The pathological and molecular diagnosis of malignant pleural mesothelioma: a literature review

Our plain-English summary of The pathological and molecular diagnosis of malignant pleural mesothelioma: a literature review, by G. Alì, R. Bruno, G. Fontanini (Journal of Thoracic Disease, 2018).

The study

• Authors: G. Alì, R. Bruno, G. Fontanini
• Journal: Journal of Thoracic Disease
• Published: 2018;10(Suppl 2):S276-S284
• Type of article: Review
• Cited by: 40 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM), an asbestos-induced tumor, represents significant diagnostic challenges for pathologists. Its histological diagnosis is stepwise and should be based on morphological assessment, supported by clinical and radiological findings, and supplemented with immunohistochemistry (IHC) and, more recently, molecular tests. The main diagnostic dilemmas are the differential diagnoses with benign mesothelial proliferations and other pleural malignant tumors. The present review is an update regarding the morphological, immunohistochemical, and molecular features with respect to MPM diagnosis. Data sources include a survey of the biomedical literature from PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and textbooks focusing on the pathological diagnosis of MPM and associated immunohistochemical and molecular markers. The histological findings of MPM could facilitate its diagnosis and provide important prognostic information. The immunohistochemical approach should rest on the application of a panel including positive (mesothelial-related) and negative markers with greater than 80% sensitivity and specificity, which need to be selected based on morphology and clinical information. Moreover, in challenging cases, fluorescent in situ hybridization (FISH) testing for the p16 deletion and IHC to evaluate the loss of BRCA1-associated protein 1 (BAP1) expression could be useful in distinguishing benign from malignant pleural proliferations.

In plain English

This article was a literature review, not a new study of patients. The authors searched PubMed up to August 15, 2017, using the terms malignant pleural mesothelioma (MPM) and diagnosis. The search found 3,809 articles, of which only English-language ones were considered, and the authors also drew on textbooks. The review described how pathologists diagnose MPM, which the authors, citing other sources, described as related mainly to asbestos exposure. It reported that published sensitivity of cytology (examining cells in pleural fluid) ranged from 30% to 75%. It described a recommended starting panel of immunohistochemistry stains: pancytokeratin plus two mesothelial markers and two markers for the other tumor under consideration. For telling benign from malignant mesothelial growths, it summarized reports that loss of BAP1 protein and p16 deletion by FISH were highly specific for mesothelioma, but that a negative result did not make a growth benign. Reported p16 sensitivity for epithelioid or biphasic MPM ranged from about 45% to 85%. The authors concluded that immunohistochemistry is fundamental to diagnosis and that these two tests could be useful in selected cases.

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 based on a PubMed search and textbooks
• Who was studied: Published literature, not patients. A PubMed search combining the terms MPM and diagnosis, updated August 15, 2017, found 3,809 articles. Only English-language publications were considered, and textbooks were also used. The authors selected detailed prospective studies in large series, evidence-based guidelines and papers on specific markers.
• Exposure: Exposure was not studied; the review concerns diagnostic methods. The introduction, citing other sources, states that asbestos is the main risk for MPM, with a latency of about 40 years.
• Main results:
  • Reviewed literature: the published sensitivity of cytology for diagnosing mesothelioma ranged from 30% to 75%.
  • Reviewed literature: MPM subtypes are epithelioid (60 to 80%) and sarcomatoid (less than 10%), with biphasic/mixed and other less common types making up the rest.
  • The International Mesothelioma Interest Group recommends an initial stain panel of pancytokeratin plus two mesothelial markers and two markers for the other tumor under consideration. The markers should have sensitivity or specificity greater than 80%.
  • Reviewed literature: approximately 5 to 10% of sarcomatoid mesotheliomas are keratin-negative.
  • Reviewed literature: 30% of MPM shows a 'null' phenotype, so negative mesothelial markers do not exclude MPM.
  • Reviewed literature: BAP1 protein loss was reported in approximately 60 to 70% of epithelioid/mixed mesotheliomas and 15% of sarcomatoid ones. Recent studies reported 100% specificity, although more data are needed.
  • Reviewed literature: p16 homozygous deletion by FISH was reported only in mesotheliomas (specificity 100%). Sensitivity for epithelioid/biphasic MPM ranged from approximately 45% to 85%, and was higher in sarcomatoid mesothelioma.
  • The low sensitivity of BAP1 and p16 testing limits their clinical use. Failure to find these losses does not make a lesion benign, and running both tests was reported to improve sensitivity.
• The authors' conclusion: The authors concluded that immunohistochemistry is fundamental for diagnosing MPM. They stated it should use a panel of positive (mesothelial-related) and negative markers chosen according to morphology and clinical information. They concluded that p16 FISH and BAP1 immunohistochemistry could be useful in selected cases to distinguish benign from malignant pleural proliferations, and that histotype is still the best predictor of prognosis.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Immunohistochemistry, Fluorescence In Situ Hybridization (FISH), BAP1.

Related studies

• Molecular markers and new diagnostic methods to differentiate malignant from benign mesothelial pleural proliferations: a literature review — R. Bruno, G. Alì, et al. (2018)
• Malignant pleural mesothelioma and mesothelial hyperplasia: A new molecular tool for the differential diagnosis — R. Bruno, G. Alì, et al. (2017)
• Pathological and molecular biological approaches to early mesothelioma — T. Tsujimura, I. Torii, et al. (2012)
• Pathological anatomy and molecular pathology — M. Krismann, K.M. Müller, et al. (2004)
• Well-differentiated papillary mesothelioma of the peritoneum: a pathological analysis and review of the literature — A.V. Hoekstra, M.W. Riben, et al. (2005)
• Advances in pathological diagnosis of mesothelioma: what pulmonologists should know — A. Louw, A. Badiei, et al. (2019)

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