Abstract
Malignant pleural mesothelioma (MPM), associated with unfavorable outcomes, is closely associated with asbestos exposure. Early detection and treatment are critical to prolong survival of patients with MPM because of the rapid progression and resistance to treatment. The recently defined malignant mesothelioma in situ (MIS) has been gaining increasing attention with advances in genome-based methods including fluorescence in situ hybridization (FISH) as well as immunohistochemistry. We herein report the case of a MIS in a 73-year-old male with a history of asbestos exposure presenting with massive pleural effusion in the right thoracic cavity. Video-assisted thoracoscopic surgery with pleural biopsy of the right side revealed a single layer of atypical mesothelial cells without invasive lesions by hematoxylin and eosin staining. However, these mesothelial cells exhibited a loss of methylthioadenosine phosphorylase (MTAP) by immunohistochemistry and homozygous deletion of CDKN2A (p16) by FISH, leading to the diagnosis of MIS.
This is a preview of subscription content, log in via an institution to check access.
References
Tsao AS, Wistuba I, Roth JA, Kindler HL (2009) Malignant pleural mesothelioma. J Clin Oncol 27(12):2081–2090
Stayner L, Welch LS, Lemen R (2013) The worldwide pandemic of asbestos-related diseases. Annu Rev Public Health 34(1):205–216
Whitaker D, Henderson DW, Shilkin KB (1992) The concept of mesothelioma in situ: implications for diagnosis and histogenesis. Semin Diagn Pathol 9(2):151–161
Hiroshima K, Yusa T, Kameya T, Ito I, Kaneko K, Kadoyama C, Kishi H, Saitoh Y, Ozaki D, Itami M, Iwata T, Iyoda A, Kawai T, Yoshino I, Nakatani Y (2009) Malignant pleural mesothelioma: clinicopathology of 16 extrapleural pneumonectomy patients with special reference to early stage features. Pathol Int 59(8):537–545
Hida T, Hamasaki M, Matsumoto S, Sato A, Tsujimura T, Kawahara K, Iwasaki A, Okamoto T, Oda Y, Honda H, Nabeshima K (2017) Immunohistochemical detection of MTAP and BAP1 protein loss for mesothelioma diagnosis: comparison with 9p21 FISH and BAP1 immunohistochemistry. Lung Cancer 104:98–105
Churg A, Hwang H, Tan L, Qing G, Taher A, Tong A, Bilawich AM, Dacic S (2018) Malignant mesothelioma in situ. Histopathology 72(6):1033–1038
Kinoshita Y, Hida T, Hamasaki M, Matsumoto S, Sato A, Tsujimura T, Kawahara K, Hiroshima K, Oda Y, Nabeshima K (2018) A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma. Cancer Cytopathol 126(1):54–63
Churg A, Sheffield BS, Galateau-Salle F (2016) New markers for separating benign from malignant mesothelial proliferations: are we there yet? Arch Pathol Lab Med 140(4):318–321
Illei PB, Rusch VW, Zakowski MF, Ladanyi M (2003) Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas. Clin Cancer Res 9(6):2108–2113
Chiosea S, Krasinskas A, Cagle PT, Mitchell KA, Zander DS, Dacic S (2008) Diagnostic importance of 9p21 homozygous deletion in malignant mesotheliomas. Modern Pathol 21(6):742–747
Husain AN, Colby TV, Ordóñez NG, Allen TC, Attanoos RL, Beasley MB, Butnor KJ, Chirieac LR, Churg AM, Dacic S, Galateau-Sallé F, Gibbs A, Gown AM, Krausz T, Litzky LA, Marchevsky A, Nicholson AG, Roggli VL, Sharma AK, Travis WD, Walts AE, Wick MR (2017) Guidelines for pathologic diagnosis of malignant mesothelioma 2017 update of the consensus statement from the international mesothelioma interest group. Arch Pathol Lab Med 142(1):89–108
Simon F, Johnen G, Krismann M, Muller KM (2005) Chromosomal alterations in early stages of malignant mesotheliomas. Virchows Arch 447(4):762–767
Krismann M, Muller KM, Jaworska M, Johnen G (2002) Molecular cytogenetic differences between histological subtypes of malignant mesotheliomas: DNA cytometry and comparative genomic hybridization of 90 cases. J Pathol 197(3):363–371
Hwang H, Tse C, Rodriguez S, Gown A, Churg A (2014) p16 FISH deletion in surface epithelial mesothelial proliferations is predictive of underlying invasive mesothelioma. Am J Surg Pathol 38(5):681–688
Acknowledgement
We would like to thank Dr. Kunimitsu Kawahara (Department of Diagnostic Pathology, Osaka Habikino Medical Center) for his contribution to the analysis and interpretation of data.
Funding
The authors received no financial support for publication of this article.
Author information
Authors and Affiliations
Contributions
Kazuhiro Minami, Naoe Jimbo, and Yugo Tanaka designed the case report and wrote the initial draft of the manuscript. All other authors have contributed to data collection and interpretation and have critically reviewed the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Statement of informed consent
Informed consent was obtained from all individual participants involved in this study.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Quality in Pathology
Rights and permissions
About this article
Cite this article
Minami, K., Jimbo, N., Tanaka, Y. et al. Malignant mesothelioma in situ diagnosed by methylthioadenosine phosphorylase loss and homozygous deletion of CDKN2A: a case report. Virchows Arch 476, 469–473 (2020). https://doi.org/10.1007/s00428-019-02674-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-019-02674-x