This study describes an unusual case of multiple myeloma that progressed to anaplastic multiple myeloma in the pleural fluid. The Wright-stained cytospin of the pleural fluid showed a predominant population of mononuclear plasma cells with pleomorphic nuclei, characterized by both small and large nuclei, which is typical of anaplastic multiple myeloma. However, there were also more binuclear plasma cells with pleomorphic nuclei. Morphometric analysis showed that the mean nuclear length was 1.9-fold and 2.3-fold higher in the large nuclei compared to the small nuclei for the mononuclear plasma cells and binuclear plasma cells, respectively (p<0.001). The patient received B cell maturation antigen chimeric antigen receptor T cell (CAR-T) therapy for relapsed disease, with a significant reduction of the serum monoclonal paraprotein level at day 51 post-therapy. Pathologists should be aware that pleomorphic binuclear plasma cells can be part of the morphologic spectrum in anaplastic multiple myeloma.

Pleural effusion occurs in both benign and malignant pleural disease. In malignant pleural effusions, the diagnostic accuracy and sensitivity of pleural fluid cytology is less than perfect, particularly for the diagnosis of malignant pleural mesothelioma, but also in some cases for the diagnosis of metastatic pleural malignancy with primary cancer in the lung, breast or other sites. Extracellular vesicles (EVs) carry an enriched cargo of microRNAs (miRNAs) which are selectively packaged and differentially expressed in pleural disease states. To investigate the diagnostic potential of miRNA cargo in pleural fluid extracellular vesicles (PFEVs), we evaluated methods for isolating the extracellular vesicle (EV) fraction including combinations of ultracentrifugation, size-exclusion chromatography (SEC) and ultrafiltration (10 kDa filter unit). PFEVs were characterized by total and EV-associated protein, nanoparticle tracking analysis and visualisation by transmission electron microscopy. miRNA expression was analyzed by Nanostring nCounter® in separate EV fractions isolated from pleural fluid with or without additional RNA purification by ultrafiltration (3 kDa filter unit). Optimal PFEV yield, purity and miRNA expression were observed when PFEV were isolated from a larger volume of pleural fluid processed through combined ultracentrifugation and SEC techniques. Purification of total RNA by ultrafiltration further enhanced the detectability of PFEV miRNAs. This study demonstrates the feasibility of isolating PFEVs, and the potential to examine PFEV miRNA cargo using Nanostring technology to discover disease biomarkers.

BACKGROUND: Chylothorax is a postoperative complication in patients with lung cancer. Diet-control approaches have been the mainstay for managing this condition. However, a surgical intervention is needed for the patients if conservative treatment is ineffective. Because of the lack of accurate indicators to assess the prognosis of the postoperative complication at an early stage, the criteria of surgical treatment were not consistent.
METHODS: We reviewed 2942 patients who underwent pulmonary resection and lymph node dissection for primary lung cancer at our hospital between March 2021 and December 2022. The prognostic implications of clinical indicators were assessed in patients with postoperative chylothorax who were managed with a low-fat diet. Binary logistic regression was used to explore the predictive value of these indicators for patient prognosis.
RESULTS: Postoperative chylothorax occurred in 108 patients and 79 patients were treated with a low-fat diet management while 29 patients were managed with TPN. In contrast to drainage volume, the pleural effusion triglyceride level after 2 days of low-fat diet exhibited enhanced predictive efficacy in predicting patient prognosis. When the pleural fluid triglyceride level of 1.33 mmol/L was used as the diagnostic threshold for prognosis, the sensitivity and specificity reached 100% and 80.6%, respectively.
CONCLUSIONS: The pleural effusion triglyceride level after 2 days of low-fat diet can serve as a valuable prognostic indicator in patients undergoing lung surgery and experiencing chylothorax. This predictive approach will help thoracic surgeons to identify patients with poor prognosis in a timely manner and make decision to perform necessary surgical interventions.

A 47-year-old male, a known case of alcoholic chronic liver disease with portal hypertension, presented with complaints of abdominal distension and shortness of breath. A provisional diagnosis of ethanol-related compensated chronic liver disease (CLD) with portal hypertension and splenomegaly, gross ascites with bilateral hepatic hydrothorax was made. The left-sided pleural effusion subsided after three pleural taps, but the right-sided effusion kept refilling even after four to five days of repeated therapeutic taps, so a pigtail catheter was left in situ. The pleural fluid was sent for culture which did not grow any pathogenic organisms. Cartridge-based nucleic acid amplification tests where Mycobacterium tuberculosis complex (MTBC) was not detected, Ziehl-Neelsen staining was done in which acid-fast bacilli were not seen, and cytology was done where no malignant cells were seen. The patient was discharged with the pigtail in situ on the right side and, after 20 days, the patient again presented with shortness of breath, and imaging revealed moderate right-side pleural effusion. Draining of pleural fluid was done and sent for investigation which again revealed no infective etiology. The patient was admitted to the hospital for one month as the right-sided effusion did not resolve. Suddenly, the patient developed shortness of breath, and a chest X-ray was done, which showed pigtail blockage; pigtail flushing was done, and the bag was drained. The patient was empirically started on IV meropenem 500 mg TID, IV teicoplanin 400 mg BD, and inj polymyxin B 500,000 IU IV BD. The pleural fluid was sent continuously for investigation for the first two months which again did not reveal any infective etiology. After two months of pigtail in situ, the pleural fluid was sent for CBNAAT where MTBC was not detected, and ZN stain showed smooth acid-fast bacilli. The sample was cultured, and it grew acid-fast bacilli in 72 hours on blood agar, MacConkey agar, and Lowenstein-Jensen media. A line probe assay done from the isolate revealed it to be Mycobacterium abscessus subsp. abscessus which was resistant to macrolides and sensitive to aminoglycosides. Mycobacterium abscessus subsp. abscessus was isolated from repeated cultures of pleural fluid, and the patient was advised on a combination treatment of amikacin, tigecycline, and imipenem. The patient was discharged with the indwelling pigtail with the advised treatment; unfortunately, we lost patient follow-up as the patient never returned to us.

Yellow nail syndrome (YNS) can induce bilateral exudative pleural effusion; however, to the best of our knowledge, no standard treatment for YNS has been established. The present study describes a patient with YNS for whom the pleural effusion was controlled by prednisolone. A 73-year-old man was referred to the University of Tsukuba Hospital (Ibaraki, Japan) complaining of shortness of breath, which was diagnosed as being due to bilateral pleural effusion. Based on the presence of yellowing and growth retardation of the toenails, lymphedema, bilateral exudative pleural fluid of unknown etiology, and lymphatic congestion on lymphoscintigraphy, the patient was diagnosed with YNS. The pleural fluid was predominantly lymphocytic and responded to systemic steroid administration [prednisolone 30 mg/day (0.5 mg/kg) for 2 weeks, with subsequent weekly tapering]. The general condition of the patient and their dyspnea also improved with treatment. These findings indicated that systemic steroid administration should be considered as one of the treatment options for patients with YNS who are reluctant to undergo chest drainage or pleurodesis due to the potential for a decrease in their ability to perform daily activities and respiratory function.

UNASSIGNED: Thoracocentesis is a less invasive and expensive procedure than pleural biopsy, enabling sample collection for cytological evaluation. Cell blocks prepared from these samples provide histopathological diagnoses; further, immunohistochemistry (IHC) can be performed for subtyping malignancies, guiding the clinician in choosing the appropriate treatment modality for the patient. We aimed to determine the various histological subtypes of malignancies using cell block IHC and compare the cell block and conventional cytology methods for diagnosing malignant pleural effusion.
UNASSIGNED: All pleural fluid samples from the clinically suspicious cases of malignancy collected at the Department of Pathology, Government Medical College Kottayam, India, during 18 months, except duplicate and inadequate samples, were included in this prospective observational study. IHC was performed on cell blocks that were positive for malignancy.
UNASSIGNED: This study analyzed 630 samples, of which 121 cell blocks demonstrated the presence of malignancy. Overall, 80%, 13%, and 7% of cases were negative, suspicious, and positive for malignancy based on conventional cytology, and 81%, 0%, and 19% were negative, suspicious, and positive for malignancy based on cell blocks, respectively. Among all malignancies, adenocarcinomas from the lung (56%) were the most common, followed by adenocarcinomas from the breast (6%), squamous cell carcinomas (5%), and adenocarcinomas from the ovary (3%). Cell blocks helped detect more malignancies (19%) than conventional cytology (7%), despite a moderate agreement between both methods.
UNASSIGNED: Adenocarcinomas were the most common cause of malignant pleural effusions, and the most frequent site of origin was the lungs. Cell blocks helped diagnose more malignancies than conventional cytology.

The cytomorphology of MPNST in effusion specimens is rarely described. In this paper, the detailed cytopathological and immunohistochemical characteristics of metastatic MPNST has been described in pleural effusion. Patients\' medical history and the judicious utilization of ancillary studies contribute to ensure precise cytological diagnoses. The cytomorphology of malignant peripheral nerve sheath tumour (MPNST) in effusion specimens can be diagnostically challenging. The author presents detailed cytopathological and immunohistochemical characteristics of a case of metastatic MPNST in pleural effusion.

Retained hemothorax (RH) is a commonly encountered and potentially severe complication of intrapleural bleeding that can organize with lung restriction. Early surgical intervention and intrapleural fibrinolytic therapy have been advocated. However, the lack of a reliable, cost-effective model amenable to interventional testing has hampered our understanding of the role of pharmacological interventions in RH management. Here, we report the development of a new RH model in rabbits. RH was induced by sequential administration of up to three doses of recalcified citrated homologous rabbit donor blood plus thrombin via a chest tube. RH at 4, 7, and 10 days post-induction (RH4, RH7, and RH10, respectively) was characterized by clot retention, intrapleural organization, and increased pleural rind, similar to that of clinical RH. Clinical imaging techniques such as ultrasonography and computed tomography (CT) revealed the dynamic formation and resorption of intrapleural clots over time and the resulting lung restriction. RH7 and RH10 were evaluated in young (3 mo) animals of both sexes. The RH7 recapitulated the most clinically relevant RH attributes; therefore, we used this model further to evaluate the effect of age on RH development. Sanguineous pleural fluids (PFs) in the model were generally small and variably detected among different models. The rabbit model PFs exhibited a proinflammatory response reminiscent of human hemothorax PFs. Overall, RH7 results in the consistent formation of durable intrapleural clots, pleural adhesions, pleural thickening, and lung restriction. Protracted chest tube placement over 7 d was achieved, enabling direct intrapleural access for sampling and treatment. The model, particularly RH7, is amenable to testing new intrapleural pharmacologic interventions, including iterations of currently used empirically dosed agents or new candidates designed to safely and more effectively clear RH.

Tuberculosis (TB) is a worldwide burden whose total control and eradication remains a challenge due to factors including false positive/negative diagnoses associated with the poor sensitivity of the current diagnostics in immune-compromised and post-vaccinated individuals. As these factors complicate both diagnosis and treatment, the early diagnosis of TB is of pivotal importance towards reaching the universal vision of a TB-free world. Here, an aptasensor for signaling an interferon gamma (IFN-γ) TB biomarker at low levels is reported. The aptasensor was assembled through gold-thiol interactions between poly(3,4-propylenedioxythiophene), gold nanoparticles, and a thiol-modified DNA aptamer specific to IFN-γ. The aptasensor sensitively detected IFN-γ in spiked pleural fluid samples with a detection limit of 0.09 pg/mL within a linear range from 0.2 pg/mL to 1.2 pg/mL. The good performance of the reported aptasensor indicates that it holds the potential for application in the early diagnosis of, in addition to TB, various diseases associated with IFN-γ release in clinical samples.

UNASSIGNED: Calprotectin (CP) is a calcium and zinc binding protein that is widely measured on faecal samples but its determination in other biological fluids might be of interest. The aim of this work was to validate the measurement of CP in pleural fluid by chemiluminescence.
UNASSIGNED: LIAISON®XL, a fully automated chemiluminescence analyzer, was used for CP quantification on pleural fluid. A validation protocol was designed using both quality control materials provided by the manufacturer and pools of pleural fluid samples. Stability, imprecision, bias, linearity, detection capability and carry over effect were evaluated.
UNASSIGNED: CP was stable on pleural fluid at least one week, under refrigerated conditions, and four weeks at -80 °C. The observed intra- and inter-day imprecision was between 2.2 and 6.49 %, with a negative bias under 5.51 %. The linearity of the method was verified up to 2,000 ng/mL. The LoQ for the assay was 48.52 ng/mL. A statistically significant carry-over effect was observed after measuring CP concentrations above the upper limit of linearity, but given the observed magnitude, a clinically relevant impact should not be expected.
UNASSIGNED: DiaSorin Liaison® calprotectin assay allows reliable measurement of CP in pleural fluid.