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.

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.

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.

Idiopathic Lymphocytic Pleuritis Responding to Corticosteroid Therapy.

An 83-year-old man presented with chronic dyspnea, and chest X-ray showed bilateral pleural effusion. Right thoracentesis revealed lymphocyte-predominant exudate with no malignancy; bacterial and mycobacterial cultures were negative. Thoracoscopy via the right chest and a biopsy of the same site were performed; these showed lymphoplasmacytic infiltration and fibrosis, ruling out malignancy or tuberculosis. We decided to start corticosteroid therapy for the diagnosis of idiopathic lymphocytic pleuritis (ILP). The patient was discharged after clinical improvement, and steroids were tapered off. An early diagnosis by thoracoscopy and the exclusion of other diseases are important for initiating steroid therapy in patients with ILP.

Effectiveness of venetoclax and azacytidine against myeloid/natural killer cell precursor acute leukemia.

Myeloid/natural killer (NK) cell precursor acute leukemia (MNKPL) is a rare leukemia subtype that possibly originates from precursor NK cells. The disease has a poor prognosis, and information on its treatment is lacking. We herein report the first case of a 46-year-old woman with MNKPL who was refractory to two lines of acute myeloid leukemia (AML)-type intensive chemotherapy but was successfully treated with venetoclax and azacytidine (VEN/AZA). She was diagnosed with MNKPL based on the conformations of immature lymphoblastoid morphology without myeloperoxidase reactivity that showed a CD7/CD33/CD34/CD56/HLA-DR positive phenotype and extramedullary regions. The disease was refractory to induction therapy with daunorubicin and cytarabine (DNR/Ara-C) and to reinduction therapy with mitoxantrone, etoposide, and cytarabine (MEC). After two lines of induction chemotherapy, massive pericardial and pleural effusion was found, and was suspected to be extramedullary lesions. The patient developed cardiac tamponade and required pericardiocentesis. Thus, VEN/AZA was administered as third-line therapy. After two cycles of VEN/AZA, the pericardial and pleural effusion disappeared, and complete remission was achieved. The patient received post-transplant cyclophosphamide-based haploidentical transplantation and has stayed relapse-free as of her last follow-up examination 2 years after diagnosis.

Heterogeneity of cancer stem cell-related marker expression is associated with three-dimensional structures in malignant pleural effusion produced by lung adenocarcinoma.

INTRODUCTION: Cancer stem cells have been described in lung adenocarcinoma-associated malignant pleural effusion. They show clinically important features, including the ability to initiate new tumours and resistance to treatments. However, their correlation with the three-dimensional tumour structures in the effusion is not well understood. METHODS: Cell blocks produced from lung adenocarcinoma patients' pleural effusion were examined for cancer stem cell-related markers Nanog and CD133 using immunocytochemistry. The three-dimensional cancer cell structures and CD133 expression patterns were visualized with tissue-clearing technology. The expression patterns were correlated with tumour cell structures, genetic variants and clinical outcomes. RESULTS: Thirty-nine patients were analysed. Moderate-to-strong Nanog expression was detected in 27 cases (69%), while CD133 was expressed by more than 1% of cancer cells in 11 cases (28%). Nanog expression was more homogenous within individual specimens, while CD133 expression was detected in single tumour cells or cells within small clusters instead of larger structures in 8 of the 11 positive cases (73%). Although no statistically significant correlation between the markers and tumour genetic variants or patient survival was observed, we recorded seven cases with follow-up specimens after cancer treatment, and four (57%) showed a change in stem cell-related marker expression corresponding to treatment response. CONCLUSIONS: Lung adenocarcinoma cells in the pleural effusion show variable expression of cancer stem cell-related markers, some showing a correlation with the size of cell clusters. Their expression level is potentially correlated with cancer treatment effects.

Spectrum of lymphatic anomalies in patients with RASA1-related CM-AVM.

BACKGROUND: Capillary malformation-arteriovenous malformation (CM-AVM) is characterized by multifocal fast-flow capillary malformations, sometimes with arteriovenous malformations/fistulas, skeletal/soft tissue overgrowth, telangiectasias, or Bier spots. Lymphatic abnormalities are infrequently reported. We describe seven patients with CM-AVM and lymphatic anomalies. METHODS: Following IRB approval, we identified patients with CM-AVM and lymphatic anomalies seen at the Vascular Anomalies Center at Boston Children's Hospital from 2003 to 2023. We retrospectively reviewed records for clinical, genetic, laboratory, and imaging findings. RESULTS: We found seven patients with CM-AVM and lymphatic abnormalities. Five patients were diagnosed prenatally: four with pleural effusions (including one suspected chylothorax) and one with ascites. Pleural effusions resolved after neonatal drainage in three patients and fetal thoracentesis in the fourth; however, fluid rapidly reaccumulated in this fetus causing hydrops. Ascites resolved after neonatal paracentesis, recurred at 2 months, and spontaneously resolved at 5 years; magnetic resonance lymphangiography for recurrence at age 19 years suggested a central conducting lymphatic anomaly (CCLA), and at age 20 years a right spermatic cord/scrotal lymphatic malformation (LM) was detected. Chylous pericardial effusion presented in a sixth patient at 2 months and disappeared after pericardiocentesis. A seventh patient was diagnosed with a left lower extremity LM at 16 months. Six patients underwent genetic testing, and all had RASA1 mutation. RASA1 variant was novel in three patients (c.1495delinsCTACC, c.434_451delinsA, c.2648del), previously reported in two (c.2603+1G>A, c.475_476del), and unavailable in another. Median follow-up age was 5.8 years (4 months-20 years). CONCLUSION: CM-AVM may be associated with lymphatic anomalies, including pericardial/pleural effusions, ascites, CCLA, and LM.

LDH/ADA ratio in pleural fluid for the diagnosis of infectious pleurisy.

Pleural effusion (PE) is a common medical concern, often requiring thoracentesis for a definitive diagnosis. An elevated pleural fluid adenosine deaminase (ADA) may indicate tuberculosis, but this is not always the case. This study aimed to evaluate the accuracy of biomarkers determined in pleural fluid and propose a new diagnostic strategy for PE in patients with high levels of ADA in pleural fluid. This retrospective analysis studied patients with PE who received thoracentesis for the first time with an ADA level of > 33 U/L in the pleural fluid analysis at two tertiary hospitals from March 2019 to March 2023. Demographic and clinical data, as well as pleural fluid biomarkers and their ratios, were studied and compared between different PE groups, and a decision tree was developed. During the study period, 259 patients were enrolled, with four different types of PE: parapneumonic (PPE) 155, tuberculosis (TPE) 41, malignant (MPE) 50, and miscellaneous 13. Biomarkers and their ratios performed well in the differential diagnosis of PE, with the LDH/ADA ratio distinguishing between PPE and non-PPE with sensitivity and specificity of 98.06% and 98.08%, respectively. The combination of LDH/ADA ratio, ADA, and mononuclear cell percentage was identified as important factors for creating a decision tree with an overall accuracy of 89.96%. The pleural fluid LDH/ADA ratio was a useful diagnostic for distinguishing PPE from non-PPE, and a decision tree with an accuracy of 89.96% was created to differentiate the four forms of PE in clinical situations.

Role of cytoblock on pleural effusion for diagnosis of malignant disease.

BACKGROUND: Thoracocentesis of pleural effusion is a simple technique for pleural fluid examination through cytology. In addition to cytological examination to assess the nature of pleural fluid content, we can also perform more detailed examinations through cytoblocks of residual fluid. These paraffin-embedded cytoblock samples are important because we can perform examinations as in other bioptic samples. In these samples, immunohistochemical and molecular analyses can be performed. METHODS: Two hundred fifty-five cytological samples from patients with pleural effusion were examined. In cases in which the presence of malignant cells was identified in the cytological examination, as well as cases that were suspicious but not definitive for the presence of a malignant effusion, a cytoblock was prepared. Histological examination and immunohistochemical analysis were performed. RESULTS: Among 255 cases with pleural effusion, 152 had the presence of malignant cells and 6 cases were suspicious, but uncertain for the presence of malignant cells, while 86 cases had inflammatory pleural effusion or other pathologies but were not malignant. After histological analysis of the cytoblock and immunohistochemical analysis, we identified 82 malignant tumors of the lung, 8 malignant tumors of the gastrointestinal tract, 15 malignant tumors of the breast, and 6 malignant tumors of the female genital tract, as well as 24 tumors of undetermined origin. CONCLUSIONS: Cytoblocks are important for the diagnosis of the primary nature of malignant pleural effusions. The highest importance is primary lung tumors, as well as those tumors in which the primary site of the tumor cannot be determined clinically.

A case of synchronous IgG4-associated pleuritis and type 1 autoimmune pancreatitis.

A 50-year-old man presented to the emergency department with left chest pain, epigastralgia, and low-grade fever for several days. A CT scan showed left pleural effusion, ground-glass opacities in the lower lobes of both lungs, and a capsule-like rim in the pancreas. ERCP showed narrowing of the main pancreatic duct. EUS-FNA was performed, but pathological findings showed no IgG4-positive cells. A thoracoscopic biopsy was performed, and pathological findings showed many IgG4-positive cells. A diagnosis of autoimmune pancreatitis and IgG4-associated pleurisy was made according to international diagnostic criteria. After that, oral steroid therapy was started, and left pleural effusion and pancreatic enlargement improved.

Comparison between original SARS-CoV-2 strain and omicron variant on thin-section chest CT imaging of COVID-19 pneumonia.

OBJECTIVES: We investigated different computed tomography (CT) features between Omicron-variant and original-strain SARS-CoV­2 pneumonia to facilitate the clinical management. MATERIALS AND METHODS: Medical records were retrospectively reviewed to select patients with original-strain SARS-CoV­2 pneumonia from February 22 to April 22, 2020, or Omicron-variant SARS-CoV­2 pneumonia from March 26 to May 31, 2022. Data on the demographics, comorbidities, symptoms, clinical types, and CT features were compared between the two groups. RESULTS: There were 62 and 78 patients with original-strain or Omicron-variant SARS-CoV­2 pneumonia, respectively. There were no differences between the two groups in terms of age, sex, clinical types, symptoms, and comorbidities. The main CT features differed between the two groups (p = 0.003). There were 37 (59.7%) and 20 (25.6%) patients with ground-glass opacities (GGO) in the original-strain and Omicron-variant pneumonia, respectively. A consolidation pattern was more frequently observed in the Omicron-variant than original-strain pneumonia (62.8% vs. 24.2%). There was no difference in crazy-paving pattern between the original-strain and Omicron-variant pneumonia (16.1% vs. 11.6%). Pleural effusion was observed more often in Omicron-variant pneumonia, while subpleural lesions were more common in the original-strain pneumonia. The CT score in the Omicron-variant group was higher than that in the original-strain group for critical-type (17.00, 16.00-18.00 vs. 16.00, 14.00-17.00, p = 0.031) and for severe-type (13.00, 12.00-14.00 vs 12.00, 10.75-13.00, p = 0.027) pneumonia. CONCLUSION: The main CT finding of the Omicron-variant SARS-CoV­2 pneumonia included consolidations and pleural effusion. By contrast, CT findings of original-strain SARS-CoV­2 pneumonia showed frequent GGO and subpleural lesions, but without pleural effusion. The CT scores were also higher in the critical and severe types of Omicron-variant than original-strain pneumonia.

Long-term stability of pleural fluid carcinoembryonic antigen and its effect on the diagnostic accuracy for malignant pleural effusion.

BACKGROUND: The in vitro stability assessment is essential for investigating the diagnostic accuracy of pleural biomarkers. This study aimed to investigate the long-term stability of pleural fluid carcinoembryonic antigen (CEA) at -80°C to -70°C. In addition, we analyzed the effects of frozen storage on the diagnostic accuracy of CEA for malignant pleural effusion (MPE). METHODS: Pleural fluid CEA of participants in two prospective cohorts were stored at -80°C to -70°C for 1-3 years. The CEA level in the stored specimen was measured with an immunoassay, and its level in the fresh specimen was extracted from medical records. The Bland-Altman method, Passing-Bablok regression, and Deming regression were used to analyze the agreement of CEA between the fresh and frozen pleural fluid. In addition, we used receiver operating characteristic (ROC) curves to evaluate the diagnostic accuracy of CEA in the fresh and frozen specimens for MPE. RESULTS: A total of 210 participants were enrolled. The median CEA levels in frozen and fresh pleural fluid specimens were similar (frozen, 2.32 ng/mL; fresh, 2.59 ng/mL; p < 0.01). The slopes and intercepts in the Passing-Bablok regression (intercept 0.01, slope 1.04) and Deming regression (intercept 0.65; slope 1.00) were not statistically significant (p > 0.05 for all). No significant difference was observed between the area under the ROC curves of CEA in the fresh and frozen specimens (p > 0.05 for all). CONCLUSION: Pleural fluid CEA is seemingly stable when stored at -80°C to -70°C for 1-3 years. Frozen storage does not significantly affect the diagnostic accuracy of CEA for MPE.

A Study of Role of Medical Thoracoscopy in Undiagnosed Pleural Effusion.

AIM AND OBJECTIVES: b/pulli>To know the diagnostic yield of pleuroscopy (medical thoracoscopy) in cases of pleural effusions which remain undiagnosed after routine initial investigations.lili>To notice the different gross pleuroscopic findings during the procedure.lili>To observe various histopathological reports of pleural biopsy taken through medical thoracoscopy.lili>To know the various complications of pleuroscopy in patients undergoing this procedure.li/ulp! MATERIALS AND METHODS: A total of 56 patients having undiagnosed pleural effusion were taken for study after informed written consent. All patients underwent medical thoracoscopy. The clinical, demographic, and radiological profile of patients was recorded. Gross pleuroscopic findings and histopathological reports of the pleural biopsy were noted. All patients were observed for any complications that occurred during or after the procedure. RESULT: Diagnostic yield of thoracoscopy in the present study was 91.07% (malignant pleural effusion 75% and tuberculous pleuritis 12.5%). Adenocarcinoma was the commonest malignancy in 60.71% of patients amongst malignant pleural effusion in the present study. Very few complications were recorded. The most common postprocedure complication was subcutaneous emphysema (12.5%) followed by pneumothorax (10.78%). CONCLUSION: Thoracoscopy gives excellent diagnostic yield in undiagnosed pleural effusion without major complications, and should be utilized wherever feasible.

3D-Autologous Culture Method for Precision Oncology.

The 3D-autologous culture method (3D-ACM) for patient-derived cancer samples utilizes a patient's own body fluid or serum to prepare a 3D scaffold and for the culture medium. 3D-ACM enables tumor cells and/or tissues from an individual patient to proliferate in vitro, in a microenvironment that is very similar to their original, in vivo surroundings. The purpose is to maximally preserve in culture the native biological properties of a tumor. This technique has been employed for two models: (1) cells isolated from malignant ascites or pleural effusions (body fluids) and (2) solid tissues from biopsies or surgically removed cancers. Here we describe the detailed procedures for these 3D-ACM models.

CT-guided transthoracic core needle biopsies of focal pleural lesions smaller than 10 mm: a retrospective study.

BACKGROUND: CT-guided transthoracic core needle biopsy (TCNB) is a minimally invasive diagnostic procedure and a useful radiological method for diagnosing pleural lesions smaller than 10 mm in the presence of loculated pleural effusion. The purpose of this study was to retrospectively assess the diagnostic accuracy of CT-guided TCNB of small pleural lesions and determine the incidence of complications. METHODS: This retrospective study included a total of 56 patients (45 men and 11 women; mean [± SD] age, 71.84 ± 10.11 years) with small costal pleural lesions (thickness of < 10 mm) who underwent TCNB performed at the Department of Radiology from January 2015 to July 2021. One of the inclusion criteria for this study was a loculated pleural effusion greater than 20 mm, with a nondiagnostic cytological analysis. Sensitivity, specificity and positive as well as negative predictive values (PPV, NPV) were calculated. RESULTS: The sensitivity of CT-guided TCNB for the diagnosis of small pleural lesions in this study was 84.6% (33 of 39), specificity 100% (17 of 17), PPV 100% (33 of 33), and NPV 73.9% (17 of 23), while diagnostic accuracy was 89.3% (50 of 56). The overall diagnostic contribution of TCNB in our study is comparable with the results of other recent reports. Loculated pleural effusion was considered a protective factor since no complications were noted. CONCLUSION: CT-guided transthoracic core needle biopsy (TCNB) is an accurate diagnostic method for small suspected pleural lesions with a near-zero complication rate in the presence of loculated pleural effusion.