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Cureus Aug 2023Malignant mesothelioma is a very rare diagnosis. Malignant mesotheliomas arise from surface linings of pleura, peritoneal cavity, or tunica vaginalis and pericardium...
Malignant mesothelioma is a very rare diagnosis. Malignant mesotheliomas arise from surface linings of pleura, peritoneal cavity, or tunica vaginalis and pericardium with pleural malignant mesotheliomas being the most common. The incidence of brain metastases has been very low with malignant pleural mesotheliomas, but to date, there have not been any cases reported of brain metastasis with malignant peritoneal mesotheliomas. We present a patient diagnosed with malignant peritoneal mesothelioma and was successfully treated with immunotherapy for over two years but later presented with brain metastases. Although the patient had a surgical resection followed by brain radiation, he died three months after his diagnosis of brain metastases. Immunotherapy has revolutionized the treatment of malignant mesothelioma, and patients are living longer than before. We present this patient to increase awareness of brain metastases with malignant peritoneal mesothelioma. This case also highlights that we need to investigate different treatment options for brain metastases in patients with malignant mesothelioma as conventional treatment options like surgical resection and brain radiation are not very effective.
PubMed: 37727202
DOI: 10.7759/cureus.43744 -
JFMS Open Reports 2023A 6.4 kg 3-year-old male neutered indoor-outdoor domestic shorthair cat was referred for further evaluation of non-resolving lethargy and hyporexia of 4 days'...
CASE SUMMARY
A 6.4 kg 3-year-old male neutered indoor-outdoor domestic shorthair cat was referred for further evaluation of non-resolving lethargy and hyporexia of 4 days' duration. Physical examination identified tachypnea with mild respiratory effort and muffled lung sounds bilaterally. Point-of-care ultrasound revealed a large volume of pleural and pericardial effusion (PCE), which was confirmed by thoracic radiography. Echocardiogram indicated normal cardiac function but revealed a mass-like structure along the left epicardium within the pericardial space. After 72 hours in hospital, re-evaluation via echocardiogram showed the epicardial mass lesion to have doubled in size and with apparent extension to involve the pericardium. The patient was hospitalized for 72 h of supportive care and intervention, including therapeutic pericardiocentesis, bilateral thoracocentesis, thoracic and cardiac imaging and infectious disease testing. On the third day of hospitalization, the patient developed cardiac tamponade. Further workup was discussed, including CT and subtotal pericardiectomy with biopsy, but the cat was euthanized due to clinical decline and rapid re-accumulation of effusion. Post-mortem histopathologic evaluation diagnosed an epicardial pleomorphic sarcoma, exclusive of mesothelioma or histiocytic sarcoma on immunohistochemistry (IHC).
RELEVANCE AND NOVEL INFORMATION
This report describes a case of epicardial undifferentiated pleomorphic sarcoma (UPS) in a young cat presenting with pleural and PCE. Pleomorphic sarcoma is a rarely reported mesenchymal neoplasia in the feline patient and has thus far primarily been identified in peripheral soft tissue structures. IHC is key to the correct histopathologic diagnosis. To our knowledge, epicardial UPS has not been previously reported in a cat.
PubMed: 37168487
DOI: 10.1177/20551169231162484 -
Cancers May 2022Mesothelin (MSLN) is a protein expressed in the mesothelial cell lining of the pleura, peritoneum, and pericardium; its biological functions in normal cells are still... (Review)
Review
Mesothelin (MSLN) is a protein expressed in the mesothelial cell lining of the pleura, peritoneum, and pericardium; its biological functions in normal cells are still unknown. Experimental studies using knockout mice have suggested that this molecule does not play an important role in development and reproduction. In contrast, it has been observed that this molecule is produced in abnormal amounts in several malignant neoplasms, such as mesotheliomas and pancreatic adenocarcinomas. Many molecular studies have also demonstrated that mesothelin is overexpressed in HSOCs. Here, we discuss the current knowledge of mesothelin and focus on its role in clinical and pathological diagnoses, as well as its impact on the prognosis of HSOC. Moreover, regarding the binding of MSLN to the ovarian cancer antigen CA125, which has been demonstrated in many studies, we also report on signal transduction pathways that may play an important role in the spread and neoplastic progression of this lethal neoplasm. Given that mesothelin is overexpressed in many solid tumours and has antigenic properties, this molecule could be considered an antigenic target for the treatment of many malignancies. Consequently, we also review the literature to report on mesothelin-targeting therapies for HSOC that have been recently investigated in many clinical studies.
PubMed: 35565412
DOI: 10.3390/cancers14092283 -
BBA Advances 2021Yes-associated protein (YAP) is involved in development, cell growth, cell size, and homeostasis and plays a key role in the progression of various cancers. Among them,...
Yes-associated protein (YAP) is involved in development, cell growth, cell size, and homeostasis and plays a key role in the progression of various cancers. Among them, constitutive activation of YAP can often be observed in malignant mesothelioma, which arises in the pleura, peritoneum, and pericardium because of inactivation of the Hippo pathway. To date, however, only less-effective treatments such as chemotherapy, radiation therapy, and surgery are available for patients with malignant mesothelioma. In this study, we identified narciclasine as a novel YAP inhibitor that prevents YAP from interacting with TEAD4 because it competes with TEAD4 for binding to YAP. Furthermore, narciclasine could perturb the cell growth and colony formation of malignant mesothelioma NCI-H290 cells in addition to inhibiting their growth in nude mice. Therefore, narciclasine might be a potential seed for a novel antitumor drug against malignant mesothelioma and other cancers in which hyperactivation and/or overexpression of YAP are observed.
PubMed: 37082014
DOI: 10.1016/j.bbadva.2021.100008 -
Cancer Reports (Hoboken, N.J.) Apr 2024Extrapleural pneumonectomy (EPP) is a complex surgical procedure involving en-bloc resection of the parietal and visceral pleura, lung, pericardium, and ipsilateral...
BACKGROUND
Extrapleural pneumonectomy (EPP) is a complex surgical procedure involving en-bloc resection of the parietal and visceral pleura, lung, pericardium, and ipsilateral diaphragm. Small case series of pleural-based sarcoma of predominantly pediatric patients suggest EPP may be a life-prolonging surgical option. We aimed to describe the characteristics and outcomes of adults who underwent EPP at a specialized sarcoma center.
METHODS
Clinicopathologic variables, surgical details, and follow-up information were extracted for patients undergoing EPP for pleural-based sarcoma between August 2017 and December 2020. Primary outcomes were event-free survival (EFS) and overall survival (OS) from the date of EPP. Secondary outcomes were disease-free interval (DFI) prior to EPP, and early and late postoperative complications.
RESULTS
Eight patients were identified, seven with soft tissue sarcoma and one with bone sarcoma. Patients had either localized disease with a primary thoracic sarcoma, sarcoma recurrent to the thorax, or de novo metastatic disease. All patients underwent resection of their pleural-based sarcoma by an experienced cardiothoracic surgeon, and some patients had pre or postoperative treatment. The perioperative morbidity was comparable with previously published reports of EPP performed in mesothelioma patients. At median follow-up of 22.5 months, median EFS was 6.0 months and OS was 20.7 months. Six patients (75%) had disease recurrence; five (62.5%) died of progressive disease. Two patients (25%) had not recurred: one died of a radiation-related esophageal rupture, and one was alive with no evidence of disease at 37.0 months. Characteristics of those with the longest EFS included low-grade histology and achieving a metabolic response to preoperative chemotherapy.
CONCLUSIONS
In adults with pleural-based sarcoma, EPP is rarely curative but appears to be a feasible salvage procedure when performed at specialized centers. Patient selection is critical with strong consideration given to multimodal therapy to optimize patient outcomes. In the absence of a confirmed response to neoadjuvant treatment, long term survival is poor and EPP should not be recommended.
Topics: Adult; Humans; Child; Pneumonectomy; Pleural Neoplasms; Neoplasm Recurrence, Local; Mesothelioma; Sarcoma
PubMed: 38627902
DOI: 10.1002/cnr2.2065 -
Cancers Feb 2021Malignant mesothelioma (MM) is a rare but highly aggressive cancer that primarily originates from the pleura, peritoneum or pericardium. There is a well-established link...
Malignant mesothelioma (MM) is a rare but highly aggressive cancer that primarily originates from the pleura, peritoneum or pericardium. There is a well-established link between asbestos exposure and progression of MM. Direct invasion of the surrounding tissues is the main feature of MM, which is dependent on dysregulated communication between the mesothelium and the microenvironment. This communication is dependent on the dynamic organization of the cytoskeleton. We have analyzed the organization and function of key cytoskeletal components in MM cell lines of increasing malignancies measured as migratory and invasive properties, and we show that highly malignant and invasive MM cells have an organization of the actin filament and vimentin systems that is distinct from the less malignant MM cell lines. In addition, the Hippo tumor suppressor pathway was inactivated in the invasive MM cells, which was seen as increased YAP nuclear localization.
PubMed: 33567673
DOI: 10.3390/cancers13040685 -
Journal of Thoracic Oncology : Official... Mar 2020Children and young adults diagnosed with malignant mesothelioma may have unique genetic characteristics. In this study, we evaluated for the presence of the anaplastic...
INTRODUCTION
Children and young adults diagnosed with malignant mesothelioma may have unique genetic characteristics. In this study, we evaluated for the presence of the anaplastic lymphoma kinase (ALK) translocations in these patients.
METHODS
In a prospective study of mesothelioma natural history (ClinicalTrials.gov number NCT01950572), we assessed for the presence of the ALK translocation in patients younger than 40 years, irrespective of the site of disease. The presence of this translocation was assessed by means of fluorescence in situ hybridization (FISH). If the patients tested positive for the ALK translocation, both immunohistochemistry and RNA sequencing were performed on the tumor specimen.
RESULTS
Between September 2013 and December 2018, 373 patients were enrolled in the mesothelioma natural history study, of which 32 patients were 40 years old or younger at the time of their mesothelioma diagnosis. There were 25 patients with peritoneal mesothelioma, five with pleural mesothelioma, one with pericardial mesothelioma, and one with bicompartmental mesothelioma. Presence of an ALK translocation by FISH was seen in two of the 32 patients (6%) with mesothelioma. Both patients, a 14-year-old female and a 27-year-old male, had peritoneal mesothelioma and had no history of asbestos exposure, prior radiation therapy, or predisposing germline mutations. Neither had detectable ALK expression by immunohistochemistry. RNA sequencing revealed the presence of an STRN fusion partner in the female patient but failed to identify any fusion protein in the male patient.
CONCLUSIONS
Young patients with peritoneal mesothelioma should be evaluated for the presence of ALK translocations. Presence of this translocation should be assessed by FISH and these patients could potentially benefit from tyrosine kinase inhibitors targeting ALK.
Topics: Adolescent; Adult; Anaplastic Lymphoma Kinase; Child; Female; Gene Rearrangement; Humans; In Situ Hybridization, Fluorescence; Lung Neoplasms; Male; Mesothelioma; Prospective Studies; Receptor Protein-Tyrosine Kinases; Young Adult
PubMed: 31783178
DOI: 10.1016/j.jtho.2019.11.011 -
Respirology Case Reports Sep 2022Malignant pericardial mesothelioma (MPM) is a rare tumour that arises from the mesothelial cells of the pericardium. No standard treatment has been established owing to...
Malignant pericardial mesothelioma (MPM) is a rare tumour that arises from the mesothelial cells of the pericardium. No standard treatment has been established owing to a poor treatment response; therefore, MPM has a poor prognosis. We herein report a rare case of MPM in a 70-year-old man that was diagnosed immunohistopathologically using cell block sections of pericardial fluid and in which long-term survival for more than 3 years was achieved with only periodic pericardial drainage. Immunohistopathological staining investigations, especially BRCA1-associated protein 1 (BAP1) immunostaining using cell block sections of pericardial effusion, are effective in making a diagnosis of MPM. Well-differentiated papillary mesothelioma (WDPM) with BAP1 loss progresses to MPM in the long term, showing that BAP1 loss may induce phenotypical evolution of WDPM. BAP1 loss may also progress to malignant mesothelioma in situ and then to invasive mesothelioma. BAP1 immunohistochemistry should be considered for the early diagnosis of MPM.
PubMed: 35950141
DOI: 10.1002/rcr2.1004 -
Environmental Research Sep 2020Measuring and mapping the occurrence of malignant mesothelioma (MM) is a useful means to monitor the impact of past asbestos exposure and possibly identify previously...
INTRODUCTION
Measuring and mapping the occurrence of malignant mesothelioma (MM) is a useful means to monitor the impact of past asbestos exposure and possibly identify previously unknown sources of asbestos exposure.
OBJECTIVE
Our goal is to decompose the observed spatial pattern of incidence of MM in the Lombardy region (Italy) in gender-specific components linked to occupational exposure and a shared component linked to environmental exposure.
MATERIALS AND METHODS
We selected from the Lombardy Region Mesothelioma Registry (RML) all incident cases of MM (pleura, peritoneum, pericardium, and tunica vaginalis testis) with first diagnosis in the period 2000-2016. We mapped at municipality level crude incidence rates and smoothed rates using the Besag York and Mollié model separately for men and women. We then decomposed the spatial pattern of MM in gender-specific occupational components and a shared environmental component using a multivariate hierarchical Bayesian model.
RESULTS
We globally analyzed 6226 MM cases, 4048 (2897 classified as occupational asbestos exposure at interview) in men and 2178 (780 classified as occupational asbestos exposure at interview) in women. The geographical analysis showed a strong spatial pattern in the distribution of incidence rates in both genders. The multivariate hierarchical Bayesian model decomposed the spatial pattern in occupational and environmental components and consistently identified some known occupational and environmental hot spots. Other areas at high risk for MM occurrence were highlighted, contributing to better characterize environmental exposures from industrial sources and suggesting a role of natural sources in the Alpine region.
CONCLUSION
The spatial pattern highlights areas at higher risk which are characterized by the presence of industrial sources - asbestos-cement, metallurgic, engineering, textile industries - and of natural sources in the Alpine region. The multivariate hierarchical Bayesian model was able to disentangle the geographical distribution of MM cases in two components interpreted as occupational and environmental.
Topics: Asbestos; Bayes Theorem; Environmental Exposure; Female; Humans; Incidence; Italy; Male; Mesothelioma; Occupational Exposure; Registries
PubMed: 32526494
DOI: 10.1016/j.envres.2020.109691 -
Cureus Sep 2021Malignant mesotheliomas (MM), as described are rare tumors that are mostly associated with occupational exposure to asbestos. They most commonly occur in the pleura....
Malignant mesotheliomas (MM), as described are rare tumors that are mostly associated with occupational exposure to asbestos. They most commonly occur in the pleura. Other unfamiliar sites where they can occur are the peritoneum, pericardium, and tunica vaginalis. There is no significant correlation between the amount and duration of asbestos exposure to mesothelioma development as reported by various studies over the years. Apart from the environmental exposure, the development of malignant mesothelioma has been linked to a mutation in the BAP1 gene, which can predispose the patient to develop other malignancies associated with BAP1 mutation. We report a case of a 43-year-old man without any significant risk factors, who presented with a complaint of abdominal discomfort and was found to have malignant peritoneal mesothelioma (MPM). With a known familial history of mesothelioma and melanoma, our patient underwent genetic testing which revealed a mutation in BAP1, affirming the strong association with the development of MPM. Young patients who develop malignant mesothelioma without risk factors for MM should have germline testing for BAP1. This case report is unique and highlights a familial variant of mesothelioma, even rare with peritoneal mesothelioma in our patient.
PubMed: 34725624
DOI: 10.7759/cureus.18380