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Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity. The host immune response plays a critical role in the immunopathology of SARS-CoV2. Here the authors combine a systems biology approach to implicate monocytes as key drivers of cytokine storm and disturbed neutrophil activation in COVID-19 disease severity.

Puumala virus (PUUV) is considered a classic Old World etiologic agent of nephropathia epidemica (NE), or hemorrhagic fever with renal syndrome (HFRS). HFRS is considered to be distinct from hantavirus (cardio-)pulmonary syndrome (HPS or HCPS), described in the New World. Here, we report a severe case, which fulfilled most, if not all, Centers for Disease Control and Prevention (CDC) criteria for HPS, needing non-invasive ventilation and subsequent acute hemodialysis. However, the etiological agent was PUUV, as proved by serological testing, real-time polymerase chain reaction (PCR), and sequencing. Viral antigen was detected by specific anti-PUUV immunostaining, showing, for the first time, greenish intracytoplasmic inclusions in bronchoalveolar lavage (BAL) macrophages. This case definitely confirms that HPS can be encountered during PUUV infections. Interestingly, special findings could render the diagnosis easier, such as greenish homogeneous cytoplasmic inclusions, surrounded by a fine clear halo in BAL macrophages. Therefore, although the diagnosis remains difficult before the onset of renal involvement, the occurrence of severe respiratory failure mimicking community-acquired pneumonia must alert the clinician for possible HPS, especially in endemic areas.

Long-term diabetes mellitus (DM) is characterized by widespread alterations of basal lamina (BL). The purpose of the present work was to verify whether the lung is also a target organ damaged in DM. Electron microscopy was performed on lung and kidney samples (autopsic material) from 6 diabetics and 6 control subjects studying the thickening of BL of different structures (alveolar epithelial BL, endothelial capillary BL, both fused BL, BL of the glomerular capillary endothelium and BL of the renal tubules). The results were as follows: (1) alveolar epithelial BL (mean ± SD) = 121 ± 11 nm in controls and 176 ± 27 nm in diabetics (p < 0.01), (2) endothelial capillary BL = 164 ± 14 nm in controls and 223 ± 27 nm in diabetics (p < 0.001), (3) both BL fused = 222 ± 23 nm in controls and 316 ± 62 nm in diabetics (p < 0.01), (4) BL of the glomerular capillary endothelium = 374 ± 44 nm in controls and 626 ± 249 in diabetics (p < 0.05) and (5) BL of the renal tubules = 602 ± 94 nm in controls and 1,083 ± 376 nm in diabetics (p < 0.05). All parts of the lung are equally affected by DM. The thickening of BL is of the same magnitude in lung and kidney. There is no relationship between the thickening of the lung BL and the known duration and type of DM.

The percentage of sarcomatoid component has an impact on prognosis in patients with biphasic malignant pleural mesothelioma. Recent study showed that the transitional pattern similar to sarcomatoid component of malignant mesothelioma has negative prognostic significance. Practice guidelines recommend quantification of sarcomatoid component despite poor diagnostic reproducibility of biphasic mesothelioma among thoracic pathologists. The aim of this study was to determine the interobserver agreement in the quantification of sarcomatoid component, and in the diagnosis of a transitional component in the biphasic malignant mesothelioma. Thirteen experts in thoracic pathology reviewed the representative H&E and cytokeratin whole-slide images of the 54 biphasic mesotheliomas, without knowledge of BAP1 or p16 deletion status, and completed the survey of 25 questions. The overall interobserver agreement in the assessment of the percentage of the sarcomatoid component in 25% increments was good (wK = 0.62). Excellent agreement was present in 14 of 54 cases (26%), and 3 cases were unanimously scored. Excellent agreement was reached for the cases with 0–24% and > 75% of the sarcomatoid component.The most commonly used criteria for the diagnosis of sarcomatoid component were malignant spindle cells, frank sarcomatoid features and high N/C ratio. The overall interobserver agreement for transitional pattern was fair (wK = 0.40). Unanimous opinion about the absence of transitional pattern was observed in only one case. At least 70% agreement regarding the presence of transitional pattern was observed in 12 cases, with the rest of the cases showing a wide range of disagreement. Morphologic characteristics that favor transitional pattern over non-transitional include sheet-like growth of cohesive, plump, elongated epithelioid cells with well-defined cell borders and a tendency to transition into spindle cells. Our study defined precise morphologic criteria that may be used in the differential diagnosis between transitional pattern and other mesothelioma subtypes including sarcomatoid and epithelioid.

Background: A flexible 19-gauge (Flex 19G) needle has been developed for endobronchial ultrasonography. Objectives: We aimed to evaluate quantitative and qualitative specimen characteristics of Flex 19G in a randomized controlled setting for patients with suspected lung cancer. Methods: We undertook a single-center, randomized, controlled trial. A computer-generated randomization assigned all enrolled patients 1: 1 to undergo endobronchial ultrasonography using a Flex 19G or a 22-gauge (22G) needle for lymph node tissue sampling. Pathologists were blinded to the group assignment. The primary end point was histological tissue core procurement. The secondary end points were diagnostic yield, specimen bloodiness and overall quality, tissue surface area and performance for next-generation sequencing (NGS), and procedure-related complications. Results: Between June 2016 and February 2017, we randomly allocated a total of 78 patients: 39 patients to Flex 19G and 39 patients to 22G. No superiority in tissue core procurement was observed for Flex 19G compared to 22G (67 vs. 72%, p = 0.81). No significant difference was observed in diagnostic yield and overall specimen quality, but transbronchial needle aspiration specimens by Flex 19G were bloodier and had a larger tissue surface area. NGS was successful for clinically relevant genes in 96% and for all 26 genes tested in 81% of the samples. There was no difference in clinically relevant complications. Conclusions: No superiority is observed for Flex 19G in histological tissue core procurement rate. The Flex 19G needle could be considered when a larger tissue surface is of special interest.

A 54-year-old man without medical history presented with a right-sided tumor of the parotid gland. The consistency of the mass was soft. The patient was asymptomatic except for the self-palpation of the process. He had unremarkable clinical examition including neck nodal areas. The ‘conventiol’ MRI examition gave significant clues for the diagnosis (Fig. A). The neoplasm displayed elevated sigl intensity on unenhanced T1-weighted images (A) suggesting a colloid content and enhanced only slightly after paramagnetic contrast agent (CA) perfusion (B), which is a valuable criterion to distinguish it from other common benign (pleiomorphic adenoma) and malignt (carcinomas) neoplasms of the parotid gland which usually exhibit strong heterogeneous enhancement. Low contrast-enhancement was confirmed by subtracting pre- and post-contrast T1-weighted images (C).

The present manuscript is a summary of two lectures which were given respectively by B. Weynd and G.R. Ferretti. The new classification of lung adenocarcinomas has changed the view of the radiologists and the pathologists especially regarding the former bronchiolo-alveolar carcinoma (BAC). The aim of this paper is to correlate radiological and histopathological images according to the 2011 classification for lung adenocarcinoma proposed by the Intertiol Association for the Study of Lung cancer, the American Thoracic Society and the European Respiratory Society and to draw attention to the way these lesions can be approached preoperatively.