Incidence of brain and bone metastases was not different between EGFR+, KRAS+ and WT patients. Post brain metastases survival, time from mNSCLC diagnosis to metastatic bone disease and 1st SRE did not differ either. Post metastatic bone disease survival was significantly longer in EGFR+ patients. Although prevention of SRE's is important for all patients, the latter finding calls for a separate study for SRE preventing agents in EGFR+ patients.

Activin A (ActA)/follistatin (FST) signaling has been shown to be deregulated in different tumor types including lung adenocarcinoma (LADC). Here, we report that serum ActA protein levels are significantly elevated in LADC patients (n=64) as compared to controls (n=46, p=0.015). ActA levels also correlated with more advanced disease stage (p<0.0001) and T (p=0.0035) and N (p=0.0002) factors. M1 patients had significantly higher ActA levels than M0 patients (p<0.001). High serum ActA level was associated with poor overall survival (p<0.0001) and was confirmed as an independent prognostic factor (p=0.004). Serum FST levels were increased only in female LADC patients (vs. female controls, p=0.031). Two out of five LADC cell lines secreted biologically active ActA, while FST was produced in all of them. Transcripts of both type I and II ActA receptors were detected in all five LADC cell lines. In conclusion, our study does not only suggest that measuring blood ActA levels in LADC patients might improve the prediction of prognosis, but also indicates that this parameter might be a novel non-invasive biomarker for identifying LADC patients with organ metastases.

Pre-analytical factors, such as fixation time, influence morphology of diagnostic and predictive immunohistochemical staining, which are increasingly used in the evaluation of lung cancer. Our aim was to investigate if variations in fixation time influence the outcome of immunohistochemical staining in lung cancer. From lung resections, specimen with tumor size bigger than 4 cm, 10 samples were obtained: 2 were put through the standard fixation protocol, 5 through the delayed, and 3 through the prolonged fixation protocol. After paraffin embedding, tissue microarrays (TMAs) were made. They were stained with 20 antibodies and scored for quality and intensity of staining. Samples with delay in fixation showed loss of TMA cores on glass slides and deterioration of tissue quality leading to reduction in the expression of CK 7, Keratin MNF116, CAM 5.2, CK 5/6, TTF-1, C-MET, Napsin A, D2-40, and PD-L1. Prolonged fixation had no influence on the performance of immunohistochemical stains. Delay of fixation negatively affects the expression of different immunohistochemical markers, influencing diagnostic (cytokeratins) and predictive (PD-L1) testing. These results emphasize the need for adequate fixation of resection specimen. Electronic supplementary material The online version of this article (10.1007/s00428-019-02595-9) contains supplementary material, which is available to authorized users.

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Most COVID-19 victims are old and die from unrelated causes. Here we present t welve complete autopsies, including two rapid autopsies of young patients where the cause of death was COVID-19 ARDS. The main virus induced pathology was in the lung parenchyma and not in the airways. Most coagulation events occurred in the intra-alveolar and not in the intra-vascular space and the few thrombi were mainly composed of aggregated thrombocytes. The dominant inflammatory response was the massive accumulation of CD163+ macrophages and the disappearance of T killer, NK and B-cells. The virus was replicating in the pneumocytes and macrophages but not in bronchial epithelium, endothelium, pericytes or stromal cells. The lung consolidations were produced by a massive regenerative response, stromal and epithelial proliferation and neovascularization. We suggest that thrombocyte aggregation inhibition, angiogenesis inhibition and general proliferation inhibition may have a roll in the treatment of advanced COVID-19 ARDS.

SummaryMost Covid-19 victims are old and die from unrelated causes. Here we present twelve complete autopsies, including two rapid autopsies of young patients where the cause of death was Covid-19 ARDS. The main virus induced pathology was in the lung parenchyma and not in the airways. Most coagulation events occurred in the intra-alveolar and not in the intra-vascular space and the few thrombi were mainly composed of aggregated thrombocytes. The dominant inflammatory response was the massive accumulation of CD163+ macrophages and the disappearance of T killer, NK and B-cells. The virus was replicating in the pneumocytes and macrophages but not in bronchial epithelium, endothel, pericytes or stromal cells. The lung consolidations were produced by a massive regenerative response, stromal and epithelial proliferation and neovascularization. We suggest that thrombocyte aggregation inhibition, angiogenesis inhibition and general proliferation inhibition may have a roll in the treatment of advanced Covid-19 ARDS.

PurposeUsing large-core biopsy needles in CT-guided percutaneous transthoracic needle biopsies (PTNB) may be advantageous in terms of larger specimens, which facilitate more extensive histopathological, immunohistochemical, and molecular examination of tumor tissue. The aim of this study was to evaluate the success rate and safety in CT-guided PTNB using 10G large-core biopsy needles.Methods and Materials35 patients with intrathoracic lesions suspected of malignancy underwent CT-guided PTNB using dedicated large-core biopsy needles (10G Spirotome™, Medinvents, Hasselt, Belgium). Location, tumor size, number of pleural passes, number of biopsies, histologic result, and complications (pneumothorax, bleeding) were recorded.ResultsLesion location varied from pleural to hilar location. Mean tumor size was 3.5 cm (range 0.7–9.2 cm). Only one pleural passage was necessary in all patients. Mean distance from the pleura to the lesion was 2.6 cm (max 9.2 cm). Large-core biopsy (10G) was successful in 88.6 %. Pneumothorax was found in 40 %. Minor intraparenchymal bleeding was present in 14 patients. No major complications were recorded.ConclusionLarge-core biopsy with 10G did not show higher complication rates compared to literature. It is technically feasible and safe. The obtained larger specimens may especially be helpful for the increasing demands of extensive molecular analysis for stratified patient care.

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