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Pathology of Mesothelioma, Subtypes, and Rare Variants: What Is the Role of Immunohistochemical Markers in Differential Diagnosis?

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Malignant Pleural Mesothelioma

Abstract

Malignant pleural mesothelioma (MPM) is an asbestos-related aggressive tumor arising from mesothelial cells on the pleural surface. The definitive diagnosis of MPM is made histopathologically, supported by clinical and radiological findings, but morphological discrimination between MPM and other malignant tumors and that between MPM and non-neoplastic reactive mesothelial hyperplasia (RMH) are often difficult. In such cases, ancillary diagnostic techniques, fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), are effective to diagnose MPM. Immunohistochemical markers, mesothelial-related positive and negative markers, are especially essential for discrimination between MPM and other malignant tumors. Immunohistochemical detection of BRCA1-associated protein 1 (BAP1) protein loss and that of methylthioadenosine phosphorylase (MTAP) protein loss are also useful for differentiating MPM from RMH similar to detection of CDKN2A (p16) homozygous deletion by FISH. Moreover, BAP1 IHC and MTAP IHC, as well as CDKN2A (p16) FISH, are effective for diagnosing early-stage MPM and assessing malignancy of mesothelial cells in pleural effusion. In this chapter, we focus on the pathological approach including auxiliary diagnostic techniques, particularly IHC, in the differential diagnosis of MPM.

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References

  1. Travis DW, Brambilla E, Burke PA, Marx A, Nicholson GA. WHO classification of tumours of the lung, pleura, thymus and heart (World health organization classification of tumours). Lyon: International Agency for Research on Cancer; 2015.

    Google Scholar 

  2. Kurman RJ, Carcangiu ML, Herrington CS, Young RH. WHO classification of tumours of female reproductive organs (World health organization classification of tumours). Lyon: International Agency for Research on Cancer; 2014.

    Google Scholar 

  3. Churg A, Cagle PT, Roggli VL. Tumors of serosal membranes (Atlas of tumor pathology series IV). Washington, DC: American Registry of Pathology; 2006.

    Google Scholar 

  4. Ordóñez NG. Application of immunohistochemistry in the diagnosis of epithelioid mesothelioma: a review and update. Hum Pathol. 2013;44:1–19. https://doi.org/10.1016/j.humpath.2012.05.014.

  5. Husain AN, Colby TV, Ordóñez NG, Allen TC, Attanoos RL, Beasley MB, et al. Guidelines for pathologic diagnosis of malignant mesothelioma 2017 update of the consensus statement from the international mesothelioma interest group. Arch Pathol Lab Med. 2018;142:89–108. https://doi.org/10.5858/arpa.2017-0124-RA.

    Article  CAS  PubMed  Google Scholar 

  6. Sheffield BS, Hwang HC, Lee AF, Thompson K, Rodriguez S, Tse CH, et al. BAP1 immunohistochemistry and p16 FISH to separate benign from malignant mesothelial proliferations. Am J Surg Pathol. 2015;39:977–82. https://doi.org/10.1097/PAS.0000000000000394.

    Article  PubMed  Google Scholar 

  7. Righi L, Duregon E, Vatrano S, Izzo S, Giorcelli J, Rondón-Lagos M, et al. BRCA1-associated protein 1 (BAP1) immunohistochemical expression as a diagnostic tool in malignant pleural mesothelioma classification: a large retrospective study. J Thorac Oncol. 2016;11:2006–17. https://doi.org/10.1016/j.jtho.2016.06.020.

    Article  PubMed  Google Scholar 

  8. Hida T, Hamasaki M, Matsumoto S, Sato A, Tsujimura T, Kawahara K, et al. Immunohistochemical detection of MTAP and BAP1 protein loss for mesothelioma diagnosis: comparison with 9p21 FISH and BAP1 immunohistochemistry. Lung Cancer. 2017;104:98–105. https://doi.org/10.1016/j.lungcan.2016.12.017.

    Article  Google Scholar 

  9. Chapel DB, Schulte JJ, Berg K, Churg A, Dacic S, Fitzpatrick C, et al. MTAP immunohistochemistry is an accurate and reproducible surrogate for CDKN2A fluorescence in situ hybridization in diagnosis of malignant pleural mesothelioma. Mod Pathol. 2020;33:245–54. https://doi.org/10.1038/s41379-019-0310-0.

    Article  CAS  Google Scholar 

  10. Kinoshita Y, Hida T, Hamasaki M, Matsumoto S, Sato A, Tsujimura T, et al. A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma. Cancer Cytopathol. 2018;126:54–63. https://doi.org/10.1002/cncy.21928.

    Article  CAS  PubMed  Google Scholar 

  11. Marchevsky AM, Khoor A, Walts AE, Nicholson AG, Zhang YZ, Roggli V, et al. Localized malignant mesothelioma, an unusual and poorly characterized neoplasm of serosal origin: best current evidence from the literature and the International Mesothelioma Panel. Mod Pathol. 2020;33:281–96. https://doi.org/10.1038/s41379-019-0352-3.

    Article  PubMed  Google Scholar 

  12. Galateau Salle F, Le Stang N, Tirode F, Courtiol P, Nicholson AG, Tsao MS, et al. Comprehensive molecular and pathologic evaluation of transitional mesothelioma assisted by deep learning approach: a multi-institutional study of the international mesothelioma panel from the MESOPATH reference center. J Thorac Oncol. 2020;20:1037–53. https://doi.org/10.1016/j.jtho.2020.01.025.

    Article  CAS  Google Scholar 

  13. Wu D, Hiroshima K, Yusa T, Ozaki D, Koh E, Sekine Y, et al. Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma. Ann Diagn Pathol. 2017;26:31–7. https://doi.org/10.1016/j.anndiagpath.2016.10.010.

    Article  PubMed  Google Scholar 

  14. Galateau Salle F, Le Stang N, Nicholson AG, Pissaloux D, Churg A, Klebe S, et al. New insights on diagnostic reproducibility of biphasic mesotheliomas: a multi-institutional evaluation by the international mesothelioma panel from the MESOPATH reference center. J Thorac Oncol. 2018;13:1189–203. https://doi.org/10.1016/j.jtho.2018.04.023.

    Article  CAS  PubMed  Google Scholar 

  15. Ordóñez NG. Value of claudin-4 immunostaining in the diagnosis of mesothelioma. Am J Clin Pathol. 2013b;139:611–9. https://doi.org/10.1309/AJCP0B3YJBXWXJII.

    Article  CAS  PubMed  Google Scholar 

  16. Kushitani K, Amatya VJ, Okada Y, Katayama Y, Mawas AS, Miyata Y, et al. Utility and pitfalls of immunohistochemistry in the differential diagnosis between epithelioid mesothelioma and poorly differentiated lung squamous cell carcinoma. Histopathology. 2017;70:375–84. https://doi.org/10.1111/his.13073.

    Article  PubMed  Google Scholar 

  17. Marchevsky AM, LeStang N, Hiroshima K, Pelosi G, Attanoos R, Churg A, et al. The differential diagnosis between pleural sarcomatoid mesothelioma and spindle cell/pleomorphic (sarcomatoid) carcinomas of the lung: evidence-based guidelines from the International Mesothelioma Panel and the MESOPATH National Reference Center. Hum Pathol. 2017;67:160–8. https://doi.org/10.1016/j.humpath.2017.07.015.

    Article  PubMed  Google Scholar 

  18. Yoshida A, Kobayashi E, Kubo T, Kodaira M, Motoi T, Motoi N, et al. Clinicopathological and molecular characterization of SMARCA4-deficient thoracic sarcomas with comparison to potentially related entities. Mod Pathol. 2017;30:797–809. https://doi.org/10.1038/modpathol.2017.11.

    Article  CAS  PubMed  Google Scholar 

  19. Churg A, Sheffield BS, Galateau-Salle F. New markers for separating benign from malignant mesothelial proliferations: are we there yet? Arch Pathol Lab Med. 2016;140:318–21. https://doi.org/10.5858/arpa.2015-0240-SA.

    Article  CAS  PubMed  Google Scholar 

  20. Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, et al. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet. 2012;43:1022–5. https://doi.org/10.1038/ng.912.

    Article  Google Scholar 

  21. Churg A, Galateau-Salle F, Roden AC, Attanoos R, von der Thusen JH, Tsao MS, et al. Malignant mesothelioma in situ: morphologic features and clinical outcome. Mod Pathol. 2020;33:297–302. https://doi.org/10.1038/s41379-019-0347-0.

    Article  CAS  PubMed  Google Scholar 

  22. Wu D, Hiroshima K, Matsumoto S, Nabeshima K, Yusa T, Ozaki D, et al. Diagnostic usefulness of p16/CDKN2A FISH in distinguishing between sarcomatoid mesothelioma and fibrous pleuritis. Am J Clin Pathol. 2013;139:39–46. https://doi.org/10.1309/AJCPT94JVWIHBKRD.

    Article  CAS  PubMed  Google Scholar 

  23. Kinoshita Y, Hamasaki M, Yoshimura M, Matsumoto S, Sato A, Tsujimura T, et al. A combination of MTAP and BAP1 immunohistochemistry is effective for distinguishing sarcomatoid mesothelioma from fibrous pleuritis. Lung Cancer. 2018;125:198–204. https://doi.org/10.1016/j.lungcan.2018.09.019.

    Article  Google Scholar 

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Correspondence to Tohru Tsujimura .

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Tsujimura, T., Yuki, M., Shinohara, Y., Sato, A. (2021). Pathology of Mesothelioma, Subtypes, and Rare Variants: What Is the Role of Immunohistochemical Markers in Differential Diagnosis?. In: Nakano, T., Kijima, T. (eds) Malignant Pleural Mesothelioma. Respiratory Disease Series: Diagnostic Tools and Disease Managements. Springer, Singapore. https://doi.org/10.1007/978-981-15-9158-7_9

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  • DOI: https://doi.org/10.1007/978-981-15-9158-7_9

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