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

Author:

Rossi Giulio12ORCID,Righi Luisella3ORCID,Barbisan Francesca4,Tiseo Marcello5ORCID,Spagnolo Paolo6ORCID,Grosso Federica7,Pisapia Pasquale8ORCID,Malapelle Umberto8ORCID,Sculco Marika9,Dianzani Irma9,Abate-Daga Laura10,Davolio Maria Cristina11,Ceresoli Giovanni Luca12ORCID,Galetta Domenico13ORCID,Pasello Giulia1415,Novello Silvia3,Bironzo Paolo3

Affiliation:

1. Pathology Unit, Services Area, Fondazione Poliambulanza Hospital Institute, Via Bissolati 57, 25124 Brescia, Italy

2. Fondazione FONICAP, Via Locchi, 26, 37124 Verona, Italy

3. Department of Oncology, University of Turin, San Luigi Hospital, 10043 Orbassano, Italy

4. Pathological Anatomy Institute, Polytechnic University of Marche Region, 60126 Ancona, Italy

5. Department of Medicine and Surgery, University of Parma and Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy

6. Respiratory Disease Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy

7. Mesothelioma Unit, AO SS. Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy

8. Department of Public Health, Federico II University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy

9. Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy

10. TU.TO.R. Tumori Toracici Rari, Patient Advocacy, 20123 Milan, Italy

11. Legal Medicine and Risk Management Department, Azienda Unità Sanitaria Locale di Modena, Strada Martiniana, 21, 41126 Modena, Italy

12. Medical Oncology, Humanitas Gavazzeni Clinic, 24125 Bergamo, Italy

13. Medical Thoracic Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, Italy

14. Medical Oncology 2, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy

15. Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padua, Italy

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.

Publisher

MDPI AG

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