Pleural mesothelioma classification-update and challenges

Our plain-English summary of Pleural mesothelioma classification-update and challenges, by S. Dacic (Modern Pathology, 2022).

The study

• Author: S. Dacic
• Journal: Modern Pathology
• Published: 2022;35(Suppl 1):51-56
• Type of article: Review
• Cited by: 76 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mesothelial tumors are classified into benign or preinvasive tumors, and mesotheliomas. The benign or preinvasive group includes adenomatoid tumors, well-differentiated papillary mesothelial tumors, and mesothelioma in situ. Malignant tumors are mesotheliomas and can be localized or diffuse. Histological classification of invasive mesotheliomas into three major subtypes-epithelioid, sarcomatoid, and biphasic is prognostically important. It also plays a significant role in the treatment decisions of patients diagnosed with this deadly disease. Grading and subtyping of epithelioid mesotheliomas have been one of the major changes in the recent WHO classification of pleural tumors. Mesothelioma in situ has emerged as a precisely defined clinico-pathologic entity that for diagnosis requires demonstration of loss of BAP1 or MTAP by immunohistochemistry, or CDKN2A homozygous deletion by FISH. The use of these two biomarkers improves the diagnostic sensitivity of effusion specimens and limited tissue samples and is valuable in establishing the diagnosis of epithelioid mesothelioma. In this review, recent changes in the histologic classification of pleural mesothelioma, importance of ancillary diagnostic studies, and molecular characteristics of mesotheliomas are discussed.

© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.

In plain English

This article is a review of recent changes in the microscopic classification of pleural mesothelioma, mainly in the 2021 World Health Organization (WHO) classification. It reported no new patient data. The author described mesothelioma in situ, an early, preinvasive form newly included by the WHO. It cannot be diagnosed by appearance alone. Diagnosis requires tests showing loss of the BAP1 or MTAP proteins, or homozygous deletion of the CDKN2A gene; the MTAP test can stand in for the CDKN2A test. Citing earlier work, the review noted that these changes tend to occur with heavy asbestos exposure, after radiation, or in patients with a family predisposition. It also noted that up to 70% progressed to invasive mesothelioma after a median follow-up of 5 years. It cited the SEER database, in which median survival after surgery was 19, 12 and 4 months for epithelioid, biphasic and sarcomatoid pleural mesothelioma. It described a new two-tier low- and high-grade system for epithelioid mesothelioma and summarized genetic studies. The author stated that BAP1, MTAP and CDKN2A tests are valuable for diagnosing mesothelioma in fluid samples and small biopsies.

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 of the pathology classification of pleural mesothelioma; no original data
• Who was studied: No patients were studied. The review covers published studies and the 2021 WHO classification of pleural mesothelioma.
• Exposure: Asbestos was not studied directly and no fiber types are named. From earlier reports, the review notes that mesothelioma in situ changes tend to occur with heavy asbestos exposure, after radiation, and in patients with familial predisposition. It also notes that EWSR1 fusions were found in rare cases in younger patients without a history of asbestos exposure.
• Main results:
  • The review cites the SEER database: median survival in patients with pleural mesothelioma who underwent surgery was 19 months (epithelioid), 12 months (biphasic) and 4 months (sarcomatoid).
  • Morphology alone is insufficient to diagnose mesothelioma in situ. Diagnosis requires loss of BAP1 or MTAP by immunohistochemistry, or CDKN2A homozygous deletion by FISH.
  • MTAP immunohistochemistry can be used as a surrogate for the CDKN2A FISH assay.
  • Citing earlier work, the review states that up to 70% of mesotheliomas in situ progressed to invasive mesothelioma after a median follow-up of 5 years.
  • A two-tier (low and high grade) grading system has been recommended for epithelioid mesothelioma in resections and biopsies.
  • Pleomorphic and transitional patterns were formerly considered epithelioid but show prognosis similar to sarcomatoid and biphasic mesotheliomas. In the 2021 WHO classification they are reclassified as cytological features.
  • Agreement between pathologists on transitional features was described as fair when based on routine staining alone (wK = 0.40).
  • More than 90% of sarcomatoid mesotheliomas harbor CDKN2A homozygous deletion or MTAP loss.
  • For a definitive diagnosis of biphasic mesothelioma in resection specimens, at least 10% of each component (epithelioid and sarcomatoid) is required.
  • Somatic BAP1 mutations occur in over 50% of pleural mesotheliomas, mostly epithelioid.
• The authors' conclusion: The author concluded that BAP1/MTAP immunohistochemistry and FISH for CDKN2A homozygous deletion are valuable tools for diagnosing mesothelioma in body fluid cytology or limited tissue biopsies. The author added that these tests should be strongly considered.
• Limitations the authors state:
  • The author notes that genomic studies in mesothelioma are still relatively limited.
  • The author notes that more data are needed before the cutoffs in the WHO definition of biphasic mesothelioma can be changed.
  • The author notes that it is unknown what other genetic alterations are early events in mesothelioma in situ.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma, Adenomatoid Tumor, Well-Differentiated, Mesothelioma in Situ, Histological Subtype, Epithelioid, Sarcomatoid.

Related studies

• Challenges and controversies in the diagnosis of malignant mesothelioma: Part 2. Malignant mesothelioma subtypes, pleural synovial sarcoma, molecular and prognostic aspects of mesothelioma, BAP1, aquaporin-1 and microRNA — D.W. Henderson, G. Reid, et al. (2013)
• BAP1 facilitates diagnostic objectivity, classification, and prognostication in malignant pleural mesothelioma — S.M. McGregor, R. Dunning, et al. (2015)
• Challenges and controversies in the diagnosis of mesothelioma: Part 1. Cytology-only diagnosis, biopsies, immunohistochemistry, discrimination between mesothelioma and reactive mesothelial hyperplasia, and biomarkers — D.W. Henderson, G. Reid, et al. (2013)
• New Markers for Separating Benign From Malignant Mesothelial Proliferations: Are We There Yet? — A. Churg, B.S. Sheffield, et al. (2016)
• Pathological and molecular biological approaches to early mesothelioma — T. Tsujimura, I. Torii, et al. (2012)
• Mesothelioma: Scientific clues for prevention, diagnosis, and therapy — M. Carbone, P.S. Adusumilli, et al. (2019)

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