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      Evaluation of prognostic histological parameters proposed for pleural mesothelioma in diffuse malignant peritoneal mesothelioma. A short report

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          Abstract

          Introduction

          Diffuse malignant peritoneal mesothelioma (DMPM) is a rare malignant neoplasm with poor survival that shares some similarities with the best-known pleural variant, pleural mesothelioma. The recent European Reference Network on Rare Adult Cancers (EURACAN)/International Association for the Study of Lung Cancer (IASLC) proposals attempted to improve the histological diagnosis and patient risk stratification. Herein, we investigated whether the pathology recommendations and suggestions of the pleural proposals were applicable to diffuse malignant peritoneal mesothelioma.

          Methods

          Fifty multiple laparoscopic biopsies of DMPM were consecutively collected at the Pathology Unit of the University of Bari. A two-tier system, i.e., low, and high grade, was used to categorize 34 epithelioid DMPMs. Architectural patterns, cytological features and stromal changes were also reported. Immunohistochemistry was performed for BRCA1-associated protein 1 (BAP1), programmed death-ligand 1 (PD-L1), and Ki67, while fluorescence in situ hybridization (FISH) was performed for p16/cyclin-dependent kinase inhibitor 2A ( CDKN2A).

          Results

          High-grade epithelioid mesothelioma, high Ki67, and p16/CDKN2A deletion were significantly associated with short survival ( p = 0.004, p < 0.0001, and p = 0.002, respectively). BAP1 loss and PD-L1 negativity were the most common findings. Multivariate analysis revealed that the nuclear grading system and p16 deletion significantly correlated with survival ( p = 0.003 each).

          Conclusions

          The present study examined the prognostic significance of several factors proposed for pleural mesothelioma in an extra pleural site. Notably, the introduction of a grading system may provide better risk stratification in epithelioid DMPM. Ki67, BAP1 and p16/ CDKN2A should also be measured whenever possible. A detailed report with all supportive data would allow us to collect sufficient information for use in further studies on larger case series.

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          Most cited references29

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          Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience.

          This multi-institutional registry study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse malignant peritoneal mesothelioma (DMPM). A multi-institutional data registry that included 405 patients with DMPM treated by a uniform approach that used CRS and HIPEC was established. The primary end point was overall survival. The secondary end point was evaluation of prognostic variables for overall survival. Follow-up was complete in 401 patients (99%). The median follow-up period for the patients who were alive was 33 months (range, 1 to 235 months). The mean age was 50 years (standard deviation [SD], 14 years). Three hundred eighteen patients (79%) had epithelial tumors. Twenty-five patients (6%) had positive lymph nodes. The mean peritoneal cancer index was 20. One hundred eighty-seven patients (46%) had complete or near-complete cytoreduction. Three hundred seventy-two patients (92%) received HIPEC. One hundred twenty-seven patients (31%) had grades 3 to 4 complications. Nine patients (2%) died perioperatively. The mean length of hospital stay was 22 days (SD, 15 days). The overall median survival was 53 months (1 to 235 months), and 3- and 5-year survival rates were 60% and 47%, respectively. Four prognostic factors were independently associated with improved survival in the multivariate analysis: epithelial subtype (P < .001), absence of lymph node metastasis (P < .001), completeness of cytoreduction scores of CC-0 or CC-1 (P < .001), and HIPEC (P = .002). The data suggest that CRS combined with HIPEC achieved prolonged survival in selected patients with DMPM.
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            The 2015 World Health Organization Classification of Tumors of the Pleura: Advances since the 2004 Classification.

            A new World Health Organization (WHO) Classification of Tumors of the Pleura has recently been published. While the histologic classification of pleural malignant mesothelioma remains the same in the 2015 WHO classification as it was in the 2004 classification, multiple new observations have been recorded. First, more detailed study has been performed of histologic subtyping of epithelioid mesothelioma. In particular, it has been recognized that the pleomorphic subtype is associated with a poor prognosis, similar to that of sarcomatoid malignant mesothelioma. Second, there is improved understanding of the role of immunohistochemistry in distinguishing mesothelioma from carcinomas of various sites. Third, the criteria for distinguishing malignant mesothelioma from reactive mesothelial proliferations has been further refined. Fourth, additional studies of sarcomatoid mesothelioma have defined the frequency and spectrum of various histologic and immunohistochemical features, including heterologous elements. Finally, pleural well-differentiated papillary mesotheliomas are better defined and cases with invasive foci are recognized. In addition, several promising observations in mesothelioma pathology and genetics have been made in the past decade. These are now the subject of further investigation to determine if they can be validated in ways that will significantly impact clinical practice. These include a preliminary study of grading, suggesting that nuclear atypia and mitotic count are independent prognostic markers. The discovery of inactivating mutations in the BRCA1-associated protein 1 gene in sporadic and hereditary mesothelioma has opened up a variety of novel molecular, clinical, and diagnostic investigations. One possible diagnostic application includes the setting of separating mesothelioma from reactive mesothelial proliferations, where it may play a role in conjunction with p16 FISH. Another useful discovery was that the NAB2-STAT6 fusion is characteristic of solitary fibrous tumors. This led to development of a STAT6 antibody that is a reliable immunohistochemical marker for solitary fibrous tumors. Genetic studies also led to the finding that WWTR1-CAMTA1 fusions are useful diagnostic markers for epithelioid hemangioendotheliomas, which can present as pleural-based masses. Finally, desmoid type fibromatosis, a locally aggressive tumor that can present in the pleura, has been shown to frequently have CTNNB1 gene mutations and express β-catenin by immunohistochemistry.
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              EURACAN/IASLC proposals for updating the histologic classification of pleural mesothelioma: towards a more multidisciplinary approach.

              Molecular and immunologic breakthroughs are transforming the management of thoracic cancer, although advances have not been as marked for malignant pleural mesothelioma where pathologic diagnosis has been essentially limited to three histologic subtypes.
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                Author and article information

                Contributors
                federica.pezzuto@unipd.it
                Journal
                Diagn Pathol
                Diagn Pathol
                Diagnostic Pathology
                BioMed Central (London )
                1746-1596
                22 July 2021
                22 July 2021
                2021
                : 16
                : 64
                Affiliations
                [1 ]GRID grid.5608.b, ISNI 0000 0004 1757 3470, Pathology Unit Department of Cardiac, Thoracic, Vascular Sciences and Public Health, , University of Padova, ; via A. Gabelli 61, 35121 Padova, Italy
                [2 ]GRID grid.7644.1, ISNI 0000 0001 0120 3326, Department of Interdisciplinary Medicine, Occupational Health Division, , University of Bari, ; 1 Umberto I Sq., 70121 Bari, Italy
                [3 ]GRID grid.7644.1, ISNI 0000 0001 0120 3326, Pathology Unit, Department of Emergency and Organ Transplantation – DETO, , University of Bari, ; 1 Umberto I Sq., 70121 Bari, Italy
                [4 ]GRID grid.10796.39, ISNI 0000000121049995, Pathology Unit, Department of Surgery, , University of Foggia, ; 121 Napoli St, 71122 Foggia, Italy
                [5 ]GRID grid.489132.5, ISNI 0000 0004 1759 6541, Pathology Unit, IRCCS National Cancer Institute “Giovanni Paolo II”, ; 65 Orazio Flacco St, 70124 Bari, Italy
                Author information
                http://orcid.org/0000-0002-8023-3108
                Article
                1125
                10.1186/s13000-021-01125-z
                8296535
                1648bb97-008c-48b3-8f9b-803f2fb31353
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 29 October 2020
                : 6 July 2021
                Categories
                Short Report
                Custom metadata
                © The Author(s) 2021

                Pathology
                pleural mesothelioma,peritoneal mesothelioma,histology,grading
                Pathology
                pleural mesothelioma, peritoneal mesothelioma, histology, grading

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