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

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.

Accuracy of pathologic diagnosis for thymic epithelial tumors: a brief report from an Italian reference Center.

Objectives - Rare tumors are diagnostic challenges for pathologists. Consultation or referral to Centers with expertise is crucial for the right diagnosis. This is particularly true for Thymic Epithelial Tumors (TETs), whose treatment strategies vary according to histological subgroup. We aimed at evaluating the accuracy of TET pathologic characterization in an Italian reference Center. Materials and methods - All the cases with diagnosis or suspicion of TETs, which underwent a pathological second opinion at Istituto Nazionale dei Tumori (INT), Milan, between 2015 and 2019 were retrospectively reviewed. All cases had been pathologically characterized through immunohistochemistry (IHC). Descriptive statistics were used for qualitative variables. Concordance was estimated through Cohen's kappa (k). Results - Out of 278 cases of TETs diagnosed in INT, 72 were referred to INT for a pathologic revision. The INT revision changed the diagnosis in 41 cases (56.9%), with a potential therapeutic shift in 32 (44.4%). In particular, 20 cases of thymoma were reviewed as a different subtype of thymoma (19/20) or lymphoma (1/20); nine cases of thymic carcinoma were reviewed as thymoma. On the other hand, three cases of lung carcinoma were reviewed as thymic carcinoma (2/3) or thymoma (1); eight cases of carcinoma Not Otherwise Specified were reviewed as thymic carcinoma; one case of lymphoma was reviewed as thymoma. Concordance between pathologists was moderate for thymoma (74.7%, k 0.447), inferior for thymic carcinoma (60.5%, k 0.139). Conclusion - A significant proportion of cases referred to INT for a presumptive TET received a different characterization. A potential shift in therapeutic indication was not rare. This underlines the importance for TETs to get a second pathological diagnosis by an expert pathologist and supports the need for networks on rare cancers.

Best practices for the management of thymic epithelial tumors: A position paper by the Italian collaborative group for ThYmic MalignanciEs (TYME).

Thymic epithelial tumors (TETs) are a heterogenous group of rare tumors, with a complex histopatological classification. Furthermore, the recent introduction of the first TNM staging system, that is scheduled to replace the Masaoka-Koga system, may create further difficulties in TET management, that remains challenging. Several guidelines for treatment of TETs are available and provide recommendations based mainly on non randomized trials and retrospective or limited series. Often the lack of evidence leads to formulation of indications based on expert opinions. As for other rare cancers it is crucial to create networks to coordinate the work among centres involved in treatment of these diseases in order to offer the best diagnostic and therapeutic tools. For this purpose, in 2014 a network named TYME (ThYmic MalignanciEs), was founded in Italy with the aim of improving care and research in TETs. In September 2017 a panel of multidisciplinary experts from TYME network and from other Italian centres strongly involved in TET diagnosis and treatment convened a first Italian Expert meeting together with representatives of association for patients affected by rare thoracic cancers Tu.To.R, to explore how these tumors are managed in the different centres of Italy compared to ESMO guidelines. In this paper we summarize the issues discussed during that meeting and we propose recommandations based on Masaoka Koga and the new TNM staging system.