Integrative approach to cytologic and molecular diagnosis of malignant pleural mesothelioma

Our plain-English summary of Integrative approach to cytologic and molecular diagnosis of malignant pleural mesothelioma, by A. Hjerpe, S. Abd Own, K. Dobra (Translational Lung Cancer Research, 2020).

The study

• Authors: A. Hjerpe, S. Abd Own, K. Dobra
• Journal: Translational Lung Cancer Research
• Published: 2020;9(3):934-943
• Type of article: Review
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The global incidence of malignant mesothelioma (MM) causes considerable disease burden, suffering and health care costs. Beside preventive measures and ban the use of asbestos, early diagnosis would largely improve the chance of curative treatment. Current histologic criteria, however, requiring presence of invasion in the surrounding fatty tissue fail to identify MM in sufficiently early stage. Unilateral accumulation of pleural effusion is one of the earliest clinical manifestations of MM that occurs in approximately 90% of the patients. Therapeutic thoracocenthesis is necessary to remove the fluid and to relieve patients' symptoms. This effusion is easily accessible and offers early and minimally invasive diagnosis by combining cytology with immunologic, molecular- and biomarker analyses. Typically, the fluid is rich in malignant cells and cell groups, but incipient stages of the disease may be difficult to recognize as the malignant cells can be masked by presence of inflammatory or reactive mesothelial cells. Recurrent, hemorrhagic and cell rich effusion should always be suspicious for MM and adequately prepared and analyzed to provide necessary information for subsequent therapy. Importantly, early detection of MM by integrating cytology and molecular approaches has high sensitivity and positive predictive value and has a major impact on patient survival. Thus, a conclusive positive MM cytology should lead to treatment without delay. This review summarizes molecular and diagnostic criteria of MM diagnosis.

2020 Translational Lung Cancer Research. All rights reserved.

In plain English

This was a review article by pathologists at Karolinska University Hospital in Stockholm, commissioned for a journal series on the 2019 Pulmonary Pathology Society meeting. It reported no new study. It described how malignant pleural mesothelioma can be diagnosed from fluid that collects around the lung (pleural effusion) by combining microscopy of the cells with antibody stains, a chromosome test called FISH, electron microscopy and fluid biomarkers. The authors noted this works mainly for epithelioid and mixed types, because sarcomatoid tumor cells are not shed into the fluid. Citing earlier work, the review stated that FISH showed abnormal chromosome numbers with 80–90% sensitivity and a 100% positive predictive value. The authors wrote that in their cohort, median survival was 20 months after diagnosis by effusion cytology and 12 months after diagnosis by histology. They also wrote that over 10 years of routine practice, cytological diagnoses meeting guideline criteria had a 100% positive predictive value. The authors concluded that such a diagnosis is reliable and on its own sufficient to start treatment. The review did not examine asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: narrative review (commissioned review article); no new study was reported
• Who was studied: No new patients were studied. The review covers published work and the authors' own earlier experience in diagnosing malignant pleural mesothelioma from pleural effusions at Karolinska University Hospital, Stockholm, Sweden.
• Exposure: Not studied. The review concerns diagnostic methods, not exposure. The background mentions only in general terms that mesothelioma is linked to carcinogenic mineral fibers.
• Main results:
  • Cytology mainly allows diagnosis of epithelioid and mixed-type mesothelioma, because sarcomatoid tumor components are not shed into pleural effusions.
  • Where clinical practice requires histology showing invasion, the authors stated that diagnosis and start of therapy are frequently delayed by as much as 6–9 months.
  • In the authors' own material, desmin staining in alcohol-fixed cytospin preparations had a sensitivity of 98%.
  • Per cited work, the combination of BAP1 and MTAP immunohistochemistry and CDKN2A FISH had a sensitivity of 80% to 90% for epithelial mesothelioma in the pleura.
  • Ploidy analysis by FISH was reported to show aneuploidy with 80–90% sensitivity and 100% positive predictive value. Homozygous loss of the 9p21 signals had a 100% positive predictive value.
  • Per a cited study, the soluble biomarkers hyaluronan and mesothelin combined in a logistic model gave an area under the curve of 0.99. The authors said this should be used only as an adjunct to the morphological diagnosis.
  • In the authors' cohort, median survival was 20 months after a mesothelioma diagnosis by effusion cytology and 12 months for those diagnosed by histology.
  • Over 10 years of clinical routine using guideline criteria and liberal use of adjuvant analyses (cited earlier work by the same authors), the positive predictive value of a cytological diagnosis fulfilling these criteria was 100%.
• The authors' conclusion: The authors concluded that when malignant mesothelioma can be diagnosed by effusion cytology using guideline criteria, the diagnosis is reliable and on its own provides sufficient ground for starting therapy.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Malignant Mesothelioma, Pleural Effusion, Cytology, Biomarker, Reactive Mesothelial Cells.

Related studies

• Recent Advances in the Diagnosis of Malignant Mesothelioma: Focus on Approach in Challenging Cases and in Limited Tissue and Cytologic Samples — S. Monaco, M. Mehrad, et al. (2018)
• Integrative Molecular Characterization of Malignant Pleural Mesothelioma — J. Hmeljak, F. Sanchez-Vega, et al. (2018)
• The role of cytologic evaluation of pleural fluid in the diagnosis of malignant mesothelioma — A.A. Renshaw, B.R. Dean, et al. (1997)
• The sensitivity of cytologic evaluation of pleural fluid in the diagnosis of malignant mesothelioma — E.A. Rakha, S. Patil, et al. (2010)
• HEG1, BAP1, and MTAP are useful in cytologic diagnosis of malignant mesothelioma with effusion — K. Hiroshima, D. Wu, et al. (2021)
• The applicability of a keratin 7 monoclonal antibody in routinely Papanicolaou-stained cytologic specimens for the differential diagnosis of carcinomas — J.H. Baars, J.L. De Ruijter, et al. (1994)

Browse more research in Translational Lung Cancer Research, or return to medical research.