Update of pathological diagnosis of pleural mesothelioma using genomic-based morphological techniques, for both histological and cytological investigations.

Publisher: Published by Blackwell Scientific Publications for the Japanese Society of Pathology Country of Publication: Australia NLM ID: 9431380 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1440-1827 (Electronic) Linking ISSN: 13205463 NLM ISO Abbreviation: Pathol Int Subsets: MEDLINE

Original Publication: Carlton South, Vic., Australia : Published by Blackwell Scientific Publications for the Japanese Society of Pathology, c1994-

Lung Neoplasms*/pathology ; Mesothelioma*/diagnosis ; Mesothelioma*/genetics ; Mesothelioma*/pathology ; Mesothelioma, Malignant*/diagnosis ; Pleural Neoplasms*/diagnosis ; Pleural Neoplasms*/genetics ; Pleural Neoplasms*/pathology; Biomarkers, Tumor/genetics ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Genomics ; Homozygote ; Humans ; In Situ Hybridization, Fluorescence ; Sequence Deletion ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics

As more than 80% of pleural mesothelioma (PM) cases start with pleural effusions, diagnosis with effusion smear cytology or pleural biopsy is important. For diagnosing PM, a three-step approach is used: (1) detecting atypical cells; (2) verifying their mesothelial origin using immunohistochemistry (IHC); and (3) discriminating PM from benign mesothelial proliferations (BMP). The third step is critical for diagnosing early lesions. In small biopsy or cytologic specimens in which tumor cell fat invasion cannot be assessed, genomic-based assays, including IHC-detected BAP1 loss and fluorescence in situ hybridization (FISH)-detected homozygous deletion (HD) of CDKN2A/p16, are effective for differentiation. Both BAP1 IHC and CDKN2A FISH can equally be applied to histologic and cytologic specimens, with 100% specificity in discriminating PM from BMP. We found that methylthioadenosine phosphorylase (MTAP) loss as detected by IHC could serve as a feasible alternative in tissue and cytologic preparations for CDKN2A FISH. However, a combination including FISH was still most effective: the addition of NF2 FISH to CDKN2A FISH and BAP1 IHC yielded a greater sensitivity of close to 100% in diagnosing PM tissues. Although IHC is more feasible than FISH, owing to remaining challenges in data interpretation, caution and familiarity are warranted when diagnosing PM.
(© 2022 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Park EK, Takahashi K, Hoshuyama T, Cheng TJ, Delgermaa V, Le GV, et al. Global magnitude of reported and unreported mesothelioma. Environ Health Perspect. 2011;119(4):514-518. https://doi.org/10.1289/ehp.1002845.
Environmental Restoration and Conservation Agency [Internet]. Amount of imported asbestos and occurrence of mesothelioma (in Japanese) [cited 2022 January 8]. 2017. Available from: https://www.erca.go.jp/asbestos/what/higai/jittai.html.
Robinson BW, Lake RA. Advances in malignant mesothelioma. N Engl J Med. 2005;353:1591-603. https://doi.org/10.1056/NEJMra050152.
Carbone M, Adusumilli PS, Alexander HR, Jr., Bass P, Bardelli F, Bononi A, et al. Mesothelioma: scientific clues for prevention, diagnosis, and therapy. CA Cancer J Clin. 2019;69:402-29.
Keshava HB, Tang A., Siddiqui HU Raja S, Raymond DP, Bribriesco A, et al. Largely unchanged annual incidence and overall survival of pleural mesothelioma in the USA. World J Surg. 2019;43(12):3239-47. https://doi.org/10.1007/s00268-019-05132-6.
Alpert N, van Gerwen M, Taioli E. Epidemiology of mesothelioma in the 21(st) century in Europe and the United States, 40 years after restricted/banned asbestos use. Transl Lung Cancer Res. 2020;9(Suppl 1):S28-38. https://doi.org/10.21037/tlcr.2019.11.11.
Baas P, Scherpereel A, Nowak AK, Fujimoto N, Peters S, Tsao AS, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021;397(10272):375-86. https://doi.org/10.1016/S0140-6736(20)32714-8.
Baas P. Nivolumab plus ipilimumab should be the standard of care for first-line unresectable epithelioid mesothelioma. J Thrac Oncol. 2022;17:30-3.
Fennell DA, Dulloo S. Chemotherapy with or without bevacizumab should be the standard of care for first-line unresectable epithelioid mesothelioma. J Thrac Oncol. 2022;17:34-7.
Flores RM, Pass HI, Seshan VE, Dycoco J, Zakowski M, Carbone M, et al. Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients. J Thorac Cardiovasc Surg. 2008;135(3):620-6, 626.e1-3 https://doi.org/10.1016/j.jtcvs.2007.10.054.
Rusch VW, Giroux D, Kennedy C, Ruffini E, Cangir AK, Rice D, et al. Initial analysis of the international association for the study of lung cancer mesothelioma database. J Thorac Oncol. 2012;7(11):1631-9. https://doi.org/10.1097/JTO.0b013e31826915f1.
Muruganandan S, Alfonso H, Franklin P, Shilkin K, Segal A, Olsen N, et al. Comparison of outcomes following a cytological or histological diagnosis of malignant mesothelioma. Br J Cancer. 2017 Mar 14;116(6):703-8. https://doi.org/10.1038/bjc.2017.20.
Bolen JW, Hammar SP, McNutt MA. Reactive and neoplastic serosal tissue. A light-microscopic, ultrastructural, and immunocytochemical study. Am J Surg Pathol. 1986;10(1):34-47. https://doi.org/10.1097/00000478-198601000-00005.
The WHO Classification of Tumours Editorial Board, editors. Thoracic tumours: WHO Classification of tumours. 5th ed. Lyon: International Agency for Research on Cancer (IARC); 2021.
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(8):1189-203. https://doi.org/10.1016/j.jtho.2018.04.023.
Ordóñez NG. Application of immunohistochemistry in the diagnosis of epithelioid mesothelioma: a review and update. Hum Pathol. 2013;44(1):1-19. https://doi.org/10.1016/j.humpath.2012.05.014.
Husain AN, Colby T, Ordonez N, Krausz T, Attanoos R, Beasley MB, et al. Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med. 2013;137(5):647-67. https://doi.org/10.5858/arpa.2012-0214-OA.
Ordóñez NG. Value of calretinin immunostaining in diagnostic pathology: a review and update. Appl Immunohistochem Mol Morphol. 2014;22(6):401-15. https://doi.org/10.1097/PAI.0b013e31829b6fbd.
Matsuda M, Ninomiya H, Wakejima R, Inamura K, Okumura S, Mun M, et al. Calretinin-expressing lung adenocarcinoma: distinct characteristics of advanced stages, smoker-type features, and rare expression of other mesothelial markers are useful to differentiate epithelioid mesothelioma. Pathol Res Pract. 2020;216(3):152817. https://doi.org/10.1016/j.prp.2020.152817.
Ordóñez NG. Value of claudin-4 immunostaining in the diagnosis of mesothelioma. Am J Clin Pathol. 2013;139(5):611-9. https://doi.org/10.1309/AJCP0B3YJBXWXJII.
Mawas AS, Amatya VJ, Kushitani K, Kai Y, Miyata Y, Okada M, et al. MUC4 immunohistochemistry is useful in distinguishing epithelioid mesothelioma from adenocarcinoma and squamous cell carcinoma of the lung. Sci Rep. 2018;8(1):134. https://doi.org/10.1038/s41598-017-18545-x.
Naso JR, Churg A. Claudin-4 shows superior specificity for mesothelioma vs non-small-cell lung carcinoma compared with MOC-31 and Ber-EP4. Hum Pathol. 2020;100:10-4. https://doi.org/10.1016/j.humpath.2020.04.005.
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.
Churg A, Naso JR. The separation of benign and malignant mesothelial proliferations: New markers and how to use them. Am J Surg Pathol. 2020;44(11):e100-12. https://doi.org/10.1097/PAS.0000000000001565.
Chapel DB, Schulte JJ, Husain AN, Krausz T. Application of immunohistochemistry in diagnosis and management of malignant mesothelioma. Transl Lung Cancer Res. 2020;9(Suppl 1):S3-27. https://doi.org/10.21037/tlcr.2019.11.29.
Hesterberg TW, Barrett JC. Induction by asbestos fibers of anaphase abnormalities: mechanism for aneuploidy induction and possibly carcinogenesis. Carcinogenesis. 1985;6(3):473-5. https://doi.org/10.1093/carcin/6.3.473.
Hagemeijer A, Versnel MA, Van Drunen E, Moret M, Bouts MJ, van der Kwast TH, et al. Cytogenetic analysis of malignant mesothelioma. Cancer Genet Cytogenet. 1990;47(1):1-28. https://doi.org/10.1016/0165-4608(90)90258-c.
Kato S, Tomson BN, Buys TP, Elkin SK, Carter JL, Kurzrock R. Genomic landscape of malignant mesotheliomas. Mol Cancer Ther. 2016;15(10):2498-507. https://doi.org/10.1158/1535-7163.MCT-16-0229.
Kukuyan AM, Sementino E, Kadariya Y, Menges CW, Cheung M, Tan Y, et al. Inactivation of Bap1 Cooperates with losses of Nf2 and Cdkn2a to drive the development of pleural malignant mesothelioma in conditional mouse models. Cancer Res. 2019;79(16):4113-23. https://doi.org/10.1158/0008-5472.CAN-18-4093.
Bott M, Brevet M, Taylor BS, Shimizu S, Ito T, Wang L, et al. The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nat Genet. 2011;43:668-72.
Nasu M, Emi M, Pastorino S, Tanji M, Powers A, Luk H, et al. High incidence of somatic BAP1 alterations in sporadic malignant mesothelioma. J Thorac Oncol. 2015;10:565-76.
Wang LM, Shi ZW, Wang JL, Lv Z, Du FB, Yang QB, et al. Diagnostic accuracy of BRCA1-associated protein 1 in malignant mesothelioma: a meta-analysis. Oncotarget. 2017;8:68863-72.
Yoshimura M, Kinoshita Y, Hamasaki M, Matsumoto S, Hida T, Oda Y, et al. Diagnostic application of BAP1 immunohistochemistry to differentiate pleural mesothelioma from metastatic pleural tumours. Histopathology. 2017;71(6):1011-4. https://doi.org/10.1111/his.13321.
Carbone M, Ferris LK, Baumann F, Napolitano A, Lum CA, Flores EG, et al. BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs. J Transl Med. 2012;10:179. https://doi.org/10.1186/1479-5876-10-179.
Andrici J, Goeppert B, Sioson L, Clarkson A, Renner M, Stenzinger A, et al. Loss of BAP1 expression occurs frequently in intrahepatic cholangiocarcinoma. Medicine (Baltimore). 2016;95(2):e2491. https://doi.org/10.1097/MD.0000000000002491.
Misumi K, Hayashi A, Shibahara J, Arita J, Sakamoto Y, Hasegawa K, et al. Intrahepatic cholangiocarcinoma frequently shows loss of BAP1 and PBRM1 expression, and demonstrates specific clinicopathological and genetic characteristics with BAP1 loss. Histopathology. 2017;70(5):766-74. https://doi.org/10.1111/his.13127.
Cheng JQ, Jhanwar SC, Klein WM, Bell DW, Lee WC, Altomare DA, et al. p16 alterations and deletion mapping of 9p21-p22 in malignant mesothelioma. Cancer Res. 1994;54:5547-51.
Illei PB, Ladanyi M, Rusch VW, Zakowski MF. The use of CDKN2A deletion as a diagnostic marker for malignant mesothelioma in body cavity effusions. Cancer. 2003;99:51-6.
Chiosea S, Krasinskas A, Cagle PT, Mitchell KA, Zander DS, Dacic S. Diagnostic importance of 9p21 homozygous deletion in malignant mesotheliomas. Mod Pathol. 2008;21:742-7.
Nabeshima K, Matsumoto S, Hamasaki M, Hida T, Kamei T, Hiroshima K, et al. Use of p16 FISH for differential diagnosis of mesothelioma in smear preparations. Diagn Cytopathol. 2016;44:774-80.
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(1):39-46.
Tochigi N, Attanoos R, Chirieac LR, Allen TC, Cagle PT, Dacic S. p16 Deletion in sarcomatoid tumors of the lung and pleura. Arch Pathol Lab Med. 2013;137(5):632-6. https://doi.org/10.5858/arpa.2012-0108-OA.
Hida T, Hamasaki M, Matsumoto S, Sato A, Tsujimura T, Kawahara K, et al. BAP1 immunohistochemistry and p16 FISH results in combination provide higher confidence in malignant pleural mesothelioma diagnosis: ROC analysis of the two tests. Pathol Int. 2016;66(10):563-70. https://doi.org/10.1111/pin.12453.
Schmid M, Malicki D, Nobori T, Rosenbach MD, Campbell K, Carson DA, et al. Homozygous deletions of methylthioadenosine phosphorylase (MTAP) are more frequent than p16INK4A (CDKN2) homozygous deletions in primary non-small cell lung cancers (NSCLC). Oncogene. 1998;17(20):2669-75. https://doi.org/10.1038/sj.onc.1202205.
Illei PB, Rusch VW, Zakowski MF, Ladanyi M. Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas. Clin Cancer Res. 2003;9:2108-13.
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.
Berg KB, Dacic S, Miller C, Cheung S, Churg A. Utility of methylthioadenosine phosphorylase compared with BAP1 immunohistochemistry, and CDKN2A and NF2 fluorescence in situ hybridization in separating reactive mesothelial proliferations from epithelioid malignant mesotheliomas. Arch Pathol Lab Med. 2018;142(12):1549-53. https://doi.org/10.5858/arpa.2018-0273-OA.
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(2):245-54. https://doi.org/10.1038/s41379-019-0310-0.
Hamasaki M, Kinoshita Y, Yoshimura M, Matsumoto S, Kamei T, Hiroshima K, et al. Cytoplasmic MTAP expression loss detected by immunohistochemistry correlates with 9p21 homozygous deletion detected by FISH in pleural effusion cytology of mesothelioma. Histopathology. 2019;75(1):153-5. https://doi.org/10.1111/his.13872.
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.
Berg KB, Churg AM, Cheung S, Dacic S. Usefulness of methylthioadenosine phosphorylase and BRCA-associated protein 1 immunohistochemistry in the diagnosis of malignant mesothelioma in effusion cytology specimens. Cancer Cytopathol. 2020;128(2):126-32. https://doi.org/10.1002/cncy.22221.
Hiroshima K, Wu D, Hamakawa S, Tsuruoka S, Ozaki D, Orikasa H, et al. HEG1, BAP1, and MTAP are useful in cytologic diagnosis of malignant mesothelioma with effusion. Diagn Cytopathol. 2021;49(5):622-32. https://doi.org/10.1002/dc.24475.
Girolami I, Lucenteforte E, Eccher A, Marletta S, Brunelli M, Graziano P, et al. Evidence-based diagnostic performance of novel biomarkers for the diagnosis of malignant mesothelioma in effusion cytology. Cancer Cytopathol. 2021 Sep 3;130:96-109. https://doi.org/10.1002/cncy.22509. Online ahead of print.
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.
Sato T, Sekido Y. NF2/Merlin inactivation and potential therapeutic targets in mesothelioma. Int J Mol Sci. 2018;19(4):988. https://doi.org/10.3390/ijms19040988.
Singhi AD, Krasinskas AM, Choudry HA, Bartlett DL, Pingpank JF, Zeh HJ, et al. The prognostic significance of BAP1, NF2, and CDKN2A in malignant peritoneal mesothelioma. Mod Pathol. 2016;29:14-24.
Kinoshita Y, Hamasaki M, Yoshimura M, Matsumoto S, Iwasaki A, Nabeshima K. Hemizygous loss of NF2 detected by fluorescence in situ hybridization is useful for the diagnosis of malignant pleural mesothelioma. Mod Pathol. 2020;33(2):235-44. https://doi.org/10.1038/s41379-019-0309-6.
Kinoshita Y, Hamasaki M, Matsumoto S, Yoshimura M, Sato A, Tsujimura T, et al. Fluorescence in situ hybridization detection of chromosome 22 monosomy in pleural effusion cytology for the diagnosis of mesothelioma. Cancer Cytopathol. 2021;129(7):526-36. https://doi.org/10.1002/cncy.22409.
Chapel DB, Husain AN, Krausz T. Immunohistochemical evaluation of nuclear 5-hydroxymethylcytosine (5-hmC) accurately distinguishes malignant pleural mesothelioma from benign mesothelial proliferations. Mod Pathol. 2019;32(3):376-86. https://doi.org/10.1038/s41379-018-0159-7.
Shinozaki-Ushiku A, Ushiku T, Morita S, Anraku M, Nakajima J, Fukayama M. Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma. Histopathology. 2017;70(5):722-33. https://doi.org/10.1111/his.13123.
Yoshimura M, Kinoshita Y, Hamasaki M, Matsumoto S, Hida T, Oda Y, et al. Highly expressed EZH2 in combination with BAP1 and MTAP loss, as detected by immunohistochemistry, is useful for differentiating malignant pleural mesothelioma from reactive mesothelial hyperplasia. Lung Cancer. 2019 Apr;130:187-93. https://doi.org/10.1016/j.lungcan.2019.02.004.
Yoshimura M, Hamasaki M, Kinoshita Y, Matsumoto S, Sato A, Tsujimura T, et al. Utility of highly expressed EZH2 in pleural effusion cytology for the diagnosis of mesothelioma. Pathol Int. 2020;70(10):831-3. https://doi.org/10.1111/pin.12990.
Whitaker D, Henderson DW, Shilkin KB. The concept of mesothelioma in situ: implications for diagnosis and histogenesis. Semin Diagn Pathol. 1992;9:151-61.
Churg A, Hwang H, Tan L, Qing G, Taher A, Tong A, et al. Malignant mesothelioma in situ. Histopathology. 2018;72(6):1033-8. https://doi.org/10.1111/his.13468.
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(2):297-302. https://doi.org/10.1038/s41379-019-0347-0.
Pulford E, Huilgol K, Moffat D, Henderson DW, Klebe S. Malignant mesothelioma, BAP1 immunohistochemistry, and VEGFA: does BAP1 have potential for early diagnosis and assessment of prognosis? Dis Markers. 2017;2017:1310478. https://doi.org/10.1155/2017/1310478.
Minami K, Jimbo N, Tanaka Y, Hokka D, Miyamoto Y, Itoh T, et al. Malignant mesothelioma in situ diagnosed by methylthioadenosine phosphorylase loss and homozygous deletion of CDKN2A: a case report. Virchows Arch. 2020 Mar;476(3):469-73. https://doi.org/10.1007/s00428-019-02674-x.
Hidaka K, Takeda T, Kinoshita Y, Nabeshima K, Tamiya S, Yoshikawa Y, et al. Development of mesothelioma in situ and its progression to invasive disease observed in a patient with uncontrolled pleural effusions for 15 years. Pathol Int. 2020;Dec 70(12):1009-14. https://doi.org/10.1111/pin.13021.
Dacic S, Roy S, Lyons MA, von der Thusen JH, Galateau-Salle F, Churg A. Whole exome sequencing reveals BAP1 somatic abnormalities in mesothelioma in situ. Lung Cancer. 2020;149:1-4. https://doi.org/10.1016/j.lungcan.2020.09.002.
Renshaw AA, Dean BR, Antman KH, Sugarbaker DJ, Cibas ES. The role of cytologic evaluation of pleural fluid in the diagnosis of malignant mesothelioma. Chest. 1997;111(1):106-9. https://doi.org/10.1378/chest.111.1.106.
Renshaw AA, Nappi D, Swanson S, Sugarbaker DJ. Effusion cytology after extrapleural pneumonectomy for treatment of malignant mesothelioma. Am J Clin Pathol. 1997;107(2):206-10. https://doi.org/10.1093/ajcp/107.2.206.
Segal A, Sterrett GF, Frost FA, Shilkin KB, Olsen NJ, Musk AW, et al. A diagnosis of malignant pleural mesothelioma can be made by effusion cytology: results of a 20 year audit. Pathology. 2013;45(1):44-8. https://doi.org/10.1097/PAT.0b013e32835bc848.
Paintal A, Raparia K, Zakowski MF, Nayar R. The diagnosis of malignant mesothelioma in effusion cytology: a reappraisal and results of a multi-institution survey. Cancer Cytopathol. 2013;121(12):703-7. https://doi.org/10.1002/cncy.21342.
Hjerpe A, Ascoli V, Bedrossian CWM, Boon ME, Creaney J, Davidson B, et al. Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology. Acta Cytol. 2015;59(1):2-16. https://doi.org/10.1159/000377697.
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(1):54-63.
Hatem L, McIntire PJ, He B, Gogineni S, Ho M, Mathew S, et al. The role of BRCA1-associated protein 1 in the diagnosis of malignant mesothelioma in effusion and fine-needle aspiration cytology. Diagn Cytopathol. 2019;47(3):160-165. https://doi.org/10.1002/dc.24061.
Siddiqui MT, Schmitt F, Churg A. Proceedings of the American Society of Cytopathology companion session at the 2019 United States and Canadian Academy of Pathology Annual meeting, part 2: effusion cytology with focus on theranostics and diagnosis of malignant mesothelioma. J Am Soc Cytopathol. 2019;8(6):352-61.
Chevrier M, Monaco SE, Jerome JA, Galateau-Salle F, Churg A, Dacic S. Testing for BAP1 loss and CDKN2A/p16 homozygous deletion improves the accurate diagnosis of mesothelial proliferations in effusion cytology. Cancer Cytopathol. 2020;128(12):939-47. https://doi.org/10.1002/cncy.22326.
Kinoshita Y, Hamasaki M, Matsumoto S, Yoshimura M, Sato A, Tsujimura T, et al. Genomic-based ancillary assays offer improved diagnostic yield of effusion cytology with potential challenges in malignant pleural mesothelioma. Pathol Int. 2020;70(9):671-9. https://doi.org/10.1111/pin.12973.
Hida T, Matsumoto S, Hamasaki M, Kawahara K, Tsujimura T, Hiroshima K, et al. Deletion status of p16 in effusion smear preparation correlates with that of underlying malignant pleural mesothelioma tissue. Cancer Sci. 2015;106(11):1635-41. https://doi.org/10.1111/cas.12769.
Hwang HC, Sheffield BS, Rodriguez S, Thompson K, Tse CH, Gown AM, et al. Utility of BAP1 Immunohistochemistry and p16 (CDKN2A) FISH in the diagnosis of malignant mesothelioma in effusion cytology specimens. Am J Surg Pathol. 2016;40(1):120-6. https://doi.org/10.1097/PAS.0000000000000529.
Matsumoto S, Nabeshima K, Kamei T, Hiroshima K, Kawahara K, Hata S, et al. Morphology of 9p21 homozygous deletion-positive pleural mesothelioma cells analyzed using fluorescence in situ hybridization and virtual microscope system in effusion cytology. Cancer Cytopathol. 2013;121(8):415-22. https://doi.org/10.1002/cncy.21269.
Matsumoto S, Hamasaki M, Kinoshita Y, Kamei T, Kawahara K, Nabeshima K. Morphological difference between pleural mesothelioma cells in effusion smears with either BAP1 loss or 9p21 homozygous deletion and reactive mesothelial cells without the gene alterations. Pathol Int. 2019;69(11):637-45. https://doi.org/10.1111/pin.12862.
The Working Group for Assessment of Cytological Diagnosis of Pleural Mesothelioma of the Japan Lung Cancer Society. Guidelines for cytological diagnosis of pleural mesothelioma (in Japanese). (2017). Accessed January 8, 2022. Available from: https://www.haigan.gr.jp/uploads/files/photos/1539.pdf.

#200598 Grant from the Ministry of the Environment; Grant from the Research Center for Advanced Molecular Medicine, Fukuoka University; #19K07451 Grants-in-Aid for Scientific Research from the Japanese Society for the Promotion of Science

Keywords: BAP1; CDKN2A; FISH; MTAP; NF2; cytology; histology; pleural mesothelioma

0 (Biomarkers, Tumor)
0 (Cyclin-Dependent Kinase Inhibitor p16)
0 (Tumor Suppressor Proteins)
EC 3.4.19.12 (Ubiquitin Thiolesterase)

Date Created: 20220521 Date Completed: 20220825 Latest Revision: 20220825

20221213

10.1111/pin.13235

35596704