Lung adenocarcinoma (LUAD) is characterized by difficult early detection, rapid tumor progression and low surgical resection rate in the late stage. The common complication of patients with lung adenocarcinoma is malignant pleural effusion (MPE). Compared with lung biopsy, cytological examination of exfoliated pleural effusion is a less invasive operation. Therefore, there is an urgent need to discover new and effective cytological biomarkers for the exfoliation of LUAD pleural effusion. This work took the differentially expressed genes of LUAD tumors and adjacent tissues in the Gepia database as the entry point and screened out Cell division cycle protein 20 (CDC20) as a new biomarker for lung adenocarcinoma. The expression levels of CDC20, TTF-1 and NapsinA in 92 cases of lung adenocarcinoma and adjacent normal tissues were analyzed, and immunohistochemical detection was performed on paraffin specimens of pleural effusion from 30 cases of lung adenocarcinoma and 30 cases of non-neoplastic patients. Immunohistochemistry indicated that CDC20 was more expressed in LUAD tissues in the 92 observation groups and was related to tumor size, T classification, and pleural invasion. In this study, the results showed the expression of CDC20 was relatively consistent with that of TTF-1 and NapsinA in LUAD and malignant pleural effusion. This study reveals the potential diagnostic value of CDC20 in biopsy specimens of LUAD and pleural effusion. Our discovery is of great significance for the pathological diagnosis of pleural effusion cytology.

Predicting Outcomes in Patients with Malignant Pleural Effusions

BackgroundLung cancer remains the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) constituting the majority of cases. Immune checkpoint inhibitors have significantly improved outcomes in advanced NSCLC, particularly for patients with programmed cell death ligand-1 (PD-L1) expression. However, obtaining tissue biopsies for PD-L1 assessment in advanced disease is often challenging. Malignant pleural effusion (MPE), frequently associated with advanced lung adenocarcinoma, offers an accessible alternative source for PD-L1 testing. Nevertheless, the reliability of PD-L1 evaluation in cytological specimens from MPE, especially regarding staining methodologies, requires further validation. This study aimed to assess the impact of PD-L1 single staining versus PD-L1/thyroid transcription factor-1 (TTF-1) dual staining on the concordance of PD-L1 tumor proportion scores between paired histologic and cytologic MPE samples.MethodsThis retrospective study involved 112 lung adenocarcinoma patients, using paired histological and MPE cytological samples for PD-L1 evaluation via immunohistochemical staining. Tumor proportion score measured PD-L1 levels, withTTF-1 marking lung adenocarcinoma cells. The study compared PD-L1 staining across samples and techniques.ResultsThis study aimed to evaluate the impact of staining methods on PD-L1 scoring in histological and MPE cytological specimens. The results indicate that the selection of PD-L1 single-stained or PD-L1/TTF-1 dual-stained methodologies within the same sample type did not lead to significant differences in the distribution of PD-L1 tumor proportion scores. However, when evaluating concordance with paired histological specimens, PD-L1/TTF-1 dual staining in MPE cytology samples achieved a significantly higher concordance rate (82.14%) compared to PD-L1 single staining (69.64%), with kappa values increasing from 0.59 to 0.75. Notably, in MPE cytology specimens with low tumor density, PD-L1/TTF-1 dual staining demonstrated a marked advantage over PD-L1 single staining, with the concordance rate of tumor proportion score with histology specimens increasing from 56.86% to 84.31%, with kappa values increasing from 0.47 to 0.78.ConclusionsThe application of PD-L1/TTF-1 dual staining in MPE cytological specimens significantly enhances the consistency of PD-L1 expression within tissue specimens, particularly in advanced lung adenocarcinoma patients. This method provides a reliable, evidence-based medical reference that complements histopathological analysis.

BackgroundProgrammed death‐ligand 1 (PD‐L1) immunocytochemical (ICC) analysis of cell blocks (CBs) has recently emerged in clinical practice. Unlike standardized immunohistochemistry on formalin‐fixed, paraffin‐embedded tissues, cytology involves various preparation methods and fixatives. This study investigated how various fixatives influence PD‐L1 immunoreactivity in CBs from malignant pleural effusions (MPEs) with metastatic pulmonary adenocarcinoma (AC).MethodsThirty‐three MPEs from patients with pulmonary AC were prospectively included. Four matched CBs per case were fixed in four different fixatives and immunostained with three PD‐L1 antibodies. Tumor proportion score and staining intensity were evaluated at multiple cutoffs.ResultsThe cytology–cytology correlation of PD‐L1 expression with the antibodies 28‐8, 22C3, and SP263 was assessed in matched CBs fixed in either formalin, PreservCyt, CytoLyt, or CytoRich Red (the latter only in 26 cases). Compared to formalin, PreservCyt and CytoLyt showed moderate concordance at the ≥1% cutoff (Cohen kappa [κ], 0.463–0.535 and 0.57–0.586, respectively), except SP263 with CytoLyt, which demonstrated only fair concordance (κ, 0.382). The corresponding figures for CytoRich Red indicated substantial concordance for 28‐8 and SP263 (κ, 0.601 and 0.669) and very good concordance for 22C3 (κ, 0.806). At the ≥50% cutoff, concordance improved for 28‐8 and 22C3 but remained largely unchanged for SP263. All alcohol‐based fixatives produced significantly weaker PD‐L1 staining intensity than formalin across all antibodies (p < .001–.007).ConclusionsPD‐L1 ICC expression in CBs depends on the fixative and antibody used. Alcohol‐based fixatives, particularly with low cutoffs, risk underestimating PD‐L1 positivity, and may contribute to false‐negative results. ICC protocol optimization is essential before diagnostic use.

The objective of this study was to investigate the protein expression of PD-L1 in the pleural fluid of lung adenocarcinoma patients with malignant pleural effusion. Additionally, we aimed to analyse the association between PD-L1 expression and the mutational status of ten driver genes: EGFR, ALK, ROS1, BRAF, KRAS, NRAS, HER2, RET, PIK3CA, and MET. A total of 161 cytological specimens were collected from patients that had been diagnosed with lung adenocarcinoma at the Fourth Hospital of Hebei Medical University between January 2021 and September 2024. The cytologic samples were tested for tumour PD-L1 expression using a VENTANA PD-L1 (SP263) assay. EGFR, ALK, ROS1, BRAF, KRAS, NRAS, HER2, RET, PIK3CA, and MET mutations in the fresh cytological samples were detected using an amplification refractory mutation system and an ABI 7500 RT-qPCR system. Among 161 pleural fluid cytological specimens, 24.2% (39/161) presented a PD-L1 tumour proportion score (TPS) of ≥ 50%, whereas 39.1% (63/161) presented a TPS ranging from 1% to 49%. Additionally, 36.7% (59/161) demonstrated a TPS of < 1%. The mutation status analysis of 160 pleural fluid cytological specimens revealed EGFR mutations in 75 cases (46.9%), no mutations in 35 cases (21.9%), KRAS mutations in 20 cases (12.5%), ALK mutations in 9 cases, BRAF mutations in 7 cases, MET mutations in 3 cases, ROS1 mutations in another set of 3 cases, and other types of mutations identified in an additional 8 cases. The expression level of PD-L1 in pleural fluid cytological samples from patients with EGFR mutations was not significantly different from that in those from patients with no mutations (p = 0.473). In contrast, the expression levels of PD-L1 in patients with KRAS, ALK, and BRAF mutations were significantly different from those in patients with no mutations (p = 0.045; p = 0.007; p = 0.01). Our findings suggest that PD-L1 immunohistochemistry is effective for evaluating pleural fluid cytological specimens and that PD-L1 expression is significantly higher in lung adenocarcinoma patients with malignant pleural effusions associated with the KRAS, ALK and BRAF mutations.

“Snow globe sign” in malignant ascites and pleural effusions: a helpful sonographic finding on endoscopic ultrasound

Medical thoracoscopy with talc poudrage and indwelling pleural catheter insertion versus medical thoracoscopy with talc poudrage alone for patients with symptomatic malignant pleural effusion (TACTIC): a randomised, controlled phase 3 trial.

ASIC3-PLCG1 axis-driven macropinocytosis promotes osimertinib drug-tolerant persistence in malignant pleural effusion-associated NSCLC.

Bone scintigraphy is one of the most heavily used imaging studies in nuclear radiology. The ability of technetium 99m-diphosphonate radiotracers to adhere to and form a complex with hydroxyapatite through the process of chemisorption highlights the sites and degree of osteoblastic activity. This mechanism results in a highly sensitive study for blastic processes of bone and serves as a valuable adjunct to cross-sectional imaging. Bone scintigraphy and its ability to capture the entire skeleton are especially useful to determine the extent of disease, most commonly for blastic metastases of breast and prostatic origin, but also for disseminated infections, Paget disease, and inflammatory arthropathies. While bone scintigraphy is typically a high-sensitivity and low-specificity modality, certain entities manifest with characteristic findings referred to as "Aunt Minnies," which may be confidently diagnosed without cross-sectional imaging. Examples include hypertrophic osteoarthropathy with the classic tram-track sign, sacral insufficiency fractures represented by the "Honda" sign, Paget disease of the spine with the "Mickey Mouse" sign, SAPHO (synovitis/acne/pustulosis/hyperostosis/osteitis) syndrome that demonstrates bullhead sign, and complex regional pain syndrome characterized by periarticular tracer uptake. Additionally, soft-tissue and nonosseous pathologic processes, including malignant pleural effusions, ascites, and paucity of soft-tissue uptake in renal osteodystrophy, may also be depicted. Overall, bone scintigraphy is a practical and low-cost imaging tool that can help assess the entire body, assist in the staging and monitoring of blastic malignancies, and provide valuable diagnostic information in multisystemic and multifocal diseases. ©RSNA, 2026 Supplemental material is available for this article.

25 Management of Malignant Pleural effusions with Indwelling pleural catheters in a District General Hospital in Dorset

In patients with malignant pleural effusions (MPE), pleural fluid reaccumulates at variable rates following therapeutic aspiration. The aim of this study was to identify variables which predict time to next procedure and use them to develop a predictive score. This prospective observational cohort study in 10 British hospitals recruited patients with known or suspected malignant effusions undergoing therapeutic aspiration. Follow-up lasted 3 months and assessed time to next clinically indicated pleural procedure. Regression analysis was performed to identify independent variables predicting time to next procedure, and a score derived. Initial validation was done in two external cohorts. 241 patients were recruited. Within the derivation cohort (n=180), baseline respiratory rate (R), pleural effusion depth on ultrasound (E) and dyspnoea measured using a visual analogue scale (D) (combined to form the RED score) were independent predictors of time to next procedure. Predictive models provided areas under the receiver operator curve of 0.73 and 0.75. Initial validity testing in two cohorts (n=31, n=57) demonstrated reasonable predictive value. In patients with MPE, baseline respiratory rate, pleural effusion depth on ultrasound and dyspnoea predict time to next procedure. ISRCTN16567838.

Indwelling pleural catheter efficacy and safety in malignant vs. non-malignant pleural effusions: a prospective study.

Non-small cell lung cancer (NSCLC) with pleural dissemination is categorized as stage IV (M1a) and traditionally deemed a contraindication for surgical intervention. This study aimed to explore the potential role of surgery in NSCLC patients with isolated pleural dissemination. Patients who either underwent primary tumour resection (PTR) or received only pleural nodules biopsy were included for analysis from the Western China Lung Cancer (WCLC) database (2005-2021) and Surveillance, Epidemiology, and End Results (SEER) database (2010-2015). Survival curves were generated using the Kaplan-Meier method, with significance assessed by the log-rank test. A total of 289 patients (261 PTR and 28 biopsy only) from the WCLC cohort and 2232 patients (278 PTR and 1954 biopsy only) from the SEER cohort were identified for analysis. In both cohorts, patients who underwent PTR showed significantly better outcomes compared to those who received only pleural nodules biopsy, with the 5-year survival rates of 28.3% versus 5.0% in the WCLC cohort (P < .0001) and 30.5% versus 7.4% in the SEER cohort (P < .0001). Subgroup analysis indicated that PTR significantly improved survival in patients without malignant pleural effusion, regardless of tumour size and T stage. Furthermore, anatomic lobectomy with systematic lymph node dissection was associated with better overall survival than partial resection or lobectomy plus lymph node sampling (P = .008). NSCLC patients with isolated pleural dissemination may represent an M1a subgroup in whom PTR is associated with longer survival, particularly in the absence of malignant pleural effusion.

Small cell lung cancer (SCLC) transformation is an incompletely characterized mechanism of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant cancers, limiting development of optimal treatment approaches. Through single-cell RNA sequencing of malignant pleural effusions from patients who underwent SCLC transformation, we identified heterogeneity and diversity, including distinct neuroendocrine (NE) and mesenchymal non-NE cancer cell subsets, which were maintained in patient-derived cell lines. We demonstrate that EZH2 regulates EGFR expression in NE cells where EGFR expression is silenced at baseline. Although neither epigenetic derepression nor exogenous overexpression of mutant EGFR sensitized the cells to EGFR inhibition, non-NE cells exhibited selective sensitivity to MEK inhibitors. Combined MEK inhibitor and chemotherapy effectively inhibited growth of both NE and non-NE cells in vitro and in vivo. Our findings demonstrate that EGFR-mutant SCLC is composed of mixed cell states with distinct therapeutic vulnerabilities and offer a therapeutic strategy to target tumor heterogeneity in highly plastic and treatment-resistant malignancies such as transformed SCLC.

Pleural effusion, an atypical accumulation of fluid in the pleural space, has been identified as a potential indicator of several diseases, including lung cancer. The presence of biomarkers in malignant pleural effusion has been a subject of investigation; however, the expression of microRNAs has received limited attention. The objective of this study is to present a narrative review of the current scientific literature regarding the presence of microRNAs in malignant pleural effusion and their association as new biomarkers in the diagnosis of lung cancer. A comprehensive search was conducted using the databases: PubMed, ScienceDirect, and EBSCO to identify all original scientific articles published through 30 April 2025. The following terms were utilized in the search: "MicroRNA AND pleural effusion AND lung cancer", "microRNA AND pleural effusion AND lung adenocarcinoma", "microRNA AND pleural effusion AND lung squamous cell carcinoma", "miRNA AND pleural effusion", miRNA AND pleural effusion AND lung cancer", "miRNA AND pleural effusion AND lung adenocarcinoma", "miRNA AND pleural effusion AND lung squamous cell carcinoma". A total of 17 studies were identified that distinguished between 106 microRNAs. These studies demonstrated the most significant overexpression and downexpression in lung cancer patients compared to patients without malignancy. However, eight of these studies distinguished between 17 microRNAs expressions and exhibited elevated area under the curve values, sensitivity, and specificity for the involvement in several hallmarks of lung cancer. The regulatory mechanisms governing microRNAs in malignant pleural effusion are intricate and involve multiple genes that play pivotal roles in several cancer mechanisms. These mechanisms encompass but are not limited to, processes such as cell growth, migration, drug resistance, proliferation, apoptosis, invasion, angiogenesis, and apoptosis.

Pleural effusion is clinically common with diverse etiologies, and differentiating benign from malignant cases is critical for treatment planning and prognosis assessment. Traditional single diagnostic methods have inherent limitations, leading to diagnostic challenges. This study aimed to develop a multi-modal diagnostic panel (MTPC) to improve the accuracy and efficiency of initial pleural effusion diagnosis. A total of 369 patients (264 with malignant pleural effusion and 105 with benign pleural effusion) were enrolled retrospectively. The MTPC panel integrated four diagnostic modalities: methylation biomarkers (PTGER4 and SHOX2), tumor markers (CEA and CYFRA21-1), DNA ploidy analysis, and cytological examination. Diagnostic performance was evaluated using sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Additional analyses were performed for cytology-undetermined and cytology-negative cases. Among immunological tumor markers, CEA exhibited the highest specificity (98.1%) and CYFRA21-1 the highest sensitivity (56.8%). Combined PTGER4 and SHOX2 methylation detection achieved a sensitivity of 65.9% and specificity of 92.4%. The MTPC panel demonstrated the best diagnostic performance, with an AUC of 0.8698, sensitivity of 90.2%, and specificity of 83.8%. In cytology-undetermined cases, MTPC reduced "cytology undetermined" reports by 78.4% and missed diagnoses via "negative" reports by 92.3%. The MTPC panel effectively integrates molecular, immunological, chromosomal, and cytomorphological data, significantly improving the diagnostic efficiency of pleural effusion. It addresses the limitations of single diagnostic methods and provides more reliable evidence for clinicians, facilitating early and accurate differentiation of benign and malignant pleural effusions.

Pleural diseases pose a significant burden on healthcare systems due to diagnostic challenges and high costs. Artificial intelligence (AI) has the potential to provide faster, more accurate, and more reliable results in the diagnosis of these diseases. This review evaluates the current status of AI technologies in the diagnosis of pleural effusion (PE), malignant PE, tuberculosis pleurisy (TP), pneumothorax, and malignant pleural mesothelioma (MPM). Deep learning algorithms developed for radiological diagnosis provide high sensitivity and specificity in determining the presence and severity of PE. AI models that integrate clinical parameters such as chest computed tomography (CT), positron emission tomography (PET)-CT, and tumour markers in distinguishing between benign and malignant effusions have significantly improved diagnostic accuracy (area under the curve: >0.90). In cytological diagnosis, computer-assisted systems such as Aitrox have demonstrated performance comparable to that of expert cytopathologists in diagnosing malignant effusions. In the diagnosis of TP, AI models outperform conventional diagnostic methods, particularly when combined with laboratory parameters such as adenosine deaminase. Food and Drug Administration-approved AI models are effectively used for the rapid diagnosis of pneumothorax and for emergency interventions. In MPM diagnosis, AI models using PET-CT images and three-dimensional segmentation offer significant advantages in prognostic evaluation and treatment response monitoring. However, large-scale, multi-centre studies are needed to standardise and generalise AI models. In light of these developments, AI may fundamentally change the diagnostic management of pleural diseases.

BackgroundIndwelling pleural catheters (IPCs) provide effective palliation for malignant pleural effusion (MPE) and may induce spontaneous pleurodesis (SP). However, risk factors causing transudative effusion, such as hypoalbuminemia, congestive cardiac failure (CCF), and renal failure (RF), may reduce pleurodesis success. Evidence on the impact of these comorbidities in MPE patients undergoing IPC placement remains limited.ObjectiveTo evaluate the impact of hypoalbuminemia, CCF and RF on successful SP in MPE.MethodsA retrospective single-centre study was conducted in a tertiary care hospital on all patients with cytologically or radiologically confirmed MPE who underwent IPC placement between January 2020 and December 2024. SP was defined as catheter removal and no fluid recurrence up to 90 days. Demographic data, albumin levels, comorbidities, cancer type, and active anti-cancer therapy were compared between the SP and non-pleurodesis (NP) group.ResultsAmong 110 patients (mean age 70 years; 54/110, 49% male), SP occurred in 30/110 (27%). Mean serum albumin was higher in the SP group (25.2 vs 20.4 g/L, p=0.001). CCF was present in 3/30 (10%) SP group compared with 15/80 (19%) NP group (p=0.005), while RF occurred only in the NP group, 4/80 (5%). Systemic anti-cancer therapy was associated with higher SP rates (26/30, 87% vs 32/80, 40%; p<0.001). SP varied by cancer type, highest in mesothelioma (6/12, 50%) and absent in small cell lung cancer (0/3, 0%).ConclusionsHigher albumin, active anti-cancer therapy, and absence of multiple comorbidities causing transudative effusion predict successful SP. Identifying these factors may improve patient selection and procedural outcomes.

ABSTRACTSarcomatoid carcinoma is a rare, aggressive lung cancer subtype. It typically presents as a pulmonary or pleural mass. Effusion‐dominant disease without an identifiable primary mass is exceptionally uncommon. We report a 59‐year‐old man presenting with dyspnoea, chest pain, and fever. Imaging showed right pleural effusion without a lung mass. Thoracoscopy revealed necrotic pleural nodules. Histology demonstrated spindle‐shaped atypical cells, positive for cytokeratin AE1/AE3 and weakly positive for TTF‐1, but negative for mesothelial markers, consistent with sarcomatoid carcinoma of probable pulmonary origin. Staging CT revealed contralateral lung nodules, mediastinal lymphadenopathy, and distant metastases, but no dominant primary lesion. The patient declined systemic therapy and received palliative care. Sarcomatoid carcinoma presenting as malignant pleural effusion without a mass is rare. Early thoracoscopy and histological confirmation are crucial. Prognosis remains poor, though emerging data suggest a role for immunotherapy.

Genome-wide cfDNA Methylation Profiling of Pleural Effusion Reveals an Immuno-epigenetic Signature for Differentiating Malignant from Benign Cases.