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Modern Pathology : An Official Journal... Jan 2022Mesothelial tumors are classified into benign or preinvasive tumors, and mesotheliomas. The benign or preinvasive group includes adenomatoid tumors, well-differentiated... (Review)
Review
Mesothelial tumors are classified into benign or preinvasive tumors, and mesotheliomas. The benign or preinvasive group includes adenomatoid tumors, well-differentiated papillary mesothelial tumors, and mesothelioma in situ. Malignant tumors are mesotheliomas and can be localized or diffuse. Histological classification of invasive mesotheliomas into three major subtypes-epithelioid, sarcomatoid, and biphasic is prognostically important. It also plays a significant role in the treatment decisions of patients diagnosed with this deadly disease. Grading and subtyping of epithelioid mesotheliomas have been one of the major changes in the recent WHO classification of pleural tumors. Mesothelioma in situ has emerged as a precisely defined clinico-pathologic entity that for diagnosis requires demonstration of loss of BAP1 or MTAP by immunohistochemistry, or CDKN2A homozygous deletion by FISH. The use of these two biomarkers improves the diagnostic sensitivity of effusion specimens and limited tissue samples and is valuable in establishing the diagnosis of epithelioid mesothelioma. In this review, recent changes in the histologic classification of pleural mesothelioma, importance of ancillary diagnostic studies, and molecular characteristics of mesotheliomas are discussed.
Topics: Biomarkers, Tumor; Diagnosis, Differential; Genes, p16; Humans; Mesothelioma, Malignant; Pleura; Pleural Neoplasms; Prognosis; Tumor Suppressor Proteins; Ubiquitin Thiolesterase
PubMed: 34465883
DOI: 10.1038/s41379-021-00895-7 -
Jornal Brasileiro de Pneumologia :... 2021Malignant mesotheliomas are rare types of cancers that affect the mesothelial surfaces, usually the pleura and peritoneum. They are associated with asbestos exposure,... (Review)
Review
Malignant mesotheliomas are rare types of cancers that affect the mesothelial surfaces, usually the pleura and peritoneum. They are associated with asbestos exposure, but due to a latency period of more than 30 years and difficult diagnosis, most cases are not detected until they reach advanced stages. Treatment options for this tumor type are very limited and survival ranges from 12 to 36 months. This review discusses the molecular physiopathology, current diagnosis, and latest therapeutic options for this disease.
Topics: Asbestos; Humans; Mesothelioma; Mesothelioma, Malignant; Pleura; Pleural Neoplasms
PubMed: 34909922
DOI: 10.36416/1806-3756/e20210129 -
Journal of Thoracic Oncology : Official... May 2022Substantial changes in the 2021 WHO Classification of Tumors of the Pleura and Pericardium since the 2015 WHO Classification include the following: (1) pleural and... (Review)
Review
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.
Topics: Biomarkers, Tumor; Homozygote; Humans; In Situ Hybridization, Fluorescence; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleura; Pleural Neoplasms; Sequence Deletion; Tumor Suppressor Proteins; Ubiquitin Thiolesterase; World Health Organization
PubMed: 35026477
DOI: 10.1016/j.jtho.2021.12.014 -
The European Respiratory Journal Jun 2020The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for...
The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009-2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including and () for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pre-therapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.
Topics: Humans; Medical Oncology; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Surgeons
PubMed: 32451346
DOI: 10.1183/13993003.00953-2019 -
Redox Biology Sep 2019Hypoxia and acidity provide microenvironment for selection under evolutionary pressure and proliferation in cancer cells. Carbonic anhydrases (CAs) are a superfamily of...
Hypoxia and acidity provide microenvironment for selection under evolutionary pressure and proliferation in cancer cells. Carbonic anhydrases (CAs) are a superfamily of metalloenzymes present in all life kingdoms, equilibrating the reactions among CO, bicarbonate and H. CA9, a membrane-associated α-CA, has been a drug target for various cancers. Whereas iron is essential not only for cancer cells but also for all the lives on earth, little is known on the association among hypoxia, iron metabolism, extracellular acidity and redox regulation. Malignant mesothelioma (MM), an aggressive tumor with poor prognosis, is an intriguing model in that asbestos-associated pathogenesis includes excess iron environment during carcinogenesis. Re-analysis of rat asbestos-induced MM model revealed an inverse association between high CA9 expression and survival. Here we used human MMs to identify the molecular events surrounding CA9 from the viewpoint of iron metabolism. CA9 expression was significantly higher in MM cells than in MeT-5A mesothelial cells, which was further amplified under hypoxia (1%O) with increased catalytic Fe(II). CA9 suppression by inhibitors (S4 and U104) decreased viability and migration of MM cells, accompanied by overexpression of TFRC, IREB1/2 and FPN1(SLC40A1) and by downregulation of FTH/FTL. This expressional pattern was similar to that of erastin-induced ferroptosis in the same cells. Furthermore, we observed mitochondrial fission and enhanced autophagy with increased catalytic Fe(II) in both mitochondria and lysosomes after CA9 inhibition, accompanied by increased peroxides, mitochondrial O and lipid peroxidation. The eventual cell death was significantly inhibited by deferoxamine, ferrostatin-1 and Z-VAD-FMK, suggesting a mixed cell death of ferroptosis and apoptosis. Therefore, CA9 plays a role in equilibrating among hypoxia, iron metabolism and redox regulation in MM cells.
Topics: Antigens, Neoplasm; Apoptosis; Biomarkers; Carbonic Anhydrase IX; Cell Line, Tumor; Ferroptosis; Humans; Hypoxia; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Mitochondria; Models, Biological; Reactive Oxygen Species
PubMed: 31442913
DOI: 10.1016/j.redox.2019.101297 -
Journal of Thoracic Oncology : Official... Jun 2020
Topics: Humans; Lung Neoplasms; Mesothelioma; Pleural Neoplasms
PubMed: 32471572
DOI: 10.1016/j.jtho.2020.03.031 -
Nature Genetics Apr 2023Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing...
Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile. We show that these four dimensions are complementary, capture major interpatient molecular differences and are delimited by extreme phenotypes that-in the case of the interdependent tumor cell morphology and adapted immune response-reflect tumor specialization. These findings unearth the interplay between MPM functional biology and its genomic history, and provide insights into the variations observed in the clinical behavior of patients with MPM.
Topics: Humans; Mesothelioma, Malignant; Mesothelioma; Multiomics; Pleural Neoplasms; Lung Neoplasms; Biomarkers, Tumor
PubMed: 36928603
DOI: 10.1038/s41588-023-01321-1 -
International Journal of Environmental... Aug 2021Sailors have long been known to experience high rates of injury, disease, and premature death. Many studies have shown asbestos-related diseases among shipyard workers,... (Review)
Review
Sailors have long been known to experience high rates of injury, disease, and premature death. Many studies have shown asbestos-related diseases among shipyard workers, but few have examined the epidemiology of asbestos-related disease and death among asbestos-exposed sailors serving on ships at sea. Chrysotile and amphibole asbestos were used extensively in ship construction for insulation, joiner bulkhead systems, pipe coverings, boilers, machinery parts, bulkhead panels, and many other uses, and asbestos-containing ships are still in service. Sailors are at high risk of exposure to shipboard asbestos, because unlike shipyard workers and other occupationally exposed groups, sailors both work and live at their worksite, making asbestos standards and permissible exposure limits (PELs). based on an 8-h workday inadequate to protect their health elevated risks of mesothelioma and other asbestos-related cancers have been observed among sailors through epidemiologic studies. We review these studies here.
Topics: Asbestos; Asbestos, Serpentine; Humans; Mesothelioma; Military Personnel; Ships
PubMed: 34444165
DOI: 10.3390/ijerph18168417 -
Archives of Pathology & Laboratory... May 2024Molecular testing has increasingly been utilized in the evaluation of mesothelioma. Diffuse mesothelioma comprises multiple distinct genetic subgroups. While most... (Review)
Review
CONTEXT.—
Molecular testing has increasingly been utilized in the evaluation of mesothelioma. Diffuse mesothelioma comprises multiple distinct genetic subgroups. While most diffuse mesotheliomas lack oncogenic kinase mutations and instead harbor alterations involving tumor suppressors and chromatin regulators, a minor subset of tumors is characterized by uncommon alterations such as germline mutations, genomic near-haploidization, ALK rearrangement, ATF1 rearrangement, or EWSR1::YY1 fusion.
OBJECTIVE.—
To provide updates on the salient molecular features of diffuse mesothelioma, mesothelioma in situ, and other mesothelial lesions: well-differentiated papillary mesothelial tumor, adenomatoid tumor, peritoneal inclusion cyst, and others. We consider the diagnostic, prognostic, and predictive utility of molecular testing in mesothelial lesions.
DATA SOURCES.—
We performed a literature review of recently described genetic features, molecular approaches, and immunohistochemical tools, including BAP1, MTAP, and merlin in mesothelioma and other mesothelial lesions.
CONCLUSIONS.—
Our evolving understanding of the molecular diversity of diffuse mesothelioma and other mesothelial lesions has led to considerable changes in pathology diagnostic practice, including the application of immunohistochemical markers such as BAP1, MTAP, and merlin (NF2), which are surrogates of mutation status. In young patients and/or those without significant asbestos exposure, unusual mesothelioma genetics such as germline mutations, ALK rearrangement, and ATF1 rearrangement should be considered.
Topics: Humans; Mesothelioma; Immunohistochemistry; Biomarkers, Tumor; Neoplasms, Mesothelial; Mesothelioma, Malignant; Mutation; Tumor Suppressor Proteins; Ubiquitin Thiolesterase
PubMed: 38190277
DOI: 10.5858/arpa.2023-0213-RA -
European Respiratory Review : An... Mar 2021Malignant pleural mesothelioma is an aggressive, incurable cancer that is usually caused by asbestos exposure several decades before symptoms arise. Despite widespread... (Review)
Review
Malignant pleural mesothelioma is an aggressive, incurable cancer that is usually caused by asbestos exposure several decades before symptoms arise. Despite widespread prohibition of asbestos production and supply, its incidence continues to increase. It is heterogeneous in its presentation and behaviour, and diagnosis can be notoriously difficult. Identification of actionable gene mutations has proven challenging and current treatment options are largely ineffective, with a median survival of 10-12 months.However, the past few years have witnessed major advances in our understanding of the biology and pathogenesis of mesothelioma. This has also revealed the limitations of existing diagnostic algorithms and identified new treatment targets.Recent clinical trials have re-examined the role of surgery, provided new options for the management of associated pleural effusions and heralded the addition of targeted therapies. The increasing complexity of mesothelioma management, along with a desperate need for further research, means that a multidisciplinary team framework is essential for the delivery of contemporary mesothelioma care.This review provides a synthesised overview of the current state of knowledge and an update on the latest research in the field.
Topics: Asbestos; Biology; Humans; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms
PubMed: 33472960
DOI: 10.1183/16000617.0226-2020