Size-dependent retention of elongate mineral particles in human lungs: modeling and implications for risk assessment

IntroductionLung deposition of elongate amphibole particles is an important process impacting the risk of cancer. There is, however, a significant gap in scientific literature characterizing the role of particle size in the differences observed for deposition and clearance rate in the human respiratory system. The purpose of the paper is to explore the relationship between size distribution of elongate mineral particles in human lungs compared to corresponding distribution in the airborne exposure.Materials and methodsPreviously published information about lung deposition for amosite and crocidolite particles in various dimensional groups, collected by the team of Pooley and Clark was reanalyzed with application of recently developed methodologies for fiber size analysis. The new metric—deposition selection ratio (DSR) is proposed; it is found by dividing the size fraction of particles in lungs to the corresponding fraction in exposure. The DSR estimations were also compared to theoretical estimations of pulmonary deposition rates of particles based on the United States Environmental Protection Agency (US EPA) Multi-Path Particle Dosimetry (MPPD) model.ResultsIt was demonstrated that DSR values can be approximated by using log–log regressions with length and width of particles as independent variables. For non-asbestiform particles (cleavage fragments), the prediction of DSR from parametric and non-parametric models is demonstrated to be less than 1 (evidence of deselection in lungs). Negative correlation was found for DSR estimations and the theoretical predictions of pulmonary deposition rates by MPPD.DiscussionThe observed data for size-specific lung deposition of elongate mineral particles can be used for quantitative estimates of risk and analysis of toxicokinetic processes in human lungs. The difference between theoretical model and observed fiber deposition pattern requires further adjustments in the methods to predict lung deposition of elongate particles

Some sage advice: A case report of sage burning causing interstitial lung disease

Cigarette smoking remains the commonest cause of chronic obstructive pulmonary disease (COPD) and respiratory bronchiolitis-associated interstitial lung disease (RB-ILD). Biomass combustion remains a high risk for causing respiratory disease. We present a case of a 41-year-old woman and never-smoker with worsening breathlessness. It was identified that she made fire pits burning sage and oils for spiritual work, but beyond this had no respiratory risk factors. Radiological evidence of RB-ILD was identified and a bronchoscopic lavage demonstrated the presence of striking green pigmented macrophages, presumed to be chlorophyll uptake. Cessation of burning sage exposure has resulted in a positive outcome. This case highlights the need for an extensive occupational or exposure history in respiratory medicine and describes histological features of interstitial lung disease not previously identified. [Abstract copyright: Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Defining control reference ranges in biologic samples in analytical laboratories

Mineral analytic laboratories define control reference ranges to interpret the significance of an individual’s prior exposures. Control reference ranges are internally compiled and defined for two scenarios: background controls—only subjects with ambient asbestos exposure and no increased risk of asbestos related disease, and asbestosis range controls, utilized for the diagnosis of asbestos-related lung fibrosis/asbestosis and for asbestos-related lung cancer causation. The objective of this study was to evaluate how different analytic laboratories have established their internal control reference ranges and to comment on their significance. The study comprised a review of the scientific literature generated from a Pubmed search of mineral analytic data from lung tissue in laboratories determining background exposures to asbestos and other elongate minerals. Twenty-six publications were found from 17 laboratories across Europe, North America, and Asia which had internally defined background control populations. The studies showed marked heterogeneity having been conducted over decades, using different criteria, different microscopic methodologies, and assessment of different fiber dimension. The most common criterion to define background control subjects was to establish individuals with no known occupational history of asbestos exposure and/or no evidence of asbestos-related diseases. In background controls with no disease, chrysotile was reported most frequently. Chrysotile and amphiboles were variably detected in lung tissue from control subjects in virtually all studies. Interlaboratory variations exist so individual results obtained in one laboratory do not transfer significance to another laboratory. The use of negative control groups in case–control studies is discussed alongside their relevance in ensuring the validity of results related to asbestos exposure and its diseases

The use of immunohistochemistry to distinguish reactive mesothelial cells from malignant mesothelioma in cytologic effusions

BACKGROUND: The distinction of benign from malignant mesothelial proliferations in cytologic specimens can be problematic. In this study, the authors investigated the utility of immunohistochemical (IHC) markers in making this distinction. METHODS: Archival paraffin-embedded cell blocks of pleural and peritoneal fluids from 52 patients with malignant meothelioma (MM) and 64 patients with reactive mesothelial hyperplasia (MH) were retrieved. IHC stains included desmin, epithelial membrane antigen (EMA), glucose-transport protein 1 (GLUT-1), Ki67, and p53. RESULTS: Desmin was positive in 84% (54 of 64) cases of reactive MH and in 6% (3 of 52) of MM cases ( P 40% of mesothelial cells in 9% (6 of 64) of benign and 16% (8 of 49) of malignant cases ( P = .38). p53 showed strong nuclear positivity in 2% (1 of 46) of benign and 47% (7 of 15) of malignant cases ( P < .001). EMA positivity and desmin negativity were found in 2% (1 of 64) of reactive MH cases and 98% (49 of 52) of MM cases ( P < .001). EMA negativity and desmin positivity were found in 86% (55 of 64) of reactive MH cases and 0% of MM cases. CONCLUSIONS: The combination of positive EMA and negative desmin strongly favors MM; conversely, a combination of negative EMA and positive desmin favors a reactive process. Likewise, strong membranous positivity for GLUT-1 and/or strong nuclear staining for p53 favors a mesothelioma. Ki67 proliferative index showed no significant difference between reactive MH and MM cases. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71361/1/20071_ftp.pd

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Macrophage plasticity and function in the lung tumour microenvironment revealed in 3D heterotypic spheroid and explant models

In non-small cell lung cancer (NSCLC), stroma-resident and tumour-infiltrating macrophages may facilitate an immunosuppressive tumour microenvironment (TME) and hamper immunotherapeutic responses. Analysis of tumour-associated macrophage (TAM) plasticity in NSCLC is largely lacking. We established a novel, multi-marker, dual analysis approach for assessing monocyte-derived macrophage (Mφ polarisation and M1/M2 phenotypic plasticity. We developed a flow cytometry-based, two-marker analysis (CD64 and CD206) of CD14+ cells. The phenotype and immune function of in vitro-induced TAMs was studied in a heterotypic spheroid and tumour-derived explant model of NSCLC. Heterotypic spheroids and NSCLC explants skewed Mφs from an M1- (CD206loCD64hi) to M2-like (CD206hiCD64lo) phenotype. Lipopolysaccharide (LPS) and IFNγ treatment reversed M2-like Mφ polarisation, indicating the plasticity of Mφs. Importantly, antigen-specific CD8+ T cell responses were reduced in the presence of tumour explant-conditioned Mφs, but not spheroid-conditioned Mφs, suggesting explants are likely a more relevant model of the immune TME than cell line-derived spheroids. Our data indicates the importance of multi-marker, functional analyses within Mφ subsets and the advantages of the ex vivo NSCLC explant model in immunomodulation studies. We highlight the plasticity of the M1/M2 phenotype using the explant model and provide a tool for studying therapeutic interventions designed to reprogram M2-like Mφ-induced immunosuppression

Ectopic primary type A thymoma located in two thoracic vertebras: a case report

<p>Abstract</p> <p>Background</p> <p>The thymus arises in the ventral portion of the third and fourth pharyngeal pouch. It descends into the anterior mediastinum at 6^thweek of gestation. Any errors occurring during this process can cause dissemination of aberrant nodules that are responsible for most atypical thymomas.</p> <p>Case Presentation</p> <p>The authors report a unusual case of type-A thymoma located in D10 and D11 vertebral bodies.</p> <p>The histology showed a uniform growth of short, spindle shaped, mitotically inactive cells. A few small, normal lymphocytes were seen scattered or in small groups. The immunohistochemical investigation for neuroectodermal, neuroendocrine, vascular and muscular markers were negative. It also confirmed the presence of CD3+, CD5+ T lymphocytes and the absence of immature T-lymphocyte markers.</p> <p>Conclusions</p> <p>The case described shows a thymic hystogenesis for spindle cell tumours. To our knowledge no other cases of vertebral thymomas have been described in international literature.</p

Primary pericardial malignant mesothelioma and response to radiation therapy

We report a case of a primary pericardial malignant mesothelioma. A 59-year-old male presented with episodic chest pain and dyspnea on exertion. Cardiac magnetic resonance imaging revealed a large mass in the pericardium attached to the right ventricle. Partial resection of the mass was undertaken revealing malignant mesothelioma, byphasic type. The patient was treated with chemotherapy intermittently over a period of 3 years, but his disease continued to progress. The patient was then treated with definitive radiation therapy to 64 Gy to the primary tumor using a six field 3D conformal technique. The patient remains free of progressive disease 86 months from the time of diagnosis and 50 months from the completion of his radiotherapy