Cytologic Differential Diagnosis of Malignant Mesothelioma and Reactive Mesothelial Cells With FISH Analysis of <i>p16</i>

Hiroshima, Kenzo; Wu, Di; Hasegawa, Mizue; Koh, Eitetsu; Sekine, Yasuo; Ozaki, Daisuke; Yusa, Toshikazu; Walts, Ann E.; Marchevsky, Alberto M.; Nabeshima, Kazuki; Tada, Yuji; Shimada, Hideaki; Tagawa, Masatoshi

doi:10.1002/dc.23490

Cited by 30 publications

(29 citation statements)

References 32 publications

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“…58,59 Therefore, EMA is not a viable IHC marker for distinguishing MPM from RMH; however, EMA still is useful to differentiate mesothelioma cells from non-neoplastic reactive mesothelial cells. 42 In the current study, double immunostaining using EMA/MTAP or EMA/BAP1 enabled the assessment of scattered MPM cells in the cell blocks from pleural effusions. However, because of its immunoreactivity in plasma cells and adenocarcinoma or squamous cell carcinoma cells, EMA IHC requires careful interpretation.…”

Section: Original Articlementioning

confidence: 86%

“…The sensitivity and specificity of EMA in distinguishing MPM from RMH is reportedly approximately 75% each . Therefore, EMA is not a viable IHC marker for distinguishing MPM from RMH; however, EMA still is useful to differentiate mesothelioma cells from non‐neoplastic reactive mesothelial cells . In the current study, double immunostaining using EMA/MTAP or EMA/BAP1 enabled the assessment of scattered MPM cells in the cell blocks from pleural effusions.…”

Section: Discussionmentioning

confidence: 99%

“…If the corresponding tissue specimens were available, deletion status of 9p21 FISH in cell block was compared with that in corresponding tissue specimens. Results of 9p21 FISH in 13 cases from Tokyo Women's Medical University Yachiyo Medical Center have been published previously …”

Section: Methodsmentioning

confidence: 99%

“…Results of 9p21 FISH in 13 cases from Tokyo Women's Medical University Yachiyo Medical Center have been published previously. 42…”

Section: Fish Assaymentioning

confidence: 99%

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A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma

Kinoshita

Hida

Hamasaki

et al. 2017

Cancer Cytopathology

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107

126

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IHC differentiated MPM from RMC with 100% specificity for both and sensitivities of 42.2% and 60.0%, respectively. The combination of MTAP and BAP1 IHC yielded a sensitivity of 77.8%, which was higher than that of BAP1 IHC alone or 9p21 FISH alone (62.2%). Moreover, a high degree of concordance was observed between the results of MTAP IHC and 9p21 FISH in cell blocks. CONCLUSIONS: A combination of MTAP and BAP1 IHC in cell blocks from pleural effusions appears to be a reliable and useful method for differentiating MPM cells from RMC and can be used in the routine diagnosis of MPM.

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Section: Original Articlementioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Results of 9p21 FISH in 13 cases from Tokyo Women's Medical University Yachiyo Medical Center have been published previously. 42…”

Section: Fish Assaymentioning

confidence: 99%

See 2 more Smart Citations

A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma

Kinoshita

Hida

Hamasaki

et al. 2017

Cancer Cytopathology

Self Cite

107

126

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“…Both p16 (locus 9p21) and BAP1 (locus 3p21.2) are frequently deleted in malignant lesions, and they have never been reported as altered in benign lesions. Therefore, they have 100% specificity for MPM; however, their sensitivity ranges between 43-93% and 61-67% for p16 and BAP1, respectively (33)(34)(35). Combination of the two assays has been reported to increase sensitivity for MPM diagnosis up to 90% in some studies; however, specificity is always 100% (29,33,36).…”

Section: Diagnostic Markers By Ihc or Fishmentioning

confidence: 99%

Molecular markers and new diagnostic methods to differentiate malignant from benign mesothelial pleural proliferations: a literature review

Bruno¹,

Alì²,

Fontanini³

2018

J. Thorac. Dis.

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Malignant pleural mesothelioma (MPM) is an aggressive tumor associated with asbestos exposure. Histopathological analysis of pleural tissues is the gold standard for diagnosis; however, it can be difficult to differentiate malignant from benign pleural lesions. The purpose of this review is to describe the most important biomarkers and new diagnostic tools suggested for this differential diagnosis. There are many studies concerning the separation between MPM and benign pleural proliferations from both pleural tissues or effusions; most of them are based on the evaluation of one or few biomarkers by immunohistochemistry (IHC) or enzyme-linked immunosorbent assays (ELISAs), whereas others focused on the identification of MPM signatures given by microRNA (miRNA) or gene expression profiles as well as on the combination of molecular data and classification algorithms. None of the reported biomarkers showed adequate diagnostic accuracy, except for p16 [evaluated by fluorescent in situ hybridization (FISH)] and BAP1 (evaluated by IHC), both biomarkers are recommended by the International Mesothelioma Interest Group guidelines for histological and cytological diagnosis. BAP1 and p16 showed a specificity of 100% in discerning malignant from benign lesions because they are exclusively unexpressed or deleted in MPM. However, their sensitivity, even when used together, is not completely sufficient, and absence of their alterations cannot confirm the benign nature of the lesion. Recently, the availability of new techniques and increasing knowledge regarding MPM genetics led to the definition of some molecular panels, including genes or miRNAs specifically deregulated in MPM, that are extremely valuable for differential diagnosis. Moreover, the development of classification algorithms is facilitating the application of molecular data for clinical practice. Data regarding new diagnostic tools and MPM signatures are absolutely promising; however, before their application in clinical practice, a prospective validation is necessary, as these approaches could surely improve the differential diagnosis between malignant and benign pleural lesions.

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Diagnostic mesothelioma biomarkers in effusion cytology

Eccher¹,

Girolami

Lucenteforte

et al. 2021

Cancer Cytopathology

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Malignant mesothelioma is a rare malignancy with a poor prognosis whose development is related to asbestos fiber exposure. An increasing role of genetic predisposition has been recognized recently. Pleural biopsy is the gold standard for diagnosis, in which the identification of pleural invasion by atypical mesothelial cell is a major criterion. Pleural effusion is usually the first sign of disease; therefore, a cytological specimen is often the initial or the only specimen available for diagnosis. Given that reactive mesothelial cells may show marked atypia, the diagnosis of mesothelioma on cytomorphology alone is challenging. Accordingly, cell block preparation is encouraged, as it permits immunohistochemical staining. Traditional markers of mesothelioma such as glucose transporter 1 (GLUT1) and insulin‐like growth factor 2 mRNA‐binding protein 3 (IMP3) are informative, but difficult to interpret when reactive proliferations aberrantly stain positive. BRCA1‐associated protein 1 (BAP1) nuclear staining loss is highly specific for mesothelioma, but sensitivity is low in sarcomatoid tumors. Cyclin‐dependent kinase inhibitor 2A (CDKN2A)/p16 homozygous deletion, assessed by fluorescence in situ hybridization, is more specific for mesothelioma with better sensitivity, even in the sarcomatoid variant. The surrogate marker methylthioadenosine phosphorylase (MTAP) has been found to demonstrate excellent diagnostic correlation with p16. The purpose of this review is to provide an essential appraisal of the literature regarding the diagnostic value of many of these emerging biomarkers for malignant mesothelioma in effusion cytology.

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Cytologic Differential Diagnosis of Malignant Mesothelioma and Reactive Mesothelial Cells With FISH Analysis of p16

Cited by 30 publications

References 32 publications

A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma

A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma

Molecular markers and new diagnostic methods to differentiate malignant from benign mesothelial pleural proliferations: a literature review

Diagnostic mesothelioma biomarkers in effusion cytology

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