Analysis of early pleural fluid samples in patients with mesothelioma: A case series exploration of morphology, BAP1, and CDKN2A status with implications for the concept of mesothelioma in situ in cytology.
Biomarkers, Tumor
/ metabolism
Cyclin-Dependent Kinase Inhibitor p16
/ genetics
Homozygote
Humans
In Situ Hybridization, Fluorescence
Lung Neoplasms
/ diagnosis
Mesothelioma
/ diagnosis
Mesothelioma, Malignant
Pleural Neoplasms
/ diagnosis
Retrospective Studies
Sequence Deletion
Tumor Suppressor Proteins
/ genetics
Ubiquitin Thiolesterase
/ genetics
BRCA1-associated protein 1 (BAP1)
cyclin-dependent kinase inhibitor 2A gene (CDKN2A)
cytology
mesothelioma
mesothelioma in situ
Journal
Cancer cytopathology
ISSN: 1934-6638
Titre abrégé: Cancer Cytopathol
Pays: United States
ID NLM: 101499453
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
11
11
2021
received:
10
09
2021
accepted:
29
11
2021
pubmed:
11
2
2022
medline:
10
5
2022
entrez:
10
2
2022
Statut:
ppublish
Résumé
The concept of mesothelioma in situ has been revisited and is a new World Health Organization diagnostic entity. The definition centers on ancillary techniques used in pleural mesothelioma (PM) assessment. At the authors' institution, most PM diagnoses are made on cytologic specimens. Effusion samples obtained before definitive PM diagnosis were interrogated using BRCA1-associated protein 1 gene (BAP1), cyclin-dependent kinase inhibitor 2A gene (CDKN2A) and cytologic evaluation to assess whether early or possible in situ disease could be characterized. All cases of PM diagnosed between January 2008 and December 2019 were identified at a tertiary referral center. Patients who had a pleural fluid sample collected 24 months before the diagnosis were selected, numbering 8 in total. The cytomorphology of each sample was reviewed; and, retrospectively, BAP1 immunohistochemistry (IHC) and CDKN2A fluorescence in situ hybridization (FISH) were performed on initial and diagnostic samples. The initial samples were deemed benign in 5 cases and atypical mesothelial proliferations in 3 cases. A spectrum of apparently normal to atypical cytomorphologic changes was identified. BAP1 loss was present in 6 of 8 initial cases, whereas CDKN2A homozygous deletion was identified in 1 of 7 initial cases. Either abnormality was identified in 7 of 8 initial samples. Detectable abnormalities of BAP1 IHC and CDKN2A FISH were present in pleural fluid specimens before the development of cytomorphologic features diagnostic of PM. This is the largest series to date describing cytology samples early in the course of PM development, thereby highlighting a possible cytological equivalent for mesothelioma in situ.
Sections du résumé
BACKGROUND
The concept of mesothelioma in situ has been revisited and is a new World Health Organization diagnostic entity. The definition centers on ancillary techniques used in pleural mesothelioma (PM) assessment. At the authors' institution, most PM diagnoses are made on cytologic specimens. Effusion samples obtained before definitive PM diagnosis were interrogated using BRCA1-associated protein 1 gene (BAP1), cyclin-dependent kinase inhibitor 2A gene (CDKN2A) and cytologic evaluation to assess whether early or possible in situ disease could be characterized.
METHODS
All cases of PM diagnosed between January 2008 and December 2019 were identified at a tertiary referral center. Patients who had a pleural fluid sample collected 24 months before the diagnosis were selected, numbering 8 in total. The cytomorphology of each sample was reviewed; and, retrospectively, BAP1 immunohistochemistry (IHC) and CDKN2A fluorescence in situ hybridization (FISH) were performed on initial and diagnostic samples.
RESULTS
The initial samples were deemed benign in 5 cases and atypical mesothelial proliferations in 3 cases. A spectrum of apparently normal to atypical cytomorphologic changes was identified. BAP1 loss was present in 6 of 8 initial cases, whereas CDKN2A homozygous deletion was identified in 1 of 7 initial cases. Either abnormality was identified in 7 of 8 initial samples.
CONCLUSIONS
Detectable abnormalities of BAP1 IHC and CDKN2A FISH were present in pleural fluid specimens before the development of cytomorphologic features diagnostic of PM. This is the largest series to date describing cytology samples early in the course of PM development, thereby highlighting a possible cytological equivalent for mesothelioma in situ.
Substances chimiques
BAP1 protein, human
0
Biomarkers, Tumor
0
CDKN2A protein, human
0
Cyclin-Dependent Kinase Inhibitor p16
0
Tumor Suppressor Proteins
0
Ubiquitin Thiolesterase
EC 3.4.19.12
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
352-362Informations de copyright
© 2022 American Cancer Society.
Références
Delgermaa V, Takahashi K, Park EK, Le GV, Hara T, Sorahan T. Global mesothelioma deaths reported to the World Health Organisation between 1994 and 2008. Bull World Health Organ. 2011;89:716-724.
Robinson BWS, Lake RA. Advances in malignant mesothelioma. N Engl J Med. 2005;353:1591-1603.
Hmeljak J, Sanchez-Vega F, Hoadley KA, et al. Integrative molecular characterization of malignant pleural mesothelioma. Cancer Discov. 2018;8:1548-1565.
Bononi A, Giorgi C, Patergnani S, et al. BAP1 regulated IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation. Nature. 2017;546:549-553.
Ventii KH, Devi NS, Friedrich KL, et al. BRCA1-associated protein-1 is a tumour suppressor that requires deubiquitinating activity and nuclear localization. Cancer Res. 2008;68:6953-6962.
Bott M, Brevet M, Taylor BS, et al. The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nat Genet. 2011;43:668-672.
Yoshikawa Y, Sato A, Tsujimura T, et al. Frequent inactivation of the BAP1 gene in epithelioid-type malignant mesothelioma. Cancer Sci. 2012;103:868-874.
Nasu M, Emi M, Pastorino S, et al. High incidence of somatic BAP1 alterations in sporadic malignant mesothelioma. J Thorac Oncol. 2015;10:565-576.
Cigognetti M, Lonardi S, Fisogni S, et al. BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations. Mod Pathol. 2015;28:1043-1057.
Sheffield BS, Hwang HC, Lee AF, et al. BAP1 immunohistochemistry and p16 FISH to separate benign from malignant mesothelial proliferations. Am J Clin Pathol. 2015;39:977-982.
Wu D, Hiroshima K, Yusa T, et al. Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma. Ann Diagn Pathol. 2017;26:31-37.
McGregor SM, McElherne J, Minor A, et al. BAP1 immunohistochemistry has limited prognostic utility as a complement of CDKN2A (p16) fluorescence in situ hybridization in malignant pleural mesothelioma. Hum Pathol. 2017;60:86-94.
Monaco SE, Shuai Y, Bansal M, Krasinskas AM, Dacic S. The diagnostic utility of p16 FISH and GLUT-1 immunohistochemical analysis in mesothelial proliferations. Am J Clin Pathol. 2011;135:619-627.
Chiosea S, Krasinskas A, Cagle PT, Mitchell KA, Zander DS, Dacic S. Diagnostic importance of 9p21 homozygous deletion in malignant mesotheliomas. Mod Pathol. 2008;21:742-747.
Wu D, Hiroshima K, Matsumoto S, et al. Diagnostic usefulness of p16/CDKN2A FISH in distinguishing between sarcomatoid mesothelioma and fibrous pleuritis. Am J Clin Pathol. 2013;139:39-46.
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;140:318-321.
Hida T, Hamasaki M, Mastumoto S, et al. Immunohistochemical detection of MTAP and BAP1 protein loss for mesothelioma diagnosis: comparison with 9p21 FISH and BAP1. Lung Cancer. 2017;104:98-105.
Hida T, Hamasaki M, Mastumoto S, 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;66:563-570.
Cozzi I, Oprescu FA, Rullo E, Ascoli A. Loss of BRCA-1 associated protein 1 (BAP1) expression is useful in diagnostic cytopathology of malignant mesothelioma in effusions. Diagn Cytopathol. 2017;46:9-14.
Liu J, Liao X, Gu Y, et al. Role of p16 deletion and BAP1 loss in the diagnosis of malignant mesothelioma. J Thoracic Dis. 2018;10:5522-5530.
Pillappa R, Maleszewski JJ, Sukov WR, et al. Loss of BAP1 expression in atypical mesothelial proliferations helps to predict malignant mesothelioma. Am J Surg Pathol. 2018;42:256-263.
Kinoshita Y, Hida T, Hamasaki M, et al. A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma. Cancer Cytopathol. 2018;126:54-63.
Churg A, Galateau-Salle F, Roden A, et al. Malignant mesothelioma in situ: morphological features and clinical outcome. Mod Pathol. 2020;33:297-302.
World Health Organization (WHO) Classification of Tumours Editorial Board. Thoracic Tumours [Internet]. WHO Classification of Tumours Series. 5th ed. Vol 5. International Agency for Research on Cancer; 2021. Accessed October 15, 2021. https://tumourclassification.iarc.who.int/chapters/35
College of American Pathologists Committee on Nomenclature and Classification of Disease. Systematized Nomenclature of Pathology. College of American Pathologists; 1965.
Hjerpe A, Ascoli A, Bedrossian CWM, 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;59:2-16.
Whitaker D. The cytology of malignant mesothelioma. Cytopathology. 2000;11:139-151.
Stevens MW, Leong AS, Fazzalari NL, Dowling KD, Henderson DW. Cytopathology of malignant mesothelioma: a stepwise logistic regression analysis. Diagn Cytopathol. 1992;8:333-341.
Bibbo M, Draganova-Tacheva R, Naylor B. Pleural, peritoneal, and pericardial effusions. In: Bibbo M, Wilbur DC, eds. Comprehensive Cytopathology. 4th ed. Elsevier Saunders; 2015:403-448.
Nicholson AG, Sauter JL, Nowak AL, et al. EURACAN/IASLC proposals for updating the histologic classification of pleural mesothelioma: towards a more multidisciplinary approach. J Thorac Oncol. 2020;15:29-49.
Whitaker D, Henderson DW, Shilkin KB. The concept of mesothelioma in situ: implications for diagnosis and histogenesis. Semin Diagn Pathol. 1992;9:151-161.
Henderson DW, Shilkin KB, Whitaker D. Reactive mesothelial hyperplasia vs mesothelioma, including mesothelioma in situ. Anat Pathol. 1998;10:397-404.
Segal A, Sterrett GF, Frost FA, et al. A diagnosis of malignant pleural mesothelioma can be made by effusion cytology: results of a 20 year audit. Pathology. 2013;45:44-48.
Pulford E, Henderson DW, Klebe S. Malignant mesothelioma in situ: diagnostic and clinical considerations. Pathology. 2020;52:635-642.
Hasegawa S, Kondo N, Matsumoto S, et al. Practical approaches to diagnose and treat for T0 malignant pleural mesothelioma: a proposal for diagnostic total parietal pleurectomy. Int J Clin Oncol. 2012;17:33-39.
Klebe S, Nakatani Y, Dobra K, et al. The concept of mesothelioma in situ, with consideration of its potential impact on cytology diagnosis. Pathology. 2021;53:446-453.
Nowak AK, Lesterhuis WJ, Kok PS, et al. Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in. Lancet. 2020;21:1213-1223.
Baas P, Scherpereel A, Nowak A, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021;397:375-386.