-
Modern Pathology : An Official Journal... Sep 2023Primary pericardial mesotheliomas are extremely rare, accounting for <1% of all mesotheliomas, and their molecular genetic features and predisposing factors remain to be...
Primary pericardial mesotheliomas are extremely rare, accounting for <1% of all mesotheliomas, and their molecular genetic features and predisposing factors remain to be determined. Here, we report the clinicopathologic, immunohistochemical, and molecular genetic findings of 3 pericardial mesotheliomas without pleural involvement. Three cases diagnosed between 2004 and 2022 were included in the study and analyzed by immunohistochemistry and targeted next-generation sequencing (NGS); corresponding nonneoplastic tissue was sequenced in all cases. Two patients were female and 1 was male, aged between 66 and 75 years. Two patients each had prior asbestos exposure and were smokers. Histologic subtypes were epithelioid in 2 cases and biphasic in 1 case. Immunohistochemical staining identified expression of cytokeratin AE1/AE3 and calretinin in all cases, D2-40 in 2 cases, and WT1 in 1 case. Staining for tumor suppressors revealed loss of p16, MTAP, and Merlin (NF2) expression in 2 cases and loss of BAP1 and p53 in 1 case. Abnormal cytoplasmic BAP1 expression was observed in an additional case. Protein expression abnormalities correlated with NGS results, which showed concurrent complete genomic inactivation of CDKN2A/p16, CDKN2B, MTAP, and NF2 in 2 mesotheliomas and of BAP1 and TP53 in 1 mesothelioma each, respectively. In addition, 1 patient harbored a pathogenic BRCA1 germline mutation, which resulted in biallelic inactivation in the mesothelioma. All mesotheliomas were mismatch repair proficient and showed several chromosomal gains and losses. All patients died from disease. Our study demonstrates that pericardial mesotheliomas share common morphologic, immunohistochemical, and molecular genetic features with pleural mesothelioma, including recurrent genomic inactivation of canonical tumor suppressors. Our study adds new insights into the genetic landscape of primary pericardial mesothelioma and highlights BRCA1 loss as a potential contributing factor in a subset of cases, thereby contributing to refined precision diagnostics for this rare cancer.
Topics: Humans; Male; Female; Aged; Lung Neoplasms; Neoplasm Recurrence, Local; Mesothelioma, Malignant; Mesothelioma; Pleural Neoplasms; Heart Neoplasms; Thymus Neoplasms; Ubiquitin Thiolesterase; Biomarkers, Tumor
PubMed: 37295554
DOI: 10.1016/j.modpat.2023.100237 -
Radiographics : a Review Publication of... Mar 2023A diverse spectrum of benign entities and malignant neoplasms originate from the monotonous mesothelium that lines the serosal membranes of the pleural, pericardial, and...
A diverse spectrum of benign entities and malignant neoplasms originate from the monotonous mesothelium that lines the serosal membranes of the pleural, pericardial, and peritoneal cavities. The mesothelium of myriad sites shows a common origin from the lateral plate mesoderm; primary mesothelial tumors thus demonstrate similar pathogenesis, imaging findings, and treatment options. Significant changes have been made in the 2021 World Health Organization (WHO) classification schemata of the pleural and pericardial tumors on the basis of recent advances in pathology and genetics. While malignant mesotheliomas are biologically aggressive malignancies that occur primarily in patients exposed to asbestos with attendant poor survival rates, well-differentiated papillary mesothelial tumors and adenomatoid tumors charter a benign clinical course with an excellent prognosis. Mesothelioma in situ is a newly characterized entity represented by recurrent unexplained pleural effusions without any identifiable mass at imaging or thoracoscopy. Immunohistochemical markers based on , and gene mutations help differentiate diffuse mesotheliomas from benign mesothelial proliferations and localized mesotheliomas. Cross-sectional imaging modalities, including US, CT, MRI, and fluorine 18-fluorodeoxyglucose (FDG) PET/CT, permit diagnosis and play a major role in staging and assessing surgical resectability. Imaging studies are invaluable in providing noninvasive and quantitative assessment of tumor response in patients with unresectable disease. Owing to significant overlap in patient characteristics and pathomorphology, accurate diagnosis based on advanced histopathology techniques and genetic abnormalities is imperative for optimal management and prognostication. While patients with nonepithelioid pleural mesotheliomas benefit from immunotherapy, novel targeted therapies for -, -, and -altered mesotheliomas are under consideration. RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.
Topics: Humans; Adenomatoid Tumor; Positron Emission Tomography Computed Tomography; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Neoplasms, Mesothelial; Biomarkers, Tumor
PubMed: 36757881
DOI: 10.1148/rg.220128 -
Seminars in Thoracic and Cardiovascular... 2022Primary pericardial mesothelioma is a rare malignancy of the mesothelial lining of the pericardium. This study aimed to evaluate the clinical characteristics and...
Primary pericardial mesothelioma is a rare malignancy of the mesothelial lining of the pericardium. This study aimed to evaluate the clinical characteristics and survival outcomes of these patients using a United States population-based cancer database. We queried the Surveillance, Epidemiology, and End Results program (1973-2015). Primary pericardial mesothelioma patients with complete follow-up data were included, and primary pleural mesothelioma patients were identified as controls. Propensity-score matching was used to balance individual characteristics. Kaplan-Meier analysis and log-rank tests were performed to compare overall survival. Forty-one primary pericardial mesothelioma and 15,970 primary pleural mesothelioma patients were identified. Before matching, when compared to the pleural mesothelioma counterparts, primary pericardial mesothelioma patients were younger (median 57 vs 73 years, P < 0.001), more likely to be female (46.3% vs 20.2%, P < 0.001), more likely to be nonwhite (24.4% vs 8.4%, P = 0.001), and less likely to have been diagnosed in the most recent study decade (2006-2015, 34.1% vs 43.5%, P = 0.002). The overall 1- and 2-year survival rates were 22.0% and 12.2%, with a median survival of 2 months (IQR: 1-6). After 1:2 nearest neighbor propensity-score matching, 38 pericardial mesothelioma and 76 matched pleural mesothelioma cases were identified. The 2 matched groups had comparable baseline characteristics, including age, sex, race, year of diagnosis, histological type, and cancer history. Compared to their pleural mesothelioma counterparts, primary pericardial mesothelioma patients were less likely to receive chemotherapy (23.7% vs 50.0%, P = 0.01) and had worse overall survival (median survival: 2 vs 10 months, log-rank P = 0.006). Primary pericardial mesothelioma has worse survival outcomes than pleural mesothelioma, with a median survival of only 2 months. These patients should seek care from experienced multidisciplinary teams at tertiary care centers that handle high volumes of mesothelioma patients.
Topics: Female; Heart Neoplasms; Humans; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Propensity Score; Thymus Neoplasms; Treatment Outcome; United States
PubMed: 34320396
DOI: 10.1053/j.semtcvs.2021.07.020 -
Journal of Clinical Medicine May 2021Mesothelioma is an aggressive disease arising from parietal pleura. Surgery is a valuable option in the frame of a multimodality treatment. Several surgical approaches... (Review)
Review
Mesothelioma is an aggressive disease arising from parietal pleura. Surgery is a valuable option in the frame of a multimodality treatment. Several surgical approaches have been standardized with the aim of a macroscopic complete resection; these often require homolateral diaphragm and pericardial resection and reconstruction. Extrapleural pneumonectomy (EPP) and extended pleurectomy decortication (EPD) have been recognized as radical surgical procedures. Nevertheless, both operations are technically challenging and associated with a significant rate of peri-operative morbidity and non-negligible mortality. The diaphragmatic and pericardial reconstruction technique is mandatory to avoid respiratory impairment and to reduce post-operative complications like gastric and cardiac herniation. Moreover, in the case of localized chest wall recurrence, surgery might be considered a valuable therapeutical option for highly selected and fit patients. All the technical aspects of the resection and reconstruction of the diaphragm, pericardium, and chest wall are described as well as the possible use of new minimally invasive techniques. In addition, the choice of different prosthetic materials, considering the most recent innovations in the field, are discussed.
PubMed: 34073544
DOI: 10.3390/jcm10112330 -
Current Oncology Reports Apr 2023This review aims to summarise the pathobiological role of mesothelin and the current data on therapeutic antibodies targeting mesothelin in solid tumours. (Review)
Review
PURPOSE OF REVIEW
This review aims to summarise the pathobiological role of mesothelin and the current data on therapeutic antibodies targeting mesothelin in solid tumours.
RECENT FINDINGS
High mesothelin expression is restricted to the pericardium, pleura, peritoneum and tunica vaginalis. Mesothelin does not seem to have any normal biological function in adult normal tissues. Mesothelin is highly expressed in mesothelioma, serous ovarian cancer, pancreatic cancer and some gastric cancer and adenocarcinoma of the lung and is responsible for tumour proliferation, metastasis, resistance to chemotherapy or radiation and evasion of immune system. To date, antibody, antibody drug conjugates and bispecific antibodies with immune checkpoints have been investigated in mesothelin expressing malignancies. After a couple of decades of clinical investigation in antibody targeting mesothelin, the therapeutic benefit is relatively modest. Novel delivery of mesothelin targeting agents, more potent payload in antibody drug conjugates and immune checkpoint inhibitor, may improve therapeutic benefit.
Topics: Humans; Adenocarcinoma; GPI-Linked Proteins; Immunoconjugates; Pharmaceutical Preparations; Mesothelin
PubMed: 36763234
DOI: 10.1007/s11912-023-01367-8 -
Cancers May 2020Mesothelioma is a malignancy of serosal membranes including the peritoneum, pleura, pericardium and the tunica vaginalis of the testes. Malignant mesothelioma (MM) is a... (Review)
Review
Mesothelioma is a malignancy of serosal membranes including the peritoneum, pleura, pericardium and the tunica vaginalis of the testes. Malignant mesothelioma (MM) is a rare disease with a global incidence in countries like Italy of about 1.15 per 100,000 inhabitants. Malignant Pleural Mesothelioma (MPM) is the most common form of mesothelioma, accounting for approximately 80% of disease. Although rare in the global population, mesothelioma is linked to industrial pollutants and mineral fiber exposure, with approximately 80% of cases linked to asbestos. Due to the persistent asbestos exposure in many countries, a worldwide progressive increase in MPM incidence is expected for the current and coming years. The tumor grows in a loco-regional pattern, spreading from the parietal to the visceral pleura and invading the surrounding structures that induce the clinical picture of pleural effusion, pain and dyspnea. Distant spreading and metastasis are rarely observed, and most patients die from the burden of the primary tumor. Currently, there are no effective treatments for MPM, and the prognosis is invariably poor. Some studies average the prognosis to be roughly one-year after diagnosis. The uniquely poor mutational landscape which characterizes MPM appears to derive from a selective pressure operated by the environment; thus, inflammation and immune response emerge as key players in driving MPM progression and represent promising therapeutic targets. Here we recapitulate current knowledge on MPM with focus on the emerging network between genetic asset and inflammatory microenvironment which characterize the disease as amenable target for novel therapeutic approaches.
PubMed: 32392897
DOI: 10.3390/cancers12051186 -
Critical Reviews in Oncology/hematology Jun 2023Malignant pleural mesothelioma (MPM) is a rare but invasive cancer, which mainly arises from mesothelial tissues of pleura, peritoneum and pericardium. Despite... (Review)
Review
Malignant pleural mesothelioma (MPM) is a rare but invasive cancer, which mainly arises from mesothelial tissues of pleura, peritoneum and pericardium. Despite significant advances in treatments, the prognosis of MPM patients remains poor, and the 5-year survival rate is less than 10%. Therefore, it is urgent to explore novel therapeutic targets for the treatment of MPM. Growing evidence has indicated that long non-coding RNAs (lncRNAs) potentially could be promising therapeutic targets for numerous cancers. In this regard, lncRNAs might also potentially therapeutic targets for MPM. Recent advances have been made to investigate the molecular basis of MPM. This review first provides a comprehensive overview of roles of lncRNAs in MPM and then discusses the relationship between molecular basis of MPM and MPM-related lncRNAs to implement them as promising therapeutic targets for MPM.
Topics: Humans; Mesothelioma, Malignant; Mesothelioma; RNA, Long Noncoding; Pleural Neoplasms; Lung Neoplasms
PubMed: 37116816
DOI: 10.1016/j.critrevonc.2023.104012 -
La Medicina Del Lavoro Oct 2022The aim of this study is to describe the incidence of malignant mesothelioma (MM) and asbestos exposure in an Italian region in the period 1996-June 2021. (Review)
Review
BACKGROUND
The aim of this study is to describe the incidence of malignant mesothelioma (MM) and asbestos exposure in an Italian region in the period 1996-June 2021.
METHODS
The study included cases with microscopic confirmation and those with instrumental confirmation. For each case, information on sex, age, tumour site, morphology and date of diagnosis was collected, along with details of exposure to asbestos.
RESULTS
3,097 cases of MM (2,233 males and 864 females) were registered: 90.8% with microscopic confirmation. A total of 2,840 cases involved the pleura (92%), 230 cases the peritoneum (7%), and a small number of cases the pericardium and testis (9 and 18, respectively). Most cases (78.0%) occurred after 65 years of age, while only 1.5% concerned individuals with age < 45 years. The standardized incidence rate for the entire period (adjusted to the 2000 Italian standard population and calculated per 100,000 person-years) was equal to 3.9 in males and 1.4 in females, and the trend showed an increase with age in both sexes. Concerning asbestos exposure, 79.7% of cases were exposed (86.7% males and 60.1% females). In 70.3%, exposure was occupational (83.4% males and 33.2% females), while 20.7% of females and 0.8% of males had familial exposure. Building construction, rolling stock manufacture/repair and metalworking were the most prevalent economic activities associated with occupational exposure.
CONCLUSIONS
This study offers an overview of MM in an Italian region characterized by high incidence and high exposure due to its particular production activities.
Topics: Female; Humans; Male; Middle Aged; Asbestos; Incidence; Italy; Mesothelioma; Mesothelioma, Malignant; Occupational Exposure; Pleural Neoplasms
PubMed: 36282034
DOI: 10.23749/mdl.v113i5.13312 -
Cureus Apr 2022This case report presents a 60-year-old gentleman with a significant smoking history and possible asbestos exposure who was referred to the emergency department for...
This case report presents a 60-year-old gentleman with a significant smoking history and possible asbestos exposure who was referred to the emergency department for atrial fibrillation with a rapid ventricular rate and symptoms of heart failure. Labs showed normal brain natriuretic peptide and troponin I. His echocardiography finding suggested constrictive pericarditis with an ejection fraction of 60%. A computed tomography scan was concerning for a pericardial mass. Left and right heart catheterization hinted more toward constrictive physiology; however, some findings were concerning for restrictive physiology. Hence, cardiac magnetic resonance imaging was done, which established the diagnosis of constrictive pericarditis. Pericardiectomy was planned with a maze procedure for atrial fibrillation. However, a malignant neoplasm was seen on a frozen biopsy. Hence, surgery was limited to partial pericardiectomy, as the patient had advanced infiltrative neoplasm that had resulted in constrictive pericarditis. The final pathology report confirmed the diagnosis of malignant pericardial mesothelioma mixed type. Malignancy is usually diagnosed in an advanced stage, like in our case, due to nonspecific initial presentation. A literature review suggests that there is a lack of established consensus on treatment. The response to therapy also seems to be poor and results only in palliation of symptoms, with a median survival of six months from diagnosis despite optimum medical management.
PubMed: 35602795
DOI: 10.7759/cureus.24270 -
Current Cardiology Reports Jul 2021Tumors of the pericardium are rare, but a wide variety of congenital, infectious, inflammatory, and neoplastic processes have been reported. Pericardial tumors can be... (Review)
Review
PURPOSE OF REVIEW
Tumors of the pericardium are rare, but a wide variety of congenital, infectious, inflammatory, and neoplastic processes have been reported. Pericardial tumors can be categorized as non-neoplastic or neoplastic. Neoplastic lesions can be further divided into benign or malignant, with malignancies being either primary or secondary (metastatic). Clinical, radiographic, and pathologic features of the most common entities are discussed.
RECENT FINDINGS
Metastatic neoplasms involving the heart and pericardium are far more common than primary pericardial neoplasms. Of primary pericardial malignancies, mesothelioma is the most common; notably, cytology of effusion fluid is relatively insensitive to the diagnosis. The prognosis for most malignancies of the pericardium, primary or secondary, is poor. Increasingly, clinically recognized diseases that involve the pericardium include Erdheim-Chester and IgG4-related disease. This article provides a comprehensive review of the most recent literature to develop a structured framework to the differential diagnosis of pericardial tumors.
Topics: Diagnosis, Differential; Heart Neoplasms; Humans; Mesothelioma; Mesothelioma, Malignant; Pericardium
PubMed: 34269901
DOI: 10.1007/s11886-021-01548-6