Frequency and Significance of Pathologic Pulmonary Findings in Postmortem Examinations—A Single Center Experience before COVID-19

Berezowska, Sabina; Schmid, Andreas; Losmanová, Tereza; Trippel, Mafalda; Blank, Annika; Banz, Yara; Jakob, Stephan M.; Langer, Rupert

doi:10.3390/diagnostics11050894

Cited by 4 publications

(1 citation statement)

References 46 publications

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“…The disease reveals a complexity of pathologic features, including acute diffuse alveolar damage (DAD) and organized pneumonia and fibrosis [1][2][3][4][5][6]. Growing evidence indicates that during disease progression, fibrotic abnormalities become more predominant, especially in fatal COVID-19 [7][8][9][10]. Similarly, post-acute phase sequelae of COVID-19 chest computed tomography (CT) scans reveal a variable degree of fibrotic abnormalities in some recovered patients [11].…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Activity and Extracellular Matrix Degradation: Drivers of Lung Tissue Destruction in Fatal COVID-19 Cases and Implications for Long COVID

Narasaraju,

Neeli,

Criswell

et al. 2024

Biomolecules

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Pulmonary fibrosis, severe alveolitis, and the inability to restore alveolar epithelial architecture are primary causes of respiratory failure in fatal COVID-19 cases. However, the factors contributing to abnormal fibrosis in critically ill COVID-19 patients remain unclear. This study analyzed the histopathology of lung specimens from eight COVID-19 and six non-COVID-19 postmortems. We assessed the distribution and changes in extracellular matrix (ECM) proteins, including elastin and collagen, in lung alveoli through morphometric analyses. Our findings reveal the significant degradation of elastin fibers along the thin alveolar walls of the lung parenchyma, a process that precedes the onset of interstitial collagen deposition and widespread intra-alveolar fibrosis. Lungs with collapsed alveoli and organized fibrotic regions showed extensive fragmentation of elastin fibers, accompanied by alveolar epithelial cell death. Immunoblotting of lung autopsy tissue extracts confirmed elastin degradation. Importantly, we found that the loss of elastin was strongly correlated with the induction of neutrophil elastase (NE), a potent protease that degrades ECM. This study affirms the critical role of neutrophils and neutrophil enzymes in the pathogenesis of COVID-19. Consistently, we observed increased staining for peptidyl arginine deiminase, a marker for neutrophil extracellular trap release, and myeloperoxidase, an enzyme-generating reactive oxygen radical, indicating active neutrophil involvement in lung pathology. These findings place neutrophils and elastin degradation at the center of impaired alveolar function and argue that elastolysis and alveolitis trigger abnormal ECM repair and fibrosis in fatal COVID-19 cases. Importantly, this study has implications for severe COVID-19 complications, including long COVID and other chronic inflammatory and fibrotic disorders.

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Section: Introductionmentioning

confidence: 99%

Neutrophil Activity and Extracellular Matrix Degradation: Drivers of Lung Tissue Destruction in Fatal COVID-19 Cases and Implications for Long COVID

Narasaraju,

Neeli,

Criswell

et al. 2024

Biomolecules

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Reporting of Incidental Thrombotic Arteriopathy in Lung Resection Specimens

Gagné,

Padera,

Putman

et al. 2024

American Journal of Surgical Pathology

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Pulmonary thrombotic arteriopathy (PTA) can be an incidental finding in lung resections performed for various indications. Historic studies largely examined PTA in autopsies. Thus, the prevalence in surgical samples, particularly in the modern era of lung cancer screening, is poorly defined. Detection of PTA in surgical samples may provide an opportunity for therapeutic intervention, but the impact of this finding on clinical management is unknown. We retrospectively examined consecutive lung surgical resections containing a report of incidental PTA between 2019 and 2022 in our institution. A retrospective chart review was performed to determine the history of systemic thromboembolism and clinical and radiographic follow-up. All slides were reviewed to morphologically characterize the vascular changes. Among 2930 pulmonary resections, 66 (2.3%) reportedly contained PTA. Twenty-four (36.4%) patients had a clinically recognized thromboembolic event either before or after surgical resection. Patients with clinically recognized thromboembolic disease were significantly more likely to have both acute and organized thrombi affecting large arteries. The presence of infarct, chronic hypertensive vasculopathy, or number of vessels with thrombi were not significantly associated with a clinically detected event. Reporting of incidental PTA led to clinical intervention in six patients and confirmed systemic thromboembolic disease in 2. Moreover, 2 patients with no further workup based on the incidental pathology findings subsequently developed pulmonary embolism. PTA is incidentally detected in 2.3% of surgical lung resections, and in two-thirds of cases, there is no clinical suspicion of thromboembolic disease. Pathologic reporting of PTA rarely led to clinical intervention, suggesting a need for improved communication of incidental pathology findings.

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Prevalence of subclinical lung cancer detected at autopsy: a systematic review

Bonney,

Togawa,

et al. 2023

BMC Cancer

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Background Lung cancer screening in high-risk populations with low-dose computed tomography is supported by international associations and recommendations. Overdiagnosis is considered a risk of screening with associated harms. The aim of this paper is to determine the prevalence of subclinical lung cancer diagnosed post-mortem to better understand the reservoir of subclinical lung cancer. Methods We searched EMBASE, PubMed, and MEDLINE databases from inception until March 2022 with no language restrictions. We considered all studies with ≥100 autopsies in adults. Two reviewers independently assessed eligibility of studies, extracted data, and assessed risk of bias of included studies. We performed a meta-analysis using a random-effects model for prevalence of subclinical lung cancer diagnosed post-mortem with sensitivity and subgroup analyses. Results A total of 13 studies with 16 730 autopsies were included. Pooled prevalence was 0.4% (95% CI 0.20 to 0.82%, I2 = 84%, tau2 = 1.19, low certainty evidence,16 730 autopsies). We performed a sensitivity analysis excluding studies which did not specify exclusion of children in their cohort, with a pooled prevalence of subclinical lung cancer of 0.87% (95% CI 0.48 to 1.57%, I2 = 71%, tau2 = 0.38, 6998 autopsies, 8 studies). Conclusions This is the first published systematic review to evaluate the prevalence of post-mortem subclinical lung cancer. Compared to autopsy systematic reviews in breast, prostate and thyroid cancers, the pooled prevalence is lower in lung cancer for subclinical cancer. This result should be interpreted with caution due to the included studies risk of bias and heterogeneity, with further high-quality studies required in target screening populations.

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Frequency and Significance of Pathologic Pulmonary Findings in Postmortem Examinations—A Single Center Experience before COVID-19

Cited by 4 publications

References 46 publications

Neutrophil Activity and Extracellular Matrix Degradation: Drivers of Lung Tissue Destruction in Fatal COVID-19 Cases and Implications for Long COVID

Neutrophil Activity and Extracellular Matrix Degradation: Drivers of Lung Tissue Destruction in Fatal COVID-19 Cases and Implications for Long COVID

Reporting of Incidental Thrombotic Arteriopathy in Lung Resection Specimens

Prevalence of subclinical lung cancer detected at autopsy: a systematic review

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