Guidelines for Pathologic Diagnosis of Mesothelioma: 2023 Update of the Consensus Statement From the International Mesothelioma Interest Group.

Context.—: Mesothelioma is an uncommon tumor that can be difficult to diagnose.

Objective.

Transcriptional profiles of pulmonary artery endothelial cells in pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is characterized by endothelial cell (EC) dysfunction. There are no data from living patients to inform whether differential gene expression of pulmonary artery ECs (PAECs) can discern disease subtypes, progression and pathogenesis. We aimed to further validate our previously described method to propagate ECs from right heart catheter (RHC) balloon tips and to perform additional PAEC phenotyping.

Serotonin reduction in post-acute sequelae of viral infection.

Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction.

Two cases of severe pulmonary toxicity from highly active mesothelin-directed CAR T cells.

Multiple clinical studies have treated mesothelin (MSLN)-positive solid tumors by administering MSLN-directed chimeric antigen receptor (CAR) T cells. Although these products are generally safe, efficacy is limited. Therefore, we generated and characterized a potent, fully human anti-MSLN CAR.

Clinical Outcomes Associated With Pembrolizumab Monotherapy Among Adults With Diffuse Malignant Peritoneal Mesothelioma.

Importance: Diffuse malignant peritoneal mesothelioma (DMPM) represents a rare and clinically distinct entity among malignant mesotheliomas. Pembrolizumab has activity in diffuse pleural mesothelioma but limited data are available for DMPM; thus, DMPM-specific outcome data are needed.

Objective: To evaluate outcomes after the initiation of pembrolizumab monotherapy in the treatment of adults with DMPM.

Defining the spatial landscape of KRAS mutated congenital pulmonary airway malformations: a distinct entity with a spectrum of histopathologic features.

The potential pathogenetic mechanisms underlying the varied morphology of congenital pulmonary airway malformations (CPAMs) have not been molecularly determined, but a subset have been shown to contain clusters of mucinous cells (MCC). These clusters are believed to serve as precursors for potential invasive mucinous adenocarcinoma, and they are associated with KRAS codon 12 mutations. To assess the universality of KRAS mutations in MCCs, we sequenced exon 2 of KRAS in 61 MCCs from 18 patients, and we found a KRAS codon 12 mutation in all 61 MCCs.

Identification and Prognosis of Patients With Interstitial Pneumonia With Autoimmune Features.

Background/objective: Patients classified as interstitial pneumonia with autoimmune features (IPAF) have interstitial lung disease (ILD) and features of autoimmunity but do not fulfill criteria for connective tissue diseases (CTDs). Our goal was to identify patients classifiable as IPAF, CTD-ILD, and idiopathic pulmonary fibrosis (IPF) from a preexisting pulmonary cohort and evaluate the prognosis of patients with IPAF.

Methods: We reviewed the medical records of 456 patients from a single-center pulmonary ILD cohort whose diagnoses were previously established by a multidisciplinary panel that did not include rheumatologists.

Pulmonary vascular inflammation with fatal coronavirus disease 2019 (COVID-19): possible role for the NLRP3 inflammasome.

Background: Pulmonary hyperinflammation is a key event with SARS-CoV-2 infection. Acute respiratory distress syndrome (ARDS) that often accompanies COVID-19 appears to have worse outcomes than ARDS from other causes. To date, numerous lung histological studies in cases of COVID-19 have shown extensive inflammation and injury, but the extent to which these are a COVID-19 specific, or are an ARDS and/or mechanical ventilation (MV) related phenomenon is not clear.

Subcellular Detection of SARS-CoV-2 RNA in Human Tissue Reveals Distinct Localization in Alveolar Type 2 Pneumocytes and Alveolar Macrophages.

The widespread coronavirus disease 2019 (COVID-19) is caused by infection with the novel coronavirus SARS-CoV-2. Currently, we have limited understanding of which cells become infected with SARS-CoV-2 in human tissues and where viral RNA localizes on the subcellular level. Here, we present a platform for preparing autopsy tissue for visualizing SARS-CoV-2 RNA using RNA fluorescence in situ hybridization (FISH) with amplification by hybridization chain reaction.

Vascular Inflammation in Lungs of Patients with Fatal Coronavirus Disease 2019 (COVID-19): Possible Role for the NLRP3 Inflammasome.

Hyperinflammation is a key event that occurs with SARS-CoV-2 infection. In the lung, hyperinflammation leads to structural damage to tissue. To date, numerous lung histological studies have shown extensive alveolar damage, but there is scarce documentation of vascular inflammation in postmortem lung tissue.

Multiplexed detection of SARS-CoV-2 genomic and subgenomic RNA using hybridization.

The widespread Coronavirus Disease 2019 (COVID-19) is caused by infection with the novel coronavirus SARS-CoV-2. Currently, we have a limited toolset available for visualizing SARS-CoV-2 in cells and tissues, particularly in tissues from patients who died from COVID-19. Generally, single-molecule RNA FISH techniques have shown mixed results in formalin fixed paraffin embedded tissues such as those preserved from human autopsies.

Molecular imaging can identify the location to perform a frozen biopsy during intraoperative frozen section consultation.

Background: Intraoperative frozen section (FS) consultation is an important tool in surgical oncology that suffers from sampling error because the pathologist does not always know where to perform a biopsy of the surgical specimen. Intraoperative molecular imaging is a technology used in the OR to visualize lesions during surgery. We hypothesized that molecular imaging can address this pathology challenge in FS by visualizing the cancer cells in the specimen in the pathology suite.

Alpha-defensins: risk factor for thrombosis in COVID-19 infection.

The inflammatory response to SARS/CoV-2 (COVID-19) infection may contribute to the risk of thromboembolic complications. α-Defensins, antimicrobial peptides released from activated neutrophils, are anti-fibrinolytic and prothrombotic in vitro and in mouse models. In this prospective study of 176 patients with COVID-19 infection, we found that plasma levels of α-defensins were elevated, tracked with disease progression/mortality or resolution and with plasma levels of interleukin-6 (IL-6) and D-dimers.

Comparison of Nuclear Grade, Necrosis, and Histologic Subtype Between Biopsy and Resection in Pleural Malignant Mesothelioma: An International Multi-Institutional Analysis.

Objectives: Numerous studies on malignant mesothelioma (MM) highlight the prognostic importance of histologic subtype, nuclear grade, and necrosis. This study compares these parameters in paired biopsy and resection specimens of pleural MM.

Methods: Histologic subtype, percentage of epithelioid morphology, nuclear grade, and the presence or absence of necrosis were compared in 429 paired biopsies and resection specimens of pleural MM from 19 institutions.

Vascular Inflammation in Lungs of Patients with Fatal Coronavirus Disease 2019 (COVID-19) Infection: Possible role for the NLRP3 inflammasome.

Hyperinflammation is a key event that occurs with SARS-CoV-2 infection. In the lung, hyperinflammation leads to structural damage to tissue. To date, numerous lung histological studies have shown extensive alveolar damage, but there is scarce documentation of vascular inflammation in postmortem lung tissue.

The concept of mesothelioma in situ, with consideration of its potential impact on cytology diagnosis.

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.

Mucinous Cell Clusters in Infantile Congenital Pulmonary Airway Malformations Mimic Adult Mucinous Adenocarcinoma But Are Not Associated With Poor Outcomes When Appropriately Resected.

Congenital pulmonary airway malformations (CPAMs) are abnormalities of the lung arising during development. At our institution the majority of type I infantile CPAMs contain mucinous cell clusters (MCCs). The overlapping histology of MCCs and adult in situ mucinous adenocarcinomas, as well as reports of metastatic mucinous adenocarcinoma arising in CPAMs resected later in childhood raise concerns about the malignant potential of these cells.

Pulmonary adenomyoma presenting as a right cardiophrenic angle mass.

Pulmonary adenomyomas are rare adenomyomatous hamartomas. In the few cases described in the literature, these benign tumors are encapsulated by lung parenchyma. We describe a case of a 59 year-old woman with acetylcholine receptor antibody-negative myasthenia gravis and a right cardiophrenic mass initially thought to be a thymoma.

Function of Human Tumor-Infiltrating Lymphocytes in Early-Stage Non-Small Cell Lung Cancer.

Cancer progression is marked by dysfunctional tumor-infiltrating lymphocytes (TIL) with high inhibitory receptor (IR) expression. Because IR blockade has led to clinical responses in some patients with non-small cell lung cancer (NSCLC), we investigated how IRs influenced CD8 TIL function from freshly digested early-stage NSCLC tissues using a killing assay and intracellular cytokine staining after T-cell restimulation. Early-stage lung cancer TIL function was heterogeneous with only about one third of patients showing decrements in cytokine production and lytic function.

Human tumor-associated monocytes/macrophages and their regulation of T cell responses in early-stage lung cancer.

Data from mouse tumor models suggest that tumor-associated monocyte/macrophage lineage cells (MMLCs) dampen antitumor immune responses. However, given the fundamental differences between mice and humans in tumor evolution, genetic heterogeneity, and immunity, the function of MMLCs might be different in human tumors, especially during early stages of disease. Here, we studied MMLCs in early-stage human lung tumors and found that they consist of a mixture of classical tissue monocytes and tumor-associated macrophages (TAMs).

A clinical trial of intraoperative near-infrared imaging to assess tumor extent and identify residual disease during anterior mediastinal tumor resection.

Background: The management of most solid tumors of the anterior mediastinum involves complete resection. Because of their location near mediastinal structures, wide resection is not possible; therefore, surgeons must use subjective visual and tactile cues to determine disease extent. This clinical trial explored intraoperative near-infrared (NIR) imaging as an approach to improving tumor delineation during mediastinal tumor resection.

A Clinical Trial of TumorGlow to Identify Residual Disease During Pleurectomy and Decortication.

Background: Macroscopic complete resection can improve survival in a select group of patients with malignant pleural mesothelioma. During resection, differentiating residual tumor from inflammation or scar can be challenging. This trial evaluated near-infrared (NIR) intraoperative imaging using TumorGlow (a novel NIR imaging approach utilizing high-dose indocyanine green and delayed imaging) technology to improve detection of macroscopic residual disease.

Localization of Pulmonary Ground-Glass Opacities with Folate Receptor-Targeted Intraoperative Molecular Imaging.

Purpose: Intraoperative localization and resection of ill-defined pulmonary ground-glass opacities (GGOs) during minimally invasive pulmonary resection is technically challenging. Current preoperative techniques to facilitate localization of GGOs include microcoil and hook wire placement, both of which have logistic limitations, carry safety concerns, and do not help with margin assessment. In this clinical trial, we explored an alternative method involving near-infrared molecular imaging with a folate receptor-targeted agent, OTL38, to improve localization of GGOs and confirmation of resection margins.