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Diffuse malignant mesothelioma (MM) is an incurable tumour of the serosal membranes, which is often caused by exposure to asbestos and commonly diagnosed at advanced stage. Malignant mesothelioma in situ (MMIS) is now included as diagnostic category by the World Health Organization (WHO). However, our international survey of 34 pulmonary pathologists with an interest in MM diagnosis highlights inconsistency regarding how the diagnosis is being made by experts, despite published guidelines. Whilst the WHO restricts the diagnosis to surgical samples, the very concept has implication for cytological diagnosis, which is already regarded as controversial in itself by some. MMIS is currently only applicable as precursor to MM with an epithelioid component, and raises the possibility for different molecular pathways for different histological MM subtypes. The clinical implications of MMIS at this stage are uncertain, but aggressive therapies are being initiated in some instances. Based on the results of the survey we here present a critical appraisal of the concept, its clinical and conceptual implications and provide practice suggestions for diagnosis. A low threshold for ancillary testing is suggested. The designations of 'malignant mesothelioma, cannot exclude MMIS' or 'atypical mesothelial proliferation with molecular indicators of malignancy, so-called MMIS' could be used on cytology samples, adding 'no evidence of invasion in sample provided' for surgical samples. Clinical and radiological correlation are integral to diagnosis and best done at multidisciplinary meetings. Finally, collaborative studies are required to improve our understanding of MMIS., (Copyright © 2021. Published by Elsevier B.V.)

Background: Severe immunopathology may drive the deleterious manifestations that are observed in the advanced stages of coronavirus disease 2019 (COVID-19) but are poorly understood., Objective: Our aim was to phenotype leukocyte subpopulations and the cytokine milieu in the lungs and blood of critically ill patients with COVID-19 acute respiratory distress syndrome (ARDS)., Methods: We consecutively included patients less than 72 hours after intubation following informed consent from their next of kin. Bronchoalveolar lavage fluid was evaluated by microscopy; bronchoalveolar lavage fluid and blood were assessed by 10-color flow cytometry and a multiplex cytokine panel., Results: Four mechanically ventilated patients (aged 40-75 years) with moderate-to-severe COVID-19 ARDS were included. Immature neutrophils dominated in both blood and lungs, whereas CD4 and CD8 T-cell lymphopenia was observed in the 2 compartments. However, regulatory T cells and T H 17 cells were found in higher fractions in the lung. Lung CD4 and CD8 T cells and macrophages expressed an even higher upregulation of activation markers than in blood. A wide range of cytokines were expressed at high levels both in the blood and in the lungs, most notably, IL-1RA, IL-6, IL-8, IP-10, and monocyte chemoattactant protein-1, consistent with hyperinflammation., Conclusion: COVID-19 ARDS exhibits a distinct immunologic profile in the lungs, with a depleted and exhausted CD4 and CD8 T-cell population that resides within a heavily hyperinflammatory milieu., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Little is known about prevalence of PD-L1 expression in tumor cells of unselected patients with all stages of non-small cell lung cancer. The objective of this study is to assess the prevalence of PD-L1 positivity in patients with non-small cell lung cancer, to analyze the association between PD-L1 positivity and patients' clinicopathological characteristics, and to assess the use of immune-oncologic treatment in eligible patients. All non-small cell lung cancer patients diagnosed in a 10-month period in an unselected population of 1.7 million Caucasian inhabitants were evaluated with the PD-L1 IHC 22C3 pharmDx kit. A total of 819 patients were diagnosed with non-small cell lung cancer. Samples analyzable for PD-L1 expression were obtained from 97% of patients. In a multivariate analysis with cut-off at tumor proportion score ≥50%, lower stage was associated with lower prevalence of PD-L1 positivity with an odds ratio of 0.31 for stage I vs. stage IV. A significant difference in PD-L1 expression between squamous-cell carcinoma and adenocarcinoma was observed with odds ratio for adenocarcinoma 1.8. With cut-off tumor proportion score ≥1%, attenuated effects of the same direction were seen. For neither cut-off did type and location of material used for PD-L1 analysis, age, sex, smoking history, or performance status have statistically significant impact on the PD-L1 expression. Fifty four percent of the patients who were eligible for immune-oncologic treatment were actually treated in first-line with pembrolizumab monotherapy. In conclusion, 97% of the patients had material analyzable for PD-L1. If a patient in need of immuno-oncologic treatment has shifted stage, a negative or low positive PD-L1 test performed on a biopsy taken in a lower stage might not mirror the PD-L1 expression in the new metastatic lesion. Therefore, a re-biopsy should be considered.