and effective option for the treatment of this disease.

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In April 2020, Pediatric Inflammatory Multisystem Syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 or SARS­CoV­2 (PIMS-TS) was described for the first time in children. Since then, many countries have registered hundreds of cases with clinical similarities to Kawasaki disease. We report the case of a five-year-old boy diagnosed with PIMS-TS who presented myocarditis with serous effusions (pleurisy, ascites, pericarditis) due to severe hypoalbuminemia. This case sheds light on the importance of hypoalbuminemia in evaluating the severity of PIMS-TS and preventing its complications. The patient was successfully treated with intravenous immunoglobulins and oral prednisone.

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OBJECTIVES: When desmoplastic small round cell tumor (DSRCT) is present in serous fluid, the cytomorphology can be diverse and can mimic metastatic carcinomas and thus present a diagnostic challenge. The aim of this study was to evaluate the cytomorphologic and immunocytochemical features of this rare tumor in serous effusion specimens. METHODS: Demographic, clinical, radiologic, and pathologic information from patients who had a DSRCT diagnosis on body fluid specimens was collected and cytologic slides were reviewed. RESULTS: Nine specimens were identified (5 pleural fluid and 4 ascitic fluid specimens) from 8 patients (5 male and 3 female). The mean patient age at diagnosis was 26 years. The most common symptoms were abdominal distension and pain, with 5 patients having abdominal masses. Other findings included peritoneal carcinomatosis, liver masses, ascites, and pleural nodules. The predominant cytomorphology was loose cellular clusters, followed by tight clusters of small cells with scant occasional vacuolated cytoplasm and a sphere-like pattern. CONCLUSIONS: Serous fluid may be the first available specimen to diagnose DSRCT. In young patients with no history of malignancy and radiologic finding of peritoneal implants, DSRCT should be considered a possibility in the differential diagnosis, and sensitive markers should be used for accurate diagnosis.

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INTRODUCTION: Metastatic melanoma (MM) is an uncommon finding in serous effusion specimens with a highly variable cytomorphology. METHODS: We reviewed specimens submitted over a 19-year period to determine (a) the range of cytologic findings in effusion specimens from melanoma patients and (b) the cytologic presentation and immunoprofile of MM in effusion specimens. RESULTS: Of 123 serous effusion specimens from patients with clinical notes of melanoma, 59% were reported negative for malignancy, 16% were reported with a non-melanoma malignancy, 19% MM, and 6% atypical, MM not excluded. Pleural fluids were twice as likely to be reported as MM than peritoneal samples. Review of 44 cases with confirmed MM showed the most common cytologic pattern was epithelioid. Most (88%) cases contained mainly dispersed plasmacytoid cells, but many (61%) also contained malignant cells arranged in loose groups. Rare cases also had spindle cells, giant bizarre cells, small lymphoid-like cells, or cells with large hard-edged vacuoles, mimicking other metastatic malignancies. MM cases containing predominantly plasmacytoid cells often mimicked reactive mesothelial cells. As well as being composed of cells of similar size, features such as bi- and multinucleation, round nuclei, mild anisokaryosis, nucleoli, and loose groups were common to both. Features seen more commonly in MM than reactive cells included large nucleoli (95%) and intranuclear cytoplasmic inclusions (41%), binucleate "bug-eyed demons," and small punctate vacuoles on the air-dried preparations. Pigment was identified in 36% of cases. Immunohistochemistry (IHC) is a valuable aid in confirming the cell type. The sensitivity for the most commonly used melanoma markers was as follows: S100 84% (21/25), pan-melanoma 100% (19/19), HMB45 92% (11/12), Melan A 92% (11/12), SOX10 91% (10/11). No staining was reported for calretinin (0/21), AE1/AE3 (0/11), EMA (0/16), Ber-Ep4 (0/13). DISCUSSION: Effusion specimens from patients with a history of melanoma are frequently (40%) malignant but almost as likely to be reported as a nonmelanoma malignancy as MM. The cytology of MM may mimic a wide range of other metastatic malignancies but also often closely resembles reactive mesothelial cells. It is important to be aware of this latter pattern so that IHC markers can be applied.

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OBJECTIVES: To explore the approach to the diagnosis of malignant serous effusion (SE) caused by angioimmunoblastic T-cell lymphoma (AITL). METHODS: The clinical, cytomorphologic, immunophenotypic, and molecular features of 6 patients were summarized. RESULTS: Clinically, SE caused by AITL was predominant in middle-aged and older male patients with multiple SEs and lymphadenopathy. Cytomorphology showed small to medium-sized, irregular lymphocytes with clear cytoplasm and mixed with various inflammatory cells and apoptosis. Hodgkin/Reed-Sternberg-like cells were detected in 2 of 6 cases. Furthermore, 2 patterns of cytomorphology were described for the first time. Flow cytometry revealed abnormal T-cell populations with loss of surface CD3 (3/4 cases) and CD7 (3/4 cases). In addition, B-cell populations lacking surface immunoglobulin (Ig) were identified in 2 of 4 cases. Immunocytochemical staining revealed expression of at least 2 T follicular helper markers. Epstein-Barr virus-encoded RNA (EBER)-positive cells were demonstrated in 4 of 5 cases. Clonal T-cell receptor γ chain rearrangement was detected in 6 cases, and 3 of them had concomitant clonal immunoglobulin gene rearrangement. Moreover, 2 cases revealed discrepant findings regarding IgH/Igκ rearrangements in cytohistologic correlation. CONCLUSIONS: This study broadens the morphologic spectrum of malignant SE caused by AITL and provides diagnostic criteria in routine practice.

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INTRODUCTION: The International Academy of Cytology and the American Society of Cytopathology recently proposed the International System for Reporting Serous Fluid Cytology (ISRSFC) to standardize serous fluid cytopathology reporting and guide further clinical management. The current study aimed to assess the feasibility of utilizing ISRSFC reporting categories for serous fluids, estimate the risk of malignancy (ROM) of each category, and scrutinize if the management protocols followed in our institution are as per the ISRFSFC recommendations. METHODS: All pleural, peritoneal, and pericardial effusions submitted for evaluation at our institute between January 2021 and December 2021 were retrieved. All these cases were reviewed and re-categorized into one of the five categories proposed by the ISRSFC: non-diagnostic (ND), negative for malignancy (NFM), atypia of uncertain significance (AUS), suspicious for malignancy (SFM), and malignant (MAL), and ROM was calculated for each category. RESULTS: The present study examined 596 serous effusions, of which 229 were pleural effusions, 358 were peritoneal effusions, and the remaining nine were pericardial effusions. Among 596 cases, 395 cases had a radiological or histological follow-up. The serous effusion samples were re-categorized as 61 (10.2%) ND, 449 (75.3%) NFM, 47 (7.8%) AUS, 17 (2.9%) SFM, and 22 (3.8%) MAL, and ROM for each above category were 10%, 4.4%, 19%, 83.3%, and 100%, respectively. CONCLUSION: Categorizing serous effusion cytology samples per the ISRSFC diagnostic categories reduces reporting variability. The ISRSFC provides a standardized format to predict the ROM and thus improves the quality of clinical care.

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INTRODUCTION: Body cavity effusions are routinely used as cytologic specimens. The distinction between metastatic carcinoma, mesothelioma, and reactive mesothelial cells remains a major challenge. Immunohistochemistry (IHC) is a supplemental method that can aid in diagnosis and often involves many markers as part of an IHC panel. Several immunohistochemical markers are now widely used. This study aims to determine the optimal immunomarkers and IHC panels to differentiate reactive mesothelial cells from metastatic cancer in body cavity fluid samples. METHODS: IHC was performed for claudin-4, MOC-31, Ber-Ep4, D2-40, and calretinin on sections derived from 152 cellblocks containing effusions. The samples consisted of 16 (10.53%) benign and 136 (89.47%) malignant tumors, including 87 (63.97%) lung cancers, nine (6.62%) breast cancers, 11 (8.09%) gynecologic cancers, seven (5.15%) pancreaticobiliary cancers, and 22 (16.17%) unspecified primary malignancies. RESULTS: Claudin-4, MOC-31, Ber-EP4, D2-40, and calretinin demonstrated sensitivities of 91.18%, 91.91%, 55.88%, 90.44%, and 98.53%, respectively. The corresponding specificities were 100.00%, 100.00%, 100.00%, 93.75%, and 100.00%. The sensitivity and specificity were both 100% when claudin-4 or MOC-31 was combined with calretinin. The combination of four markers as an IHC panel (claudin-4, MOC-31, calretinin, and D2-40) had a sensitivity of 97.79% and a specificity of 100.00%. CONCLUSION: Claudin-4 and MOC-31 both demonstrated significant diagnostic value in distinguishing metastatic epithelial carcinoma from reactive mesothelium. The sensitivity, specificity, and accuracy of these two markers, one of which is an epithelial marker and one of which is a mesothelial marker, reached 100%. Therefore, a combination of these two markers may be appropriate.

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OBJECTIVE: To investigate the expression level of vascular endothelial growth factor (VEGF) in serum of patients with multiple myeloma (MM) and its possible clinical significance. METHODS: 68 patients with MM who were admitted to The First Affiliated Hospital of Bengbu Medical College from July 2019 to June 2020 were collected. The expression level of VEGF was detected by VEGF enzyme-linked immunosorbent assay, the correlation of VEGF expression with serous effusion in MM was explored, and the relationship between VEGF expression level and clinical features and prognosis of patients with MM was analyzed. RESULTS: The positive rate of VEGF was 36.76% (25/68) in 68 patients with MM, 10 cases (58.82%, 10/17) were VEGF positive in 17 MM patients with serous effusion. The expression level of VEGF in patients with positive serous effusion was significantly higher than that in patients with negative serous effusion (P<0.05); the expression level of VEGF in MM patients of the newly diagnosed and untreated group was significantly higher than that in the remission group after treatment (P<0.05), but there was no significant difference in the expression level of VEGF between the newly diagnosed group and the refractory/relapsed (R/R) group (P>0.05). Among 68 patients with MM, 48 patients underwent FISH examination, 28 cases had normal karyotype (58.33%), and 20 cases had abnormal karyotype (41.67%). The abnormal karyotype was mainly IgH rearrangement, with a total of 10 cases (20.83%); other cases: 1q21+, del (13q14), del (17p13) were 3 cases (6.25%), 2 cases (4.17%), 7 cases (14.58%), respectively. Compared with VEGF- group, the incidence of IgH rearrangement and del (17p13) in VEGF+ group was higher [IgH rearrangement: 35% vs 10.71%, P=0.043; del(17p13): 30% vs 3.57%, P=0.011]. Compared with negative serous effusion group, the incidence of del (17p13) in positive serous effusion group was higher (31.25% vs 6.25%, P=0.021). The proportion of patients with positive VEGF and serous effusion was 14.71% (10/68), and the proportion of patients with negative VEGF and negative serous effusion was 52.94% (36/68). There was a correlation between serous effusion and VEGF expression (r=0.264, P=0.029). CONCLUSION: The prognosis of MM patients with serous effusion is poor, and the expression of VEGF in serum of these patients is significantly high. The increased VEGF may be involved in the occurrence and development of serous effusion.

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BACKGROUND: Gorham-Stout syndrome (GSS) is a rare disorder with various presentations and unpredictable prognoses. Previous understandings of GSS mainly focused on progressive bone destruction, while we identified a group of GSS patients with serous effusion as the first symptom. This study aimed to investigate the clinical characteristics of patients with GSS having serous effusion as the first symptom. METHODS: Patients diagnosed with GSS were identified through the Peking Union Medical College Hospital Medical Record System. The demographic, clinical, laboratory, and imaging data were collected. Patients who first presented with serous effusion were recruited into the serous group, while those with bone destruction were recruited into the bone group. RESULTS: Of the 23 patients with GSS enrolled, 13 were in the bone group and 10 in the serous group. The median disease duration was shorter and exercise tolerance was lower in the serous group. Despite less frequent bone pain in the serous group, the frequency of bone involvement was similar to that in the bone group. Patients in the serous group had higher rates of bilateral pleural effusion and multiple serous effusion. However, serous effusion also developed with disease progression in the bone group. Of the 17 patients treated with bisphosphonates, 14 reached bone-stable state. However, 5 out of 10 patients with serous effusion still had refractory effusions after bisphosphonates treatment. Three patients received sirolimus treatment, with an improvement in serous effusion. Seventeen patients were followed up; three patients died, two in the bone group and one in the serous group. CONCLUSIONS: This study discovered that GSS could first be presented with serous effusion. We believe that this may be a new phenotype of the disease. Sirolimus might help in controlling serous effusion and improving prognosis.

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CONTEXT: The International System for Reporting Serous Fluid Cytopathology (ISRSFC) standardises the reporting of serous effusion cytology under five categories: Non-Diagnostic (ND), Negative for Malignancy (NFM), Atypia of Undetermined Significance (AUS), Suspicious for Malignancy (SFM), and Malignant (M). Very few studies have been conducted so far to confirm the risk of malignancy of the different categories. AIMS: The main objectives of our study were to classify serous effusions according to the ISRSFC categories and assess their risk of malignancy (ROM) and performance parameters. MATERIALS AND METHODS: All serous effusion samples received from January 2019 to December 2020 were reclassified according to the ISRSFC. Using histopathological diagnosis as the gold standard, ROM and performance parameters were calculated. RESULTS: A total of 831 pleural effusion samples were reclassified as follows: ND, 3 (0.4%); NFM, 635 (76.4%); AUS, 65 (7.8%); SFM, 60 (7.2%); and M, 68 (8.2%). For 457 peritoneal effusion samples, the reclassifications were ND, 5 (1.1%); NFM, 368 (80.5%); AUS, 19 (4.2%); SFM, 17 (3.7%); and M, 48 (10.5%). All 12 (100%) pericardial effusions belonged to the NFM category. The ROM for the ND, NFM, AUS, SRM, and M categories was 0%, 2.1%, 33.3%, 94.1%, 100%, respectively, in pleural effusions, and 50%, 4.8%, 22.2%, 83.3%, 100%, respectively, in peritoneal effusions. The ROM was 0% for NFM in pericardial effusions. CONCLUSION: The ISRSFC is an excellent system for accurately classifying serous effusions with greater reproducibility of reports and better communication between pathologist and clinician.

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The International System for Reporting Serous Fluid Cytopathology (TIS) classifies serous effusions into five categories: non-diagnostic (ND), negative for malignancy (NFM), atypia of unknown significance (AUS), suspicious for malignancy (SFM) and malignant (MAL). The main objectives of this classification comprise the establishment of a universal code of communication between cytopathologists and clinicians and histopathologists, as well as between different laboratories worldwide, paving the way for the setting of clinical management guidelines based on the risk of malignancy assessment for each diagnostic category. We retrieved the total number of pleural and peritoneal effusion cases of our department for the three-year time period between 2018 and 2020, yielding a total of 528 and 500 cases, respectively. We then proceeded to reclassify each specimen according to TIS guidelines and calculate the risk of malignancy (ROM) for each category by searching each patients' histology records, medical history and clinical follow-up. For pleural effusions, 3 (0.57%) cases were classified as ND, 430 (81.44%) cases as NFM, 15 (2.84%) as AUS, 15 (2.84%) as SFM and 65 (12.31%) as MAL. ROM amounted to 0%, 5.3%, 33.33%, 93.33% and 100% for each category, respectively. As far as peritoneal effusions are concerned, 6 (1.2%) were categorized as ND with ROM estimated at 16.66%, 347 (69.4%) as NFM (ROM = 9%), 13 (2.6%) as AUS (ROM = 38.46%), 12 (2.4%) as SFM (ROM = 83.33%) and 122 (24.4%) as MAL (ROM = 100%). Our results underline the utility of the current classification, both as a means of communication between doctors of different specialties and as general guidelines for the further clinical management of patients.

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BACKGROUND: Recently, the International System for Reporting Serous Fluid Cytopathology (TIS) has been established, with an aim to standardize reporting and guide clinical decision making. METHODS: The cytological and clinicopathological data of pleural effusions were retrieved from the pathology database and electronic medical records. All specimens were evaluated and reclassified in accordance with the TIS recommendations. Finally, the risk of malignancy (ROM) and performance parameters were measured. RESULTS: A total of 2454 pleural effusion specimens were included, among which 30 (1.2%), 1670 (68.1%), 151 (6.2%), 54 (2.2%) and 549 (22.4%) patients were classified into non-diagnostic (ND), negative for malignancy (NFM), atypia of undetermined significance (AUS), suspicious for malignancy (SFM) and malignancy (MAL) groups, respectively. The most commonly diagnosed malignancies were lung cancer (48.4%), ovary cancer (10.2%), breast cancer (7.5%), and 21.3% unknown primary site (UPS). Among the 36 UPS patients, the most common site of origin was lung (36.1%), followed by ovary (13.9%) and breast (11.1%) via immunocytochemistry of cell block. The calculated ROM values were 26.7%, 12%, 62.3%, 77.8% and 100% for ND, NFM, AUS, SFM and MAL groups, respectively. When considering MAL as the only positive group, the diagnostic accuracy, sensitivity, specificity, positive and negative predictive values were determined to be 95.2%, 81.9%, 100%, 100% and 93.6%, respectively. CONCLUSION: The newly proposed TIS is an easy-to-master, user-friendly, and standardized classification system, especially when applying on pleural effusions. An adequate serous sample, application of immunocytochemistry, review of cytomorphological data and past medical history could enhance the accuracy of cytological diagnosis.

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INTRODUCTION: Involvement of body fluids by lymphoreticular malignancies (LRM) is rare and often associated with poor prognosis and decreased overall survival. The present study was conducted to analyze the characteristic cytomorphologic, flow cytometric and immunocytochemical features of LRMs in serous effusions. MATERIALS AND METHODS: This was a three-year retrospective study. A total of 218 effusion samples, reported as involved by lymphoreticular malignancies, on cytology, were reviewed. All the cases wherein the cytological diagnosis was confirmed by flow cytometric (FCM) and/or immunocytochemical (ICC) studies were retrieved and studied in detail. FCM and/or ICC were performed in a total of 51/218(23.4%) samples, including 30 pleural (58.8%), 18 peritoneal (35.3%), and 3 pericardial fluid (5.9%) samples. RESULTS: The cytomorphologic diagnoses included infiltration by non-Hodgkin lymphoma (NHL;n = 27), infiltration by LRM (n = 19), infiltration by chronic lymphocytic leukemia (CLL;n = 2), Hodgkin's lymphoma (HL;n = 1) and suggestive of infiltration by LRM (n = 2). FCM and/or ICC confirmed the diagnoses as infiltration by T-cell lymphoblastic lymphoma in 18; mature B-cell NHL in 10; Burkitt lymphoma in 7; diffuse large B-cell lymphoma in 4; follicular lymphoma, T- cell NHL and CLL in 2 samples each and hairy cell leukemia, plasmablastic lymphoma and HL in 1 sample each. 94.1% concordance was noted between the initial and final cytologic diagnosis. CONCLUSIONS: Involvement of body fluids and effusions by LRMs, though rare, carries an immense prognostic significance and hence the prompt detection is crucial. Detection of these malignancies by cytologic examination of effusions is challenging yet potentially useful and the least invasive method available to establish an early diagnosis.

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Cytological examination of the effusion fluid provides valuable information regarding the presence of malignancy. At times, it is challenging to diagnose malignant cells in serous effusion. The various ancillary techniques are available to solve the problem including immunocytochemistry, DNA ploidy, and multicolored flow cytometry. At present, the molecular tests on the effusion sample are of growing interest. The effusion sample is rich in cells and cell-free fluid that contains free DNA, cytokines, and extracellular vesicles. Molecular tests in effusion sample not only provide a diagnosis of malignancy but can also give valuable information that may be essential for the individualized therapy, management, and prognostic assessment. In this paper, we reviewed the application of the different molecular tests in the effusion sample.