The 2015 World Health Organization Classification of Tumors of the Pleura: Advances since the 2004 Classification

Our plain-English summary of The 2015 World Health Organization Classification of Tumors of the Pleura: Advances since the 2004 Classification, by F. Galateau-Salle, A. Churg, V. Roggli, et al (Journal of Thoracic Oncology, 2016).

The study

• Authors: F. Galateau-Salle, A. Churg, V. Roggli, W.D. Travis, World Health Organization Committee for Tumors of the Pleura
• Journal: Journal of Thoracic Oncology
• Published: 2016;11(2):142-54
• Type of article: Review
• Cited by: 216 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A new World Health Organization (WHO) Classification of Tumors of the Pleura has recently been published. While the histologic classification of pleural malignant mesothelioma remains the same in the 2015 WHO classification as it was in the 2004 classification, multiple new observations have been recorded. First, more detailed study has been performed of histologic subtyping of epithelioid mesothelioma. In particular, it has been recognized that the pleomorphic subtype is associated with a poor prognosis, similar to that of sarcomatoid malignant mesothelioma. Second, there is improved understanding of the role of immunohistochemistry in distinguishing mesothelioma from carcinomas of various sites. Third, the criteria for distinguishing malignant mesothelioma from reactive mesothelial proliferations has been further refined. Fourth, additional studies of sarcomatoid mesothelioma have defined the frequency and spectrum of various histologic and immunohistochemical features, including heterologous elements. Finally, pleural well-differentiated papillary mesotheliomas are better defined and cases with invasive foci are recognized. In addition, several promising observations in mesothelioma pathology and genetics have been made in the past decade. These are now the subject of further investigation to determine if they can be validated in ways that will significantly impact clinical practice. These include a preliminary study of grading, suggesting that nuclear atypia and mitotic count are independent prognostic markers. The discovery of inactivating mutations in the BRCA1-associated protein 1 gene in sporadic and hereditary mesothelioma has opened up a variety of novel molecular, clinical, and diagnostic investigations. One possible diagnostic application includes the setting of separating mesothelioma from reactive mesothelial proliferations, where it may play a role in conjunction with p16 FISH. Another useful discovery was that the NAB2-STAT6 fusion is characteristic of solitary fibrous tumors. This led to development of a STAT6 antibody that is a reliable immunohistochemical marker for solitary fibrous tumors. Genetic studies also led to the finding that WWTR1-CAMTA1 fusions are useful diagnostic markers for epithelioid hemangioendotheliomas, which can present as pleural-based masses. Finally, desmoid type fibromatosis, a locally aggressive tumor that can present in the pleura, has been shown to frequently have CTNNB1 gene mutations and express β-catenin by immunohistochemistry.

Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

In plain English

This article was a concise review, written on behalf of the World Health Organization (WHO) Committee for Tumors of the Pleura. It presented the 2015 WHO classification of tumors of the pleura (the lining around the lungs) and summarized diagnostic advances since the 2004 edition. It did not study patients and did not discuss asbestos exposure. The authors reported the classification's basic structure was similar to 2004. Epithelioid mesotheliomas with a pleomorphic pattern stayed in the epithelioid category but were regarded as a poor-prognosis subset. Organ-specific marker panels for telling mesothelioma apart from carcinomas were introduced. Unless overt tumor fragments were present, stromal invasion remained the single best criterion for diagnosing malignant mesothelioma. Citing other studies, the authors described tests that showed promise but needed further confirmation. These included p16 FISH and BAP1 staining for separating mesothelioma from benign reactions, though neither finds every mesothelioma. They included a preliminary grading system based on nuclear atypia and mitotic count, and markers for other pleural tumors. The authors concluded that genetic advances had led to improved diagnostic methods.

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: Review (concise state-of-the-art review) presenting the 2015 WHO classification of pleural tumors, written on behalf of the WHO Committee for Tumors of the Pleura
• Who was studied: No patient population; the article reviewed the 2015 WHO classification of pleural tumors and published research since 2004 on diagnosing them
• Main results:
  • The essential structure of the 2015 WHO classification of pleural tumors was similar to the 2004 version
  • Two cited studies found poorer prognosis for the pleomorphic subtype of epithelioid diffuse malignant mesothelioma. The WHO panel did not accept moving it to the sarcomatoid type and regarded these tumors as a poor-prognosis subset of epithelioid mesothelioma
  • Organ-specific carcinoma marker panels for distinguishing mesothelioma from carcinomas were introduced in the 2015 classification
  • Unless overt tumor fragments are present, invasion of the stroma remained the single best criterion for diagnosing malignant mesothelioma
  • In one cited study of 326 sarcomatoid mesothelioma cases, 44% were conventional sarcomatoid tumors
  • A cited preliminary grading study of pleural epithelioid mesothelioma found by multivariate analysis that nuclear atypia and mitotic count were independent prognostic factors. These were used to create a three-tier grade separating patients into three prognostic groups
  • Cited studies reported that p16 loss by FISH is never seen in benign mesothelial processes
  • BAP1 mutations were reported in roughly 40 to 60% of epithelioid mesotheliomas and fewer than 20% of sarcomatoid mesotheliomas, according to cited studies
  • In a cited study, combining BAP1 staining with p16 FISH was highly specific for diagnosing malignant mesothelioma in problem cases, and the combination was 58% sensitive for detecting malignancy
  • STAT6 staining was described as usually positive in solitary fibrous tumors and negative in diffuse malignant mesotheliomas, but it is not a specific marker
  • Sporadic desmoid-type fibromatosis was reported, in a cited study, to have CTNNB1 gene mutations in about 85% of cases
  • Pleural well-differentiated papillary mesotheliomas were described as having an indolent clinical outcome, in contrast to diffuse malignant mesotheliomas
• The authors' conclusion: The authors concluded that, while the 2015 classification's structure was similar to 2004, genetic advances had led to improved diagnostic methods
• Limitations the authors state:
  • The authors stated that more data are needed before histologic subtyping of epithelioid mesothelioma can be formally introduced into the classification
  • The authors noted that no other published studies have attempted to validate the proposed grading system in pleural mesothelioma
  • The authors stated that p16 FISH detects loss only in a proportion of mesotheliomas, so failure to find p16 loss does not make a process benign. The same applies to BAP1 loss

Topics

Medical terms in this study, explained in our Lexicon: Pleura, Mesothelioma, WHO Classification, Epithelioid, Pleomorphic, Prognosis, Sarcomatoid, Immunohistochemistry.

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