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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 -
Histopathology Jan 2024This review article examines some new and some problem areas in mesothelial pathology, four of which are discussed, as follows. (1) The concept of mesothelioma in situ:... (Review)
Review
This review article examines some new and some problem areas in mesothelial pathology, four of which are discussed, as follows. (1) The concept of mesothelioma in situ: this lesion is defined as a single layer of bland mesothelial cells without evidence of invasion, but that have lost BAP1 and/or MTAP by immunohistochemistry. Benign reactions can exactly mimic mesothelioma in situ, but a hint to the correct diagnosis is a story of recurrent pleural effusions/ascites of unknown aetiology without radiological or direct visual evidence of tumour. (2) The nature of well-differentiated papillary mesothelial tumour (WDPMT): WDPMT has a long history of arguments regarding its behaviour, and this uncertainty can now be seen to arise, in part, from the observation that some forms of mesothelioma in situ microscopically look exactly like WDPMT. Hence, it is recommended to always run at least a BAP1 stain on any lesion that looks like WDPMT. Both flat and WDPMT-like mesothelioma in situ are strongly associated with eventual development of invasive mesothelioma, but this process is relatively slow. (3) New immunostains for separating mesothelioma from other tumours: here, it is proposed that in most cases, and particularly when the differential is epithelioid mesothelioma versus non-small cell lung cancer, one can make this separation with extremely high sensitivity and specificity using just two stains: HEG1 and claudin-4. (4) Markers for separating benign from malignant mesothelial proliferations: this topic is briefly reviewed, with an indication of which markers are generally accepted and the best utilisation and possible limitations of each marker.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Biomarkers, Tumor; Tumor Suppressor Proteins; Mesothelioma, Malignant; Mesothelioma; Neoplasms, Mesothelial; Diagnosis, Differential; Ubiquitin Thiolesterase; Pleural Neoplasms
PubMed: 37694811
DOI: 10.1111/his.15007 -
Modern Pathology : An Official Journal... Jan 2022We report nine examples of a previously undescribed type of peritoneal circumscribed nodular mesothelial tumor characterized by nests or sheets of mesothelial cells with...
We report nine examples of a previously undescribed type of peritoneal circumscribed nodular mesothelial tumor characterized by nests or sheets of mesothelial cells with sharp cell borders and extremely bland, sometimes grooved, nuclei. In some cases, nests were separated by fibrous bands. All patients were women, age range 30-72 years (median 52 years). All tumors were incidental findings during surgery and grossly were either solitary nodules or a few small nodules on the peritoneal surface. Referring pathologic diagnoses included diffuse malignant mesothelioma, localized malignant mesothelioma, well-differentiated papillary mesothelioma, and adenomatoid tumor. No tumor showed BAP1 loss by immunohistochemistry nor deletion of CDKN2A by FISH. RNA-seq revealed that these tumors clustered together and were distinct from peritoneal diffuse malignant mesotheliomas. Very few mutations or translocations were found, none of them recurrent from tumor to tumor, and no tumor showed an abnormality in any of the genes typically mutated/deleted in diffuse malignant mesothelioma. Array CGH on three cases revealed two with a completely flat profile and one with a small deletion at 3q26-3q28. On follow-up (range 5-60, median 34 months), there were no deaths, no recurrences, and no evidence of metastatic disease nor local spread; one case that initially had scattered nodules on the pelvic peritoneum had the same pattern of nodules at a second look operation 2 years later. We propose the name solid papillary mesothelial tumor for these lesions. These appear to be either benign or very low-grade tumors that need to be separated from malignant mesotheliomas.
Topics: Adult; Aged; Carcinoma, Papillary; Chi-Square Distribution; Cluster Analysis; Cohort Studies; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humans; In Situ Hybridization, Fluorescence; Incidental Findings; Middle Aged; Mutation; Neoplasms, Mesothelial; Peritoneal Neoplasms; Prognosis; Sequence Analysis, RNA; Signal Transduction; Time Factors; Translocation, Genetic
PubMed: 34480081
DOI: 10.1038/s41379-021-00899-3 -
Surgical Pathology Clinics Mar 2020Mesothelioma is a rare neoplasm that arises from mesothelial cells lining body cavities including the pleura, pericardium, peritoneum, and tunica vaginalis. Most... (Review)
Review
Mesothelioma is a rare neoplasm that arises from mesothelial cells lining body cavities including the pleura, pericardium, peritoneum, and tunica vaginalis. Most malignant mesotheliomas occur in the chest and are frequently associated with a history of asbestos exposure. The diagnosis of malignant mesothelioma is challenging and fraught with pitfalls, particularly in small biopsies. This article highlights what the pathologist needs to know regarding the clinical and radiographic presentation of mesothelioma, histologic features including subtypes and variants, and recent advances in immunohistochemical markers and molecular testing.
Topics: Biopsy; Humans; Lung; Lung Neoplasms; Magnetic Resonance Imaging; Mesothelioma; Radiography; Tomography, X-Ray Computed
PubMed: 32005436
DOI: 10.1016/j.path.2019.10.001 -
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 -
Advances in Anatomic Pathology Jul 2023Mesotheliomas are rare and aggressive tumors that originate from mesothelial cells. Although exceedingly rare, these tumors may occur in children. Different from adult...
Mesotheliomas are rare and aggressive tumors that originate from mesothelial cells. Although exceedingly rare, these tumors may occur in children. Different from adult mesotheliomas, however, environmental exposures particularly to asbestos do not appear to play a major role in mesotheliomas in children, in whom specific genetic rearrangements driving these tumors have been identified in recent years. These molecular alterations may increasingly offer opportunities for targeted therapies in the future, which may provide better outcomes for these highly aggressive malignant neoplasms.
Topics: Adult; Humans; Child; Mesothelioma; Asbestos
PubMed: 37217834
DOI: 10.1097/PAP.0000000000000403 -
Recent Results in Cancer Research.... 2011Malignant pleural mesothelioma (MPM) is an asbestos-related neoplasm that originates in pleural mesothelial cells and progresses locally along the pleura until it... (Review)
Review
Malignant pleural mesothelioma (MPM) is an asbestos-related neoplasm that originates in pleural mesothelial cells and progresses locally along the pleura until it encases the lungs and mediastinum, ultimately causing death. Imaging plays a crucial role in diagnosis and optimal management. Computed tomography (CT) continues to be the primary and initial imaging modality. Magnetic resonance imaging (MRI) complements CT scan and is superior in determining chest wall and diaphragmatic invasion. FDG18-PET/CT provides anatamo-metabolic information and is superior to both CT and MRI in overall staging and monitoring response to therapy. This chapter will detail the imaging finding of MPM and role of imaging in guiding management.
Topics: Asbestos; Humans; Magnetic Resonance Imaging; Mediastinal Neoplasms; Mesothelioma; Neoplasm Staging; Pleural Neoplasms; Positron-Emission Tomography; Tomography, X-Ray Computed
PubMed: 21479894
DOI: 10.1007/978-3-642-10862-4_3 -
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 -
Seminars in Diagnostic Pathology Nov 2000Mesothelial lesions involving the paratesticular region include mesothelial cysts, reactive mesothelial hyperplasia, adenomatoid tumors, benign cystic mesothelioma,... (Review)
Review
Mesothelial lesions involving the paratesticular region include mesothelial cysts, reactive mesothelial hyperplasia, adenomatoid tumors, benign cystic mesothelioma, well-differentiated papillary mesothelioma, and malignant mesothelioma. The diagnosis and management of these lesions are often difficult for surgical pathologists, surgeons, and oncologists alike. Mesothelial lesions are relatively uncommon and most benign and malignant tumors present as testicular tumors with no specific findings. A preoperative diagnosis of malignancy is rarely made, and there is no established effective therapy for malignant mesothelioma. This article reviews the clinicopathologic features of paratesticular mesothelial lesions with emphasis in their differential diagnosis and prognosis.
Topics: Adenomatoid Tumor; Adolescent; Adult; Animals; Cysts; Diagnosis, Differential; Epithelium; Female; Humans; Hyperplasia; Male; Mesothelioma, Cystic; Middle Aged; Prognosis; Testicular Neoplasms; Testis
PubMed: 11202546
DOI: No ID Found