bims-mesote Biomed News
on Mesothelioma
Issue of 2021‒02‒28
nine papers selected by
Laura Mannarino
Mario Negri Institute

  1. Nucl Med Commun. 2021 Feb 19.
      AIM: 18F-Fluorodeoxyglucose (FDG) PET/computerized tomography (CT) is a valuable method in the diagnosis of malignant pleural mesothelioma (MPM). But, some infections, particularly tuberculosis, are known to mimic cancer. We aimed to compare the FDG PET/CT findings of tuberculosis pleurisy (TP) and malignant mesothelioma and evaluate its role of differential diagnosis.MATERIAL AND METHOD: We retrospectively reviewed the data from 85 patients (45 patients with MPM and 40 patients with TP) who underwent FDG PET/CT. All images were reevaluated and pleural thickening, maximum standardized uptake values (SUVmax), lymphatic uptake and accompanying parenchymal findings were noted.
    RESULTS: There was no significant difference in age and sex between the two groups. Pleural thickening was more prominent in the MPM group. Mean pleural thickness was 21.4 ± 18.6 mm in the MPM group and 6.8 ± 3.5 mm in the TP group (P = 0.0). Besides pleural pathology, lymph nodes involvement in the thoracic (P = 0.0) and extrathoracic area (P = 0.34) and parenchymal findings were prominent in the TP group (P = 0.0). However, there was no significant difference in pleural SUVmax values between the two groups (P = 0.61).
    CONCLUSION: Intense pleural FDG uptake can be observed in TP like malignant mesothelioma. For the evaluation of the pleural pathologies in the tuberculosis endemic countries, it should be considered that FDG PET/CT may have false-positive results. Evaluation of increased pleural FDG uptake together with the detected parenchymal findings and lymphatic involvement may help us to make more accurate interpretation of the diagnosis.
  2. J Immunother Cancer. 2021 Feb;pii: e001601. [Epub ahead of print]9(2):
      BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasia affecting the lung mesothelium. Immune checkpoint inhibitors (ICI) in MPM have not been extremely successful, likely due to poor identification of suitable candidate patients for the therapy. We aimed to identify cellular immune fractions associated with clinical outcome and classify patients with MPM based on their immune contexture. For each defined group, we sought for molecular specificities that could help further define our MPM classification at the genomic and transcriptomic level, as well as identify differential therapeutic strategies based on transcriptional signatures predictive of drug response.METHODS: The abundance of 20 immune cell fractions in 516 MPM samples from 7 gene expression datasets was inferred using gene set variation analysis. Identification of clinically relevant fractions was performed with Cox proportional-hazards models adjusted for age, stage, sex, and tumor histology. Immune-based groups were defined based on the identified fractions.
    RESULTS: T-helper 2 (TH2) and cytotoxic T (TC) cells were found to be consistently associated with overall survival. Three immune clusters (IG) were subsequently defined based on TH2 and TC immune infiltration levels: IG1 (54.5%) was characterized by high TH2 and low TC levels, IG2 (37%) had either low or high levels of both fractions, and IG3 (8.5%) was defined by low TH2 and high TC levels. IG1 and IG3 groups were associated with worse and better overall survival, respectively. While no differential genomic alterations were identified among immune groups, at the transcriptional level, IG1 samples showed upregulation of proliferation signatures, while IG3 samples presented upregulation of immune and inflammation-related pathways. Finally, the integration of gene expression with functional signatures of drug response showed that IG3 patients might be more likely to respond to ICI.
    CONCLUSIONS: This study identifies a novel immune-based signature with potential clinical relevance based on TH2 and TC levels, unveiling a fraction of patients with MPM with better prognosis and who might benefit from immune-based therapies. Molecular specificities of the different groups might be used to tailor specific potential therapies in the future.
    Keywords:  computational biology; gene expression profiling; lung neoplasms; tumor biomarkers; tumor microenvironment
  3. Sci Rep. 2021 Feb 25. 11(1): 4530
      Immune profiling is becoming a vital tool for identifying predictive and prognostic markers for translational studies. The study of the tumor microenvironment (TME) in paraffin tumor tissues such as malignant pleural mesothelioma (MPM) could yield insights to actionable targets to improve patient outcome. Here, we optimized and tested a new immune-profiling method to characterize immune cell phenotypes in paraffin tissues and explore the co-localization and spatial distribution between the immune cells within the TME and the stromal or tumor compartments. Tonsil tissues and tissue microarray (TMA) were used to optimize an automated nine-color multiplex immunofluorescence (mIF) panel to study the TME using eight antibodies: PD-L1, PD-1, CD3, CD8, Foxp3, CD68, KI67, and pancytokeratin. To explore the potential role of the cells into the TME with this mIF panel we applied this panel in twelve MPM cases to assess the multiple cell phenotypes obtained from the image analysis and well as their spatial distribution in this cohort. We successful optimized and applied an automated nine-color mIF panel to explore a small set of MPM cases. Image analysis showed a high degree of cell phenotype diversity with immunosuppression patterns in the TME of the MPM cases. Mapping the geographic cell phenotype distribution in the TME, we were able to identify two distinct, complex immune landscapes characterized by specific patterns of cellular distribution as well as cell phenotype interactions with malignant cells. Successful we showed the optimization and reproducibility of our mIF panel and their incorporation for comprehensive TME immune profiling into translational studies that could refine our ability to correlate immunologic phenotypes with specific patterns of cells distribution and distance analysis. Overall, this will improve our ability to understand the behavior of cells within the TME and predict new treatment strategies to improve patient outcome.
  4. Semin Thorac Cardiovasc Surg. 2021 Feb 17. pii: S1043-0679(21)00023-X. [Epub ahead of print]
      In recent years, there has been a shift from extrapleural pneumonectomy (EPP) toward pleurectomy/decortication (P/D) as the preferred surgical technique. However, we occasionally encounter difficult cases wherein visceral pleurectomy requires conversion to EPP from P/D. We sought to clarify the preoperative risk factors and clinical outcomes associated with conversion to EPP. We compared and analyzed conversion to EPP and P/D between September 2012 and December 2019. Conversion to EPP was decided in case of diffuse tumor invasion to the pulmonary parenchyma or due to failure of decortication. Univariable regression analysis was performed to determine the association of preoperative variables with conversion to EPP. Survival was analyzed by the Kaplan-Meier method and log-rank test. Of the 181 patients who underwent intended P/D, 145 (80.1%) patients underwent P/D and 18 (9.9%) patients underwent conversion to EPP. The sum of 3-level pleural thickness (P < 0.001), maximum of 3-level pleural thickness (P = 0.006), and clinical T stage (P < 0.001) demonstrated association with conversion to EPP. Overall survival and progression-free survival were significantly worse in the conversion to EPP group (median overall survival, 29.2 mo vs 57.0 mo [P = 0.008]; median progression-free survival, 15.3 mo vs 23.2 mo [P = 0.005]. Our data show that approximately 1 of every 10 patients with P/D intention converted to EPP. Preoperative pleural thickness and clinical T stage may be risk factors associated with conversion to EPP. The survival rate of conversion to EPP was worse than that of P/D.
    Keywords:  conversion; extrapleural pneumonectomy; malignant pleural mesothelioma; pleurectomy/decortication
  5. Int J Surg Pathol. 2021 Feb 24. 1066896921997559
      Malignant mesothelioma (MM) has a wide range of clinical, radiologic, and pathologic presentations, mimicking lung cancer or interstitial lung diseases when predominantly involving the lung parenchyma. The case herein refers to a 79-year-old man, active smoker without asbestos exposure, incidentally discovered to have a pulmonary nodule in the right upper lobe (1.5 cm). The lesion was misinterpreted as primary lung adenocarcinoma at the frozen section in light of the predominant lepidic growth pattern. Definitive examination confirmed neoplastic proliferation along alveolar structures. However, the unusual globous shape of tumor cells along the alveoli abruptly merging with normal pneumocytes prompted us to perform some immunostains that surprisingly revealed a mesothelial differentiation (positive staining with calretinin, cytokeratins (CK5/6), D2-40, and negativity with BRCA-associated protein 1 (BAP1), Thyroid Transcription Factor 1 [TTF-1], claudin-4, carcinoembryonic antigen [CEA], and napsin). MM represents the pathologic counterpart of so-called pseudomesotheliomatous carcinoma, since it appears as a localized pulmonary neoplastic nodule displaying a predominant lepidic growth pattern (pseudocarcinomatous mesothelioma). The challenging diagnostic features of this unique case and a review of similar cases in the literature are discussed.
    Keywords:  adenocarcinoma; immunohistochemistry; lepidic; lung; mesothelioma; nodule; pleura
  6. Int J Surg Pathol. 2021 Feb 26. 1066896921998000
      The long delay between asbestos exposure and the development of mesothelioma will likely result in an increased incidence of mesothelioma in our industrialized societies. Radiation therapy is another factor known to induce these tumors. We describe a rare case of foamy looking mesothelioma in a 63-year-old patient with a long oncology history of a supposed peritoneal carcinomatosis. The pathologist was faced with a diagnostic pitfall as this peritoneal clear cell tumor expressed transcription factor binding to immunoglobulin heavy constant mu enhancer 3 (TFE3) at the nuclear level. Fortunately, the pathologist performed an extensive panel of immunomarkers, leading to a final diagnosis of epithelioid mesothelioma. Thus, we describe the first case of mesothelioma expressing TFE3. Note that there was no rearrangement of TFE3 in fluorescence in situ hybridization.
    Keywords:  hibernoma-like foamy morphology; mesothelioma; renal cell carcinoma
  7. Toxicol Appl Pharmacol. 2021 Feb 19. pii: S0041-008X(21)00068-5. [Epub ahead of print] 115461
      Cosmetic talc has been suggested to cause mesothelioma. To assess a potential causal relationship between cosmetic talc and mesothelioma, a quantitative weight of evidence analysis was performed in accordance with Hill's nine original guidelines for causal inference using a published empirical model to weight each respective guideline. Various epidemiological, toxicological, and exposure studies related to cosmetic talc and risk of mesothelioma were included in an evaluation of each of Hill's guidelines. Probabilities that the guidelines were true were assigned based on expert judgment. We applied a sensitivity analysis to evaluate the variability of our probability estimates. The overall probability of causality for cosmetic talc and mesothelioma was approximately 1.29% (range: 0.73%-3.96%). This low probability of causality supports the conclusion that cosmetic talc is not related to the development of mesothelioma.
    Keywords:  Asbestos; Causal criteria; Causal viewpoints; Pleural mesothelioma; Risk assessment; Sir Bradford Hill
  8. Rare Tumors. 2021 ;13 2036361320984527
      Peritoneal mesotheliomas are very rare tumors. Their prognosis is poor, average survival does not exceed 1 year after peritoneal cytoreduction. Systemic chemotherapy is considered to have no proven value in the management of peritoneal mesotheliomas. Objective responses with systemic chemotherapy are very rare. We report here a case of an advanced peritoneal mesothelioma which achieved an unexpected partial response with chemotherapy, allowing the patient to have a right colectomy. The patient was referred to a specialized center on HIPEC, but taking in account the long awaiting interval, the HIPEC was judged to be inefficient and then the poursuit of 6 cycles of systemic chemotherapy was decided. The patient is still alive without any symptom and with a good performance status at 59 months after diagnosis. Throughout our case, we provide an encouraging evidence of the role of initial systemic chemotherapy in the downstaging of initially unresectable primary malignant mesothelioma and in the improvement of overall survival.
    Keywords:  Peritoneal mesothelioma; chemotherapy; surgery; survival
  9. Monoclon Antib Immunodiagn Immunother. 2021 Feb;40(1): 21-27
      Malignant mesotheliomas (MMs) are aggressive therapy-resistant tumors that generally have a poor prognosis. We previously reported the establishment of four new monoclonal antibodies (mAbs) for the diagnosis and treatment of MM. In this report, we characterized one of these antibodies, JMAM-1. The molecules whose antibodies were calibrated were picked up, transfected assuming CD10, and elucidated by fluorescence activated cell sorter. Survival experiments were performed using tumor-bearing mice model. JMAM-1 mAb was found to bind with CD10 antigen. The Kaplan-Meier survival curve showed a small but prolonged survival effect. JMAM-1 mAb-treated MSTO-211H cells showed increased cell cycle arrest involved by cyclin-dependent-kinase. JMAM-1 antibody has cytostatic effect and may be a candidate for the treatment of MM. Among mesothelioma, CD10-positive cases have been reported to have a poorer prognosis than negative cases, which can be used as a tool for diagnosis.
    Keywords:  CD10; JMAM-1; malignant mesothelioma; monoclonal antibody