Mesothelioma: Scientific clues for prevention, diagnosis, and therapy.

Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.

Evolving topological order in the postnatal visceral pleura.

BACKGROUND: Changes in epithelial cell shape reflects optimal cell packing and the minimization of surface free energy, but also cell-cell interactions, cell proliferation, and cytoskeletal rearrangements. RESULTS: Here, we studied the structure of the rat pleura in the first 15 days after birth. After pleural isolation and image segmentation, the analysis demonstrated a progression of epithelial order from postnatal day 1 (P1) to P15. The cells with the largest surface area and greatest shape variability were observed at P1. In contrast, the cells with the smallest surface area and most shape consistency were observed at P15. A comparison of polygonal cell geometries demonstrated progressive optimization with an increase in the number of hexagons (six-sided) as well as five-sided and seven-sided polygons. Analysis of the epithelial organization with Voronoi tessellations and graphlet motif frequencies demonstrated a developmental path strikingly distinct from mathematical and natural reference paths. Graph Theory analysis of cell connectivity demonstrated a progressive decrease in network heterogeneity and clustering coefficient from P1 to P15. CONCLUSIONS: We conclude that the rat pleura undergoes a striking change in pleural structure from P1 to P15. Further, a geometric and network-based approach can provide a quantitative characterization of these developmental changes.

Radiologic Features of Nodules Attached to the Mediastinal or Diaphragmatic Pleura at Low-Dose CT for Lung Cancer Screening.

Background Pulmonary noncalcified nodules (NCNs) attached to the fissural or costal pleura with smooth margins and triangular or lentiform, oval, or semicircular (LOS) shapes at low-dose CT are recommended for annual follow-up instead of immediate workup. Purpose To determine whether management of mediastinal or diaphragmatic pleura-attached NCNs (M/DP-NCNs) with the same features as fissural or costal pleura-attached NCNs at low-dose CT can follow the same recommendations. Materials and Methods This retrospective study reviewed chest CT examinations in participants from two databases. Group A included 1451 participants who had lung cancer that was first present as a solid nodule with an average diameter of 3.0-30.0 mm. Group B included 345 consecutive participants from a lung cancer screening program who had at least one solid nodule with a diameter of 3.0-30.0 mm at baseline CT and underwent at least three follow-up CT examinations. Radiologists reviewed CT images to identify solid M/DP-NCNs, defined as nodules 0 mm in distance from the mediastinal or diaphragmatic pleura, and recorded average diameter, margin, and shape. General descriptive statistics were used. Results Among the 1451 participants with lung cancer in group A, 163 participants (median age, 68 years [IQR, 61.5-75.0 years]; 92 male participants) had 164 malignant M/DP-NCNs 3.0-30.0 mm in average diameter. None of the 164 malignant M/DP-NCNs had smooth margins and triangular or LOS shapes (upper limit of 95% CI of proportion, 0.02). Among the 345 consecutive screening participants in group B, 146 participants (median age, 65 years [IQR, 59-71 years]; 81 female participants) had 240 M/DP-NCNs with average diameter 3.0-30.0 mm. None of the M/DP-NCNs with smooth margins and triangular or LOS shapes were malignant after a median follow-up of 57.8 months (IQR, 46.3-68.1 months). Conclusion For solid M/DP-NCNs with smooth margins and triangular or LOS shapes at low-dose CT, the risk of lung cancer is extremely low, which supports the recommendation of Lung Imaging Reporting and Data System version 2022 for annual follow-up instead of immediate workup. © RSNA, 2024 See also the editorial by Goodman and Baruah in this issue.

CT Predictors of Visceral Pleural Invasion in Patients with Non-Small Cell Lung Cancers 30 mm or Smaller.

Background CT-defined visceral pleural invasion (VPI) is an important indicator of prognosis for non-small cell lung cancer (NSCLC). However, there is a lack of studies focused on small subpleural NSCLCs (≤30 mm). Purpose To identify CT features predictive of VPI in patients with subpleural NSCLCs 30 mm or smaller. Materials and Methods This study is a retrospective review of patients enrolled in the Initiative for Early Lung Cancer Research on Treatment (IELCART) at Mount Sinai Hospital between July 2014 and February 2023. Subpleural nodules 30 mm or smaller were classified into two groups: a pleural-attached group and a pleural-tag group. Preoperative CT features suggestive of VPI were evaluated for each group separately. Multivariable logistic regression analysis adjusted for sex, age, nodule size, and smoking status was used to determine predictive factors for VPI. Model performance was analyzed with the area under the receiver operating characteristic curve (AUC), and models were compared using Akaike information criterion (AIC). Results Of 379 patients with NSCLC with subpleural nodules, 37 had subsolid nodules and 342 had solid nodules. Eighty-eight patients (22%) had documented VPI, all in solid nodules. Of the 342 solid nodules (46% in male patients, 54% in female patients; median age, 71 years; IQR: 66, 76), 226 were pleural-attached nodules and 116 were pleural-tag nodules. VPI was more frequent for pleural-attached nodules than for pleural-tag nodules (31% [69 of 226] vs 16% [19 of 116], P = .005). For pleural-attached nodules, jellyfish sign (odds ratio [OR], 21.60; P < .001), pleural thickening (OR, 6.57; P < .001), and contact surface area (OR, 1.05; P = .01) independently predicted VPI. The jellyfish sign led to a better VPI prediction (AUC, 0.84; 95% CI: 0.78, 0.90). For pleural-tag nodules, multiple tags to different pleura surfaces enabled independent prediction of VPI (OR, 9.30; P = .001). Conclusions For patients with solid NSCLC (≤30 mm), CT predictors of VPI were the jellyfish sign, pleural thickening, contact surface area (pleural-attached nodules), and multiple tags to different pleura surfaces (pleural-tag nodules). © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Nishino in this issue.

Single-cell transcriptomic analysis of human pleura reveals stromal heterogeneity and informs in vitro models of mesothelioma.

The pleural lining of the thorax regulates local immunity, inflammation and repair. A variety of conditions, both benign and malignant, including pleural mesothelioma, can affect this tissue. A lack of knowledge concerning the mesothelial and stromal cells comprising the pleura has hampered the development of targeted therapies. Here, we present the first comprehensive single-cell transcriptomic atlas of the human parietal pleura and demonstrate its utility in elucidating pleural biology. We confirm the presence of known universal fibroblasts and describe novel, potentially pleural-specific, fibroblast subtypes. We also present transcriptomic characterisation of multiple in vitro models of benign and malignant mesothelial cells, and characterise these through comparison with in vivo transcriptomic data. While bulk pleural transcriptomes have been reported previously, this is the first study to provide resolution at the single-cell level. We expect our pleural cell atlas will prove invaluable to those studying pleural biology and disease. It has already enabled us to shed light on the transdifferentiation of mesothelial cells, allowing us to develop a simple method for prolonging mesothelial cell differentiation in vitro.

A randomised phase II study of extended pleurectomy/decortication preceded or followed by chemotherapy in patients with early-stage pleural mesothelioma: EORTC 1205.

BACKGROUND: The role of surgery in pleural mesothelioma remains controversial. It may be appropriate in highly selected patients as part of a multimodality treatment including chemotherapy. Recent years have seen a shift from extrapleural pleuropneumonectomy toward extended pleurectomy/decortication. The most optimal sequence of surgery and chemotherapy remains unknown. METHODS: EORTC-1205-LCG was a multicentric, noncomparative phase 2 trial, 1:1 randomising between immediate (arm A) and deferred surgery (arm B), followed or preceded by chemotherapy. Eligible patients (Eastern Cooperative Oncology Group 0-1) had treatment-naïve, borderline resectable T1-3 N0-1 M0 mesothelioma of any histology. Primary outcome was rate of success at 20 weeks, a composite end-point including 1) successfully completing both treatments within 20 weeks; 2) being alive with no signs of progressive disease; and 3) no residual grade 3-4 toxicity. Secondary end-points were toxicity, overall survival, progression-free survival and process indicators of surgical quality. FINDINGS: 69 patients were included in this trial. 56 (81%) patients completed three cycles of chemotherapy and 58 (84%) patients underwent surgery. Of the 64 patients in the primary analysis, 21 out of 30 patients in arm A (70.0%; 80% CI 56.8-81.0%) and 17 out of 34 patients (50.0%; 80% CI 37.8-62.2%) in arm B reached the statistical end-point for rate of success. Median progression-free survival and overall survival were 10.8 (95% CI 8.5-17.2) months and 27.1 (95% CI 22.6-64.3) months in arm A, and 8.0 (95% CI 7.2-21.9) months and 33.8 (95% CI 23.8-44.6) months in arm B. Macroscopic complete resection was obtained in 82.8% of patients. 30- and 90-day mortality were both 1.7%. No new safety signals were found, but treatment-related morbidity was high. INTERPRETATION: EORTC 1205 did not succeed in selecting a preferred sequence of pre- or post-operative chemotherapy. Either procedure is feasible with a low mortality, albeit consistent morbidity. A shared informed decision between surgeon and patient remains essential.

The Prognostic Role of the Number of Involved Structures in Thymic Epithelial Tumors: Results from the ESTS Database.

BACKGROUND: The role of the number of involved structures (NIS) in thymic epithelial tumors (TETs) has been investigated for inclusion in future staging systems, but large cohort results still are missing. This study aimed to analyze the prognostic role of NIS for patients included in the European Society of Thoracic Surgeons (ESTS) thymic database who underwent surgical resection. METHODS: Clinical and pathologic data of patients from the ESTS thymic database who underwent surgery for TET from January 2000 to July 2019 with infiltration of surrounding structures were reviewed and analyzed. Patients' clinical data, tumor characteristics, and NIS were collected and correlated with CSS using Kaplan-Meier curves. The log-rank test was used to assess differences between subgroups. A multivariable model was built using logistic regression analysis. RESULTS: The final analysis was performed on 303 patients. Histology showed thymoma for 216 patients (71.3%) and NET/thymic carcinoma [TC]) for 87 patients (28.7%). The most frequently infiltrated structures were the pleura (198 cases, 65.3%) and the pericardium in (185 cases, 61.1%), whereas lung was involved in 96 cases (31.7%), great vessels in 74 cases (24.4%), and the phrenic nerve in 31 cases (10.2%). Multiple structures (range, 2-7) were involved in 183 cases (60.4%). Recurrence resulted in the death of 46 patients. The CSS mortality rate was 89% at 5 years and 82% at 10 years. In the univariable analysis, the favorable prognostic factors were neoadjuvant therapy, Masaoka stage 3, absence of metastases, absence of myasthenia gravis, complete resection, thymoma histology, and no more than two NIS. Patients with more than two NIS presented with a significantly worse CSS than patients with no more than two NIS (CSS 5- and 10-year rates: 9.5% and 83.5% vs 93.2% and 91.2%, respectively; p = 0.04). The negative independent prognostic factors confirmed by the multivariable analysis were incomplete resection (hazard ratio [HR] 2.543; 95% confidence interval [CI] 1.010-6.407; p = 0.048) and more than two NIS (HR 1.395; 95% CI 1.021-1.905; p = 0.036). CONCLUSIONS: The study showed that more than two involved structures are a negative independent prognostic factor in infiltrative thymic epithelial tumors that could be used for prognostic stratification.

Pathological Pleural Invasion is a Risk Factor for Late Recurrence in Long-Term Survivors of Non-small Cell Lung Cancer after Complete Resection.

BACKGROUND: Information regarding late recurrence after pulmonary resection for non-small cell lung cancer (NSCLC) is limited. This study aimed to analyze the risk factors for late recurrence after surgery for NSCLC in the current era. PATIENTS AND METHODS: We conducted a retrospective study of patients who underwent complete resection for pathological I-III NSCLC between 2006 and 2015. Late recurrence was defined as a recurrence that met the following conditions: (1) the patient underwent chest computed tomography (CT) at or after 54 months after surgery and recurrence was not detected at that time, and (2) recurrence that occurred more than 5 years after surgery. The factors influencing late recurrence, relapse-free survival (RFS), and overall survival (OS) after surgery were analyzed. RESULTS: A total of 1275 with 5-year relapse-free survival after surgery were enrolled in this study. The mean age of the patients was 66.4 years and 54% of the patients were men. The median interval between surgery and the latest follow-up examination was 98 months. In total, 35 patients (2.7%) experienced late recurrence and 138 patients have died thus far. The cumulative recurrence, RFS, and OS rates at 10 years were 3.9%, 84.9%, and 86.3%, respectively. A multivariate analysis revealed that pleural invasion was an independent risk factor for late recurrence. Pleural invasion was a poor prognostic factor for both RFS and OS. CONCLUSIONS: Pleural invasion was a predictor of late recurrence. Age > 67 years, preoperative serum carcinoembryonic antigen (CEA) > 5 ng/ml, non-adenocarcinoma, and pleural invasion were poor prognostic factors for RFS.

Mesothelioma in the pleura, pericardium and peritoneum: Recommendations from the International Collaboration on Cancer Reporting (ICCR).

AIMS: Mesothelioma is a rare malignancy of the serosal membranes that is commonly related to exposure to asbestos. Despite extensive research and clinical trials, prognosis to date remains poor. Consistent, comprehensive and reproducible pathology reporting form the basis of all future interventions for an individual patient, but also ensures that meaningful data are collected to identify predictive and prognostic markers. METHODS AND RESULTS: This article details the International Collaboration on Cancer Reporting (ICCR) process and the development of the international consensus mesothelioma reporting data set. It describes the 'core' and 'non-core' elements to be included in pathology reports for mesothelioma of all sites, inclusive of clinical, macroscopic, microscopic and ancillary testing considerations. An international expert panel consisting of pathologists and a medical oncologist produced a set of data items for biopsy and resection specimens based on a critical review and discussion of current evidence, and in light of the changes in the 2021 WHO Classification of Tumours. The commentary focuses particularly upon new entities such as mesothelioma in situ and provides background on relevant and essential ancillary testing as well as implementation of the new requirement for tumour grading. CONCLUSION: We recommend widespread and consistent implementation of this data set, which will facilitate accurate reporting and enhance the consistency of data collection, improve the comparison of epidemiological data, support retrospective research and ultimately help to improve clinical outcomes. To this end, all data sets are freely available worldwide on the ICCR website (www.iccr-cancer.org/data-sets).

Mesenchymal tumours of the pleura: review and update.

Primary mesenchymal tumours of the pleura are uncommon and can be diagnostically challenging due to their overlapping histopathologic and immunophenotypic features. Herein we discuss selected mesenchymal tumours of the pleura, including solitary fibrous tumour, calcifying fibrous tumour, desmoid fibromatosis, synovial sarcoma, schwannoma, malignant peripheral nerve sheath tumour, inflammatory myofibroblastic tumour, follicular dendritic cell sarcoma, epithelioid hemangioendothelioma, and desmoplastic small round cell tumour. We review their clinicopathologic characteristics, along with an update on the relevant immunohistochemical and molecular features.

NCCN Guidelines® Insights: Mesothelioma: Pleural, Version 1.2024.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.

Diagnostic performance and prognostic value of CT-defined visceral pleural invasion in early-stage lung adenocarcinomas.

OBJECTIVES: To analyze the diagnostic performance and prognostic value of CT-defined visceral pleural invasion (CT-VPI) in early-stage lung adenocarcinomas. METHODS: Among patients with clinical stage I lung adenocarcinomas, half of patients were randomly selected for a diagnostic study, in which five thoracic radiologists determined the presence of CT-VPI. Probabilities for CT-VPI were obtained using deep learning (DL). Areas under the receiver operating characteristic curve (AUCs) and binary diagnostic measures were calculated and compared. Inter-rater agreement was assessed. For all patients, the prognostic value of CT-VPI by two radiologists and DL (using high-sensitivity and high-specificity cutoffs) was investigated using Cox regression. RESULTS: In 681 patients (median age, 65 years [interquartile range, 58-71]; 382 women), pathologic VPI was positive in 130 patients. For the diagnostic study (n = 339), the pooled AUC of five radiologists was similar to that of DL (0.78 vs. 0.79; p = 0.76). The binary diagnostic performance of radiologists was variable (sensitivity, 45.3-71.9%; specificity, 71.6-88.7%). Inter-rater agreement was moderate (weighted Fleiss κ, 0.51; 95%CI: 0.43-0.55). For overall survival (n = 680), CT-VPI by radiologists (adjusted hazard ratio [HR], 1.27 and 0.99; 95%CI: 0.84-1.92 and 0.63-1.56; p = 0.26 and 0.97) or DL (HR, 1.44 and 1.06; 95%CI: 0.86-2.42 and 0.67-1.68; p = 0.17 and 0.80) was not prognostic. CT-VPI by an attending radiologist was prognostic only in radiologically solid tumors (HR, 1.82; 95%CI: 1.07-3.07; p = 0.03). CONCLUSION: The diagnostic performance and prognostic value of CT-VPI are limited in clinical stage I lung adenocarcinomas. This feature may be applied for radiologically solid tumors, but substantial reader variability should be overcome. CLINICAL RELEVANCE STATEMENT: Although the diagnostic performance and prognostic value of CT-VPI are limited in clinical stage I lung adenocarcinomas, this parameter may be applied for radiologically solid tumors with appropriate caution regarding inter-reader variability. KEY POINTS: • Use of CT-defined visceral pleural invasion in clinical staging should be cautious, because prognostic value of CT-defined visceral pleural invasion remains unexplored. • Diagnostic performance and prognostic value of CT-defined visceral pleural invasion varied among radiologists and deep learning. • Role of CT-defined visceral pleural invasion in clinical staging may be limited to radiologically solid tumors.

Accidental Detection of Tuberculous Empyema at Health Check-Up.

BACKGROUND: Patients with tuberculous empyema (TE) can have a serious impact on lung function as their disease progresses, and, if left untreated, can cause damage to other parts of the body such as the thorax and spine, causing pain and inconvenience to the patient. Early diagnosis and the search for appropriate treatment are key to improving the survival rate of the disease. METHODS: We report a case of a young patient with an unexpected finding of right pleural effusion on physical examination, who was eventually diagnosed with TE using next-generation sequencing of pleural tissue. We analyzed the literature to improve clinicians' understanding of TE and how to properly diagnose and treat the disease. RESULTS: Laboratory results of the pleural effusion suggested a possible Mycobacterium tuberculosis infection, but pathogen-related tests were negative, and the diagnosis was eventually successfully confirmed by thoracoscopic pleural biopsy. CONCLUSIONS: The diagnosis of TE should be considered in young patients with pleural thickening of the empyema. Adenosine deaminase may provide diagnostic direction in patients with unexplained thorax abscess. Pleural biopsy, although an invasive procedure, is an essential diagnostic tool in some cases.

The Biological Role of Pleural Fluid PAI-1 and Sonographic Septations in Pleural Infection: Analysis of a Prospectively Collected Clinical Outcome Study.

Rationale: Sonographic septations are assumed to be important clinical predictors of outcome in pleural infection, but the evidence for this is sparse. The inflammatory and fibrinolysis-associated intrapleural pathway(s) leading to septation formation have not been studied in a large cohort of pleural fluid (PF) samples with confirmed pleural infection matched with ultrasound and clinical outcome data. Objectives: To assess the presence and severity of septations against baseline PF PAI-1 (Plasminogen-Activator Inhibitor-1) and other inflammatory and fibrinolysis-associated proteins as well as to correlate these with clinically important outcomes. Methods: We analyzed 214 pleural fluid samples from PILOT (Pleural Infection Longitudinal Outcome Study), a prospective observational pleural infection study, for inflammatory and fibrinolysis-associated proteins using the Luminex platform. Multivariate regression analyses were used to assess the association of pleural biological markers with septation presence and severity (on ultrasound) and clinical outcomes. Measurements and Main Results: PF PAI-1 was the only protein independently associated with septation presence (P < 0.001) and septation severity (P = 0.003). PF PAI-1 concentrations were associated with increased length of stay (P = 0.048) and increased 12-month mortality (P = 0.003). Sonographic septations alone had no relation to clinical outcomes. Conclusions: In a large and well-characterized cohort, this is the first study to associate pleural biological parameters with a validated sonographic septation outcome in pleural infection. PF PAI-1 is the first biomarker to demonstrate an independent association with mortality. Although PF PAI-1 plays an integral role in driving septation formation, septations themselves are not associated with clinically important outcomes. These novel findings now require prospective validation.

Ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis: a case report.

BACKGROUND: The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare. CASE PRESENTATION: A 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant 18F-FDG uptake on 18F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis. CONCLUSION: Physicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis.

Pleural line slope in point of care ultrasound assessment of paediatric wheeze may reflect respiratory effort.

AIM: Asthma scoring systems rely on physical examination findings. Point of care ultrasound may provide an objective means to document improvement in the work of breathing in paediatric lower airway obstruction. METHODS: Thirty children with wheeze on physical examination (cases) and 15 children presenting with abdominal pain (controls) were studied. Using point-of-care ultrasound, m-mode tracing of lung was recorded above the right hemidiaphragm at the midclavicular line. Pleural line slope and excursion were measured before and after treatment. RESULTS: Twenty patients had a final slope measurement under 20°, and only three were admitted-one for hypoxia that resolved prior to ascending to the ward and another for poor compliance. Average decrease in pleural line slope after treatment was 43% and average decrease in pleural line excursion was 32%. Of the 10 children admitted, 8 had measurements over 25°. The correlation coefficient between pleural slope and pleural excursion was 0.67. All controls had a horizontal m-mode tracing at the pleural line. CONCLUSION: Oscillation of the m-mode line at the pleura is seen in children with lower airway obstruction and is absent in controls. There appears to be a correlation between beta-agonist therapy and decreased pleural line slope and excursion.

Recognizing the pleura in asbestos-related pleuropulmonary disease: Known and new manifestations of pleural fibrosis.

Pleural thickening (PT) is a major consequence of exposure to all fiber types of asbestos. In recent decades, it is more prevalent than parenchymal asbestosis. Its manifestations occupy a full clinical and radiographic spectrum. Six major manifestations can be identified: (a) acute pleuritis generally with effusion; (b) diffuse PT or fibrous pleuritis; (c) rounded atelectasis; (d) circumscribed PT or plaques; (e) chronic pleuritic pain; and (f) mesothelioma. Review of the experience of workers and community members in Libby, MT to asbestiform fibers in vermiculite has confirmed the appearance of these previously known benign and malignant asbestos-related diseases as well as a unique pleuropulmonary disease characterized as lamellar PT and associated with progressive decline in pulmonary function and pleuritic pain. Despite previous literature asserting that PT represents a marker for asbestos exposure without significant effect on pulmonary function and physiology, the experience of Libby amphibole (LA) disease, along with other studies, indicates that PT plays a role in declining vital capacity in those with prolonged or unusual exposures such as those arising from LA.

Primary pulmonary epithelioid hemangioendothelioma metastatic to the pleura and mediastinal lymph node with a prominent rhabdoid cytomorphology showing CAMTA1::WWTR1 fusion and novel PRDM1 and TNFRSF14 mutations.

Cases of epithelioid hemangioendothelioma with WWTR1::CAMTA1 fusion can show rhabdoid cytomorphology. Lack of intracytoplasmic luminal spaces, marked rhabdoid cytomorphology, and variability in the expression of vascular markers makes the diagnosis of EHE challenging. Therefore, a high level of suspicion and ancillary studies (immunohistochemistry and next generation sequencing) help reach a definitive diagnosis in these cases.

Sonography of the pleura. / Sonografie der Pleura.

The CME review presented here is intended to explain the significance of pleural sonography to the interested reader and to provide information on its application. At the beginning of sonography in the 80 s of the 20th centuries, with the possible resolution of the devices at that time, the pleura could only be perceived as a white line. Due to the high impedance differences, the pleura can be delineated particularly well. With the increasing high-resolution devices of more than 10 MHz, even a normal pleura with a thickness of 0.2 mm can be assessed. This article explains the special features of the examination technique with knowledge of the pre-test probability and describes the indications for pleural sonography. Pleural sonography has a high value in emergency and intensive care medicine, preclinical, outpatient and inpatient, in the general practitioner as well as in the specialist practice of pneumologists. The special features in childhood (pediatrics) as well as in geriatrics are presented. The recognition of a pneumothorax even in difficult situations as well as the assessment of pleural effusion are explained. With the high-resolution technology, both the pleura itself and small subpleural consolidations can be assessed and used diagnostically. Both the direct and indirect sonographic signs and accompanying symptoms are described, and the concrete clinical significance of sonography is presented. The significance and criteria of conventional brightness-encoded B-scan, colour Doppler sonography (CDS) with or without spectral analysis of the Doppler signal (SDS) and contrast medium ultrasound (CEUS) are outlined. Elastography and ultrasound-guided interventions are also mentioned. A related further paper deals with the diseases of the lung parenchyma and another paper with the diseases of the thoracic wall, diaphragm and mediastinum.

Breast ultrasound: An opportunity to detect unsuspected pleural and pulmonary abnormalities.

PURPOSE: While scanning women for breast US, is possible to observe changes in the appearance of the pleural line or in the most superficial portion of the lung. The objective of this single-center, prospective study was to determine the prevalence of a variety of pleural and pulmonary US findings during routine breast US. METHODS: In this study, there were 200 women undergoing standard breast US examination. The presence of pleural and pulmonary abnormalities in these cases was recorded. Two off-site reviewers confirmed the presence of pleura and lung changes. RESULTS: There was no abnormal finding in 168 out of 200 cases (84%) while there were one or more abnormal findings in 32 cases (16%). Pleural effusion was observed in 0.5% of cases, thickening of the pleural line 5% of cases, irregularity of the pleural line in 6% of cases, increased number of vertical artifacts in 9% of cases, subpleural nodulations in 2% of cases, and lung consolidation in 0.5%. CONCLUSION: Pleural and lung changes are not uncommon during breast US. Operators performing breast US examinations should be aware of the possibility to identify unsuspected pleuro-pulmonary abnormalities.