Highlights of the 14th international mesothelioma interest group meeting: Pathologic separation of benign from malignant mesothelial proliferations and histologic/molecular analysis of malignant mesothelioma subtypes

Our plain-English summary of Highlights of the 14th international mesothelioma interest group meeting: Pathologic separation of benign from malignant mesothelial proliferations and histologic/molecular analysis of malignant mesothelioma subtypes, by A. Churg, K. Nabeshima, G. Ali, et al (Lung Cancer, 2018).

The study

• Authors: A. Churg, K. Nabeshima, G. Ali, R. Bruno, L. Fernandez-Cuesta, F. Galateau-Salle
• Journal: Lung Cancer
• Published: 2018;124:95-101
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: The separation of benign from malignant mesothelial proliferations and exact subclassification of mesothelioma subtypes is crucial to determining patient care and prognosis but morphologically can be very difficult.

Methods: This session of the 2018 IMIG meeting addressed these problems.

Results: A new immunohistochemical marker, methylthioadenosine phosphorylase, was shown to correlate well with CDKN2A FISH and is cheaper and faster to run. A 117 gene expression panel also provided good separation on both tissue biopsy and cytology samples. Review of a series of mesotheliomas thought to be biphasic produced only a moderate level of agreement among expert pathologists with some cases being classified as purely epithelioid or sarcomatoid; these classifications had prognostic significance. The entity called transitional mesothelioma was found to behave exactly like sarcomatoid mesothelioma. RNA-seq analysis of a large series of mesotheliomas from a public database showed that, genetically, the morphologic breakdown into epithelioid, sarcomatoid, or biphasic mesotheliomas is artificial because there is a continuous spectrum of genomic changes. There are now criteria for the diagnosis of mesothelioma in situ and this is potentially important, since such cases might be curable.

Conclusions: This session documented new morphological and molecular approaches to separating benign from malignant mesothelial proliferations and to subclassifying malignant mesoteheliomas in clinical relevant ways.

Copyright © 2018 Elsevier B.V. All rights reserved.

In plain English

This article was a meeting report. It summarized one session of the 2018 International Mesothelioma Interest Group meeting on telling benign (reactive) mesothelial growths from malignant mesothelioma and on classifying mesothelioma subtypes. It described separate studies by different groups and did not study asbestos exposure. One group tested tissue from 114 malignant pleural mesotheliomas and 37 reactive proliferations; combined BAP1 and MTAP staining identified epithelioid mesothelioma with 82.6% sensitivity and 100% specificity. A second group reported that a 117-gene panel correctly separated all 29 epithelioid mesotheliomas from all 16 mesothelial hyperplasias. A third group found the same panel allowed 92% of 25 pleural fluid samples to be classed as malignant or benign. In 42 cases first diagnosed as biphasic mesothelioma, 14 expert pathologists identified biphasic type in 71%. Biphasic cases with a transitional pattern had a median survival of 6 months, compared with 12 months for those without it. Another group analyzed public RNA data on 297 pleural mesotheliomas and reported that, at a molecular level, they formed a continuous spectrum rather than distinct subtypes.

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: Meeting report summarizing several separate studies presented at one session of the 2018 International Mesothelioma Interest Group (IMIG) meeting, plus a concluding overview drawing on the literature and the author's own experience
• Who was studied: Several separate case series from different groups. Tissue from 114 malignant pleural mesotheliomas (86 epithelioid, 28 sarcomatoid) and 37 reactive proliferations, plus pleural effusion cell blocks from 90 epithelioid mesotheliomas and 31 non-mesothelioma cases. Tissue from 29 epithelioid mesotheliomas and 16 mesothelial hyperplasias. Pleural effusions from 15 epithelioid mesothelioma and 10 hyperplasia patients. 42 cases originally diagnosed as biphasic mesothelioma, drawn from 971 French cases collected 1998 to 2016. Public RNA-seq data on 297 malignant pleural mesotheliomas.
• Main results:
  • In tissue, combined BAP1 and MTAP staining separated epithelioid malignant pleural mesothelioma from reactive proliferations with 82.6% sensitivity and 100% specificity (Nabeshima et al).
  • In 29 epithelioid mesotheliomas and 16 hyperplasias, BAP1 and p16 testing each had 100% specificity, with sensitivities of 62.1% and 51.7%; the combination had 79.3% sensitivity. The 117-gene panel achieved 100% specificity and 100% sensitivity in the same cases (Ali et al).
  • On pleural effusion samples (15 epithelioid mesothelioma, 10 hyperplasia), the 117-gene profile allowed 92% of cases to be classed as malignant or benign (Bruno et al).
  • Fourteen expert pathologists reviewing 42 cases originally called biphasic identified pure epithelioid type in 17%, biphasic in 71% and pure sarcomatoid in 12%. Agreement between observers was moderate (weighted kappa 0.45) (Galateau-Salle et al).
  • Among the biphasic cases, those with a transitional pattern had a median survival of 6 months, compared with 12 months for those without it (p less than 0.0001). In multivariate analysis, the transitional pattern had a hazard ratio of 3.2 (95% CI 1.6 to 8.0, p = 0.003).
  • In unsupervised analysis of public RNA-seq data on 297 malignant pleural mesotheliomas, the molecular profile and prognosis were better explained by a continuous model than by the WHO epithelioid, biphasic and sarcomatoid types (Fernandez-Cuesta et al; work described as submitted).
  • The concluding author reported 2 cases in which BAP1 staining and CDKN2A FISH allowed a diagnosis of mesothelioma in situ.
• The authors' conclusion: In the concluding section, the author stated that classification of mesotheliomas by light microscopy remains the gold standard. The author added that gene expression profiling may prove useful for subclassifying the morphologic categories and for selecting patients for surgery or other treatments. The MTAP group concluded that BAP1 staining combined with 9p21 FISH remains the most accurate ancillary method.
• Limitations the authors state:
  • The MTAP group reported that evaluating staining in cell blocks was sometimes difficult because of artifacts and scattered single tumor cells.
  • The tissue gene-panel group stated that prospective validation is needed.
  • The effusion gene-panel group stated that the results have to be validated with more samples.
  • The concluding author noted that the sensitivity of CDKN2A FISH in the peritoneal cavity is poor and that MTAP is presumably no better.
  • The concluding author noted lab-to-lab variation in gene sets until specific gene panels are validated.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Prognosis, IMIG, CDKN2A, Fluorescence In Situ Hybridization (FISH), Biopsy, Cytology.

Related studies

• BAP1 immunohistochemistry and p16 FISH to separate benign from malignant mesothelial proliferations — B.S. Sheffield, H.C. Hwang, et al. (2015)
• Molecular pathways and diagnosis in malignant mesothelioma: A review of the 14th International Conference of the International Mesothelioma Interest Group — D.B. Chapel, A. Churg, et al. (2019)
• New Markers for Separating Benign From Malignant Mesothelial Proliferations: Are We There Yet? — A. Churg, B.S. Sheffield, et al. (2016)
• Guidelines for Pathologic Diagnosis of Malignant Mesothelioma 2017 Update of the Consensus Statement From the International Mesothelioma Interest Group — A.N. Husain, T.V. Colby, et al. (2018)
• The role of radiation treatment in pleural mesothelioma: Highlights of the 14th International Conference of the International mesothelioma interest group — R.M. MacRae, M. Ashton, et al. (2019)
• CD146 immunohistochemical staining for the separation of benign from malignant mesothelial proliferations — T. Salisbury, A. Churg (2021)

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