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PURPOSE Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone. PATIENTS AND METHODS Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1, or cisplatin 75 mg/m2 on day 1. Both regimens were given intravenously every 21 days. RESULTS A total of 456 patients were assigned: 226 received pemetrexed and cisplatin, 222 received cisplatin alone, and eight never received therapy. Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm ( P = .020, two-sided log-rank test). The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77. Median time to progression was significantly longer in the pemetrexed/cisplatin arm: 5.7 months versus 3.9 months ( P = .001). Response rates were 41.3% in the pemetrexed/cisplatin arm versus 16.7% in the control arm ( P < .0001). After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxicity, resulting in a significant reduction in toxicities in the pemetrexed/cisplatin arm. CONCLUSION Treatment with pemetrexed plus cisplatin and vitamin supplementation resulted in superior survival time, time to progression, and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma. Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time.

Introduction Desmoplastic malignant pleural mesothelioma (DMPM) is a sarcoma type mesothelioma, comprising about 5% of malignant pleural mesotheliomas. Although effusion cytology is commonly used as the primary diagnostic approach for mesothelioma, this may not be useful for DMPM due to its desmoplastic nature and bland cellular atypia. We hereby report a case of DMPM diagnosed through autopsy along with its cytological features that have not been described previously. Case presentation A male in his 60s with a history of occupational asbestos exposure was referred to our hospital with right chest pain. Chest computed tomography scan showed right pleural effusion. Thirteen months later, the patient died of respiratory failure. In autopsy, the scrape-imprint smear and the pleural effusions cytology were performed. The scrape-imprint smear samples exhibited spindle cells with mild nuclear atypia and grooves with fibrous stroma. In the pleural effusion cytology, spindle cells having mild nuclear atypia and grooves with loose epithelial connections were observed. Histological examination of the right pleura showed spindle cells proliferating with dense collagen fibers, as seen in cytological samples, thus rendering the diagnosis of DMPM. Diagnosis was confirmed by fluorescence in situ hybridization. Conclusion Cytological procedures, such as pleural effusion cytology and scrape-imprinting method, may be useful as an ancillary tool in the diagnosis of rare tumors such as DMPM.

Background: Since the increasing use of asbestos occurred in China and the long latency period after asbestos exposure, predicting the incidence of malignant mesothelioma played an important role in attracting the attention of clinicians. The Bayesian age-period-cohort prediction model was fitted to predict the development trend from 2016 to 2030 based on the publicly available data of the national cancer registration network. Methods: Malignant mesothelioma incidence data were retrieved from the national cancer registration annual reports from 2005 to 2015. The Bayesian Age-Period-Cohort (APC) Modeling and Prediction package (Institute of Biomedical Engineering, Imperial College, London, UK) was used to describe the trend of malignant mesothelioma incidence and to predict the incidence rate and number of cases until the year of 2030. Findings: The crude incidence rates of malignant mesothelioma decreased from 0.22 per 100 000 in 2005 to 0.16 per 100000 in 2015. After age standardization, the incidence rates remained stable over the 11-year period. The trends were mainly caused by aging. The Bayesian APC model showed that increased from 0.14 per 100 000 in 2016 to 0.19 per 100000 in 2030 and the estimated number of new incident cases was predicted to increase to 2775 in 2030. The age-standardized incidence rate would remain steady. Interpretation: The incidence of malignant mesothelioma would remain stable in the next ten years, but due to its high degree of malignancy, the cancer still needs to be taken more attention at. Funding: Ministry of Science and Technology of the People's Republic of China; Beijing Hope Run Special Fund; Chinese Academy of Medical Sciences; Beijing Municipal Health Commission. Conflict of Interest: All authors declare no competing interests.

Malignant mesotheliomas (MMs) are malignancies of the mesothelium, with primary deposits originating in the pleura, peritoneum, pericardium and the tunica vaginalis (ie, testicular). Metastatic spread is commonly reported to affect the liver, adrenal glands, kidney and contralateral lung (in cases of malignant pleural mesothelioma). Metastases to distant sites are uncommon. Spread to the oral cavity in particular is very rare. A total of 23 cases of metastatic spread to the oral cavity have been reported in the literature to date; of those, 9 cases have been to the tongue. Given the rarity of the site of metastasis, the management remains challenging. This case highlights a rare site of metastasis in MM, discusses treatment options available and briefly talks about technical limitations in treating a mobile structure such as the tongue. Good palliative and supportive care is crucial in managing cases where no curative treatment is possible.

Introduction: The favorable outcomes with immunotherapy for mesothelioma were somewhat unexpected because this tumor has a low tumor mutation burden which has been associated with benefit in other cancers. Because chromosomal rearrangements are common in mesothelioma and have neoantigenic potential, we sought to determine whether they are associated with survival in patients treated with immunotherapy.Methods: Pleural biopsies of mesothelioma after at least one line of therapy were obtained from patients (n = 44) before treatment with nivolumab alone (NCT29908324) or in combination with ipilimumab (NCT30660511). RNA and whole-genome sequencing were performed to identify the junctions resulting from chromosomal rearrangements and antigen processing and presentation gene set expression. Associations with overall survival (OS) were estimated using Cox models. An OS cutoff of 1.5 years was used to distinguish patients with and without durable benefit for use in receiving operating characteristic curves.Results: Although tumor junction burdens were not predictive of OS, we identified significant interactions between the junction burdens and multiple antigen processing and presentation gene sets. The "regulation of antigen processing and presentation of peptide antigen" gene set revealed an interaction with tumor junction burden and was predictive of OS. This interaction also predicted 1.5-year or greater survival with an area under the receiving operating characteristic curve of 0.83. This interaction was not predictive of survival in a separate cohort of patients with mesothelioma who did not receive immune checkpoint inhibitors.Conclusions: Analysis of structural variants and antigen presentation gene set expression may facilitate patient selection for immune checkpoint inhibitors. (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

BAP1 is a tumor suppressor gene implicated in DNA repair and cell growth. Individuals with germline BAP1 mutations are at a significantly increased risk for developing many different cancers including malignant mesothelioma, uveal melanomas, cutaneous melanomas and renal clear cell carcinomas. Meningiomas with absent BAP1 expression have been reported to be more aggressive and present often with rhabdoid features. Here, we report the co-occurrence of pleural mesotheliomas and meningiomas in patients with germline BAP1 mutations. We describe the cancer history, family pedigrees, clinical management, and outcomes of four BAP1 germline mutation carrier families with a history of malignant mesothelioma and meningioma.

BACKGROUND: Pleural mesothelioma is a deadly asbestos induced cancer. Less than 10% of mesothelioma patients survive 5 years post diagnosis. However survival can range from a few months to a number of years. Accurate prediction of survival is important for patients to plan for their remaining life, and for clinicians to determine appropriate therapy. One unusual feature of mesothelioma is that patients frequently present with tumor-associated pleural effusions early in the course of the disease. OBJECTIVE: To study whether cells and molecules present in pleural effusions provide prognostic information for mesothelioma. METHODS: We profiled the cellular constituents and concentrations of 40 cytokines, chemokines and cellular factors (collectively “soluble factors”) involved in inflammatory and immune signalling pathways in pleural effusion samples from 50 mesothelioma patients. Associations with survival were evaluated by Cox proportional hazards regression methods. Results for the two soluble factors most significantly and independently associated with survival were validated in an independent set of samples (n= 51) using a separate assay system. RESULTS: Survival analysis revealed that IL8, IL2Ra (CD25) and PF4 were independent determinants of a more negative prognosis in mesothelioma patients, independent of other known prognostic factors. Lipocalin2 and IL4 were associated with better prognosis. CONCLUSIONS: This study demonstrates that pleural effusions rich in a range of soluble factors are associated with poor prognosis. These findings will enhance our ability to prognosticate outcomes in mesothelioma patients.

Background. Difficulties of differential diagnostics of exudative pleuritis due to pleura mesothelioma and such one of tubercular etiology can take a long time that is the reason of delayed well-timed and correct treatment order. Etiological diagnostics of exudative pleuritis has to be based on an integrated approach taking into account the data of clinical inspection of a patient, a laboratory research of pleural exudate, radial, instrumental, pathomorphological and surgical methods. The aim of our study is to establish the features of diagnosis of exudative pleuritis due to pleura mesothelioma by determining of informativeness and value of applied diagnostic methods for further use for differential diagnostics with exudative pleuritis of tubercular etiology on the cases of own clinical observations. Materials and methods. Four clinical cases of diagnostics of pleura mesothelioma in the patients with exudative pleuritis at Municipal Institution “Zaporizhzhia Regional Antituberculous Clinical Dispensary” were analyzed. Results. Four cases of pleura mesothelioma were diagnosed at Municipal Institution “Zaporizhzhia Regional Antituberculous Clinical Dispensary” within differential diagnostics of exudative pleuritis of obscure origin. In all cases the following similar features of pleura mesothelioma were observed: patients were male; patients complained about dyspnoea at exercise stress, thorax pain (on the side of mesothelioma localization), general weakness, periodic cough; the patients denied tuberculosis contact; the general blood test revealed only lymphopenia against the background of the accelerated ESR; micobacteria of tuberculosis were not revealed at all; steady accumulation of an exudate, despite its systematic evacuation; cytologic research of pleural liquid was characterized by a moderate turbidity, serous (serous and hemorrhagic) character, with the specific weight of 1015–1016, rising of protein to 33–66 g/l, positive Rivalta’s test, a lymphocytosis of 93–100 %, a proliferation of mesothelium with dystrophia signs in cytoplasma, groups of cells with enlarged nucleoluses in cell cores; aspirate of epithelial lining fluid (even in the absence of pathology of a tracheobronchial tree) is presented by alveolus cells and bronchial epithelium, glandular groups of cells with hyperplasia signs; typical signs of pleura mesothelioma of pleural cavity at ultrasound examination were: identification of formations of rounded shape, various echogenicity, the sizes and quantity (depending on a form: nodular or diffusive), with accurate contours of masses which intimately adjoins to visceral pleura and the structure often contains from single to numerous small hyperechogenic inclusions against the background of liquid; in all cases video-assisted thoracoscopy data of visceral pleura was confirmed by pathohistological examination. Conclusions. All applied diagnostic methods were high-informative that allowed quickly diagnose and prescribe the correct treatment. On their basis the algorithm of differential diagnostics of specific exudative pleuritis and caused pleura mesotheliomas were roentgenography of thoracic organs (if possible computer tomography), an ultrasonic examination of thoracic organs, cytologic research of pleural liquid, video thoracoscopy with biopsy of parietal pleura, research of pleura smear and pathohistological examination of biopsy material.

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, P0.001), more likely to be female (46.3% vs 20.2%, P0.001), 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.

Introduction Peritoneal malignant mesothelioma is an extremely rare tumor and is a difficult diagnosis to be made on cytology alone. We report 3 cases where the cytologic features were misdiagnosed as carcinoma/lymphoma but histopathology and immunohistochemistry (IHC) established the diagnosis of malignant mesothelioma. Clinical details Case 1 was a 60-year-old man with multiloculated ascites and omental caking. Peritoneal fluid was reported as malignant on cytology but was misclassified as adenocarcinoma. Case 2, a 45-year-old man with ascites and peritoneal nodularity, radiologically mimicking peritoneal carcinomatosis, was also reported positive for malignancy on ascitic fluid cytology. Fine-needle aspiration (FNAC) from omental fat revealed signet ring cells, thus misleading to cytologic diagnosis of adenocarcinoma. Case 3 was a 63-year-old man with perisplenic mass with extensive omental caking and peritoneal nodularity that was also suspected to be peritoneal carcinomatosis on radiology. FNAC smears from perisplenic mass showed sheets of plasmacytoid cells. On cytology, the differential diagnoses offered were neuroendocrine tumor or non-Hodgkin lymphoma. The diagnosis of malignant mesothelioma was established only after IHC on histopathologic sections in all these cases. None of our patients had history of prior asbestos exposure. Conclusion In such clinical scenarios, with radiology suggesting peritoneal carcinomatosis, the cytologic features need corroboration by IHC/fluorescence in situ hybridization on cell block or biopsy to correctly identify malignant mesothelioma and differentiate it from metastatic carcinomatous deposits and benign mesothelial proliferation.

Background Overall survival (OS) for malignant pleural mesothelioma (MPM) in vulnerable subgroups remains poorly understood with scarce data available to guide treatment decisions. The study describes real-world detailed treatment patterns and outcomes of patients with advanced MPM overall and specifically in elderly and poor performance status (PS) patients. Methods Retrospective chart review was performed for all patients with histologically confirmed MPM seen at University Health Network/Princess Margaret Cancer Centre (UHN-PM). Results A total of 667 patients with MPM were identified and 304 advanced-disease MPM (aMPM) patients had continuing care at U HN- P M (UP-cohort). In the UP-cohort, 77% of patients received ≥ one line of systemic treatment. Systemic therapy trial participation was 39%. Patients not treated with systemic therapy (29%) were more likely to be ≥ 75 years and PS ≥ 2. Median OS was 15.3 months (95%CI 13.6-18.3), with longer survival in treated vs. untreated patients (17.4 vs. 10.6 months; P = .01). Longer survival with systemic treatment was seen in patients ≥75 years (12.7 vs. 6.6 months) and patients with poor PS (9.1 vs. 5.9 months). Median progression-free-survival (PFS) and OS for patients treated with second-line therapy was poor (3.0 and 8.9 months, respectively). Discussion In our real-world analysis of patients with aMPM treated at an academic referral centre, systemic treatment was given to the majority of patients and benefit was seen even in the elderly and poor PS patients frequently underrepresented in clinical trials. Trial participation was potentially facilitated by the formation of a dedicated multidisciplinary MPM clinic.

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.

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.

The peritoneum is a unique serosal membrane, which can be the site of primary tumors and, more commonly, secondary pathologic processes. Peritoneal carcinomatosis is the most common malignant condition to affect the peritoneal cavity, and the radiologist plays an important role in making the diagnosis and assessing the extent of disease, especially in sites that may hinder surgery. In this review, we address the role of the radiologist in the setting of peritoneal pathology, focusing on peritoneal carcinomatosis as this is the predominant malignant process, followed by revising typical imaging findings that can guide the differential diagnosis. We review the most frequent primary and secondary peritoneal tumor and tumor-like lesions, proposing a systemic approach based on clinical history and morphological appearance, namely distinguishing predominantly cystic from solid lesions, both solitary and multiple.

Background: Malignant Mesothelioma (MM) is a rare but aggressive tumor that arises in the lungs. Commonly, costly imaging and laboratory resources, i.e. (X-rays imaging, Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) scans, biopsies, and blood tests) have already been utilized for the diagnosis of MM. Even though these diagnostic measures are expensive and unavailable in distant areas, some of these diagnosis methods are also very painful for the patient, i.e., biopsy and cytology of pleural fluid. Objective: In this study, we proposed a diagnosis model for early identification of MM via machine learning techniques. We explored the health records of 324 Turkish patients, which show the symptoms related to MM. The data of patients include socio-economic, geographical, and clinical features. Methods: Different feature selection methods have been employed for the selection of significant features. To overcome the data imbalance problem, various data-level resampling techniques have been utilized to obtain efficient results. The Gradient Boosted Decision Tree (GBDT) method has been used to develop the diagnostic model. The performance of the GBDT model is also compared with traditional machine learning algorithms. Results : Our model's results outperformed other models, both on balance and imbalance data. The results clearly show that undersampling techniques outperformed by imbalanced data even without resampling based on accuracy and Receiving Operating Characteristic (ROC) value. Conversely, it has also been observed that oversampling techniques outperformed undersampling and imbalanced data based on accuracy and ROC. All classifiers employed in this study achieved efficient results utilizing feature selection-based methods (OneR, information gain, and Relief-F), but the results of the other two methods (gain ratio and Correlation) were not entirely promising. Finally, when the combination of Synthetic Minority Oversampling Technique (SMOTE) and OneR was applied with GBDT, it gave the most favorable results based on accuracy, F-measure, and ROC. Conclusion: The diagnosis model has also been deployed to assist doctors, patients, medical practitioners, and other healthcare professionals for early diagnosis and better treatment of MM.

PURPOSE Pathogenic BAP1 germline variants cause a tumor-predisposition syndrome ( BAP1-TPDS) linked to uveal melanoma, mesothelioma, cutaneous melanoma, and renal cell carcinoma. Surveillance of carriers of pathogenic BAP1 variants provides an opportunity for early tumor detection; however, there are no evidence-based guidelines for management of BAP1-TPDS, nor health economic evaluation; this study aims to provide this evidence. METHODS We created a Markov microsimulation health state transition model of BAP1 germline carriers to predict if active surveillance for the four main tumors influences survival and improves associated economic costs with a time horizon of 100 years from the perspective of the healthcare system (N = 10,000). Model inputs were derived from data published by the BAP1 Interest Group Consortium and other studies. Management and healthcare costs were extracted from Australian costing schedules (final figures converted to US dollars [USD]), and outcomes compared for individuals receiving surveillance with those in a nonsurveillance arm. Robustness was evaluated on 10,000 iterations of a 100-sample random sampling of the model output. RESULTS On average, surveillance of BAP1 carriers increased survival by 4.9 years at an additional cost of $6,197 USD for the healthcare system including surveillance costs ($1,265 USD per life year gained). The nonsurveillance arm had more diagnosed late tumors (62.8% v 10.7%) and a higher rate of BAP1-related deaths (50.2% v 35.4%; a 29.5% increase). The model was cost-effective under all sensitivity analyses. Our secondary robustness analysis estimated that 99.86% of 100-sample iterations were cost-effective and 19.67% of these were cost-saving. CONCLUSION It is recommended that carriers of BAP1 germline variants are identified and undertake active surveillance, as this model suggests that this could improve survival and be cost-effective for the healthcare system.

Malignant pleural mesothelioma is a rare tumor arising from the pleural mesothelial cells. Imaging plays a crucial role in the diagnosis, staging, and management of patients with mesothelioma. Accurate staging to stratify patients into homogeneous groups is required to evaluate the effectiveness of multimodality therapeutic regimens. CT and PET/CT are recommended for the initial staging of MPM. MRI adds value to further assess invasion of the tumor into the diaphragm, chest wall, and mediastinum. This review will discuss pearls and pitfalls in the imaging of mesothelioma with emphasis on the roles of CT, MRI, and PET/CT.

A 61-year-old woman was diagnosed with an incidental liver lesion with a satellite lesion that had features of a secondary liver metastasis. Investigations for primary sites did not reveal a primary tumour. The lesion was not amenable to biopsy due to location. Intraoperatively, the two lesions were adjacent, but the first was on the diaphragm and the lesion was in segment 7 of the liver. The liver lesion underwent non-anatomical resection and the diaphragmatic lesion was resected separately. The histopathology diagnosed peritoneal mesothelioma in the lesion removed from diaphragm and the liver lesion to be local metastatic spread to an area of liver that was in close contact (a ‘kissing’ lesion). This report portrays a rare occurrence of liver metastases from peritoneal mesothelioma and discusses the current evidence for diagnosis and treatment.