New Insights in Pleural Mesothelioma Classification Update: Diagnostic Traps and Prognostic Implications

Our plain-English summary of New Insights in Pleural Mesothelioma Classification Update: Diagnostic Traps and Prognostic Implications, by M.G. Mastromarino, A. Lenzini, V. Aprile, et al (Diagnostics, 2022).

The study

• Authors: M.G. Mastromarino, A. Lenzini, V. Aprile, G. Alì, D. Bacchin, S. Korasidis, M.C. Ambrogi, M. Lucchi
• Journal: Diagnostics
• Published: 2022;12(12)
• Type of article: Review
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The 2021 WHO Classification of Tumors of the Pleura has introduced significant changes in mesothelioma codification beyond the three current histological subtypes-epithelioid, sarcomatoid and biphasic. Major advances since the 2015 WHO classification include nuclear grading and the introduction of architectural patterns, cytological and stromal features for epithelioid diffuse mesothelioma. Mesothelioma in situ has been recognized as a diagnostic category. Demonstration of loss of BAP1 or MTAP by immunohistochemistry, or CDKN2A homozygous deletion by FISH, is valuable in establishing the diagnosis of epithelioid mesothelioma. Recent emerging data proved that grading and histological subtypes have prognostic implications and may be helpful to patient risk stratification and clinical management. Nevertheless, the latest mesothelioma classification increases the already non-negligible diagnostic pitfalls, especially concerning differential diagnosis of pre-invasive tumors. In this review, recent changes in histologic classification of mesothelioma and advances in molecular markers are presented and their relation to diagnostic challenges and prognostic implications is discussed.

In plain English

This article was a review, not a new study of patients. The authors searched the PubMed/Medline databases for English-language studies published from 2012 to May 2022 on how pleural mesothelioma is classified under the microscope. They described the changes made in the 2021 World Health Organization (WHO) classification. These included recognizing mesothelioma in situ as a diagnostic category and introducing nuclear grading for epithelioid diffuse mesothelioma. The review summarized earlier studies by other researchers that linked tumor grade to survival. For example, in a study of 776 patients with epithelioid mesothelioma by Rosen and colleagues, median survival was 8 months for grade III, 14 months for grade II and 27 months for grade I tumors. In a series of 10 patients with mesothelioma in situ reported by Churg and colleagues, 7 developed invasive mesothelioma 12 to 92 months after biopsy. The authors concluded that the updated classification may improve how patients are sorted by risk. The article did not discuss 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 literature review of the 2021 WHO classification of pleural mesothelioma and of studies on grading, histologic subtypes and diagnostic markers
• Who was studied: Published English-language studies from 2012 to May 2022 on the histopathological classification of pleural mesothelioma, plus WHO guidelines. The number of included studies is not stated in the text.
• Main results:
  • The 2021 WHO classification recognized mesothelioma in situ as a defined entity and introduced nuclear grading for epithelioid diffuse mesothelioma for the first time.
  • In a reviewed study by Kadota et al. (2012) of 232 patients with epithelioid MPM, the median overall survival was 28 months for nuclear grade I (n = 107), 14 months for grade II (n = 91) and 5 months for grade III (n = 34).
  • In a reviewed multi-institution study by Rosen et al. (2018) of 776 patients with epithelioid MPM, the median overall survival was 8 months for nuclear grade III, 14 months for grade II and 27 months for grade I tumors.
  • In a reviewed study by Pelosi et al. (2018) of 940 patients with MPM, each 1-point increase in the Pathologic Grading System score was linked to a 46% higher risk of death in the training set (H.R. 1.46; 95% C.I. 1.36 to 1.56). In the validation set the figure was 28% (H.R. 1.28; 95% C.I. 1.22 to 1.34).
  • In a reviewed validation study by Zhang et al. (2020) of 563 epithelioid MPM cases, the two-tier grading gave a median overall survival of 19.3 months for low-grade tumors and 8.9 months for high-grade tumors.
  • In a reviewed series by Churg et al. of 10 patients with mesothelioma in situ, 7 developed invasive MPM 12 to 92 months after biopsy.
  • BAP1 and CDKN2A loss occur in up to 70% of cases, so a diagnosis of MPM cannot be excluded when these abnormalities are absent.
• The authors' conclusion: The authors concluded that the updated classification, by acknowledging the prognostic value of grading and subtyping of epithelioid MPM, may improve patient risk stratification and have future therapeutic implications.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, WHO Classification, Pleura, Mesothelioma, Histological Subtype, Epithelioid, Sarcomatoid, Biphasic Mesothelioma.

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