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British Journal of Cancer Jan 2020Malignant pleural mesothelioma (MPM) is a rare malignancy of mesothelial cells with increasing incidence, and in many cases, dismal prognosis due to its aggressiveness... (Review)
Review
Malignant pleural mesothelioma (MPM) is a rare malignancy of mesothelial cells with increasing incidence, and in many cases, dismal prognosis due to its aggressiveness and lack of effective therapies. Environmental and occupational exposure to asbestos is considered the main aetiological factor for MPM. Inhaled asbestos fibres accumulate in the lungs and induce the generation of reactive oxygen species (ROS) due to the presence of iron associated with the fibrous silicates and to the activation of macrophages and inflammation. Chronic inflammation and a ROS-enriched microenvironment can foster the malignant transformation of mesothelial cells. In addition, MPM cells have a highly glycolytic metabolic profile and are positive in F-FDG PET analysis. Loss-of-function mutations of BRCA-associated protein 1 (BAP1) are a major contributor to the metabolic rewiring of MPM cells. A subset of MPM tumours show loss of the methyladenosine phosphorylase (MTAP) locus, resulting in profound alterations in polyamine metabolism, ATP and methionine salvage pathways, as well as changes in epigenetic control of gene expression. This review provides an overview of the perturbations in metabolism and ROS homoeostasis of MPM cells and the role of these alterations in malignant transformation and tumour progression.
Topics: Animals; Antineoplastic Agents; Asbestos; Cell Transformation, Neoplastic; Cisplatin; Humans; Loss of Function Mutation; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Oxidation-Reduction; Pleural Neoplasms; Reactive Oxygen Species; Transforming Growth Factor beta; Transforming Growth Factor beta1; Tumor Suppressor Proteins; Ubiquitin Thiolesterase
PubMed: 31819191
DOI: 10.1038/s41416-019-0661-9 -
Journal of Veterinary Diagnostic... Jan 2021Herein we describe a rare case of systemic infection with concurrent pleural mesothelioma in a stray cat that was found dead and submitted for autopsy. Gross pathology...
Herein we describe a rare case of systemic infection with concurrent pleural mesothelioma in a stray cat that was found dead and submitted for autopsy. Gross pathology changes consisted of thoracic clear yellow fluid admixed with suspended fibrin strands; clear-to-tan, variably sized, <3 mm diameter pulmonary nodules; and enlargement of the submandibular, retropharyngeal, and prescapular lymph nodes. Histologic changes consisted of extensive areas of suppurative inflammation and necrosis with mineralization that partially effaced the pulmonary parenchyma and lymph nodes. Random, distinct necrotic foci were present throughout the hepatic parenchyma. Extending from the pleura, within perinecrotic alveolar spaces, and infiltrating the submandibular, retropharyngeal, and prescapular lymph nodes were dense sheets of neoplastic epithelioid cells with moderate pleomorphism and occasional karyomegaly and multinucleation. Neoplastic cells exhibited immunolabeling for pancytokeratin AE1/AE3 and vimentin, consistent with pleural mesothelioma. Aerobic bacterial culture of lung yielded heavy growth of . Immunohistochemistry (IHC) for revealed clusters of bacteria in the lung, lymph node, and liver. Pathologic changes were consistent with systemic listeriosis, confirmed by bacterial culture and IHC, and concurrent pleural mesothelioma.
Topics: Animals; Cat Diseases; Cats; Diagnosis, Differential; Female; Listeria monocytogenes; Listeriosis; Mesothelioma; Pleural Neoplasms
PubMed: 33054600
DOI: 10.1177/1040638720966321 -
Respirology (Carlton, Vic.) Feb 2021Probe based confocal laser endomicroscopy (pCLE) is an optical imaging technique allowing live tissue imaging at a cellular level. Currently, this tool remains...
BACKGROUND AND OBJECTIVE
Probe based confocal laser endomicroscopy (pCLE) is an optical imaging technique allowing live tissue imaging at a cellular level. Currently, this tool remains experimental. Two studies regarding pleural disease have been published and suggest that pCLE could be valuable for pleural disease investigations. However, normal and malignant pleural pCLE features remain unknown. Therefore, we conducted a prospective trial of pCLE during medical thoracoscopy to study and describe the malignant and benign pleural pCLE features.
METHODS
Every patient >18 years referred to our department for medical thoracoscopy was eligible. Medical thoracoscopy was performed under sedation, allowing spontaneous breathing. Five millilitres of fluorescein (10%) was intravenously administrated 5 min before image acquisition. The pCLE was introduced through the working channel of the thoracoscope and gently placed on the parietal pleura to record videos. Afterwards, biopsies were performed on the corresponding sites. Malignant and benign pleural pCLE features were precisely described and compared using 11 preselected criteria.
RESULTS
A total of 62 patients were included in the analysis including 36 benign and 26 malignant pleura. Among our preselected criteria, 'abnormal tissue architecture' and 'dysplastic vessels' were strongly associated with malignancies (100% and 85% ss, 721% and 74% sp, respectively) whereas, the 'full chia seeds sign' and 'cell shape homogeneity' were associated with benignity (36% and 56% ss, 100% and 70% sp, respectively). No study-related adverse events occurred.
CONCLUSION
Benign and malignant pleural involvement have clearly distinct pCLE features.
Topics: Feasibility Studies; Female; Humans; Male; Microscopy, Confocal; Middle Aged; Pleural Neoplasms; Prospective Studies
PubMed: 33001538
DOI: 10.1111/resp.13945 -
Interactive Cardiovascular and Thoracic... Oct 2022Although the diagnosis of malignant pleural mesothelioma at an in situ stage was traditionally challenging, it is now possible owing to advances in molecular biological...
Although the diagnosis of malignant pleural mesothelioma at an in situ stage was traditionally challenging, it is now possible owing to advances in molecular biological methods such as P16 fluorescence in situ hybridization or BRCA1-associated protein 1 immunohistochemistry. Here, we report the first case, to our knowledge, of total parietal pleurectomy for mesothelioma in situ. Future follow-up and accumulation of cases are necessary to determine whether total parietal pleurectomy could be applied as a treatment for mesothelioma in situ or not.
Topics: Humans; Mesothelioma, Malignant; Pleural Neoplasms; In Situ Hybridization, Fluorescence; Lung Neoplasms; Mesothelioma
PubMed: 36205712
DOI: 10.1093/icvts/ivac255 -
BMC Pulmonary Medicine Apr 2022As promising novel treatments develop for malignant pleural mesothelioma (MPM), early prognostication has become increasingly important. Circulating and local... (Observational Study)
Observational Study
BACKGROUND
As promising novel treatments develop for malignant pleural mesothelioma (MPM), early prognostication has become increasingly important. Circulating and local inflammatory cells are known to play a significant role in other tumour types. We assessed the proportion of lymphocyte populations within blood, pleural fluid and tumour stroma to prognosticate patients with MPM at diagnosis.
METHODS
Consecutive patients diagnosed with biopsy-proven MPM were prospectively recruited to an observational cohort study and followed up for a minimum of 7.5 years. Blood and pleural fluid results at presentation were extracted from the medical records. Biopsy specimens were independently reviewed by 2 pathologists who scored the degree of lymphocytic and neutrophilic infiltration.
RESULTS
Baseline results were available for 184 patients. The predominant pleural fluid cell type was calculable for 84 patients and 118 patients had biopsy specimens available for review. A low blood neutrophil/lymphocyte ratio (NLR < 4) inferred a better prognosis with a median survival of 420 days versus 301 days (p < 0.01). Survival was better for patients with a lymphocyte-predominant pleural effusion (430 vs 306 days, p < 0.01). Lymphocyte infiltration of tumour stroma was also associated with improved survival (n = 92, survival 430 days) compared with neutrophilic or acellular samples (n = 26, survival 342 days p < 0.01). In multivariable modelling lymphocyte predominance in blood, pleural fluid and tumour stroma were all associated with a better prognosis.
CONCLUSIONS
Lymphocyte predominance within tumour stroma, pleural fluid or blood infers a better prognosis in patients with MPM.
Topics: Humans; Lymphocytes; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Prognosis
PubMed: 35501755
DOI: 10.1186/s12890-022-01968-2 -
Polish Journal of Pathology : Official... 2023Mesothelioma is a locally aggressive malignant tumor that arises on the mesothelial surfaces of the pleura, peritoneum and tunica vaginalis. There are three histologic...
Mesothelioma is a locally aggressive malignant tumor that arises on the mesothelial surfaces of the pleura, peritoneum and tunica vaginalis. There are three histologic subtypes of mesothelioma: epithelioid, biphasic, and sarcomatoid. Pleural mesothelioma is usually characterized by diffuse pleural thickening. Disease progression is characterized by local invasion of the chest wall and lung. Lymphatic metastasis is rare and hematogenous metastasis is much rarer. The purpose of these case reports is to emphasize that pleural mesothelioma metastases can occur in unexpected places and to contribute to the literature.
Topics: Humans; Scalp; Mesothelioma, Malignant; Mesothelioma; Pleural Neoplasms; Lung; Lung Neoplasms; Biomarkers, Tumor
PubMed: 38477094
DOI: 10.5114/pjp.2023.134322 -
Respiratory Research Apr 2017Malignant pleural mesothelioma (MPM) is a rare and highly drug resistant tumor arising from the mesothelial surfaces of the lung pleura. The standard method to confirm... (Review)
Review
Malignant pleural mesothelioma (MPM) is a rare and highly drug resistant tumor arising from the mesothelial surfaces of the lung pleura. The standard method to confirm MPM is the tedious, time-consuming cytological examination of cancer biopsy. Biomarkers that are detectable in pleural effusion or patient serum are reasonable options to provide a faster and noninvasive diagnostic approach. As yet, the current biomarkers for MPM lack specificity and sensitivity to discriminate this neoplasm from other lung tumors. CD44, a multifunctional surface receptor has been implicated in tumor progression in different cancers including MPM. The interaction of CD44 with its ligand, hyaluronan (HA) has demonstrated an important role in modulating cell proliferation and invasiveness in MPM. In particular, the high expression levels of these molecules have shown diagnostic relevance in MPM. This review will summarize the biology and diagnostic implication of CD44 and HA as well as the interaction of both molecules in MPM that will demonstrate their potential as biomarkers. Augmentation of the current markers in MPM may lead to an earlier diagnosis and management of this disease.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Evidence-Based Medicine; Female; Humans; Hyaluronan Receptors; Hyaluronic Acid; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Middle Aged; Pleural Neoplasms; Prevalence; Reproducibility of Results; Sensitivity and Specificity
PubMed: 28403901
DOI: 10.1186/s12931-017-0546-5 -
British Journal of Cancer Mar 2017Radiological markers of treatment response and prognostication in malignant pleural mesothelioma have limitations due to the morphology of the disease. Serum or pleural... (Review)
Review
BACKGROUND
Radiological markers of treatment response and prognostication in malignant pleural mesothelioma have limitations due to the morphology of the disease. Serum or pleural fluid biomarkers that could act as an adjunct to radiological assessment would be of significant value. The aim of this review was to collate and summarise the literature relating to this topic.
METHODS
A systematic review was performed on the databases Pubmed and EMBASE to identify relevant studies. Two independent researchers read the abstracts and used the Quality in Prognostic Studies tool to assess the quality of the evidence.
RESULTS
Forty-five studies were identified from the current literature. Twenty studies investigated the role of serum soluble mesothelin with majority suggesting that it has variable utility as a baseline test but when measured serially correlates with treatment response and prognosis. Several studies demonstrated that serum osteopontin correlated with survival at baseline. Other biomarkers have shown prognostic utility in individual studies but are yet to be reproduced in large cohort studies.
CONCLUSIONS
From the available literature no serum or pleural fluid biomarker was identified that could be recommended currently for routine clinical practice. However, a falling serum soluble mesothelin might correlate with treatment response and improved survival.
Topics: Biomarkers, Tumor; Humans; Mesothelioma; Pleural Neoplasms; Prognosis
PubMed: 28170372
DOI: 10.1038/bjc.2017.22 -
Molecular Cancer Jul 2023Malignant Pleural Mesothelioma (MPM) is a dreadful disease escaping the classical genetic model of cancer evolution and characterized by wide heterogeneity and...
BACKGROUND
Malignant Pleural Mesothelioma (MPM) is a dreadful disease escaping the classical genetic model of cancer evolution and characterized by wide heterogeneity and transcriptional plasticity. Clinical evolution of MPM is marked by a progressive transdifferentiation that converts well differentiated epithelioid (E) cells into undifferentiated and pleomorphic sarcomatoid (S) phenotypes. Catching the way this transition takes place is necessary to understand how MPM develops and progresses and it is mandatory to improve patients' management and life expectancy. Bulk transcriptomic approaches, while providing a significant overview, failed to resolve the timing of this evolution and to identify the hierarchy of molecular events through which this transition takes place.
METHODS
We applied a spatially resolved, high-dimensional transcriptomic approach to study MPM morphological evolution. 139 regions across 8 biphasic MPMs (B-MPMs) were profiled using the GeoMx™Digital Spatial Profiler to reconstruct the positional context of transcriptional activities and the spatial topology of MPM cells interactions. Validation was conducted on an independent large cohort of 84 MPMs by targeted digital barcoding analysis.
RESULTS
Our results demonstrated the existence of a complex circular ecosystem in which, within a strong asbestos-driven inflammatory environment, MPM and immune cells affect each other to support S-transdifferentiation. We also showed that TGFB1 polarized M2-Tumor Associated Macrophages foster immune evasion and that TGFB1 expression correlates with reduced survival probability.
CONCLUSIONS
Besides providing crucial insights into the multidimensional interactions governing MPM clinical evolution, these results open new perspectives to improve the use of immunotherapy in this disease.
Topics: Humans; Mesothelioma, Malignant; Mesothelioma; Transcriptome; Ecosystem; Pleural Neoplasms; Lung Neoplasms; Prognosis; Biomarkers, Tumor; Immunotherapy
PubMed: 37460925
DOI: 10.1186/s12943-023-01816-9 -
Current Problems in Cancer Dec 2023Pleural mesothelioma (PM) is a cancer of the pleural surface, which is aggressive and may be rapidly fatal. PM is a rare cancer worldwide, but is a relatively common... (Review)
Review
Pleural mesothelioma (PM) is a cancer of the pleural surface, which is aggressive and may be rapidly fatal. PM is a rare cancer worldwide, but is a relatively common disease in Turkey. Asbestos exposure is the main risk factor and the most common underlying cause of the disease. There have been significant improvements in diagnoses and treatments of many malignancies; however, there are still therapeutic challenges in PM. In this review, we aimed to increase the awareness of health care professionals, oncologists, and pulmonologists by underlining the unmet needs of patients with PM and by emphasizing the need for a multidisciplinary treatment and management of PM. After reviewing the general information about PM, we further discuss the treatment options for patients with PM using immunotherapy and offer evidence for improvements in the clinical outcomes of these patients because of these newer treatment modalities.
Topics: Humans; Immunotherapy; Mesothelioma; Pleura; Pleural Neoplasms; Turkey
PubMed: 37845104
DOI: 10.1016/j.currproblcancer.2023.101017