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.

The diagnosis of asbestosis in the 21 century: a clinicopathological correlation of 102 cases.

Asbestosis, defined as diffuse pulmonary fibrosis caused by inhalation of asbestos fibers, occurs after heavy exposures to asbestos dust over several decades. Because workplace exposures have been significantly curtailed since the banning of asbestos in insulation products, we were interested in examining the clinicopathological characteristics of cases diagnosed in the 21 century. The consultation files of one of the authors (VLR) were reviewed for cases of asbestosis diagnosed since 1/1/2001.

Diagnostic approach to prevascular (anterior) mediastinal lymphomas: when thoracic pathology meets hematopathology.

Lymphomas are among the most common malignant tumors occurring in the anterior/prevascular mediastinum. Their diagnoses can be challenging in small biopsies, the current most common method of sampling of an anterior mediastinal mass. Because the initial clinical and/or imaging impression may not be that of lymphoma, these specimens may first be evaluated by cytopathologists, surgical pathologists, and thoracic pathologists rather than hematopathologists.

Mesothelioma in the pleura, pericardium and peritoneum: Recommendations from the International Collaboration on Cancer Reporting (ICCR).

Aims: Mesothelioma is a rare malignancy of the serosal membranes that is commonly related to exposure to asbestos. Despite extensive research and clinical trials, prognosis to date remains poor. Consistent, comprehensive and reproducible pathology reporting form the basis of all future interventions for an individual patient, but also ensures that meaningful data are collected to identify predictive and prognostic markers.

The Interplay Between the Immune System, Tumor Suppressor Genes, and Immune Senescence in Mesothelioma Development and Response to Immunotherapy.

Despite efforts to ban asbestos mining and manufacturing, mesothelioma deaths in the United States have remained stable at approximately 2500 cases annually. This trend is not unique to the United States but is also a global phenomenon, associated with increased aging of populations worldwide. Although geoeconomic factors such as lack of regulations and continued asbestos manufacturing in resource-poor countries play a role, it is essential to consider biological factors such as immune senescence and increased genetic instability associated with aging.

Asbestos and Iron.

Theories of disease pathogenesis following asbestos exposure have focused on the participation of iron. After exposure, an open network of negatively charged functional groups on the fiber surface complexes host metals with a preference for iron. Competition for iron between the host and the asbestos results in a functional metal deficiency.

Alveolar Mitochondrial Quality Control During Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a leading cause of respiratory failure and death in patients in the intensive care unit. Experimentally, acute lung injury resolution depends on the repair of mitochondrial oxidant damage by the mitochondrial quality control (MQC) pathways, mitochondrial biogenesis, and mitophagy, but nothing is known about this in the human lung. In a case-control autopsy study, we compared the lungs of subjects dying of ARDS (n = 8; cases) and age-/gender-matched subjects dying of nonpulmonary causes (n = 7; controls).

Mechanisms and shapes of causal exposure-response functions for asbestos in mesotheliomas and lung cancers.

This paper summarizes recent insights into causal biological mechanisms underlying the carcinogenicity of asbestos. It addresses their implications for the shapes of exposure-response curves and considers recent epidemiologic trends in malignant mesotheliomas (MMs) and lung fiber burden studies. Since the commercial amphiboles crocidolite and amosite pose the highest risk of MMs and contain high levels of iron, endogenous and exogenous pathways of iron injury and repair are discussed.

Mucus increases cell iron uptake to impact the release of pro-inflammatory mediators after particle exposure.

We tested the hypothesis that (1) mucus production can be included in the cell response to iron deficiency; (2) mucus binds iron and increases cell metal uptake; and subsequently (3) mucus impacts the inflammatory response to particle exposure. Using quantitative PCR, RNA for both MUC5B and MUC5AC in normal human bronchial epithelial (NHBE) cells decreased following exposures to ferric ammonium citrate (FAC). Incubation of mucus-containing material collected from the apical surface of NHBE cells grown at air-liquid interface (NHBE-MUC) and a commercially available mucin from porcine stomach (PORC-MUC) with iron demonstrated an in vitro capacity to bind metal.

Cigarette Smoke Particle-Induced Lung Injury and Iron Homeostasis.

It is proposed that the mechanistic basis for non-neoplastic lung injury with cigarette smoking is a disruption of iron homeostasis in cells after exposure to cigarette smoke particle (CSP). Following the complexation and sequestration of intracellular iron by CSP, the host response (eg, inflammation, mucus production, and fibrosis) attempts to reverse a functional metal deficiency. Clinical manifestations of this response can present as respiratory bronchiolitis, desquamative interstitial pneumonitis, pulmonary Langerhans' cell histiocytosis, asthma, pulmonary hypertension, chronic bronchitis, and pulmonary fibrosis.

The 2021 WHO Classification of Tumors of the Pleura: Advances Since the 2015 Classification.

Substantial changes in the 2021 WHO Classification of Tumors of the Pleura and Pericardium since the 2015 WHO Classification include the following: (1) pleural and pericardial tumors have been combined in one chapter whereas in the 2015 WHO, pericardial tumors were classified with cardiac tumors; (2) well-differentiated papillary mesothelioma has been renamed well-differentiated papillary mesothelial tumor given growing evidence that these tumors exhibit relatively indolent behavior; (3) localized and diffuse mesothelioma no longer include the term "malignant" as a prefix; (4) mesothelioma in situ has been added to the 2021 classification because these lesions can now be recognized by loss of BAP1 and/or MTAP by immunohistochemistry and/or CDKN2A homozygous deletion by fluorescence in situ hybridization; (5) the three main histologic subtypes (i.e., epithelioid, biphasic, and sarcomatoid) remain the same but architectural patterns and cytologic and stromal features are more formally incorporated into the 2021 classification on the basis of their prognostic significance; (6) nuclear grading for epithelioid diffuse mesothelioma is introduced, and it is recommended to record this and other histologically prognostic features in pathology reports; (7) BAP1, EZH2, and MTAP immunohistochemistry have been found to be useful in separating benign mesothelial proliferations from mesothelioma; (8) biphasic mesothelioma can be diagnosed in small biopsies having both epithelioid and sarcomatoid components even if the amount of one component is less than 10%; and (9) the most frequently altered genes in diffuse pleural mesothelioma include BAP1, CDKN2A, NF2, TP53, SETD2, and SETDB1.

Diacetyl exposure disrupts iron homeostasis in animals and cells.

Objective: Several mechanisms have been proposed for the biological effect of diacetyl. We tested the postulate that animal and cell exposures to diacetyl are associated with a disruption in iron homeostasis.

Materials And Methods: Male, Sprague-Dawley rats were intratracheally-instilled with either distilled water or diacetyl.

Heparin-based blood purification attenuates organ injury in baboons with pneumonia.

Bacterial pneumonia is a major cause of morbidity and mortality worldwide despite the use of antibiotics, and novel therapies are urgently needed. Building on previous work, we aimed to ) develop a baboon model of severe pneumococcal pneumonia and sepsis with organ dysfunction and ) test the safety and efficacy of a novel extracorporeal blood filter to remove proinflammatory molecules and improve organ function. After a dose-finding pilot study, 12 animals were inoculated with [5 × 10 colony-forming units (CFU)], given ceftriaxone at 24 h after inoculation, and randomized to extracorporeal blood purification using a filter coated with surface-immobilized heparin sulfate ( = 6) or sham treatment ( = 6) for 4 h at 30 h after inoculation.

Case Report: Flavoring-Related Lung Disease in a Coffee Roasting and Packaging Facility Worker With Unique Lung Histopathology Compared With Previously Described Cases of Obliterative Bronchiolitis.

Occupational exposure to diacetyl, a butter flavor chemical, can result in obliterative bronchiolitis. Obliterative bronchiolitis is characterized by exertional dyspnea, fixed airflow obstruction, and histopathologic constrictive bronchiolitis, with bronchiolar wall fibrosis leading to luminal narrowing and obliteration. We describe a case of advanced lung disease with histopathology distinct from obliterative bronchiolitis in a 37-year-old male coffee worker following prolonged exposure to high levels of diacetyl and the related compound 2,3-pentanedione, who had no other medical, avocational, or occupational history that could account for his illness.

Perls' Prussian Blue Stains of Lung Tissue, Bronchoalveolar Lavage, and Sputum.

Perls' Prussian blue (PPB) stain recognizes Fe3+ associated with hemosiderin. The employment of this stain in clinical medicine and research has been extensive and novel applications continue to evolve. Ferruginous bodies are intracellular structures in lung tissue, bronchoalveolar lavage (BAL), and sputum that stain with PPB.

Malignant Peritoneal Mesothelioma Arising in Young Adults With Long-standing Indwelling Intra-abdominal Shunt Catheters.

Only 50% to 70% of patients with mesothelioma report asbestos exposure. Other exposures (eg, radiation) play a role in some cases, but some patients have no obvious cause. We describe a series of patients with long-standing indwelling intra-abdominal shunt catheters who developed malignant peritoneal mesothelioma, suggesting a novel association.

Talc and mesothelioma: mineral fiber analysis of 65 cases with clinicopathological correlation.

Malignant mesothelioma is strongly associated with prior asbestos exposure. Recently there has been interest in the role of talc exposure in the pathogenesis of mesothelioma. We have analyzed lung tissue samples from a large series of malignant mesothelioma patients.

Comprehensive Molecular and Pathologic Evaluation of Transitional Mesothelioma Assisted by Deep Learning Approach: A Multi-Institutional Study of the International Mesothelioma Panel from the MESOPATH Reference Center.

Introduction: Histologic subtypes of malignant pleural mesothelioma are a major prognostic indicator and decision denominator for all therapeutic strategies. In an ambiguous case, a rare transitional mesothelioma (TM) pattern may be diagnosed by pathologists either as epithelioid mesothelioma (EM), biphasic mesothelioma (BM), or sarcomatoid mesothelioma (SM). This study aimed to better characterize the TM subtype from a histological, immunohistochemical, and molecular standpoint.

Malignant Diffuse Mesothelioma in Women: A Study of 354 Cases.

We reviewed 354 cases of malignant diffuse mesothelioma (MM) in women from a database of 2858 histologically confirmed MM cases. There was a pleural predominance with 78% pleural MM and 22% peritoneal MM. The pleural tumors consisted of 72% epithelioid, 19% biphasic, and 9% sarcomatoid variant.

Silica Exposure Differentially Modulates Autoimmunity in Lupus Strains and Autoantibody Transgenic Mice.

Inhalational exposure to crystalline silica is linked to several debilitating systemic autoimmune diseases characterized by a prominent humoral immune component, but the mechanisms by which silica induces autoantibodies is poorly understood. To better understand how silica lung exposure breaks B cell tolerance and unleashes autoreactive B cells, we exposed both wildtype mice of healthy C57BL/6 and lupus-prone BXSB, MRL, and NZB strains and mice carrying an autoantibody transgene on each of these backgrounds to instilled silica or vehicle and monitored lung injury, autoimmunity, and B cell fate. Silica exposure induced lung damage and pulmonary lymphoid aggregates in all strains, including in genetically diverse backgrounds and in autoantibody transgenic models.