RESUMEN
Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.
Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores de Tumor/análisis , Mesotelioma/terapia , Neoplasias Pleurales/terapia , Neumonectomía/métodos , Amianto/efectos adversos , Australia/epidemiología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinogénesis/inducido químicamente , Carcinogénesis/genética , Carcinogénesis/patología , Terapia Combinada/métodos , Errores Diagnósticos , Europa (Continente)/epidemiología , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Carga Global de Enfermedades , Humanos , Incidencia , Exposición por Inhalación/efectos adversos , Cooperación Internacional , Mesotelioma/diagnóstico , Mesotelioma/epidemiología , Mesotelioma/etiología , Terapia Molecular Dirigida/métodos , Exposición Profesional/efectos adversos , Pleura/efectos de los fármacos , Pleura/patología , Pleura/cirugía , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/epidemiología , Neoplasias Pleurales/etiología , Pronóstico , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina Tiolesterasa/genética , Ubiquitina Tiolesterasa/metabolismo , Estados Unidos/epidemiologíaRESUMEN
9p21 deletions involving MTAP/CDKN2A genes are detected in diffuse pleural mesotheliomas (DPM) but are absent in benign mesothelial proliferations. Loss of MTAP expression by immunohistochemistry (IHC) is well accepted as a surrogate for 9p21 deletion to support a diagnosis of DPM. Accurate interpretation can be critical in the diagnosis of DPM, but variations in antibody performance may impact interpretation. The objectives of this study were to compare the performance of MTAP monoclonal antibodies (mAbs) EPR6893 and 1813 and to compare MTAP expression by IHC with 9p21 copy number status in DPM. Cytoplasmic expression of MTAP IHC with mAbs EPR6893 (ab126770; Abcam) and 1813 (NBP2-75730, Novus Biologicals) was evaluated in 56 DPM (47 epithelioid, 7 biphasic, and 2 sarcomatoid) profiled by targeted next-generation sequencing. 9p21 Copy number status was assessed by Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing (FACETS) analysis and also by CDKN2A fluorescence in situ hybridization in discrepant cases when material was available. MTAP mAb 1813 showed stronger immunoreactivity, more specific staining, and no equivocal interpretations compared to mAb EPR6893 which showed equivocal staining in 19 (34%) of cases due to weak or heterogenous immunoreactivity, lack of definitive internal positive control, and/or nonspecific background staining. MTAP expression with mAb 1813 showed near perfect agreement with 9p21 copy number by combined FACETS/fluorescence in situ hybridization calls (κ = 0.85; 95% CI, 0.71-0.99; P < .001). MTAP IHC with mAb 1813 was 96% sensitive, 86% specific, and 93% accurate for 9p21 homozygous deletion. The findings of this study suggest that interpretation of MTAP IHC is improved with mAb 1813 because mAb EPR6893 was often limited by equivocal interpretations. We show that MTAP IHC and molecular assays are complementary in detecting 9p21 homozygous deletion. MTAP IHC may be particularly useful for low tumor purity samples and in low-resource settings.
Asunto(s)
Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Biomarcadores de Tumor/análisis , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Homocigoto , Inmunohistoquímica , Hibridación Fluorescente in Situ , Mesotelioma/diagnóstico , Mesotelioma/genética , Mesotelioma/patología , Mesotelioma Maligno/genética , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/genética , Neoplasias Pleurales/patología , Eliminación de Secuencia , Ubiquitina Tiolesterasa/genéticaRESUMEN
Mesothelioma is a rare disease with an historically poor prognosis. Over the past decade, a grading system has been developed that is a powerful prognostic tool in epithelioid mesothelioma. Grading of epithelioid mesothelioma is now required or strongly recommended by expert consensus, the College of American Pathologists, the World Health Organization, and the International Mesothelioma Interest Group. The original nuclear grading system for epithelioid mesothelioma, developed in the United States, split epithelioid mesotheliomas into three prognostic groups with marked differences in survival. Now, this three-tiered nuclear grading system has been combined with the presence or absence of necrosis to form the currently recommended two-tiered grading system of low- and high-grade epithelioid mesothelioma. This review will focus on the development of this grading system in mesothelioma, the grading system's shortcomings, and the application of the grading system to cytology specimens and other extra-pleural sites. Lastly, this review will briefly discuss alternative grading systems and future considerations.
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Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Neoplasias Pleurales/diagnóstico , Neoplasias Pulmonares/diagnóstico , Clasificación del Tumor , Mesotelioma/diagnóstico , Pronóstico , Biomarcadores de TumorRESUMEN
Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.
Asunto(s)
Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Pleura , Mesotelioma/diagnóstico , Mesotelioma/terapia , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/terapiaRESUMEN
BACKGROUND: The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare. CASE PRESENTATION: A 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant 18F-FDG uptake on 18F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis. CONCLUSION: Physicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis.
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Neoplasias Óseas , Linfocitosis , Neoplasias Pleurales , Timoma , Humanos , Femenino , Persona de Mediana Edad , Timoma/patología , Timoma/diagnóstico por imagen , Timoma/complicaciones , Timoma/diagnóstico , Linfocitosis/patología , Linfocitosis/diagnóstico , Neoplasias Pleurales/secundario , Neoplasias Pleurales/patología , Neoplasias Pleurales/complicaciones , Neoplasias Pleurales/diagnóstico , Neoplasias Óseas/secundario , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias del Timo/patología , Neoplasias del Timo/complicaciones , Neoplasias del Timo/diagnóstico , Linfocitos T/patología , Fluorodesoxiglucosa F18 , Diagnóstico Diferencial , Pleura/patología , Pleura/diagnóstico por imagenRESUMEN
BACKGROUND: The diagnosis of mesothelioma may be challenging. We investigated a large database of cases in order to determine the frequency with which a diagnosis of mesothelioma was made incorrectly and the most frequent causes of error. DESIGN: A database including more than 4000 consultation cases of histologically confirmed mesothelioma was examined to identify cases in which mesothelioma was diagnosed by at least one pathologist when the available information pointed towards a different diagnosis. RESULTS: There were 311 cases misdiagnosed as mesothelioma. The most common category was metastatic carcinoma to the pleura or peritoneum (129 cases: 73 lung carcinomas, 15 renal cell carcinomas). The next most common category was primary lung cancer (111 cases: 55 sarcomatoid carcinoma, 56 pseudomesotheliomatous carcinoma). The third most common category was primary malignancies arising from or near the serosal membranes (33 cases). The fourth most common category was fibrous pleurisy (38 cases). The most common errors were failure to consider important radiographic information regarding the gross distribution of tumor, lack of awareness or consideration of another malignancy, overreliance on certain immunohistochemical results, and failure to perform certain diagnostic histochemical, immunohistochemical, or ultrastructural studies. CONCLUSIONS: There are a number of diagnostic pitfalls that can lead to the over diagnosis of mesothelioma. Careful attention to clinical and radiographic information as well as performance of appropriate ancillary tests can help to prevent such misdiagnoses. Detailed examples will be presented to assist in the avoidance of these pitfalls with emphasis on the most commonly observed errors.
Asunto(s)
Carcinoma , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Sobrediagnóstico , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/metabolismo , Neoplasias Pleurales/patología , Biomarcadores de Tumor/análisis , Mesotelioma/diagnóstico , Mesotelioma/patología , Mesotelioma Maligno/diagnóstico , Carcinoma/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Diagnóstico DiferencialRESUMEN
OBJECTIVES: The investigators conducted a psychosocial needs assessment of mesothelioma patients through self-report measures of quality of life (QOL), coping, depression, and social support. METHODS: Patients with malignant pleural mesothelioma (MPM) (N = 67) completed a battery of assessments at a single timepoint after being approached during routine medical oncology clinic appointments or by letter. RESULTS: Participants were predominately male (70.0%; n = 47) and ranged in age from 35 to 83 years old (M = 65.61, SD = 9.71). Most participants were white (88.0%; n = 59), and 10.0% (n = 7) were identified as Hispanic. The majority were married or living with a partner (93.0%; n = 62) and had some college or more education (64.0%; n = 43). Fourteen percent of participants (n = 11) endorsed significantly elevated depression symptoms. No significant demographic or clinical differences in depressed compared to nondepressed participants were observed, with a trend toward those identifying as Hispanic and those who were divorced as being more likely to be depressed. For the total sample, the most frequently endorsed coping strategies were active coping, emotional support, and acceptance. SIGNIFICANCE OF RESULTS: The present study did not identify any clear correlates of depression or QOL among patients with MPM. This research contributes to the small literature on psychosocial functioning in patients with MPM and provides putative directions for future larger studies and the development of interventions to provide appropriate support to diverse patients with MPM.
Asunto(s)
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Masculino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Calidad de Vida/psicología , Neoplasias Pleurales/complicaciones , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/patología , Neoplasias Pulmonares/complicaciones , Mesotelioma/complicaciones , Mesotelioma/diagnóstico , Mesotelioma/patologíaRESUMEN
The asbestos-related malignant mesothelioma (MM) is one of the common occupational cancers in Germany with approximately 1000 new cases per year. Provided that the appropriate diagnostic criteria are fulfilled, MM can be diagnosed with high specificity from both histological and cytological specimens. However, many MM are detected cyto-/histologically only at advanced stages. Clinical/radiological aspects complement each other and enable interdisciplinary assessment of tumor stage and individualized decisions on the best possible therapeutic options. Diagnostically, video-assisted thoracoscopy (VATS) has the highest priority. Therapy planning is based on the MM subtype, tumor spread and stage, and the patient's clinical condition. MM has generally a very unfavorable prognosis. Accordingly, the standard therapy aims at a macroscopic radical tumor resection in terms of cytoreduction within the framework of a suitable multimodal therapy concept (chemotherapy, radiotherapy, psychooncology). The aim of palliative measures should be primarily symptom control. Overall, interdisciplinary diagnosis and therapy of MM is crucial for the best possible care of MM patients.
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Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Mesotelioma/terapia , Mesotelioma/tratamiento farmacológico , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/terapia , Neoplasias Pleurales/patología , Pronóstico , Terapia CombinadaRESUMEN
Mesotheliomas are neoplasia developed from the mesothelium, a layer covering the viscera (visceral layer) and the cavity where the organs are (parietal layer). The best known, and the most frequently encountered is the pleural mesothelioma. This disease has a close link with exposure to asbestos, a mineral fibre now banned in several countries. However, other exposure factors have also been incriminated, including another one recognised as a certain carcinogenic agent for several years now : erionite. We present the case of a patient with pleural mesothelioma whose exposure to erionite could be demonstrated. The presentation of this clinical case will be complemented by a literature review on this less known and mostly environmental exposure, contrary to asbestos which is mostly professional.
Les mésothéliomes sont des néoplasies se développant à partir du mésothélium, feuillet recouvrant, d'une part, les viscères (feuillet viscéral) et, d'autre part, la cavité où se trouvent les organes (feuillet pariétal). Le plus connu, et le plus fréquemment rencontré, est le mésothéliome pleural. Cette maladie a un lien étroit avec l'exposition à l'amiante, fibre minérale maintenant interdite dans plusieurs pays. Cependant, d'autres facteurs expositionnels ont également été incriminés, dont un autre reconnu comme cancérogène certain depuis plusieurs années : l'érionite. Nous présentons le cas d'un patient atteint d'un mésothéliome pleural pour lequel une exposition à l'érionite a pu être étayée. La présentation du cas clinique sera complétée d'une revue de la littérature sur cette exposition particulière moins connue et majoritairement environnementale, contrairement à l'amiante dont l'exposition est majoritairement professionnelle.
Asunto(s)
Mesotelioma , Neoplasias Pleurales , Humanos , Neoplasias Pleurales/etiología , Neoplasias Pleurales/diagnóstico , Mesotelioma/etiología , Mesotelioma/inducido químicamente , Masculino , Zeolitas/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Mesotelioma Maligno/patologíaRESUMEN
Pleural mesothelioma (PMe) was associated with asbestos exposure.The Diagnosis of PMe is difficult due to the lack of specificity of clinical signs and symptoms, although there are many tools available for early diagnosis of mesothelioma. Most PMe patients are diagnosed at an advanced stage. This article reviews advances in strategies for early diagnosis of mesothelioma, focusing on breath analysis, early diagnosis of pleural effusion cytology in patients with mesothelioma, serum biomarkers and miRNA.
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Detección Precoz del Cáncer , Mesotelioma , Neoplasias Pleurales , Humanos , Mesotelioma/diagnóstico , Neoplasias Pleurales/diagnóstico , Detección Precoz del Cáncer/métodos , MicroARNs/sangre , Neoplasias Pulmonares/diagnóstico , Biomarcadores de Tumor/sangre , Pruebas Respiratorias , Diagnóstico Precoz , Mesotelioma Maligno/diagnósticoRESUMEN
Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mainly caused by asbestos exposure. Specific and sensitive noninvasive biomarkers may facilitate and enhance screening programs for the early detection of cancer. We investigated DNA methylation (DNAm) profiles in MPM prediagnostic blood samples in a case-control study nested in the European Prospective Investigation into Cancer and nutrition (EPIC) cohort, aiming to characterise DNAm biomarkers associated with MPM. From the EPIC cohort, we included samples from 135 participants who developed MPM during 20 years of follow-up and from 135 matched, cancer-free, controls. For the discovery phase we selected EPIC participants who developed MPM within 5 years from enrolment (n = 36) with matched controls. We identified nine differentially methylated CpGs, selected by 10-fold cross-validation and correlation analyses: cg25755428 (MRI1), cg20389709 (KLF11), cg23870316, cg13862711 (LHX6), cg06417478 (HOOK2), cg00667948, cg01879420 (AMD1), cg25317025 (RPL17) and cg06205333 (RAP1A). Receiver operating characteristic (ROC) analysis showed that the model including baseline characteristics (age, sex and PC1wbc) along with the nine MPM-related CpGs has a better predictive value for MPM occurrence than the baseline model alone, maintaining some performance also at more than 5 years before diagnosis (area under the curve [AUC] < 5 years = 0.89; AUC 5-10 years = 0.80; AUC >10 years = 0.75; baseline AUC range = 0.63-0.67). DNAm changes as noninvasive biomarkers in prediagnostic blood samples of MPM cases were investigated for the first time. Their application can improve the identification of asbestos-exposed individuals at higher MPM risk to possibly adopt more intensive monitoring for early disease identification.
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Amianto , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Preescolar , Mesotelioma/diagnóstico , Mesotelioma/genética , Mesotelioma/patología , Metilación de ADN , Estudios de Casos y Controles , Estudios Prospectivos , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/genética , Neoplasias Pleurales/patología , Biomarcadores de Tumor/metabolismo , Amianto/efectos adversos , Marcadores Genéticos , Células Sanguíneas , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologíaRESUMEN
Pleural mesotheliomas represent one of the most common diagnostic challenges in thoracic pathology. The diagnosis of pleural mesothelioma weighs heavily on clinical and radiologic information. In addition, in the past, before the era of immunohistochemistry, the diagnosis was aided with the use of special histochemical stains-PAS, D-PAS, and mucicarmine, which now very much have been replaced by immunohistochemical stains. In the era of immunohistochemistry, a combination of carcinomatous epitopes and positive mesothelioma markers has become paramount in the diagnosis of mesothelioma, and more recently the use of molecular techniques has become another ancillary tool in supporting such a diagnosis. At the same time, the treatment and clinical outcome of these patients may in some measure be determined by the histopathological features of the tumor and one that also over the years has changed from a palliative type to surgery, chemotherapy, radiotherapy, or a combination of these types. The histopathological growth patterns of mesothelioma are also wide, and in some cases may mimic other tumors that may be primary or metastatic to the pleura. Therefore, the assessment of the diagnosis of mesothelioma is one that requires a global view of the different factors including clinical, radiologic, pathologic-including immunohistochemistry and molecular diagnosis.
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Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Mesotelioma/diagnóstico , Mesotelioma/patología , Mesotelioma Maligno/diagnóstico , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/terapia , Neoplasias Pleurales/química , Inmunohistoquímica , Diagnóstico Diferencial , Biomarcadores de TumorRESUMEN
Primary pericardial mesothelioma (PM) is a rare tumor arising from the mesothelial cells of the pericardium. It has an incidence of <0.05% and comprises <2% of all mesotheliomas; however, it is the most common primary malignancy of the pericardium. PM should be distinguished from secondary involvement by the spread of pleural mesothelioma or metastases, which are more common. Although data are controversial, the association between asbestos exposure and PM is less documented than that with other mesotheliomas. Late clinical presentation is common. Symptoms may be nonspecific but are usually related to pericardial constriction or cardiac tamponade, and diagnosis can be challenging usually requiring multiple imaging modalities. Echocardiography, computed tomography, and cardiac magnetic resonance demonstrate heterogeneously enhancing thickened pericardium, usually encasing the heart, with findings of constrictive physiology. Tissue sampling is essential for diagnosis. Histologically, similar to mesotheliomas elsewhere in the body, PM is classified as epithelioid, sarcomatoid, or biphasic, with the biphasic type being the most common. Combined with morphologic assessment, the use of immunohistochemistry and other ancillary studies is helpful for distinguishing mesotheliomas from benign proliferative processes and other neoplastic processes. The prognosis of PM is poor with about 22% 1-year survival. Unfortunately, the rarity of PM poses limitations for comprehensive and prospective studies to gain further insight into the pathobiology, diagnosis, and treatment of PM.
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Neoplasias Cardíacas , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Sarcoma , Humanos , Estudios Prospectivos , Mesotelioma Maligno/complicaciones , Mesotelioma/diagnóstico , Mesotelioma/patología , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/etiología , Neoplasias Pleurales/patología , Sarcoma/patología , Neoplasias Cardíacas/diagnósticoRESUMEN
OBJECTIVES: Combination of Breast Cancer 1 protein-associated protein 1 (BAP1) and methylthioadenosine phosphorylase (MTAP) in the peritoneal mesothelioma (PeM) has yet to be explored. We aim to assess the diagnostic value of combined BAP1 and MTAP to distinguish biphasic mesothelioma (BM) from epithelioid mesothelioma (EM) with reactive stroma in peritoneum, as well as its prognostic value in PeM. METHODS: This is a retrospective study from June 2014 to December 2021. This study included 18 cases of BM and 27 cases of EM with reactive stroma, excluded sarcomatoid, and EM without reactive stroma cases, and clinicopathological information was collected. The associations between MTAP and BAP1 levels and clinicopathological features or prognosis were analyzed. Clinical follow-up data were reviewed to correlate with pathological prognostic factors using Kaplan-Meier estimator and univariate/multivariate Cox proportional hazards regression models. RESULTS: Loss/decrease of BAP1/MTAP was observed in 6 (33.3%) BM cases and 12 (44.4%) EM cases. In 5 (27.8%) cases, loss of or decreased BAP1/MTAP expression was observed in both EC and SC of BM. BAP1/MTAP loss/decrease was observed in 12 (44.4%) cases of only EC of EM but not in reactive stroma. Compared with histology alone, a combination of BAP1 and MTAP immunohistochemistry (IHC) in spindled PeM provides a more objective mean to distinguish BM from EM with reactive stroma. Loss/decrease of BAP1/MTAP was associated with peritoneal cancer index (PCI) score (P = 0.047) and completeness of cytoreduction (CC) score (P = 0.038). BM patients have worse overall survival (OS) than EM with reactive stroma (P = 0 .007). CONCLUSIONS: Combination of BAP1/MTAP by IHC is helpful for differential diagnosis of peritoneal BM from EM with reactive stroma. Nevertheless, BAP1/MTAP may help to evaluate the biological behavior of PeM.
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Neoplasias de la Mama , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Femenino , Humanos , Biomarcadores de Tumor/metabolismo , Proteína BRCA1 , Neoplasias de la Mama/diagnóstico , Neoplasias Pulmonares/patología , Mesotelioma/diagnóstico , Mesotelioma/metabolismo , Mesotelioma/patología , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/metabolismo , Neoplasias Pleurales/patología , Estudios Retrospectivos , Proteínas Supresoras de Tumor/metabolismoRESUMEN
OPINION STATEMENT: Malignant pleural mesothelioma (MPM) is an aggressive asbestos-associated thoracic malignancy that is usually incurable. As demonstrated in the landmark MARS2 trial, surgical resection does not improve survival outcomes and its role in managing MPM is limited. Whilst platinum-pemetrexed chemotherapy in combination with bevacizumab was the standard first-line approach for unresectable disease, landmark phase 3 trials have now established the role of immune checkpoint inhibitors (CPIs) in the upfront management of unresectable disease: either nivolumab-ipilimumab or carboplatin-pemetrexed-pembrolizumab. Patient selection for optimal strategy remains an ongoing question. For relapsed disease novel genomic-based therapies targeting a range of aberrations including losses of the tumour suppressor genes BAP1, CDKN2A and NF2, are being evaluated. Nonetheless, the future of MPM therapeutics holds promise. Here we overview current treatment strategies in the management of MPM.
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Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Mesotelioma/diagnóstico , Mesotelioma/etiología , Mesotelioma/terapia , Pemetrexed/uso terapéutico , Neoplasias Pulmonares/patología , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/etiología , Neoplasias Pleurales/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
In this review, we provide an update on the status of cancer biomarkers for the clinical management of pleural mesothelioma, an aggressive cancer associated with asbestos exposure. Mesothelioma can be difficult to diagnose, and response to treatment is transient, even with recently adopted immune checkpoint inhibitor (ICI) combinations. Identification of mesothelioma-specific biomarkers could facilitate early diagnosis and tailor treatment strategies. Mesothelioma is characterized by frequent loss or alteration of the tumor suppressor genes cyclin-dependent kinase inhibitor 2A (CDKN2A) and BRCA1-associated protein-1 (BAP1). Accumulating data show these genes and/or their related protein products will be valuable tissue-based biomarkers for mesothelioma. Loss of BAP1, CDKN2A, p16, or methylthioadenosine phosphorylase provide pathologists with a reliable means of differentiating between mesothelioma and reactive mesothelial cell proliferations. This can aid diagnosis in difficult cases and is requisite for the identification of the new pathological entity malignant mesothelioma in situ. However, limited progress in identifying clinically useful soluble biomarkers in this cancer type has been made, with mesothelin remaining the benchmark. To date, results from studies to identify predictive biomarkers for ICI response have been disappointing. A recent retrospective study demonstrated BAP1 loss was predictive of improved survival following combination pemetrexed- and platinum-based chemotherapy. Validation of this result could have important clinical implications. Clinical trials aimed at targeting therapy based on biomarker expression are generally in the early phase setting, with overall results being moderate. The identification of biomarkers for mesothelioma remains a key research question due to their potential to improve patient outcomes in this deadly cancer.
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Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mesotelioma/diagnóstico , Mesotelioma/terapia , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/tratamiento farmacológico , Biomarcadores de Tumor/genéticaRESUMEN
OBJECTIVE: Traditionally, the diagnosis of pleural mesothelioma is based on histological material. Minimally invasive effusion cytology specimens are an alternative that, like biopsies, require ancillary analyses. Validation of immunohistochemical (IHC) analyses on cytology, including the surrogate markers for molecular alterations BAP1 and MTAP, is of interest. METHODS: IHC for eight different markers was performed on 59 paired formalin-fixed, paraffin-embedded pleural biopsies and pleural effusion cell blocks with mesothelioma. Immunoreactivity in ≥10% of tumour cells was considered positive/preserved. The concordance between histological and cytological materials was assessed. RESULTS: The overall percentage of agreement between the histological epithelioid component in 58 biopsies and paired cell blocks was 93% for calretinin, 98% for CK5, 97% for podoplanin, 90% for WT1, 86% for EMA, 100% for desmin, 91% for BAP1, and 72% for MTAP. For 11 cases with biphasic or sarcomatoid histology, the concordance between cytology and the histological sarcomatoid component was low for calretinin, CK5, and WT1 (all ≤45%). For the whole cohort, loss of both BAP1 and MTAP was seen in 40% while both markers were preserved in 11% of the biopsies for epithelioid histology. The corresponding numbers were 54% and 8%, respectively, for the paired cell blocks. CONCLUSIONS: Generally, a high concordance for IHC staining was seen between paired biopsies and pleural effusion cell blocks from mesotheliomas, but the somewhat lower agreement for WT1, EMA, and especially MTAP calls for further investigation and local quality assurance. The lower concordance for the sarcomatoid subtype for some markers may indicate biological differences.
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Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Derrame Pleural , Neoplasias Pleurales , Sarcoma , Humanos , Calbindina 2 , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Proteínas Supresoras de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Inmunohistoquímica , Mesotelioma/diagnóstico , Mesotelioma/patología , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/patología , Derrame Pleural/diagnóstico , Biopsia , Sarcoma/diagnóstico , Diagnóstico DiferencialRESUMEN
Malignant pleural mesothelioma (MPM) is an aggressive, almost universally fatal cancer with limited therapeutic options. Despite efforts, a real breakthrough in treatment and outcomes has been elusive. Pleural effusion with significant breathlessness and pain is the most typical presentation of individuals with MPM. Although thoracentesis provides relief of breathlessness, most such pleural effusions recur rapidly, and a definitive procedure is often required to prevent a recurrence. Unfortunately, the optimal treatment modality for individuals with recurrent MPM-related effusion is unclear, and considerable variation exists in practice. In addition, non-expandable lung is common in pleural effusions due to MPM and makes effective palliation of symptoms more difficult. This review delves into the latest advances in the available management options (both surgical and non-surgical) for dealing with pleural effusion and non-expandable lung related to MPM. We discuss factors that determine the choice of definitive procedures that need to be tailored to the individual patient.
Asunto(s)
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Derrame Pleural Maligno , Derrame Pleural , Neoplasias Pleurales , Humanos , Derrame Pleural Maligno/etiología , Derrame Pleural Maligno/terapia , Mesotelioma/complicaciones , Mesotelioma/terapia , Mesotelioma/diagnóstico , Neoplasias Pleurales/complicaciones , Neoplasias Pleurales/terapia , Neoplasias Pleurales/diagnóstico , Derrame Pleural/patología , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/diagnósticoRESUMEN
More than 30 years have passed since the beginning of the epidemiological surveillance of mesothelioma (MM). The Italian National Mesothelioma Register (ReNaM), part of the research department of the National Institute for insurance against industrial injuries (INAIL), has published 7 reports with the description of the cas-es concerning the assessment of diagnoses and exposures to asbestos suffered mainly during working activities but also environmental, in the family premises and during personal activities.Today we are witnessing a reduction in the commitment by some regions which negatively affects those who develop the pathology. Reading the ReNaM reports it emerges, among others, the problem of the delay in reporting new cases which limits the collection of information directly from patients. This contribution, discussing various topics, invites to develop a debate that should allow to update and resolve the critical aspects that arise after decades of activity regarding, in particular, the asbestos exposure assessment. It is the primary interest of the authors to give continuity and improve the ReNaM which remains the most prestigious MM register among those active in other countries.
Asunto(s)
Amianto , Mesotelioma Maligno , Mesotelioma , Exposición Profesional , Neoplasias Pleurales , Humanos , Exposición Profesional/efectos adversos , Vigilancia de la Población , Italia/epidemiología , Sistema de Registros , Mesotelioma/epidemiología , Mesotelioma/etiología , Amianto/toxicidad , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/epidemiología , Neoplasias Pleurales/etiologíaRESUMEN
Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, characterized by insidious onset, strong local invasiveness, short survival period, and poor prognosis. Clinical diagnosis is of paramount importance for the treatment and prognosis of MPM. Currently, the gold standard for diagnosing MPM is the results of histopathological examinations. Immunohistochemistry (IHC) is an effective auxiliary method in pathological diagnosis. Preliminary examinations can use two positive markers and two negative markers to distinguish pleural metastatic tumors, with additional antibodies selected based on differential diagnosis. The combined use of IHC markers plays a crucial role in the differential diagnosis between MPM and other tumors. This article primarily introduces commonly used IHC markers in MPM and the research progress of novel IHC markers in screening and differential diagnosis, aiming to provide reference for the clinical diagnosis and treatment of MPM.