A case of t-cell lymphoblastic lymphoma characterized by pleural effusion combined with pericardial effusion.

This case underscores the pivotal role of early cytological examination of bodily fluids in the preliminary detection of lymphoma, a conclusion reinforced by subsequent pathological findings and refined through immunohistochemical characterization. A morphological analysis of pleural effusion cells was conducted in a 25-year-old male presenting initially with concurrent pleural and pericardial effusions. Initial morphological assessment of effusion specimens indicated the likelihood of a lymphoproliferative disorder. Subsequent detailed pathological and immunohistochemical investigations confirmed this suspicion, culminating in a definitive diagnosis of T-cell lymphoblastic lymphoma (T-LBL). The case emphasizes the necessity of employing a comprehensive and synergistic diagnostic approach, facilitating prompt and accurate diagnosis and subtyping of lymphoma.

An update on the minimally invasive diagnosis of lymphoma for the chest physicians.

Mediastinal lymphadenopathy has a broad differential diagnosis which includes lymphoma. The current preferred biopsy technique for mediastinal lymph nodes is transbronchial needle aspiration which has mixed results in terms of sensitivity, specificity and diagnostic yields; there are also limitations with subtyping lymphomas with needle aspiration alone which can be a barrier to determine management strategies. Invasive mediastinal lymph node sampling such was with mediastinoscopy provides higher yields and preserved lymph node architecture for both diagnosis and subtyping of lymphoma but carries a higher risk of morbidity and complications. Novel techniques that may increase the diagnostic yield of bronchoscopy in the diagnosis of lymphoma are core biopsy needles, intranodal forcep biopsy, and intranodal cryobiopsy. The evidence is limited due to a relatively small number of cases, so further research is needed to standardize best practices for the bronchoscopic diagnosis of lymphoma. Pleural effusions in lymphoma can be present in up to 30 % of cases with the majority being non-Hodgkins's lymphoma. The presence of exudative effusion in the setting of an existing or prior diagnosis of lymphoma should raise clinical suspicions. Other less common subtypes of lymphoma presenting as primary pleural effusions are explored as well.

[Application of cell blocks to assist in precise cytological diagnosis of serous effusion].

Objective: To investigate the importance of cell block and immunohistochemistry in the accurate diagnosis of serous effusion. Methods: A retrospective study was conducted on 3 124 cases of serous effusion from the Department of Pathology, Beijing Hospital from 2018 to 2022, include 2 213 cases of pleural effusion, 768 cases of peritoneal effusion, 143 cases of pericardial effusion. There were 1 699 males (54.4%) and 1 425 females (45.6%), average age 69 years old. Of which 1 292 cases were prepared with cell blocks and examined with immunohistochemical stain. Results: The percentage of malignant diagnosis increased from 64.9% (839/1 292) to 84.0% (1 086/1 292) after cell block preparation, and 1 086 cases were accurately diagnosed with histological type and/or origin of primary tumor. The undetermined diagnosis of suspected malignancy decreased from 13.3% (172/1 292) to 0.1% (1/1 292) and that of atypical hyperplasia from 18.8% (243/1 292) to 0.4% (5/1 292). The negative result for malignancy rate increased from 3.0% (38/1 292) to 15.5% (200/1 292). The differences highlighted above were statistically significant (Pearson's chi-squared test=12.739, P<0.01). Conclusion: Application of immunohistochemistry based on cell block can significantly improve malignant diagnosis in serous effusion, identify tumor origin and histological type as well as decrease the uncertain diagnosis.

Emperipolesis in pleural fluid mesothelial cells. A phenomenon not associated with Rosai-Dorfman disease, report of a case.

Emperipolesis is a cell-within-cell phenomenon distinct from phagocytosis more often described in Rosai-Dorfman disease, where usually lymphocytes or other bone marrow cells (plasma cells, erythroblasts or neutrophils) are entirely surrounded but not engulfed by macrophages as the host cell, but occasionally megakaryocytes and neoplastic could be. Mesothelial cell has been described in a couple of cases of lymphomas affecting serous membranes, but never described in pleuritis. In the present work, the first case of emperipolesis by mesothelial cells in a patient with self-limited pleural effusion was demonstrated by immunohistochemistry and Electron Microscopy studies.

Intrapleural nivolumab in cancer patients with pleural effusion.

ABSTRACT: We assessed the preliminary efficacy and toxicity of intrapleural instillation of nivolumab in patients with large pleural effusion. Patients with metastatic cancers who have a large volume of pleural effusion and required evacuation were eligible. Thoracentesis followed by nivolumab (40 mg, single intrapleural instillation) was performed. The primary endpoint was 3-month recurrence-free survival. A total of 13 patients were enrolled. The study was terminated after stage 1 as no efficacy was observed; 7 patients (54%) had a recurrence of pleural effusion at 3 months. Thirteen (100%) patients had no recurrence, dyspnea, or cough within 1 month, and the median time to recurrence was 1.9 months (95% confidence interval [CI], 1.35-2.5). No adverse events were identified. We concluded that a single intrapleural instillation of the nivolumab at 40 mg was ineffective and well-tolerated in cancer patients with pleural effusion.

Fluoroscopy-Guided Percutaneous Transthoracic Pleural Forceps Biopsy in Patients With Exudative Pleural Effusion.

OBJECTIVE: This study aimed to evaluate the diagnostic performance and procedural characteristics of fluoroscopy-guided percutaneous transthoracic pleural forceps biopsy (PTPFB) in patients with exudative pleural effusion. MATERIALS AND METHODS: Patients with exudative pleural effusion who underwent PTPFB between May 1, 2014, and February 28, 2023, were included in this retrospective study. The interval between percutaneous catheter drainage (PCD) and PTPFB, number of biopsies, procedural time, and procedure-related complications were evaluated. The sensitivity, specificity, and accuracy of diagnosing malignancy were computed for pleural cytology using PCD drainage, PTPFB, and combined PTPFB and pleural cytology. RESULTS: Seventy-one patients, comprising 50 male and 21 female (mean age, 69.5 ± 15.3 years), were included in this study. The final diagnoses were benign lesions in 48 patients (67.6%) and malignant in 23 patients (32.4%). The overall interval between PCD and biopsy was 2.4 ± 3.7 days. The interval between PCD and biopsy in the group that underwent delayed PTPFB was 5.2 ± 3.9 days. The mean number of biopsies was 4.5 ± 1.3. The mean procedural time was 4.4 ± 2.1 minutes. Minor bleeding complications were reported in one patient (1.4%). The sensitivity, specificity, and accuracy for pleural cytology, PTPFB, and combined PTPFB and pleural cytology were 47.8% (11/23), 100% (48/48), and 83.1% (59/71), respectively; 65.2% (15/23), 100% (48/48), and 88.7% (63/71), respectively; and 78.3% (18/23), 100% (48/48), and 93.0% (66/71), respectively. The sensitivity and accuracy of cytology combined with PTPFB were significantly higher than those of cytological testing alone (P = 0.008 and 0.001, respectively). CONCLUSION: Fluoroscopy-guided PTPFB is an accurate and safe diagnostic technique for patients with exudative pleural effusion, with acceptable diagnostic performance, low complication rates, and reasonable procedural times.

Needle Biopsy of Pleura in the Aetiological Diagnosis of Pleural Effusion.

Exudative pleural effusion appears as manifestation of underlying specific disease process and pleural biopsy is usually enough to find out the underlying causative disease. The aim of the study was to find out the efficacy of needle biopsy of pleura in the aetiological diagnosis of pleural effusion. This cross-sectional study was conducted for a period of one year from January 2008 to December 2008 in the Department of Medicine, Shaheed Ziaur Rahman Medical College Hospital, Bogura, Bangladesh enrolling 50 subjects with exudative pleural effusion. The cases with transudative pleural effusion were not included. Needle biopsy was done in all the cases. Histopathological reports of pleural biopsy specimen were correlated with other data and analyzed to detect the causes of effusion. Major incidence of malignant effusion occurred between 41 to 70 years of age. No malignant effusion was found before 30 years of age. Incidence of tuberculous and malignant pleural effusion was much more common in males than in females. Sensitivity and specificity of combined pleural biopsy and pleural fluid analysis in the diagnosis of pleural effusion was 97.06% and 100.% for tuberculosis and 81.82% and 100.0% for malignancy. The present study reveals that pleural biopsy was very effective method in the diagnosis of cause of pleural effusion.

Differences in microenvironment of lung cancer and pleural effusions by single-cell RNA sequencing.

BACKGROUND: Direct comparison of tumor microenvironment of matched lung cancer biopsies and pleural effusions (PE) from the same patients is critical in understanding tumor biology but has not been performed. This is the first study to compare the lung cancer and PE microenvironment by single-cell RNA sequencing (scRNA-seq). METHODS: Matched lung cancer biopsies and PE were obtained prospectively from ten patients. We isolated CD45+ cells and performed scRNA-seq to compare the biopsies and PE. RESULTS: PE had a higher proportion of CD4+ T cells but lower proportion of CD8+ T cells (False detection rate, FDR = 0.0003) compared to biopsies. There was a higher proportion of naïve CD4+ T cells (FDR = 0.04) and naïve CD8+ T cells (FDR = 0.0008) in PE vs. biopsies. On the other hand, there was a higher proportion of Tregs (FDR = 0.04), effector CD8+ (FDR = 0.006), and exhausted CD8+ T cells (FDR = 0.01) in biopsies. The expression of inflammatory genes in T cells was increased in biopsies vs. PE, including TNF, IFN-É£, IL-1R1, IL-1R2, IL-2, IL-12RB2, IL-18R1, and IL-18RAP (FDR = 0.009, 0.013, 0.029, 0.043, 0.009, 0.013, 0.004, and 0.003, respectively). The gene expression of exhaustion markers in T cells was also increased in tumor biopsies including PDCD1, CTLA4, LAG 3, HAVCR2, TIGIT, and CD160 (FDR = 0.008, 0.003, 0.002, 0.011, 0.006, and 0.049, respectively). CONCLUSIONS: There is a higher proportion of naïve T cells and lower proportion of exhausted T cells and Tregs in PE compared to lung cancer biopsies, which can be leveraged for prognostic and therapeutic applications.

Second opinion for pulmonary and pleural cytology is valuable for patient care.

INTRODUCTION: Thoracic cytology can be challenging due to limited procured material or overlapping morphology between benign and malignant entities. In such cases, expert consultation might be sought. This study aimed to characterize all pulmonary and pleural cytology consult cases submitted to our practice and provide recommendations on approaching difficult cases. MATERIALS AND METHODS: All thoracic (pulmonary and pleural) cytology cases submitted for expert consultation to the University of Michigan (MLabs) from 2013 to mid-2022 were reviewed. Cases where cytology was only part of a hematopathology or surgical pathology consult were excluded. Patient demographics, specimen location, procedure performed, referring diagnosis, and our diagnoses were recorded for each case. Diagnoses were categorized according to the Papanicolaou Society of Cytopathology recommendations for pulmonary and effusion cytology. Discordant diagnoses were stratified as major or minor. Data was analyzed using chi-square analysis and logistic models. RESULTS: We received 784 thoracic cytology consult cases, including 530 exfoliative samples and 307 fine-needle aspirations. The most common anatomic locations sampled were the bronchial wall (n = 194, 23%), lung nodule (n = 322, 38%), and pleura (n = 296, 35%). 413 cases had a diagnostic discrepancy (48.3%), with 274 (66%) minor and 139 (34%) major discrepancies. By location, pleural effusion specimens had the highest probability of a discrepant diagnosis (P = 0.003). By specimen type, fine-needle aspiration samples were more likely to have a discrepant diagnosis (P = 0.09), approaching significance. CONCLUSION: Nearly half of the thoracic cytology cases submitted for expert second opinion had diagnostic discrepancies. Consequently, consulting a tertiary medical care center with cytopathology expertise for challenging thoracic cytology diagnoses is beneficial.

Diagnostic yields and safety of thoracoscopic cryobiopsies in Japan: A single-center retrospective observational study.

BACKGROUND: Thoracoscopy is useful for diagnosing unexplained pleural effusions. A sufficient specimen volume is often difficult to obtain using forceps biopsies (FBs) but can be obtained with pleural cryobiopsies (CBs). This study aimed to assess the utility and safety of CB during thoracoscopy in the Japanese population. METHODS: Patients who underwent thoracoscopic CBs at the Japanese Red Cross Medical Center between January 2017 and August 2023 were included in the study. Data were retrospectively analyzed, including clinical data, thoracoscopic findings, specimen size, diagnostic yield, and complications. The number of collected specimens and the freezing time were left to the discretion of the attending physician. RESULTS: Twenty-six patients underwent thoracoscopic CB. Specimens obtained by CB were larger than those obtained by FB. Primary lung cancer was the most common cause of pleural effusion, followed by malignant pleural mesothelioma. CB contributed to the diagnosis in 24 of 26 cases (92.3%) and FB contributed to the diagnosis in 11 of 18 cases (61.1%). Severe fibrosis could be diagnosed in all 3 cases by CB, but not by FB. The common complications of CB included bleeding at the biopsy site and atelectasis, but no severe complications occurred. CONCLUSIONS: The utility and safety of thoracoscopic CB for diagnosing pleural effusions in Japan were verified. The diagnostic yield, specimen size, and safety profile of CB support the diagnostic utility of this method.

Tuberculous pleural effusion-induced Arg-1+ macrophage polarization contributes to lung cancer progression via autophagy signaling.

BACKGROUND: The association between tuberculous fibrosis and lung cancer development has been reported by some epidemiological and experimental studies; however, its underlying mechanisms remain unclear, and the role of macrophage (MФ) polarization in cancer progression is unknown. The aim of the present study was to investigate the role of M2 Arg-1+ MФ in tuberculous pleurisy-assisted tumorigenicity in vitro and in vivo. METHODS: The interactions between tuberculous pleural effusion (TPE)-induced M2 Arg-1+ MФ and A549 lung cancer cells were evaluated. A murine model injected with cancer cells 2 weeks after Mycobacterium bovis bacillus Calmette-Guérin pleural infection was used to validate the involvement of tuberculous fibrosis to tumor invasion. RESULTS: Increased CXCL9 and CXCL10 levels of TPE induced M2 Arg-1+ MФ polarization of murine bone marrow-derived MФ. TPE-induced M2 Arg-1+ MФ polarization facilitated lung cancer proliferation via autophagy signaling and E-cadherin signaling in vitro. An inhibitor of arginase-1 targeting M2 Arg-1+ MФ both in vitro and in vivo significantly reduced tuberculous fibrosis-induced metastatic potential of lung cancer and decreased autophagy signaling and E-cadherin expression. CONCLUSION: Tuberculous pleural fibrosis induces M2 Arg-1+ polarization, and M2 Arg-1+ MФ contribute to lung cancer metastasis via autophagy and E-cadherin signaling. Therefore, M2 Arg-1+ tumor associated MФ may be a novel therapeutic target for tuberculous fibrosis-induced lung cancer progression.

Analysis of invasive diagnostic techniques for pathological confirmation of pleural mesothelioma.

BACKGROUND AND OBJECTIVES: Mesothelioma is an infrequent neoplasm with a poor prognosis that is related to exposure to asbestos and whose peak incidence in Europe is estimated from 2020. Its diagnosis is complex; imaging techniques and the performance of invasive pleural techniques being essential for pathological confirmation. The different diagnostic yields of these invasive techniques are collected in the medical literature. The present work consisted of reviewing how the definitive diagnosis of mesothelioma cases in our centre was reached to check if there was concordance with the data in the bibliography. MATERIALS AND METHODS: Retrospective review of patients with a diagnosis of pleural mesothelioma in the period 2019-2021, analysing demographic data and exposure to asbestos, the semiology of the radiological findings and the invasive techniques performed to reach the diagnosis. RESULTS: Twenty-six mesothelioma cases were reviewed. 22 men and 4 women. Median age 74 years. 9 patients had a history of asbestos exposure. Moderate-severe pleural effusion was the most frequent radiological finding (23/26). The sensitivity of the invasive techniques was as follows: Cytology 13%, biopsy without image guidance 11%, image-guided biopsy 93%, surgical biopsy 67%. CONCLUSIONS: In our review, pleural biopsy performed with image guidance was the test that had the highest diagnostic yield, so it should be considered as the initial invasive test for the study of mesothelioma.

"Cell blocking" the parasitic imposter: In a rare case of isolated pulmonary cysticercosis.

Isolated pulmonary cysticercosis is a rare manifestation of human cysticercosis which mainly affects central nervous system, skeletal muscles, eyes and subcutaneous tissues. Pulmonary involvement is usually a part of disseminated disease and mainly presents as bilateral pulmonary nodules. We report a rare case of isolated pulmonary cysticercosis presenting as lung cyst with pleural effusion. The diagnosis was made on pleural fluid cytology and cell block preparation. Herein we wish to recapitulate the importance of cell block as a diagnostic aid for parasitic infections, where morphological features and architectural patterns are as clearly discernable as in histopathology.

Recurrent leishmaniasis infection isolated in the pleural fluid.

We present a rare case of recurrent leishmaniasis infection in a female in her 80s who re-presented with a pleural effusion. The patient was initially investigated as an outpatient for cytopenia and underwent a bone marrow biopsy which subsequently diagnosed visceral leishmaniasis. Following full treatment, and apparent recovery, she re-presented with pleural effusion, hypoalbuminaemia and cytopenia. Leishmania was eventually isolated in a pleural fluid sample obtained on therapeutic drainage, and she was treated for a recurrence at a tertiary infectious disease unit. This interesting and challenging case demonstrates the importance of suspecting leishmaniasis recurrence in previously treated cases and the diagnostic benefit of pleural fluid analysis in the context of suspected leishmaniasis.

Image-Assisted Pleural Needle Biopsy or Medical Thoracoscopy: Which Method for Which Patient? A Randomized Controlled Trial.

BACKGROUND: Image-guided or assisted needle biopsies and the increasing use of medical thoracoscopy (MT) have increased the diagnostic accuracy of pleural diseases significantly. However, no consensus exists regarding which patients with pleural effusion should undergo MT and which patients should undergo image-guided or assisted needle biopsy as the first procedure to ensure greater diagnostic accuracy. RESEARCH QUESTION: Which biopsy method is more appropriate for which patient to provide the highest diagnostic accuracy in the diagnosis of pleural effusion? STUDY DESIGN AND METHODS: This prospective, randomized, parallel study included 228 patients with undiagnosed exudative pleural effusion. Patients were divided into two groups based on CT scan findings. Group 1 included patients with pleural effusion only. Group 2 included patients with pleural thickening or lesion in addition to pleural effusion. Patients in each group were assigned randomly to an image-assisted Abrams needle pleural biopsy (IA-ANPB) or MT arm. The diagnostic sensitivity, reliability, and safety were determined for both groups. RESULTS: The false-negative rate was 30.3% for the IA-ANPB arm and 3.1% for the MT arm in group 1. The same rates were 11.9% for IA-ANPB and 4.7% for MT in group 2. In group 1, the sensitivity for the IA-ANPB arm was 69.7%, and the negative likelihood ratio was 0.30. The same rates for the MT arm were 96.9% and 0.03 (P = .009). In group 2, these values were 88.1% and 0.12 for the IA-ANPB arm and 95.4% and 0.05 for the MT arm (P = .207). The rate of complications between the two biopsy methods was not different (8.5% and 15.8%, respectively; P = .107). INTERPRETATION: MT showed a high diagnostic success in all patients with pleural fluid. However, IA-ANPB showed similar diagnostic success as MT in patients with pleural effusion and associated pleural thickening or lesions. Therefore, in the latter case, IA-ANPB could be preferable to MT. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT05428891; URL: www. CLINICALTRIALS: gov.

Myelomatous pleural effusion in multiple myeloma- A rare presentation.

Multiple myeloma is a malignant plasma cell condition that mostly affects the skeletal system and bone marrow. Pleural effusions are uncommon and typically result from other conditions coexisting with multiple myeloma. Malignant myelomatous pleural effusions are rare complications of multiple myeloma, occurring in less than 1% of patients and are associated with poor prognosis having mean survival of less than 4 months. The present case report is a 41-year-old multiple myeloma patient who developed bilateral pleural effusion at a disease relapse. Chemotherapeutic regimen of cyclophosphamide, bortezomib, and dexamethasone given. Despite a positive response to treatment, the patient's condition worsened over the course of following month and he eventually passed away. Myelomatous pleural effusion indicates poor prognosis and early consideration helps in quick diagnosis and initiation of treatment which may help in improving prognosis.

Pleural epithelioid hemangioendothelioma in a 39-Year-old female: a case report.

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is a rare malignancy of vascular origin which can be primarily be seen in various tissues. EHE originating from the pleura is an even more uncommon subtype which may mimic mesothelioma and pleural carcinomatosis. The prognosis of pleural EHE is poor and there is no consensus on the optimal therapeutic approach. CASE PRESENTATION: A 39-year-old middle-eastern female presented with progressive dyspnea and left shoulder discomfort. Chest computed tomography scan revealed a left side pleural effusion and pleural thickening. Pleuroscopy was done and biopsies were taken which were positive for CD31, CD34, CK, factor 8-R-antigen, and vimentin. Patient was diagnosed with pleural epithelioid hemangioendothelioma (PEHE) and chemotherapy was started and underwent extrapleural pneumonectomy 7 months later. Unfortunately, the patient passed away 10 months after diagnosis due to disease complications. CONCLUSIONS: Once PEHE is suspected in histology it can be confirmed with immunohistochemistry. Chemotherapy, surgery or a combination of both is currently used as the treatment but the standard treatment remains a question.

Cell-free DNA methylation analysis as a marker of malignancy in pleural fluid.

Diagnosis of malignant pleural effusion (MPE) is made by cytological examination of pleural fluid or histological examination of pleural tissue from biopsy. Unfortunately, detection of malignancy using cytology has an overall sensitivity of 50%, and is dependent upon tumor load, volume of fluid assessed, and cytopathologist experience. The diagnostic yield of pleural fluid cytology is also compromised by low abundance of tumor cells or when morphology is obscured by inflammation or reactive mesothelial cells. A reliable molecular marker that may complement fluid cytology for the diagnosis of malignant pleural effusion is needed. The purpose of this study was to establish a molecular diagnostic approach based on pleural effusion cell-free DNA methylation analysis for the differential diagnosis of malignant pleural effusion and benign pleural effusion. This was a blind, prospective case-control biomarker study. We recruited 104 patients with pleural effusion for the study. We collected pleural fluid from patients with: MPE (n = 48), indeterminate pleural effusion in subjects with known malignancy or IPE (n = 28), and benign PE (n = 28), and performed the Sentinel-MPE liquid biopsy assay. The methylation level of Sentinel-MPE was markedly higher in the MPE samples compared to BPE control samples (p < 0.0001) and the same tendency was observed relative to IPE (p = 0.004). We also noted that the methylation signal was significantly higher in IPE relative to BPE (p < 0.001). We also assessed the diagnostic efficiency of the Sentinel-MPE test by performing receiver operating characteristic analysis (ROC). For the ROC analysis we combined the malignant and indeterminate pleural effusion groups (n = 76) and compared against the benign group (n = 28). The detection sensitivity and specificity of the Sentinel-MPE test was high (AUC = 0.912). The Sentinel-MPE appears to have better performance characteristics than cytology analysis. However, combining Sentinel-MPE with cytology analysis could be an even more effective approach for the diagnosis of MPE. The Sentinel-MPE test can discriminate between BPE and MPE. The Sentinel-MPE liquid biopsy test can detect aberrant DNA in several different tumor types. The Sentinel-MPE test can be a complementary tool to cytology in the diagnosis of MPE.