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Extramedullary involvement of multiple myeloma is an uncommon and aggressive condition characterized by proliferation of monoclonal plasma cells located outside the bone marrow. This report describes the imaging findings of a patient who presented with continuous soft-tissue disease on the ribs, suspected as extrapleural space tumors on chest CT. The patient was diagnosed with multiple myeloma through surgical biopsy of the tumor and bone marrow. [ABSTRACT FROM AUTHOR]

Rationale: Malignant pleural effusions (MPEs) are associated with significant health service use and healthcare costs, but the current evidence is limited. Objectives: To compare 12-month post-procedure: 1) health service utilization; and 2) healthcare costs after indwelling pleural catheter (IPC) insertion with at-home drainage performed by home care nursing services, versus in-hospital chemical pleurodesis. Methods: We performed a retrospective population-based study on a cohort of adults with MPEs who underwent IPC insertion or chemical pleurodesis between January 1, 2015 and December 31, 2019 using provincial health administrative data (Ontario, Canada). Patients were followed from the procedure date until death or until 12 months after the procedure. Inverse probability of treatment weighting was performed to adjust for imbalances in baseline characteristics. Differences in length of stay, readmissions, emergency department visits, home care visits, and healthcare costs were estimated using weighted regression analysis. Results: Of 5,752 included individuals, 4,432 (77%) underwent IPC insertion and 1,320 (23%) had pleurodesis. In the weighted sample, individuals who received an IPC had fewer inpatient days (12.4 d vs. 16 d; standardized mean difference, 0.229) but a higher proportion of subsequent admissions for empyema (2.7% vs. 1.1%; P = 0.0002) than those undergoing pleurodesis. Individuals with IPCs received more hours of nursing home care (41 h vs. 21.1 h; standardized mean difference, 0.671) but overall had lower average healthcare costs ($40,179 vs. $46,640 per patient; standardized mean difference, 0.177) than those receiving pleurodesis. Conclusions: IPCs with home nursing drainage are associated with reduced health resource use compared with pleurodesis in adults with MPEs, even after controlling for important baseline and clinical characteristics. Given that both procedures have similar health outcomes, our findings support the ongoing promotion of IPCs to increase outpatient management of patients with MPEs. [ABSTRACT FROM AUTHOR]

We reported a rare case of patient affected by pleural lipoma, studied with ultrasound, X-rays, CT, and MRI examination, with both conventional and functional MR imaging modality (DWI), in order to highlight the diagnostic contribution of the DWI sequence. It is necessary to make an adequate evaluation with dedicated imaging to make a correct differential diagnosis from the corresponding malignant forms which would require more radical treatment. In this case we evaluated the effectiveness of the DWI sequence in reaching the correct diagnosis. DWI highlighted the absence of restriction signal, both in the lesion and in any contextual nodules. ADC map revealed a mean ADC value= 0.38 × 10−3 mm2/s. indicative for benign lesion (lipoma). In our case, The DWI/ADC sequence has contributed to orienting us towards the correct diagnosis representing an added value by showing both the absence of restriction nodules related to the lesion as well as an ADC value compatible with lipoma. Therefore, it is suggested to include the DWI sequence in the protocol for MRI evaluation of pleural masses.

Calcifying fibrous tumors are rare lesions that occur throughout the body. A 35-year-old man presented with exertional dyspnea. Computed tomography showed a polypoid mass abutting pericardium, diaphragm, and left chest wall, and a pleural-based lesion adjacent to T12. Thoracoscopy revealed a large mass with diaphragmatic stalk, two pleural-based nodules, and four diaphragmatic nodules. Pathologic analysis of resected lesions showed calcifying fibrous tumors. Three lesions contained heterogenous mutations associated with this tumor type. The patient is disease free 1 year later. Calcifying fibrous tumors should be recognized as rare multifocal pleural and diaphragmatic-based tumors. Complete resection leads to excellent survival for patients with this uncommon disease.

Simple Summary: The current imaging method recommended in patients with a suspicion of pleural malignancy is CT which has been shown to have certain downsides and limitations—from requiring the administration of the contrast agent and a relatively high radiation dosage to its restricted capacity for the differentiation of the pleural malignancies from the surrounding tissues. During the last few years, numerous studies have suggested that MRI could provide a solution to some of these issues, as various MRI sequences could not only detect and delineate pleural tumors more effectively than CT but also provide additional data on the tumors' physiology or histology. In this review we summarize current knowledge on the primary pleural neoplasms and discuss potential applications of MRI in patients with pleural malignancies, as well as the current limitations of both the method itself and the research involving it. The primary pleural neoplasms constitute around 10% of the pleural tumors. The currently recommended method for their imaging is CT which has been shown to have certain limitations. Strong development of the MRI within the last two decades has provided us with a number of sequences that could potentially be superior to CT when it comes to the pleural malignancies' detection and characterization. This literature review discusses the possible applications of the MRI as a diagnostic tool in patients with pleural neoplasms. Although selected MRI techniques have been shown to have a number of advantages over CT, further research is required in order to confirm the obtained results, broaden our knowledge on the topic, and pinpoint the sequences most optimal for pleural imaging, as well as the best methods for reading and analysis of the obtained data. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase 7 (CDK7) is a protein kinase that plays a major role in transcription initiation. Yes-associated protein (YAP) is a main effector of the Hippo/YAP signalling pathway. Here, we investigated the role of CDK7 on YAP regulation in human malignant pleural mesothelioma (MPM). We found that in microarray samples of human MPM tissue, immunohistochemistry staining showed correlation between the expression level of CDK7 and YAP (n = 70, r = .513). In MPM cells, CDK7 expression level was significantly correlated with GTIIC reporter activity (r = .886, P = .019). Inhibition of CDK7 by siRNA decreased the YAP protein level and the GTIIC reporter activity in the MPM cell lines 211H, H290 and H2052. Degradation of the YAP protein was accelerated after CDK7 knockdown in 211H, H290 and H2052 cells. Inhibition of CDK7 reduced tumour cell migration and invasion, as well as tumorsphere formation ability. Restoration of the CDK7 gene rescued the YAP protein level and GTIIC reporter activity after siRNA knockdown in 211H and H2052 cells. Finally, we performed a co-immunoprecipitation analysis using an anti-YAP antibody and captured the CDK7 protein in 211H cells. Our results suggest that CDK7 inhibition reduces the YAP protein level by promoting its degradation and suppresses the migration and invasion of MPM cells. Cyclin-dependent kinase 7 may be a promising therapeutic target for MPM.

A solitary fibrous tumor (SFT) of the pleura is a rare chest wall mesenchymal neoplasm which usually arises from CD34-positive sub-mesothelial mesenchymal cells of visceral pleura. It is rare, accounting for less than 5% of all pleural neoplasms. Recently, steroid hormone receptors were recognized in the cells of extra-pleural SFT. Progesterone may participate as a growth factor in many CD34 (+) stromal neoplasms. During pregnancy, the amount of plasma progesterone gradually increases. As a result, it could promote the development of cancers that rely on progesterone. However, the link between SFT and pregnancy has not yet been established. There are only six extra-thoracic SFT-reported cases with accelerated growth during pregnancy, on the literature. Hence, we reported an interesting case of SFT which is the first reported case of thoracic SFT presenting during pregnancy. Moreover, we attempted to clarify the mechanism of this tumor's rapid growth by examining its hormonal receptors status in the cells of this tumor.

PurposeAntiangiogenic agents combined with chemotherapy have efficacy in the treatment of unresectable malignant pleural mesothelioma (MPM). Cediranib (AstraZeneca, Cheshire, United Kingdom), a vascular endothelial growth factor receptor and platelet-derived growth factor receptor inhibitor, demonstrated therapeutic potential in a prior phase I trial. We evaluated a phase II trial for efficacy.Patients and methodsSWOG S0905 (ClinicalTrials.gov identifier: NCT01064648) randomly assigned cediranib or placebo with platinum-pemetrexed for six cycles followed by maintenance cediranib or placebo in unresectable chemotherapy-naïve patients with MPM of any histologic subtype. Primary end point was Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 progression-free survival (PFS). Secondary end points included overall survival, PFS by modified RECIST v1.1, response (modified RECIST and RECIST v1.1), disease control, and safety/toxicity. The trial was designed to detect a difference in RECIST v1.1 PFS at the one-sided 0.1 level using a stratified log-rank test.ResultsNinety-two eligible patients were enrolled (75% epithelioid and 25% biphasic or sarcomatoid). The cediranib arm had more grade 3 and 4 diarrhea, dehydration, hypertension, and weight loss. Cediranib improved PFS by RECIST v1.1 (hazard ratio, 0.71; 80% CI, 0.54 to 0.95; P = .062; 7.2 months v 5.6 months) and increased modified RECIST v1.1 response (50% v 20%; P = .006). By modified RECIST v1.1, cediranib numerically increased PFS (hazard ratio, 0.77; 80% CI, 0.59 to 1.02; P = .12; median, 6.9 months v 5.6 months). No significant difference in overall survival was observed.ConclusionThe addition of cediranib to platinum-pemetrexed improved PFS by RECIST v1.1 and response rate by modified RECIST in patients with unresectable MPM. Whereas adding antiangiogenics to chemotherapy has been a successful strategy for some patients, the cediranib toxicity profile and small incremental survival benefit precludes additional development in MPM.

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.

BACKGROUND: While asbestos has long been known to cause mesothelioma, quantitative exposure-response data on the relation of mesothelioma risk and exposure to chrysotile asbestos are sparse. METHODS: Quantitative relationships of mortality from mesothelioma and pleural cancer were investigated in an established cohort of 5397 asbestos textile manufacturing workers in North Carolina, USA. Eligible workers were those employed between 1950 and 1973 with mortality follow-up through 2003. Individual exposure to chrysotile fibres was estimated on the basis of 3420 air samples covering the entire study period linked to work history records. Exposure coefficients adjusted for age, race, and time-related covariates were estimated by Poisson regression. RESULTS: Positive, statistically significant associations were observed between mortality from all pleural cancer (including mesothelioma) and time since first exposure (TSFE) to asbestos (rate ratio [RR], 1.19; 95% confidence interval [CI], 1.06-1.34 per year), duration of exposure, and cumulative asbestos fibre exposure (RR, 1.15; 95% CI, 1.04-1.28 per 100 f-years/mL; 10-year lag). Analyses of the shape of exposure-response functions suggested a linear relationship with TSFE and a less-than-linear relationship with cumulative exposure. Restricting the analysis to years when mesothelioma was coded as a unique cause of death yielded stronger but less precise associations. CONCLUSIONS: These observations support with quantitative data the conclusion that chrysotile causes mesothelioma and encourage exposure-response analyses of mesothelioma in other cohorts exposed to chrysotile.

Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune-checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy. Our findings highlight new avenues for further investigation of MPM biology and novel therapeutic options. SIGNIFICANCE: Through a comprehensive integrated genomic study of 74 MPMs, we provide a deeper understanding of histology-independent determinants of aggressive behavior, define a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity, and discovered strong expression of the immune-checkpoint gene VISTA in epithelioid MPM.See related commentary by Aggarwal and Albelda, p. 1508.This article is highlighted in the In This Issue feature, p. 1494.

A solitary fibrous tumor (SFT) of the pleura is a rare chest wall mesenchymal neoplasm which usually arises from CD34-positive sub-mesothelial mesenchymal cells of visceral pleura. It is rare, accounting for less than 5% of all pleural neoplasms. Recently, steroid hormone receptors were recognized in the cells of extra-pleural SFT. Progesterone may participate as a growth factor in many CD34 (+) stromal neoplasms. During pregnancy, the amount of plasma progesterone gradually increases. As a result, it could promote the development of cancers that rely on progesterone. However, the link between SFT and pregnancy has not yet been established. There are only six extra-thoracic SFT-reported cases with accelerated growth during pregnancy, on the literature. Hence, we reported an interesting case of SFT which is the first reported case of thoracic SFT presenting during pregnancy. Moreover, we attempted to clarify the mechanism of this tumor's rapid growth by examining its hormonal receptors status in the cells of this tumor. [ABSTRACT FROM AUTHOR]

Although tumour PD-L1 (CD274) expression had been used as a predictive biomarker in checkpoint immunotherapy targeting the PD1/PD-L1 axis in various cancers, the regulation of PD-L1 (CD274) expression is unclear. Yes-associated protein (YAP), an important oncogenic protein in Hippo signalling pathway, reportedly promotes cancer development. We investigated whether inhibition of YAP down-regulates PD-L1 (CD274) in human malignant pleural mesothelioma (MPM). Western blotting showed that 2 human MPM cell lines (H2052 and 211H) had increased PD-L1 protein expression compared to H290, MS-1 and H28 cells. In H2052 and 211H cells, PD-L1 mRNA expression was significantly increased compared to other MPM cell lines; YAP knockdown by small interfering RNA decreased PD-L1 protein and mRNA expression. Forced overexpression of the YAP gene increased PD-L1 protein expression in H2452 cells. Chromatin immunoprecipitation (ChIP) assay showed the precipitation of PD-L1 enhancer region encompassing 2 putative YAP-TEAD-binding sites in H2052 cells. We found that, in human MPM tissue microarray samples, YAP and PD-L1 concurrently expressed in immunohistochemistry stain (n = 70, P

Malignant pleural mesothelioma (MPM) is an aggressive cancer for which more effective treatments are needed. In this study, strong to moderate staining of MET and ERK5 was detected in 67.1 and 48% of the analyzed 73 human mesothelioma tumors, and significant correlation of MET and ERK5 expression was identified (P

Background: Lung cancer is one of the most common cancers worldwide. Lung and pleural biopsies are the most commonly performed procedures for the diagnosis of suspicious lesions in the lungs and pleura. The main objective of the study was to identify the incidence pattern of lung and pleural neoplasms in the tertiary care center of Nepal. Methods: A hospital-based cross-sectional study was carried out from April 20, 2019, to April 19, 2020, taking the histopathological specimens with suspicion of lung or pleural neoplasms. Demographic data, type of biopsy obtained, laterality of involvement, smoking status, and histopathological diagnosis in lungs and pleura were collected in the pro forma and entered in Microsoft excel. The statistical analysis was done by using SPSS version 16. Results: Out of 7859 biopsies and resection specimens, 272 (3.5%) cases of lung and pleural specimens were obtained during the study period, out of which 101 (37.1%) were lung and 16 (5.9%) were pleural neoplasms altogether constituting 117 (43.01%) cases of the total lung and pleural biopsies. Out of 117 cases, trucut biopsy was done for 104 (88.9%) cases and 62 (53%) cases specimens were obtained from the right side. Among the lung neoplasms, 87 (86.1%) were epithelial tumors among which 38 (43.7%) cases were Squamous cell carcinoma. Among the pleural neoplasms, 9 (56.3%) cases were metastatic tumors. Smokers with more than 20 pack years were at significant risk of developing epithelial lung neoplasms (p≡0.042). The adjusted odds ratio for epithelial lung neoplasm was 15.26 [95% Confidence Interval (CI) 2.91-20.07] in persons who smoke. Conclusion: Lung and pleural neoplasms were more prevalent in males in this study. Squamous cell carcinoma is the commonest histological type of lung cancer, closely followed by Adenocarcinoma in our study. Smokers were 15 times more likely to have epithelial lung neoplasms than non-smokers.

Solitary fibrous tumors of the pleura are less than 5% of the pleural tumors. Eighty percent of the cases are caused by visceral pleura and 20% by parietal pleura. They are usually asymptomatic. These tumors, which can reach very large dimensions, can cause coughing and shortness of breath due to compression. Hypoglycemia and hypertrophic pulmonary osteoarthropathy are other symptoms. Definitive diagnosis is usually made after tumor excision. Abundant cellular structure with histologically dense and overlapping nuclei, more than 4 mitotic activities per site, pleomorphism with cytonuclear atypia, presence of large necrotic and hemorrhagic areas support malignancy. In addition, pleural effusion coexistence and atypical localization of the lesion are other findings supporting malignancy. Complete resection of the tumor is the most effective treatment and at the same time the most effective way to prevent recurrence. [ABSTRACT FROM AUTHOR]

Introduction. Pleural synovial sarcoma (SS) is a rare type of mesenchymal tumor, that can easily be misdiagnosed. Case report. We presented a case of primary monophasic SS of the pleura in a middle-aged woman who initially presented with dyspnoea and a large pleural effusion. Computed tomography (CT) scans showed a large, well-demarcated right lung tumor mass. After a blind closed biopsy of the pleura, the tumor was misdiagnosed as adenocarcinoma and treated with chemotherapy but without response. The correct diagnosis was established after surgery and histological and immunohistochemical analyses. The diagnosis was fulfilled with cytogenetic analysis showing the typical translocation t (X,18). The tumor was completely extirpated during surgery. CT of the chest done four, and positron emission tomography done six months after surgery showed encapsulated re-active pleural effusion without tumor rest or relapse. In contrast, a CT scan done nine months after surgery showed an extrapulmonary soft-tissue mass in contact with the lower right lobe highly suspicious of tumor relapse. Surgery was performed, and the described mass was extirpated, but histological analysis showed no presence of malignant tissue. CT scan performed three months later showed no signs of the disease relapse. Conclusion. Considering that pleural SS can easily be misdiagnosed, immunohistochemical as well as cytogenetic analysis should always be performed in order to reach the proper diagnosis.

These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Malignant Pleural Mesothelioma (MPM). These NCCN Guidelines Insights discuss systemic therapy regimens and surgical controversies for MPM. The NCCN panel recommends cisplatin/pemetrexed (category 1) for patients with MPM. The NCCN panel also now recommends bevacizumab/cisplatin/pemetrexed as a first-line therapy option for patients with unresectable MPM who are candidates for bevacizumab. The complete version of the NCCN Guidelines for MPM, available at NCCN.org, addresses all aspects of management for MPM including diagnosis, evaluation, staging, treatment, surveillance, and therapy for recurrence and metastasis; NCCN Guidelines are intended to assist with clinical decision-making.

Malignant pleural mesothelioma (MPM), a rare malignancy with a poor prognosis, is mainly caused by exposure to asbestos or other organic fibers, but the underlying genetic mechanism is not fully understood. Genetic alterations and causes for multiple primary cancer development including MPM are unknown. We used whole exome sequencing to identify somatic mutations in a patient with MPM and two additional primary cancers who had no evidence of venous, arterial, lymphovascular, or perineural invasion indicating dissemination of a primary lung cancer to the pleura. We found that the MPM had R282W, a key TP53 mutation, and genome-wide allelic loss or loss of heterozygosity, a distinct genomic alteration not previously described in MPM. We identified frequent inactivating SETDB1 mutations in this patient and in 68 additional MPM patients (mutation frequency: 10%, 7/69) by targeted deep sequencing. Our observations suggest the possibility of a new genetic mechanism in the development of either MPM or multiple primary cancers. The frequent SETDB1 inactivating mutations suggest there could be new diagnostic or therapeutic options for MPM.

Objectives: The purpose of this study was to analyze the diagnostic performance and clinical application of diffusion-weighted imaging (DWI) in patients with suspected pleural malignancy (PM). Methods: A retrospective review of patients with suspected PM was performed from March 2014 to August 2018 (NCT 02320617). All patients underwent chest DWI and computed tomography (CT) with cytological or histopathological findings as reference standards. The diagnostic performance of DWI and CT was analyzed and compared. A DWI diagnostic algorithm with three sequential steps was established. Results: Seventy patients (61.6 ± 13.6 years; 47 males and 23 females) were included. The sensitivity of DWI (94.2%, 49/52) for the diagnosis of PM was significantly higher compared with CT (67.3%, 35/52), with similar specificity (72.2% vs. 72.2%, respectively). The apparent diffusion coefficient of malignant lesions (1.15 ± 0.32 × 10−3 mm2/s) was lower compared with benign lesions (1.46 ± 0.68 × 10−3 mm2/s), but the cutoff value was difficult to define for overlap between groups. Approximately 62.5% (5/8) of invasive procedures were avoided when using the DWI diagnostic algorithm in patients with suspected PM without N3 lymph node or extra-thoracic metastasis. Conclusion: Including DWI into the diagnostic algorithm of suspected PM can effectively identify malignancy and avoid unnecessary invasive procedures, which may have some potential in clinical application. Key Points: • Diffusion-weighted imaging can identify pleural malignancy much more efficiently than CT. • A diffusion-weighted imaging diagnostic algorithm helped to avoid unnecessary invasive procedures in patients without N3 lymph node or extra-thoracic lesions. • A hyperintense signal on DWI at a high b value (800 s/mm2) but not at a low b value (50 s/mm2) was a reliable signature of PM. [ABSTRACT FROM AUTHOR]

Extramedullary involvement of multiple myeloma is an uncommon and aggressive condition characterized by proliferation of monoclonal plasma cells located outside the bone marrow. This report describes the imaging findings of a patient who presented with continuous soft-tissue disease on the ribs, suspected as extrapleural space tumors on chest CT. The patient was diagnosed with multiple myeloma through surgical biopsy of the tumor and bone marrow., Competing Interests: The author declares no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Although considered a disease of the elderly, a subset of patients with mesothelioma are young (

BackgroundThe Hedgehog (Hh) signaling pathway has been implicated in stem cell maintenance and its activation is aberrant in several types of cancer including mesothelioma. Protein kinase CK2 affects several cell signaling pathways through the mechanism of phosphorylation.MethodsProtein and mRNA levels of CK2α and Gli1 were tested by quantitative RT-PCR and immunohistochemistry staining in mesothelioma samples and cell lines. Down-regulated Gli1 expression and transcriptional activity were demonstrated by RT-PCR, Western blot and luciferase reporter assay.ResultsIn this study, we show that CK2α is over-expressed and a positive regulator of Hegdehog/Gli1 signaling in human malignant pleural mesothelioma. First of all, we found that the mRNA levels of CK2α and Gli1 were broadly elevated and correlated (n = 52, r = 0.401, P

Malignant pleural mesothelioma (MPM) poses diagnostic challenges due to its resemblance to benign pleural pathologies and different histological subtypes. Several immunohistochemistry markers have been employed to aid in accurate diagnosis. The present systematic review and meta-analysis aimed to assess the diagnostic performance of various immunohistochemistry markers in malignant pleural mesothelioma diagnosis and its histological subtypes. Following the PRISMA guidelines, we systematically searched the literature for articles on using different immunohistochemical markers in MPM and its histological subtypes. EMBASE, LILACS, MEDLINE, and Virtual Health Library were searched for studies published up to August 2023. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) criteria to assess the quality of the included articles. Meta-analyses were performed to determine prevalence using a random-effects model. 103 studies met the inclusion criteria, comprising a diverse range of immunohistochemistry markers. EMA and desmin-loss exhibited high sensitivity (96% and 92%, respectively) in distinguishing malignant pleural mesothelioma from benign pleural pathologies. Specificity was notably high for both BAP1-loss and survivin expression at 100%. Subtype-specific analyses demonstrated that EMA and HEG1 were sensitive markers for epithelioid mesothelioma, while GLUT1 showed high sensitivity for sarcomatoid mesothelioma. In cases comparing epithelioid mesothelioma and lung adenocarcinoma, CAM5.2 and calretinin displayed high sensitivity, while WT1 and BAP1-loss demonstrated exceptional specificity for malignant epithelioid mesothelioma. In the case of sarcomatoid mesothelioma and sarcomatoid lung carcinoma, GATA3 exhibited the most heightened sensitivity, while GATA3 and D2–40 displayed the best specificity for sarcomatoid malignant mesothelioma diagnosis. Immunohistochemistry markers are essential in accurately diagnosing malignant pleural mesothelioma and its histological subtypes. This systematic review and meta-analysis provide a comprehensive insight into the diagnostic performance of these markers, facilitating their potential clinical utility in the discrimination of malignant pleural mesothelioma from other pleural pathologies and the differentiation of malignant pleural mesothelioma subtypes. [ABSTRACT FROM AUTHOR]

Malignant pleural mesothelioma (MPM) is a rare malignancy of the pleura that is frequently resistant to conventional therapies. Immunotherapy is a promising investigational approach for MPM that has shown some evidence of clinical benefit in select patients. However, tumor-induced immunosuppression is likely a major impediment to achieving optimal clinical responses to immunotherapeutic intervention. MPM contains a variable degree of infiltrating T-regulatory cells and M2 macrophages, which are believed to facilitate tumor evasion from the host immune system. Additional immunosuppressive factors identified in other human tumor types, such as tumor-associated programmed death ligand-1 expression, may be relevant for investigation in MPM. Conventional cytoreductive therapies, such as radiation, chemotherapy, and surgery, may play a critical role in successful immunotherapeutic strategies by ablating intratumoral and/or systemic immunosuppressive factors, thus creating a host environment more amenable to immunotherapy. This article reviews the immunotherapeutic approaches being evaluated in patients with MPM and discusses how immunotherapy might be rationally combined with conventional tumor cytoreductive therapies for this disease.

BackgroundMalignant mesothelioma is an aggressive, treatment-resistant tumor arising from mesothelium of pleura, peritoneum and pericardium. Despite current combined regimen, its prognosis remains dismal, calling for more effective targeted therapies. We investigated whether aberrant Hh activation may play a role in mesothelioma.MethodsSMO and SHH expression levels were analyzed in 46 mesothelioma tissue specimens with real-time RT-PCR, and correlation with survival was analyzed with univariate and multivariate Cox proportional hazards models, Kaplan-Meier survival curves, and the log-rank test. We also examined multiple mesothelioma cell lines for SMO expression and the effect of Hh inhibition by a specific SMO antagonist on cell proliferation by MTS assay.ResultsWe observed strong correlation between higher SMO and SHH expression levels with poorer overall survival. Remarkably, Hh inhibition by a specific SMO inhibitor significantly suppressed cell proliferation in the mesothelioma cell lines examined.ConclusionOur data strongly support that Hh signaling deregulation plays critical roles in proliferation of mesothelioma, and consistently exerts significant impact on prognosis of the disease. Therefore our findings revealed the hitherto unappreciated role of Hh activation in mesothelioma, and pinpointed Hh signaling antagonist as a potential new therapy against this devastating disease.

Objective: To explore the relationship between clinicopathological features, treatment and prognosis of patients with malignant mesothelioma, and provide theoretical basis for the prevention and treatment of malignant mesothelioma. Methods: In November 2022, the clinical data of 37 patients with malignant mesothelioma diagnosed in Qingdao Central Hospital from July 2014 to November 2022 were retrospectively analyzed, and the prognostic factors were analyzed by Kaplan-Meier and log-rank tests. Results: The median age of the 37 patients was 66 years old, all patients were confirmed by pathology. The median survival time of all patients was 30.00 months. The 1-year, 2-year, 3-year and 5-year cumulative survival rates were 70.27% (26/37), 48.65% (18/37), 16.22% (6/37) and 13.51% (5/37), respectively. Compared with different treatments, the median survival time of palliative care patients was 5.00 months, which was significantly lower than that of operation group (30.33 months), chemotherapy group (30.00 months), surgery combined with chemotherapy group (30.00 months) and chemotherapy combined with bevacizumab targeted therapy group (47.42 months) ( P <0.05). Gender, age (≥60 years old or <60 years old), smoking history, occupational exposure history, disease site, and surgical history were not factors affecting the survival of malignant mesothelioma patients ( P >0.05) . Conclusion: The clinical symptoms of malignant mesothelioma are not specific, but early initiation of treatment can still prolong survival, and chemotherapy combined with anti-vascular targeted therapy shows better therapeutic effect.