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Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Diagnostic mesothelioma biomarkers in effusion cytology
Albino Eccher1, Ilaria Girolami2, Ersilia Lucenteforte3
1Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Abstract:
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.
Insights
Diagnosing malignant mesothelioma, a rare cancer linked to asbestos, is challenging in cytology. Emerging biomarkers like BAP1 and CDKN2A/p16 offer improved specificity and sensitivity for accurate diagnosis in effusions.
Area of Science:
- Oncology
- Pathology
- Cytology
Background:
- Malignant mesothelioma is a rare cancer with poor prognosis, primarily linked to asbestos exposure.
- Genetic predisposition is increasingly recognized as a factor in mesothelioma development.
- Pleural effusion cytology is often the initial diagnostic specimen, but distinguishing atypical reactive mesothelial cells from mesothelioma is challenging.
Purpose of the Study:
- To review and appraise the diagnostic value of emerging biomarkers for malignant mesothelioma in effusion cytology.
- To highlight the utility of cell block preparations for immunohistochemical staining in mesothelioma diagnosis.
- To compare the effectiveness of traditional and novel biomarkers in challenging cytological cases.
Main Methods:
- Literature review of diagnostic markers for malignant mesothelioma in effusion cytology.
- Analysis of immunohistochemical markers including GLUT1, IMP3, BAP1, and CDKN2A/p16 (assessed by FISH).
- Evaluation of the surrogate marker MTAP and its correlation with p16.
Main Results:
- Traditional markers (GLUT1, IMP3) can be difficult to interpret due to aberrant staining in reactive proliferations.
- Loss of BAP1 nuclear staining is specific but has low sensitivity in sarcomatoid tumors.
- CDKN2A/p16 homozygous deletion (FISH) shows high specificity and sensitivity, even in sarcomatoid variants, with MTAP demonstrating excellent correlation.
Conclusions:
- Emerging biomarkers, particularly CDKN2A/p16 deletion and MTAP, significantly improve the diagnostic accuracy of malignant mesothelioma in effusion cytology.
- Cell block preparation and immunohistochemistry are crucial for definitive diagnosis.
- Accurate diagnosis of mesothelioma in cytology is essential for timely and appropriate patient management.
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