Update on the pathologic diagnosis of malignant mesothelioma

Our plain-English summary of Update on the pathologic diagnosis of malignant mesothelioma, by J.J. Schulte, A.N. Husain (Translational Lung Cancer Research, 2020).

The study

• Authors: J.J. Schulte, A.N. Husain
• Journal: Translational Lung Cancer Research
• Published: 2020;9(3):917-923
• Type of article: Review
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma is an uncommon tumor that may be difficult to diagnose. The International Mesothelioma Interest Group has been writing guidelines for pathological diagnosis that are periodically updated. The guidelines are being updated based on published literature in the last 3 years, and experience of more than 20 leading international pathologists in the field who will be co-authors. Updates were discussed by attendees of the Pulmonary Pathology Society Biennial Meeting (Dubrovnik, Croatia, June 2019). Areas with significant advancements/changes include utilization of immunohistochemistry (establishing mesothelial lineage and benign versus malignant), prognosis and nuclear grading, biphasic malignant mesothelioma, transitional pattern, malignant mesothelioma in situ, and therapeutic/molecular targets.

2020 Translational Lung Cancer Research. All rights reserved.

In plain English

This article was a review by two authors from the Department of Pathology at the University of Chicago. It covered how pathologists diagnose malignant mesothelioma from tissue samples. It did not study any patients and did not discuss asbestos exposure. The authors summarized published research from the previous three years, along with expert discussions, to inform updated diagnostic guidelines from the International Mesothelioma Interest Group. The findings described came from other studies. According to the review, claudin-4 was viewed as a superior marker of epithelial (carcinoma-type) differentiation. Loss of the BAP1 or MTAP proteins pointed to malignancy but did not occur in every mesothelioma. BAP1 loss was reported in 50–65% of epithelioid and around 15% of sarcomatoid malignant mesotheliomas. The review also described a proposed two-tier (high and low) grading system for epithelioid mesothelioma and debate over the 10% rule that defines biphasic mesothelioma. It reported studies favoring placing the transitional pattern with the sarcomatoid subtype, and a few reported cases termed malignant mesothelioma in situ. The authors noted that some of this evidence was limited.

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 commissioned for a journal series on highlights of the 2019 Pulmonary Pathology Society Biennial Meeting; no original data collected
• Who was studied: No patients were studied. The review drew on published literature from the last 3 years and on the experience of an international group of pathologists.
• Main results:
  • Reported from other studies: claudin-4 is viewed by many expert mesothelioma pathologists, with support from the literature, as a superior marker of epithelial differentiation when distinguishing epithelial from mesothelial proliferations.
  • HEG1 was described as a sensitive and specific marker of mesothelial differentiation, but its use is limited because it is not widely available outside Japan.
  • Reported from other studies: nuclear loss of BAP1 is a specific marker of malignancy but lacks sensitivity. It occurs in only 50–65% of epithelioid malignant mesotheliomas and around 15% of sarcomatoid malignant mesotheliomas.
  • BAP1 loss is not entirely specific for malignant mesothelioma and can also be seen in melanoma, renal cell carcinoma and other malignancies.
  • Cytoplasmic loss of MTAP is also a specific marker of malignancy in mesothelial proliferations but, like BAP1, lacks sensitivity. The authors stated that combining such markers should allow the vast majority of cases to be properly classified as benign or malignant.
  • For epithelioid malignant mesothelioma, a two-tier grading system is favored and proposed. High grade is nuclear grade 2 with necrosis or nuclear grade 3. Low grade is nuclear grade 1 or nuclear grade 2 without necrosis.
  • The WHO defines biphasic malignant mesothelioma as having at least 10% each of sarcomatoid and epithelioid components. Some experts favor dropping the 10% requirement altogether.
  • Reported from other studies: tumors with transitional features had survival curves and genetics closer to sarcomatoid than to epithelioid mesothelioma. These studies favor treating transitional features as a subset of the sarcomatoid subtype.
  • A few reported cases showed loss of BAP1 and MTAP in mesothelium without invasion, termed malignant mesothelioma in situ. These cases support the notion that such a lesion likely exists before invasive disease.
• The authors' conclusion: The authors identified the areas with significant advancements or changes in diagnosis: use of immunohistochemistry (establishing mesothelial lineage and telling benign from malignant), prognosis and nuclear grading, biphasic mesothelioma, the transitional pattern, malignant mesothelioma in situ, and therapeutic/molecular targets.
• Limitations the authors state:
  • The evidence that GATA3 helps distinguish sarcomatoid mesothelioma from sarcomatoid lung carcinoma still needs large confirmatory studies.
  • Robust data are lacking on prognostic cutoffs for the percentage of sarcomatoid component in biphasic mesothelioma.
  • The role, if any, of immunohistochemistry in the workup of biphasic mesothelioma has not yet been determined.
  • Malignant mesothelioma in situ rests on only a few reported cases.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pathology, Immunohistochemistry, Prognosis, Nuclear Grading, Biphasic Mesothelioma.

Related studies

• 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)
• Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group — A.N. Husain, T. Colby, et al. (2013)
• Commentary on pathologic diagnosis of asbestosis and critique of the 2010 Asbestosis Committee of the College of American Pathologists (CAP) and Pulmonary Pathology Society's (PPS) update on the diagnostic criteria for pathologic asbestosis — S.P. Hammar, J.L. Abraham (2015)
• Current issues in the pathologic and mineralogic diagnosis of asbestos-induced disease — A. Churg (1983)
• Differential Diagnosis of Epithelioid Malignant Mesothelioma With Lung and Breast Pleural Metastasis: A Systematic Review Compared With a Standardized Panel of Antibodies-A New Proposal That May Influence Pathologic Practice — N. Le Stang, L. Burke, et al. (2020)
• Malignant peritoneal mesothelioma: prognostic significance of clinical and pathologic parameters and validation of a nuclear-grading system in a multi-institutional series of 225 cases — D.B. Chapel, J.J. Schulte, et al. (2021)

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