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Background: Malignant Pleural Mesothelioma (MPM) is a dreadful disease escaping the classical genetic model of cancer evolution and characterized by wide heterogeneity and transcriptional plasticity. Clinical evolution of MPM is marked by a progressive transdifferentiation that converts well differentiated epithelioid (E) cells into undifferentiated and pleomorphic sarcomatoid (S) phenotypes. Catching the way this transition takes place is necessary to understand how MPM develops and progresses and it is mandatory to improve patients' management and life expectancy. Bulk transcriptomic approaches, while providing a significant overview, failed to resolve the timing of this evolution and to identify the hierarchy of molecular events through which this transition takes place., Methods: We applied a spatially resolved, high-dimensional transcriptomic approach to study MPM morphological evolution. 139 regions across 8 biphasic MPMs (B-MPMs) were profiled using the GeoMx™Digital Spatial Profiler to reconstruct the positional context of transcriptional activities and the spatial topology of MPM cells interactions. Validation was conducted on an independent large cohort of 84 MPMs by targeted digital barcoding analysis., Results: Our results demonstrated the existence of a complex circular ecosystem in which, within a strong asbestos-driven inflammatory environment, MPM and immune cells affect each other to support S-transdifferentiation. We also showed that TGFB1 polarized M2-Tumor Associated Macrophages foster immune evasion and that TGFB1 expression correlates with reduced survival probability., Conclusions: Besides providing crucial insights into the multidimensional interactions governing MPM clinical evolution, these results open new perspectives to improve the use of immunotherapy in this disease., (© 2023. The Author(s).)

Pseudomyxoma peritonei (PMP) is an uncommon disease with locally-invasive attitude. Intrathoracic spread is rarely reported and its management extremely challenging. A 51-year-old Caucasian female presented with left pleural carcinosis 9-months after two sequential abdominal surgical procedures combined with HIPEC for low-grade PMP. Cytoreductive surgery (pleurectomy/decortication) was followed by 60-minutes hyperthermic intrathoracic chemotherapy mitomycin-C (215 mg/m2) infusing at same temperature (42°C) and intrapleural pression (2-4 mmH2O). No intra-operative complication occurred, the post-op stay was uneventful and no sign of recurrence was observed 9-months after surgery. Cytoreductive thoracic surgery and hyperthermic chemotherapy (HITHOC) could be a feasible therapeutic option in very selected cases.

Purpose: Several meta-analyses have reported data about the diagnostic performance of positron emission tomography or positron emission tomography/computed tomography (PET or PET/CT) with different radiotracers in patients with suspicious lung cancer (LC) or pleural tumours (PT). This review article aims at providing an overview on the recent evidence-based data in this setting., Methods: A comprehensive literature search of meta-analyses published in PubMed/MEDLINE and Cochrane Library database from January 2010 through March 2020 about the diagnostic performance of PET or PET/CT with different radiotracers in patients with suspicious LC or PT was performed. This combination of keywords was used: (A) "PET" OR "positron emission tomography" AND (B) "lung" OR "pulmonary" OR "pleur ∗ " AND (C) meta-analysis. Only meta-analyses on PET or PET/CT in patients with suspicious LC or PT were selected., Results: We have summarized the diagnostic performance of PET or PET/CT with fluorine-18 fluorodeoxyglucose ( 18 F-FDG) and other radiotracers taking into account 17 meta-analyses. Evidence-based data demonstrated a good diagnostic performance of 18 F-FDG PET or PET/CT for the characterization of solitary pulmonary nodules (SPNs) or pleural lesions with overall higher sensitivity than specificity. Evidence-based data do not support the routine use of dual time point (DTP) 18 F-FDG PET/CT or fluorine-18 fluorothymidine ( 18 F-FLT) PET/CT in the differential diagnosis of SPNs. Even if 18 F-FDG PET/CT has high sensitivity and specificity as a selective screening modality for LC, its role in this setting remains unknown., Conclusions: Evidence-based data about the diagnostic performance of PET/CT with different radiotracers for suspicious LC or PT are increasing, with good diagnostic performance of 18 F-FDG PET/CT. More prospective multicenter studies and cost-effectiveness analyses are warranted., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Filippo Lococo et al.)

Although 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan has been generally validated in the staging of malignant pleural mesothelioma (MPM), its diagnostic and prognostic performances are not clearly established. Aiming to identify possible factors causing 18F-fluorodeoxyglucose PET/CT false-negative results and influencing prognosis in MPM patients, we analysed clinical, radiometabolic and pathological features in 141 MPM patients who underwent diagnostic 18F-fluorodeoxyglucose PET/CT scan (January 2009-July 2018) at 2 high-volume institutions. The Fisher's exact test and the Cox model were used in statistical analysis. Overall detection rate was 88.3% with 16 patients (11.6%) presenting with a standardized uptake value (SUV) max <2.5 (PET-negative). PET-negative cases were more frequently detected in older patients (P = 0.027) and early-stage tumours (33.3% false-negative in stage I and 40.0% false-negative in T1-tumours, with P = 0.014 both). Mean SUVmax value was higher in sarcomatoid (11.8 ± 4.6) and biphasic MPM (9.3 ± 7.0), rather than in epithelioid MPM (6.9 ± 3.8, P < 0.001). Concerning overall survival, SUVmax (both as continuous and as categorical variable) was found to be a prognostic factor, in addition to stage (P = 0.032) and histology (P = 0.014) as confirmed by multivariable analysis (hazard ratio 2.65, confidence interval 1.23-5.70; P < 0.001). In the light of such results, we highlight that a low fluorodeoxyglucose uptake might be observed in more than 10% MPMs, especially in early-stage tumours affecting elderly patients. Furthermore, high SUVmax values significantly correlated with a worse prognosis., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: The best strategy of care for biphasic malignant pleural mesothelioma (Biph-MPM) is controversial. In this study, a large dataset of Biph-MPM cases was reviewed to identify prognostic factors and to evaluate the role of a multimodal approach, including cancer-directed surgery., Methods: A total of 213 patients with Biph-MPM treated at 4 tertiary centers who experienced MPM from January 2009 to December 2016 were selected, and clinical, pathologic, and surgical information was retrieved. A Cox regression model was used to identify predictors of survival, and the Kaplan-Meier method was used to summarize overall survival., Results: The mean age and the male/female ratio were 68.4 ± 9.5 years and 5:1, respectively. Tumors were assigned to stages I (127, 59.6%), II (3, 1.4%), III (76, 35.4%), and IV (7, 3.3%) according to the Eighth Tumor, Node, Metastasis (TNM) edition. A multimodal treatment including pleurectomy/decortication was performed in 58 patients (27.2%), chemotherapy alone in 99 patients (46.5%), and best supportive care in 56 (26.3%). The median overall survival was 11 months. A univariate analysis revealed that survival was significantly associated with the percentage forced expiratory volume in 1 second (P < .0001), performance status (P = .0002), multimodal treatment including surgery (P < .0001), and TNM stage (P = .011). A multivariable analysis confirmed performance status, percentage forced expiratory volume in 1 second, TNM, and a multimodal approach as independent variables affecting long-term survival., Conclusions: Despite the overall poor prognosis of biphasic histology, a multimodal approach, including cancer-directed surgery, is associated with improved long-term results in very selected patients with Biph-MPM., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

We report a rare case of a IgG4-related disease presenting with recurrent pleural effusion, pleural thickness and multiple mediastinal lymphadenopathies and no involvement of other extrathoracic organs. A 65-year-old man with a previous asbestos exposure presented with cough and pain discomfort. A large right pleural effusion was detected and evacuated (siero-haematic liquid). With the suspicious of a pleural mesothelioma, a CT-scan before and a 18F -FDG PET/CT-scan later were performed revealing multiple pleural thickenings and multiple mediastinal lymphadenopathies with radiotracer uptake. EBUS-TBNA EBUS-TBNA did not result in a formal pathological diagnosis; thus, multiple pleural biopsy were performed via right thoracoscopy. At pathology the pleura was markedly thickened by a chronic fibroinflammatory process with scattered lymphoid follicles and a large number of mature plasma cells. Immunohistochemistry shows a mixed B (CD20+) and T (CD3+) population of lymphocytes, without light chain restriction and an increased number of IgG4-positive plasma cells. A presumptive diagnosis of IgG4-related disease was formulated. Total body CT-scan excluded other organ involvement. Blood test showed elevated serum IgG4 concentrations (253 mg/dL) and mild elevation of acute-phase reactants (C-reactive protein 10.7 mg/L). Autoimmune profile was negative. A diagnosis of definite IgG4-related disease was made, and treatment with prednisone 50 mg/day was started.

Malignant pleural mesothelioma remains an incurable disease for which the optimal therapeutic approach remains an extremely debated issue. Though not yet clearly defined, a subset of patients may benefit from a surgery-based multimodal treatment plan, beyond what would be expected with non-surgical therapies only. Indeed, despite some disappointing results on the feasibility of a multimodality treatment (chemotherapy ± surgery and post-operative radiation therapy) based on a lung sacrificing surgery (extrapleural pleuropnemonectomy) have been recently reported, the question concerning the role of extrapleural pneumonectomy in selected mesothelioma patients is still unanswered. In the light of this, we have reviewed our mono-institutional retrospective experience in the mesothelioma management, discussing on the role of extrapleural pneumonectomy in the multimodality treatment., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To systematically review and meta-analyze published data about the diagnostic performance of Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the assessment of pleural abnormalities in cancer patients., Methods: A comprehensive literature search of studies published through June 2013 regarding the role of (18)F-FDG-PET and PET/CT in evaluating pleural abnormalities in cancer patients was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odd ratio (DOR) of (18)F-FDG-PET or PET/CT on a per patient-based analysis were calculated. The area under the summary ROC curve (AUC) was calculated to measure the accuracy of these methods in the assessment of pleural abnormalities. Sub-analyses considering (18)F-FDG-PET/CT and patients with lung cancer only were carried out., Results: Eight studies comprising 360 cancer patients (323 with lung cancer) were included. The meta-analysis of these selected studies provided the following results: sensitivity 86% [95% confidence interval (95%CI): 80-91%], specificity 80% [95%CI: 73-85%], LR+ 3.7 [95%CI: 2.8-4.9], LR- 0.18 [95%CI: 0.09-0.34], DOR 27 [95%CI: 13-56]. The AUC was 0.907. No significant improvement considering PET/CT studies only and patients with lung cancer was found., Conclusions: (18)F-FDG-PET and PET/CT demonstrated to be useful diagnostic imaging methods in the assessment of pleural abnormalities in cancer patients, nevertheless possible sources of false-negative and false-positive results should be kept in mind. The literature focusing on the use of (18)F-FDG-PET and PET/CT in this setting remains still limited and prospective studies are needed., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Rationale and Objectives: To systematically review and meta-analyze published data about the diagnostic accuracy of fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the differential diagnosis between malignant and benign pleural lesions., Methods and Materials: A comprehensive literature search of studies published through June 2013 regarding the diagnostic performance of (18)F-FDG-PET and PET/CT in the differential diagnosis of pleural lesions was carried out. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odds ratio (DOR) of (18)F-FDG-PET or PET/CT in the differential diagnosis of pleural lesions on a per-patient-based analysis were calculated. The area under the summary receiver operating characteristic curve (AUC) was calculated to measure the accuracy of these methods. Subanalyses considering device used (PET or PET/CT) were performed., Results: Sixteen studies including 745 patients were included in the systematic review. The meta-analysis of 11 selected studies provided the following results: sensitivity 95% (95% confidence interval [95%CI]: 92-97%), specificity 82% (95%CI: 76-88%), LR+ 5.3 (95%CI: 2.4-11.8), LR- 0.09 (95%CI: 0.05-0.14), DOR 74 (95%CI: 34-161). The AUC was 0.95. No significant improvement of the diagnostic accuracy considering PET/CT studies only was found., Conclusions: (18)F-FDG-PET and PET/CT demonstrated to be accurate diagnostic imaging methods in the differential diagnosis between malignant and benign pleural lesions; nevertheless, possible sources of false-negative and false-positive results should be kept in mind., (Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.)

Transesophageal EUS-FNA have become a useful tool in the evaluation of the mediastinum, especially during the staging work-up examination of patients with non-small-cell lung cancer (NSCLC) or other malignancies. We report a challenging case of a 53 years-old woman with an endometrial adenocarcinoma who subsequently presented with right pleural effusion, diffuse pleural thickening with few pleural lesions. The patient referred a long history of exposure to amiantum, this posing a differential diagnosis between primary pleural tumour (mesothelioma) and neoplastic pleural localization of the endometrial cancer. The cytological examination of the pleural effusion (sampled via thoracenthesis) was not adequate to reach a diagnosis. Although a right-video-assisted thoracoscopy was considered the gold standard in this clinical setting to achieve a tissue acquisition of the pleura, an EUS (as the least invasive procedure) was attempted to reach a definitive diagnosis. EUS-FNTA of the pleura was done using a 19-Gauge needle and the pathological and immunophenotypic features were diagnostic for a pleural metastasis of high-grade endometrial serous carcinoma. The patient received adjuvant chemotherapy with a complete regression of the pleural lesions. We take the opportunity of this challenging case to discuss the efficacy and safety of EUS-FNAT to sample the pleural lesions with the use of a large calibre needle if the lesion lies just under the EUS cursor. We may assume that, in selected patients, this technique could be presented as a viable option to the more invasive surgical procedure, which has been previously the gold standard for the pleural tissue acquisition.

Purpose of Review: Solitary fibrous tumor of the pleura (SFTP) is a rare neoplasm of the pleura. Although an increasing number of case series have been reported in recent years, so far clinical behavior is still unpredictable. The following article presents a detailed review of the recent larger series of SFTP with particular attention to the clinical presentation, pathologic characteristics and surgical features in order to define more precisely the long-term outcome after treatment of this rare entity., Recent Findings: Usually, after a complete surgical resection a very long survival could be expected in almost all cases. However, the preoperative detection and management of malignant SFTPs are still challenging issues., Summary: SFTP remains an enigmatic tumor. Clinical and radiological assessment is often unsatisfactory to obtain a definitive diagnosis. Benign SFTPs are almost always cured with complete surgical resection, and in cases of recurrence the re-do resection of benign recurrences is usually curative. Long-term survivals are also possible for malignant SFTPs, although a higher recurrence rate and higher tumor-related mortality can be expected in these cases. Histologic characteristics distinguishing benign from malignant variants are crucial in estimating the risk of recurrence and planning adjuvant therapies.