BAP1 Loss, Nuclear Grading, and Nonepithelioid Features in the Diagnosis of Mesothelioma in Italy: Nevermore without the Pathology Report

Our plain-English summary of BAP1 Loss, Nuclear Grading, and Nonepithelioid Features in the Diagnosis of Mesothelioma in Italy: Nevermore without the Pathology Report, by G. Rossi, L. Righi, F. Barbisan, et al (Journal of Personalized Medicine, 2024).

The study

• Authors: G. Rossi, L. Righi, F. Barbisan, M. Tiseo, P. Spagnolo, F. Grosso, P. Pisapia, U. Malapelle, M. Sculco, I. Dianzani, L. Abate-Daga, M.C. Davolio, G.L. Ceresoli, D. Galetta, G. Pasello, S. Novello, P. Bironzo
• Journal: Journal of Personalized Medicine
• Published: 2024;14(4)
• Type of article: Review
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The pathologic diagnosis of pleural mesothelioma is generally based on international guidelines, but no compulsory points based on different drugs approvals in different European countries are required to be reported. According to the last (2021) edition of the World Health Organization classification of pleural tumors, the nuclear grade of epithelioid-type mesothelioma should be always inserted in the pathologic report, while the presence of BRCA-associated protein-1 (BAP1) (clone C4) loss and a statement on the presence of the sarcomatoid/nonepithelioid component are fundamental for both a screening of patients with suspected BAP1 tumor predisposition syndrome and the eligibility to perform first-line immunotherapy at least in some countries. Several Italian experts on pleural mesothelioma who are deeply involved in national scientific societies or dedicated working groups supported by patient associations agreed that the pathology report of mesothelioma of the pleura should always include the nuclear grade in the epithelioid histology, which is an overt statement on the presence of sarcomatoid components (at least 1%, in agreement with the last classification of pleural mesothelioma) and the presence of BAP1 loss (BAP1-deficient mesothelioma) or not (BAP1-retained mesothelioma) in order to screen patients possibly harboring BAP1 tumor predisposition syndrome. This review aims to summarize the most recent data on these three important elements to provide evidence regarding the possible precision needs for mesothelioma.

In plain English

This article was a review by a group of Italian pleural mesothelioma experts. It created no new data. It summarized published research on three items the authors want included in every pathology report for pleural mesothelioma: whether the BAP1 protein is lost or retained on tissue staining, the nuclear grade of epithelioid tumors, and whether any sarcomatoid (nonepithelioid) component is present. The authors wrote that BAP1 loss has 100% specificity for telling malignant from benign mesothelial growths. It can also help flag patients who may carry an inherited BAP1 mutation (BAP1 tumor predisposition syndrome). One cited Italian study found such mutations in 7 of 101 people with suspected syndrome. Cited studies linking BAP1 to survival gave mixed results. The review described grading schemes that separated patients by survival. In Italy, first-line ipilimumab plus nivolumab for unresectable pleural mesothelioma is approved and reimbursed only for the nonepithelioid subtype. The review noted that this makes reporting any sarcomatoid component matter for treatment eligibility. The review did not study asbestos exposure. The authors concluded that these three points should always be included in pathology reports.

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 published literature (no new data)
• Who was studied: No patients were studied directly. The review covered published studies on pleural mesothelioma and was written by Italian experts.
• Main results:
  • The authors concluded from the reviewed data that loss of BAP1 protein distinguishes malignant from benign mesothelial growths with 100% specificity.
  • In a cited Italian study by Sculco et al., 7 of 101 individuals with suspected BAP1 tumor predisposition syndrome (6.9%) carried germline BAP1 pathogenic variants.
  • Cited evidence on BAP1 and survival was mixed. In Cantini et al., median overall survival was 14.8 months with negative BAP1 expression and 18.1 months with positive BAP1 expression. This difference was not statistically significant (p = 0.2).
  • A cited study by Fuchs et al. applied a proposed weighted grading scheme to 369 consecutive pleural mesotheliomas. Median survival was 17.1, 10.1 and 4.1 months for low, intermediate and high grades.
  • In the cited CheckMate-743 trial update, the hazard ratio for survival with immunotherapy was 0.48 (95% CI 0.34 to 0.68) for nonepithelioid patients and 0.84 (95% CI 0.69 to 1.03) for epithelioid patients.
  • In Italy, approval and reimbursement of first-line immune checkpoint inhibitors (ipilimumab plus nivolumab) is limited to patients with unresectable nonepithelioid pleural mesothelioma.
  • The authors wrote that an epithelioid diagnosis on the initial biopsy could change to biphasic or sarcomatoid in up to 19.5% of cases.
• The authors' conclusion: The authors agreed that pathology reports of pleural mesothelioma should always include three items: the nuclear grade of epithelioid tumors, a statement on any sarcomatoid/nonepithelioid component, and whether BAP1 is lost (BAP1-deficient) or retained (BAP1-retained). Their conclusions section calls these compulsory points.

Topics

Medical terms in this study, explained in our Lexicon: BAP1, Nuclear Grading, Mesothelioma, Pathology Report, Pleural Mesothelioma, Nuclear Grade, Epithelioid, Sarcomatoid.

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• 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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