Serous Effusions Research Articles

Patient-derived organoids to predict the drug response in locally advanced or metastatic lung cancer: A real-world study.

9136 Background: Lung cancer organoids (LCOs) were expected to be the potential precision medicine approach for clinical response prediction. However, the clinical applications of both tissue and malignant serous effusions (MSE) derived LCOs were rarely reported. Our previous work demonstrated that MSE-derived LCOs maintain the genomic signature of the original tumor. In this study, we aimed to create LCOs using tissue or MSE, then validate the reliability of the model by comparing LCOs and their origin from the pathological and molecular levels. Furthermore, drug sensitivity tests of LCOs were also performed to evaluate the feasibility of LCO drug test as an approach for personalized medicine. Methods: Primary or metastatic tumor tissues were obtained from advanced lung cancer patients through core biopsy or surgically resected biopsy at the Guangdong Provincial People’s Hospital. MSEs were also collected. LCOs were generated from the obtained tissue and MSE, and the pathological features and genomic profiles were verified by analyzing the consistency with their origin. Then, the drug sensitivity scheme was formulated to follow the principles of clinical medication. In addition, proteomics analysis by 4D LC-MS/MS was also performed to analysis the molecular details of combinational therapy. Results: In our study, we generated 213 LCOs from 106 patients, mainly from MSE. The success rate to generate LCOs derived from MSE was 81.4% (131/161). The concordance rate of pathological phenotypes of LCOs samples verified by immunohistochemistry with clinical samples was 75% (63/84). In our cohort, LCO based drug sensitivity tests (LCO-DST) of targeted therapies were performed to predict the tumor response, and the AUC value of ROC analysis of osimertinib in EGFR-mutant adenocarcinoma reached 0.94(LCOs samples = 15, p= 0.0047). There were 2 patients with advanced lung adenocarcinoma, one with de novo EGFR mutation /MET amplification and the other with EGFR mutation combined with acquired RET fusion. The results of LCO based drug tests of 2 patients showed that combined targeted therapy (osimertinib plus savolitinib/cabozantinib) showed high tumor inhibition rate validated in clinical treatment and made differences. Then, 4D label-free high through-put proteomic analysis was performed in the patient with EGFR mutation and acquired RET fusion, demonstrating caspase 3 increased dramatically in combination of osimertinib and BLU-667 and the downstream proteins of EGFR and RET were down-regulated. Conclusions: LCOs derived from MSE faithfully reflected the pathological and genomic features of their original patients. The LCOs based drug test results are remarkably consistent with the tumor response. These results suggested the important prospects of LCO as an in vitro model for lung cancer precision medicine.

Small Bowel Obstruction After Neonatal Repair of Congenital Diaphragmatic Hernia-Incidence and Risk-Factors Identified in a Large Longitudinal Cohort-Study.

ObjectiveIn patients with a congenital diaphragmatic hernia (CDH), postoperative small bowel obstruction (SBO) is a life-threatening event. Literature reports an incidence of SBO of 20% and an association with patch repair and ECMO treatment. Adhesions develop due to peritoneal damage and underly various biochemical and cellular processes. This longitudinal cohort study is aimed at identifying the incidence of SBO and the risk factors of surgical, pre-, and postoperative treatment.MethodsWe evaluated all consecutive CDH survivors born between January 2009 and December 2017 participating in our prospective long-term follow-up program with a standardized protocol.ResultsA total of 337 patients were included, with a median follow-up of 4 years. SBO with various underlying causes was observed in 38 patients (11.3%) and significantly more often after open surgery (OS). The majority of SBOs required surgical intervention (92%). Adhesive SBO (ASBO) was detected as the leading cause in 17 of 28 patients, in whom surgical reports were available. Duration of chest tube insertion [odds ratio (OR) 1.22; 95% CI 1.01–1.46, p = 0.04] was identified as an independent predictor for ASBO in multivariate analysis. Beyond the cut-off value of 16 days, the incidence of serous effusion and chylothorax was higher in patients with ASBO (ASBO/non-SBO: 2/10 vs. 3/139 serous effusion, p = 0.04; 2/10 vs. 13/139 chylothorax, p = 0.27). Type of diaphragmatic reconstruction, abdominal wall closure, or ECMO treatment showed no significant association with ASBO. A protective effect of one or more re-operations has been detected (RR 0.16; 95% CI 0.02–1.17; p = 0.049).ConclusionThoracoscopic CDH repair significantly lowers the risk of SBO; however, not every patient is suitable for this approach. GoreTex®-patches do not seem to affect the development of ASBO, while median laparotomy might be more favorable than a subcostal incision. Neonates produce more proinflammatory cytokines and have a reduced anti-inflammatory capacity, which may contribute to the higher incidence of ASBO in patients with a longer duration of chest tube insertion, serous effusion, chylothorax, and to the protective effect of re-operations. In the future, novel therapeutic strategies based on a better understanding of the biochemical and cellular processes involved in the pathophysiology of adhesion formation might contribute to a reduction of peritoneal adhesions and their associated morbidity and mortality.

Cytologic manifestations of Hodgkin lymphoma in serous effusions.

Serous effusions occur in a small group of patients with classic Hodgkin lymphoma (cHL). Most effusions are benign inflammatory fluids. Malignant effusionspredominantly in patients with treated relapsed diseases or rarely as a primary manifestation are diagnostically challenging to cytopathologists. Established cases of cHL with effusions were retrieved. Cytology slides were screened looking for Reed-Sternberg-Hodgkin (RSH) cells and patterns of background inflammatory cells. Cellblocks and their corresponding immunocytochemistry (ICC) slides were examined. The cytologic findings were correlated with nodal biopsy histopathologic and immunohistochemical features. We found six cases of benign and malignant pleural and pericardial effusions in patients with mediastinal nodular sclerosis-type cHL. Various cytomorphologic patterns were observed. Slides revealed sparsely scattered either isolated or aggregated mononuclear, binucleated and multinucleated RSH-like cells. Some may have been either disregarded as reactive mesothelial or histiocytic cells, or confused with other RSH-like malignant cells. The background varied between characteristic mixed inflammatory milieu, predominantly small lymphocytic or lymphohistiocytic with or without reactive mesothelial cells. Cytologic examination showed three positive cases (two cases with RSH cells confirmed by cellblock section ICC, one case with a mixed inflammatory infiltrate), and three benign effusions (one case with atypical RSH-like reactive mesothelial cells confirmed by ICC). Effusions associated with cHL exhibit different cytologic patterns. A high level of vigilance with utility of ICC has an important role in suspecting primary cases and confirming recurrences in known cases. The various cytologic patterns of cHL-associated benign and malignant effusions might reflect parallel pathophysiologic mechanisms.

Commentary: Retinal detachment in eyes treated with Aurolab aqueous drainage implant for refractory glaucoma - Incidence and outcomes

The principal indication for glaucoma drainage devices (GDDs) is usually glaucoma refractory to filtering surgery.[1] Currently, commonly available GDDs are either valved like the Ahmed glaucoma valve (AGV; New World Medical Inc., Rancho Cucamonga, CA, USA) or non-valved GDDs like the Baerveldt glaucoma implant (BGI; Abbott Medical Optics, Abbott Park, IL, USA) and Aurolab aqueous drainage implant (AADI; Aurolab, Aravind Eye Hospital, Madurai, India), which have been shown to be safe and effective in both pediatric and adult populations. AADI has certain advantages over AGV. Since it is indigenously manufactured, it is highly cost-effective when compared to AGV. Studies have shown that it has a higher success rate, achieves significantly lower intraocular pressure (IOP), and the patients require less number of anti-glaucoma medications postoperatively. Some studies also indicate that the long-term IOP control is better with AADI when compared to that with AGV.[123] Postoperative posterior segment complications that may arise after usage of GDDs are hypotony and its consequences like hypotony maculopathy, serous choroidal effusion, choroidal detachment, suprachoroidal hemorrhage, retinal detachment, and endophthalmitis.[45] Overall, retinal complications have been described in 14%-50% of eyes with GDD implantation and majority occur within 35 days after GDD implantation.[5] Rhegmatogenous retinal detachment (RRD) occurs in approximately 5% of eyes after aqueous humor shunt implantation, with most occurring within 4 months of surgery.[6] Khan et al.[7] reported the incidence of RRD after AADI and AGV implantation to be 5.4% and 4.3%, respectively. The present authors analyzed the outcomes of 10 cases of RRD/1158 (0.86%) cases after AADI implantation.[8] Few points are to be kept in mind in these cases. As has been pointed out by the authors, some predisposing factors for the development of retinal detachment may have been there, such as uveitis, vitreous incarceration, scleral perforation, and retinal dialysis after pars plana tube placement. Nowadays, vitrectomy is often the preferred mode of treatment than scleral buckling procedure. Intraoperative choroidal drainage is often required as these RRDs are frequently associated with choroidal detachment. Rarely, suprachoroidal hemorrhage (SCH) is also a concomitant complication and intraoperative drainage of SCH is sometimes required. Moreover, retinal detachment after appositional choroidal effusion or expulsive hemorrhage can result in retinal adhesions, which are to be tackled meticulously. Use of heavy fluid perfluorocarbon liquid is particularly beneficial for retinal reattachment. Silicone oil is the preferred mode of endotamponade and it is recommended to use it at the end of surgery. Postoperative visual prognosis is often compromised as the chance of recurrence of retinal detachment is high. The present authors have also highlighted that poor visual recovery is primarily due to recurrent RRD as well as preexisting glaucoma. Tube blockade by silicone oil droplets may result in rise of IOP postoperatively, further worsening the glaucoma status. Many times, migration of emulsified silicone oil particles into the subconjunctival space through both the valved and non-valved devices has been reported.[910] When a scleral buckle is to be placed in a case with a preexisting GDD, utmost care should be taken to avoid the displacement of the tube placed in the anterior chamber. Studies have also shown the occurrence of phthisis bulbi following aqueous humor shunt implantation.[11] So, as has been concluded by the authors, vitrectomy with silicone oil tamponade appears to be the preferred approach in the management of these eyes, with IOP being well controlled post-vitrectomy, but it should be kept in mind that the visual outcomes are largely unsatisfactory due to recurrent RRD and preexisting advanced glaucoma.

Reassessing the optimal volume for malignancy detection in serous fluid cytology.

The international system for reporting serous fluid cytopathology (TIS) recommends submitting at least 50-75 mL of serous fluid to decrease false-negative results. However, prior studies did not agree on specific volume requirements or consensus adequacy criteria. Our study aims to assess whether fluid volume affects the adequacy rate and to assess the minimum volume necessary for optimal adequacy in pleural and peritoneal fluids. A total of 8530 serous fluid cytology cases were identified in the laboratory information system. Differences in mean fluid volume received in the laboratory were compared using an ANOVA Games-Howell test based on TIS category. The percentage of malignant diagnoses across the volume ranges of 0 to 5 mL, 5 to 10 mL, 10 to 25 mL, 25 to 50 mL, 50 to 75 mL, 75 to 100 mL, 100 to 150 mL, 150 to 250 mL, 250 to 500 mL, 500 to 2000 mL was compared in pleural and peritoneal fluids using a chi-square test, and a SiZer analysis was performed. Mean fluid volume in inadequate, atypical, and negative cases was significantly lower compared to positive cases. A SiZer analysis showed a positive relationship between the malignancy fraction of pleural and peritoneal fluids and fluid volume. The percentage of malignant diagnoses in pleural and peritoneal fluid samples increased significantly up to a volume range of 75-100 mL. There is a significant relationship between fluid volume, adequacy and detection of malignancy in serous effusion cytopathology. The malignancy fraction increases with larger fluid volumes but at least 75-100 mL of fluid should be submitted for optimal diagnosis of malignancy in pleural and peritoneal fluids.

Molecular Diagnostics of Lung Cancer in Serous Effusion Samples

For molecular diagnostics of lung cancer samples, often only a small amount of material is available. The ever-increasing number of biomarker testing is in contrast to the amount of material obtained. In that case, cytological specimens, such as serous effusion samples, are one possible option. Effusion samples were prepared as sediment smears or cytospins or as a cell block if needed. Suitable tumor cells areas were marked by a cytopathologist and used for molecular diagnostics, including fast track analysis, parallel sequencing, and/or fluorescence in situ hybridization. In 62 cases of malignant effusion with cells of pulmonary adenocarcinoma, molecular diagnostics were carried out. A fast-track result with the high-resolution melting method for hotspot mutation of KRAS Exon 2 and EGFR exon 21 and fragment length analysis of EGFR exon 19 was available for 43 out of 47 samples (92%). Parallel sequencing was successful for 56 out of 60 samples (93.3%). In the same period, 108 FISH analyses were performed for MET amplification, followed by ROS1, RET, and ALK translocation analysis. If only a limited amount of tissue/biopsy is available, a malignant effusion is advisable to perform on the molecular diagnostics with a high success rate.

Refractory serositis in Gorham\u2013Stout syndrome

BackgroundGorham–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.MethodsPatients 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.ResultsOf 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.ConclusionsThis 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.

AL amyloidosis with primary presentation of multiple serous cavity effusion and severe cholestasis: a case report and review of literature

BackgroundImmunoglobulin light chain (AL) amyloidosis commonly affects the kidney or heart, but may also involve the liver at a histopathological level. Early diagnosis of AL amyloidosis is important for proper management with desirable outcome. We reported here an unusual case of AL amyloidosis, presenting primarily with multiple serous cavity effusion, accompanied with rapidly progressive cholestasis.Case presentationA previously healthy 63-year-old man presented with dysuria, frequent urination, oliguria and oedema of lower extremities for one month, accompanied with jaundice and hypoproteinemia. CT demonstrated multiple serous cavity effusion, focal hypodense lesions in the liver, and focal low-density in the spleen. Laparoscopy with liver biopsy revealed liver and spleen fibrosis with congestion, no visceral rupture, following haemorrhagic ascites from abdominocentesis. This patient was transferred to our (tertiary) hospital. The diagnosis of amyloidosis was confirmed with histopathology/immunohistochemistry. Haematopoietic stem cell transplantation was not applicable, however chemotherapy was advised, due to the patient’s Mayo score 3. The patient declined chemotherapy and was self-discharged back to his hometown hospital with palliative care, however only lasted a further one-month.DiscussionThe lesson we have learnt from this case that any patients with multiple serous cavity effusion and isolated hepatic involvement, primary amyloidosis should be considered. Multiple serous cavity effusion may serve as an indicator for poor prognosis of hepatic AL amyloidosis.

Serous Effusion Cytology in Sudanese Patients

The purpose of this study was to determine the etiology and cytological patterns of serous effusions among Sudanese patients. Methods and Results: This descriptive study was carried out in hospitals of Khartoum state in the period from February 2019 to June 2020. One hundred and seventy-eight patients “clinically and/or radiological” diagnosed as having an accumulation of serous effusions were included in this study. Smears were prepared and stained according to the conventional pap staining procedure. The majority of the study population (121[68%]) had malignant effusion (MEs), and the other group (57[32%]) - benign effusions (BEs). Among patients with MEs, breast cancer was the major etiology (75[62%]), followed by lung (23[19%]), GIT (12[9.9%]), and thyroid cancers (11[9.1%]), while among patients with BEs, parapneumonic conditions were the main factor (28[49.1%]), followed by tuberculosis (18[31.6%]) and pulmonary embolism (11[19.3%]). The majority of patients with MEs were pleural effusion (109[90.1%]), followed by peritoneal effusion (12[9.9%]), whereas no patients in this group had pericardial effusion. Pleural effusion (29[50.9%]) was also the major one among patients with BEs, followed by peritoneal (21[36.8%]) and pericardial effusions(7[3.9%]). Conclusion: Malignant serous effusion is commonly seen among patients with malignant tumors; pleural effusions presented a large proportion, especially among females with breast cancer. Thoracentesis and cytological methods (i.e., conventional smear and cell block technique) should be the first line for the diagnosis of malignant pleural effusions, along with confirmatory adjunct techniques such as immunohistochemistry and immunocytochemistry.

Application of the International System for Reporting Serous Fluid Cytopathology (TIS): A retrospective institutional study

AbstractBackgroundCytology of serous effusions is an important diagnostic tool for the diagnosis of cancer, staging, and prognosis of the patient. Herein, we retrospectively applied the International System for Reporting Serous Fluid Cytopathology (TIS) and provided the corresponding risks of malignancy (ROMs).MethodsPleural, pericardial, and peritoneal effusion samples were retrieved from the archives of our department and reclassified according to the TIS. The ROM for each category was calculated based on available surgical follow‐up.ResultsA total of 3790 effusions were studied. Pleural samples (1292) were reclassified as follows: 27 (2.1%) as non‐diagnostic (ND), 1014 (78.5%) as negative for malignancy (NFM), 86 (6.6%) as atypia of undetermined significance (AUS), 29 (2.3%) as suspicious of malignancy (SFM), and 136 (10.5%) as malignant (M). Pericardial samples (241) were reclassified as follows: 4 (1.6%) as ND, 173 (71.8%) as NFM, 10 (4.1%) as AUS, 7 (3%) as SFM, and 47 (19.5%), as M. Peritoneal cases (2257) were re‐categorised as follows: 31 (1.4%) as ND, 1897 (84%) as NFM, 39 (1.7%) as AUS, 53 (2.4%) as SFM, and 237 (10.5%) as M. The respective ROM values for each category were 18.5%, 15%, 45.3%, 93%, and 100% in pleural effusions; 25%, 13.2%, 35%, 100%, and 100% in pericardial effusions; and 19.3%, 10.4%, 43.5%, 100%, and 100% in peritoneal effusions.ConclusionsPleural, pericardial, and peritoneal cytology show high specificity and moderate sensitivity in the evaluation of serous effusions. The ROMs reported in our study were mostly concordant with those published according to the TIS.

Signet-ring cells in pleural and peritoneal effusions identified on Wright stains – A diagnostic pitfall

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.

Screening for malignant tumor cells in serous effusions with an automatic hematology analyzer using a novel diagnostic algorithm.

BackgroundDue to the high false-positive rate of the high-fluorescence body fluid (HF-BF) cell parameter of the hematology analyzer in BF mode, a novel algorithm based on the Mindray BC-6800 Plus hematology analyzer (BC-6800Plus), with higher diagnostic accuracy compared to that of the traditional HF-BF algorithm, was used to screen for malignant tumor cells in clinical BF samples. In this study, the body fluid mode of BC-6800Plus was applied to investigate the ability of its available parameters and characteristic regional particles in tumor cells screening.MethodsA total of 220 BF samples (including pleural effusion and ascites) were randomly classified into a training cohort (154 samples) and a validation cohort (66 samples), and detected on the BC-6800Plus in BF mode. Based on the scatter plot analysis of the instrument, a novel gating algorithm, malignant cell algorithm-body fluid (MA-BF), was designed to detect the aggregated cells expressing highest fluorescence (FL) signals and side-scatter (SS) signals than other cells. BF collection and analyses were performed in compliance with the CLSI H56-A guideline. tumor cell-positive samples were defined as greater than or equal to confirIIIb (Papanicolaou class system) by the pathological examination. The diagnostic accuracy of HF-BF and MA-BF were determined by the receiver operating characteristic (ROC) curve analysis.ResultsWhen the cutoff values of the absolute count (HF-BF#) and relative count (HF-BF%) were set as 0.022×109/L and 3.0%, respectively, the area under curve (AUC), sensitivity, and specificity were 0.76, 0.85 and 0.55 for HF-BF#, and were 0.70, 0.85, and 0.49 for HF-BF%, respectively. The new parameters, the absolute tumor cell count (MA-BF#) and relative count (MA-BF%), were established in the training cohort using the novel algorithm. We confirmed the cutoff values of MA-HF# and MA-HF% in BF were set as 0.006×109/L and 0.2% in the training cohort, respectively. In the validation cohort, the AUC, sensitivity, and specificity were 0.89, 0.93, and 0.78 for MA-BF#, and were 0.89, 0.87 and 0.75 for MA-BF%, respectively.ConclusionsThe MA-BF parameters of the novel algorithm output had better diagnostic accuracy for BF tumor cells than the traditional HF-BF parameters.

Systemic therapy in patients with metastatic Xp11.2 translocation renal cell carcinoma.

341 Background: Xp11.2 translocation renal cell carcinoma (RCC) is a unique RCC subtype with high malignant potential and poor prognosis, its natural course and response to systemic therapy are not fully understood. We analyzed the clinic features of this distinct entity and the benefit of systemic therapy in these patients. Methods: Between May 2006 and December 2019, 1113 consecutive patients diagnosed with RCC from Peking university cancer hospital (Beijing, China) were reviewed, data of the clinical characteristics and outcome of patients with metastatic Xp11.2 RCC were retrospectively collected. Tumor response to systemic therapy was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions. Results: Metastatic Xp11.2 tRCC was found in 45 patients. The median PFS and median OS was 7.4 months (4.5 - 8.8) and 17.9 months (12.4 - 24.4), respectively. First-line treatment mainly included sunitinib (n = 14), sorafenib (n = 15), axitinib (n = 6), and pazopanib (n = 5), and the median PFS of these regimens were 7.4 months, 5.4 months, 9.4 months, 8.9 months, respectively. Two patients who received Vascular endothelial growth factor receptor - tyrosine kinase inhibitor (VEGFR-TKI) plus immune checkpoint inhibitor (ICI) as first line therapy had a PFS of more than 16.6 months and more than 25.6 months, respectively. Twenty-four patients received subsequent therapies, which included VEGFR-TKI/ICI, axitinib and mTOR inhibitor, the median PFS for these regimens was 8.5, 7.2 and 2.0 months, respectively. Patients with serous cavity effusion or IMDC poor risk groups had significantly shorter median PFS and median OS. Conclusions: Metastatic Xp11.2 tRCC is an aggressive disease. VEGFR-TKI agents appeared to demonstrate some efficacy, VEGFR-TKI/ICI combination might be a useful tool for the treatment of metastatic Xp11.2 tRCC.

Malignant Serous Effusions among Hospital In-patients in a Tertiary Care Hospital: A Descriptive Cross-sectional Study.

Cell block technique is an adjunct to conventional smears in the diagnosis of malignancy in effusion fluid. It aims at retrieving cellular material and concentrating cells in a small field, with preservation of cytomorphologic details. The objective of this study was to find the proportion of malignant serous effusions using cell block technique among hospital in-patients in a tertiary care centre. This was a descriptive cross-sectional study conducted among patients visiting a tertiary care centre between 1st June 2020 to 30th November 2020. Ethical approval was taken from the Institutional Review Committee (Reference number: 305202001). Using a convenience sampling method, 96 hospital in-patients were included in the study. Serous effusions were evaluated by conventional smears and cell block sections. Data was analysed using the Statistical Package for the Social Sciences version 23. Point estimate at 95% Confidence Interval was calculated along with frequency, percentage, mean and standard deviation. Among 96 hospital in-patients, 15 (15.62%) (8.35-22.88 at 95% Confidence Interval) were diagnosed as positive for malignancy by using cell block technique. By conventional smears, 80 (83.33%) cases turned out to be negative for malignancy, 13 (13.54%) were positive for malignancy and three (3.12%) were suspicious for malignancy. Of the three (3.12%) cases suspected for malignancy, two turned out to be positive for malignancy and one was found to be negative for malignancy on cell block technology. The proportion of malignant serous effusions was similar in comparison to other studies. Cell block technique could be routinely incorporated along with conventional smears for a more accurate diagnosis of malignancy on serous effusion.

Metastatic Carcinoma in Effusions.

Serous cavity may be involved by any neoplasm, including very rare examples of involvement by central nervous system tumors leading to a malignant effusion. The serous cavity lining is rich in lymphatics with lymphatic lacunae opening directly through narrow gaps (stoma) in the lining. Carcinomas mainly metastasize to serosa via the lymphatic vessels, which may be blocked leading to effusion. Primary carcinomas of organs such as lung, intestines, liver, ovary, etc., lined by serosal membranes may spread by direct extension, resulting in malignant effusions. As standard of practice, unless specified, cytopathologic examination of serous effusions implies detection of malignant cells.As compared to a surgical biopsy from a small focal area of an extensive serosal surface, effusion fluid from respective cavity exfoliates the cells from the entire serosal surface with minimal chance of sampling artifact. Because of this, effusion fluid cytology generally provides a higher diagnostic yield as compared to biopsy of the serous lining, as demonstrated by some studies. However, various challenges related to effusion fluid cytology makes the interpretation of effusion fluid cytology a field with potential misinterpretations, especially for those without proper experience or training.Developing and following a methodical approach is important for appropriate cytologic examination of effusion fluids. Proper approach may achieve definitive interpretation even without ancillary tests. However, lack of appropriate approach and processing may introduce a significant variation in interpretation due to combination of well-recognized diagnostic pitfalls, which may lead to lower reproducibility and even serious misinterpretations.Current review discusses in brief appropriate approach to processing and evaluating effusion fluid cytology for metastatic carcinoma. At general level, this is comparable to that of other specimens; however, it is critical to modify with reference to the limitations associated with effusion cytology.

Exosomes in Pathogenesis, Diagnosis, and Treatment of Hepatocellular Carcinoma.

Exosomes are extracellular vesicles with a diameter of 30-150 nm that are released by most types of cells and have been confirmed to be involved in many physical and pathological processes, especially in cell to cell communication. Compared with other vesicles, exosomes have a unique double-layer saclike structure that allows them to be present stably in various body fluids, including blood, cerebrospinal fluid, urine, saliva, and serous cavity effusion. The cargoes of exosomes reflect the characteristics of host cells. Due to the nature of hepatocellular carcinoma (HCC) cells, heterogeneity in the bioactive substances usually exist in exosomes. In addition, exosomes can efficiently deliver cargoes to the target cells to exert pathological functions, playing important role in tumor occurrence, development, metastasis, immune regulation, and drug resistance. Previous studies have been shown that exosomes have wide applications in diagnosis and treatment of HCC. In this review, we discuss these recent findings and highlight the significant roles of exosomes in HCC, focusing on the effect and underlying mechanisms of exosomes to regulate HCC progression and the potential clinical value of exosomes as biomarkers and therapeutic targets.

The Role of Pre-therapeutic 18F-FDG PET/CT in Pediatric Hemophagocytic Lymphohistiocytosis With Epstein-Barr Virus Infection.

ObjectiveTo evaluate the role of pre-therapeutic 18F-FDG PET/CT in pediatric hemophagocytic lymphohistiocytosis (HLH) with Epstein-Barr virus (EBV) infection.MethodsThis retrospective study included 29 HLH children (1–16 years) with EBV infection, who underwent pre-therapeutic 18F-FDG PET/CT from July 2018 to November 2020. Pathology results were considered as the reference standard. These patients were divided into two groups: EBV-induced malignancy-associated HLH (M-HLH, N = 9) and EBV-induced non-malignancy-associated HLH (NM-HLH, N = 20). The regions of interest (ROIs) of the liver, spleen (Sp), bone marrow (BM), lymph nodes (LN), hypermetabolic lesions, liver background (LiBG), and mediastinum (M) were drawn with software 3D-Slicer. The volumetric and metabolic parameters, including maximum standard uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis of these ROIs, clinical parameters, and laboratory parameters were compared between the two groups. The efficiency of the above parameters in predicting the treatment response and overall survival (OS) was analyzed.ResultsReceiver operating characteristic curve analysis indicated that SUVmax-lesions and SUVmax-LN/M (AUC = 0.822, 0.819, cut-off = 6.04, 5.74, respectively) performed better in differentiating M-HLH from NM-HLH. It had the best diagnostic performance when age was added with the SUVmax-LN/M (AUC = 0.933, sensitivity = 100%, specificity = 85.0%). The presence of extranodal hypermetabolic lesions in multiple organs indicated the M-HLH (P = 0.022). Older age, higher SUVmax-LN and SUVmax-lesions, and the presence of serous effusion were associated with poorer treatment response at the 2nd and 4th week (not reaching partial remission). Multivariate analysis showed that SUVmax-lesions > 7.66 and SUVmax-Sp/LiBG > 2.01 were independent prognostic factors for overall survival (P = 0.025, 0.036, respectively).Conclusions18F-FDG PET/CT could be a valuable technique for identifying the underlying malignancy and predicting prognosis in pediatric HLH with EBV infection. M-HLH could be considered when SUVmax-lesions > 6.04, SUVmax-LN/M > 5.74, and the presence of extranodal hypermetabolic lesions in multiple organs on 18F-FDG PET/CT. SUVmax-lesions and SUVmax-Sp/LiBG might be independent prognostic factors for OS.

Combination of Biochemical and Cytological Findings for Better Diagnosis in Pleural Effusions.

Serous pleural effusions result from increased permeability and changed hydrostatic or colloid osmotic pressure. Laboratory biochemical findings provide conclusions about the effusion compositions. Together with the anamnesis and clinical assessment, they enable the evaluation of the effusion nature. The present study retrospectively analyzed combined biochemical and morphological findings in 2307 effusions of patients from two clinical centers: LungenClinic Grosshansdorf in Germany and Duzce University in Turkey. The effusion cytology results of 1771 and 536 patients from the respective centers were combined with clinical/radiological/biochemical findings and counter compared with the final diagnoses. Cytology verified 738 malignant tumors (643 and 95, respectively). Most effusions were benign (n=1569; 77%) and 367 of them were paramalignant (293 and 74, respectively) and 594 were inflammatory (465 and 129, respectively). There was a distinctly lower number of malignant tumors in transudates than exudates (87 vs. 725; p<0.0001). Squamous cell carcinoma was more frequent in paramalignant pleura effusions (122 cases out of the 367 effusions) than pleural carcinomatosis (32 cases out of the 780 malignant tumors; p<0.0001). The cell formula was a suitable marker for malignant mesothelioma, predominantly mesothelial, or neutrophilic characterized by elevated LDH (>500U/L) in the early stage of empyema or its late manifestation. İn conclusion, most effusions are benign. Cytologists, assisted by clinical and biochemical data and microscopic findings, can make significant differential diagnostic contributions beyond the sole detection of malignancy.

The Indian Academy of Cytologists Guidelines for Reporting Serous Effusion (IACGRSE): An Interobserver Agreement Analysis.

Context:The Indian Academy of Cytologists published Guidelines and categories for Reporting Serous Effusions (IACGRSE) in 2020 to improve consistency and reproducibility of fluid cytology reporting and to guide patient management.Aims:To evaluate category-wise agreement while using IACGRSE 2020 categories. To analyze interobserver agreement among participants with different level of training and years of experience.Settings and Design:A retrospective interobserver variability study.Methods and Material:Study was done with four participants: an expert cytopathologist and three cytopathology fellows with varying experience. Fluid smears from 60 cases with clinical and/or radiological evidence of malignancy were categorized into one of the five IACGRSE 2020 categories. The interpretations of expert cytopathologist were taken as standard.Statistical Analysis Used:Interobserver agreement was analyzed using Kappa statistics.Results:Previous cases without definitive category got classified into “Atypical cells NOS” (3.33%) and “Atypical cells, Suspicious of Malignancy” (15%). Agreement analysis for IACGRSE 2020 categories showed better concordance for inadequate (I), malignant (V), and benign (II) categories. The range of Kappa for interobserver agreement of fellows was fair to substantial (range 0.1692–0.7249). The participant with substantial diagnostic agreement with expert (κ = 0.729, 88.3%) had the most experience. Causes of major discordance were pertaining to paucity and distribution of cells, and to misinterpretation of reactive mesothelial cells.Conclusions:IACGRSE 2020 categories and participants’ experience were important determinants in classifying the effusion fluid cytology smears and interobserver agreement; emphasizing the need to use IACGRSE2020, and sufficient time and training required for accurate diagnosis of fluid specimens.

Cytological Diagnosis of Malignant Mesothelioma: A Case Series.

Background:Mesotheliomas are neoplasms of the serosal lining of the body cavities. Diagnosis requires a multimodal approach of clinical findings, cytology, and histopathology with immunohistochemistry (IHC). The published sensitivity of cytology for diagnosing mesothelioma ranges from 30% to 75%.Aim and Objectives:This study aimed to calculate the incidence of malignant mesothelioma (MM) at our institute and to study the cytological features of MM.Materials and Methods:A retrospective study of pleural, peritoneal, and pericardial fluids submitted at our institute was done. The duration of the study was 8 years (2011–2019). Apart from examining Giemsa smears, a panel of immunocytochemical (ICC) and cell block immunohistochemical (IHC) markers was applied to achieve the diagnosis. These included calretinin, mesothelin, CK5/6, Hector Battifora mesothelial cell antibody (HBME), WT1, MOC31, CK7 and CK20. Histopathological correlation was done wherever possible.Result:In the present study, we compiled four cases of MM over 8 years diagnosed on serous effusion cytology and confirmed by immunocytochemistry (ICC)/cell block immunohistochemistry (IHC)/biopsy. This indicates a rare incidence of MM. The Cytological features of MM were studied.Conclusion:The diagnosis of MM is difficult, especially cytologically. It was found to be a rare entity in the malignant cases diagnosed on effusion cytology.