Molecular Pathology in a Mesothelioma Diagnosis

Abstract

In recent years, the conditions in routine mesothelioma practice have changed dramatically. These changes include (1) the aging of patients, (2) the introduction of a combination of immune checkpoint inhibitors (nivolumab plus ipilimumab) that is superior to conventional chemotherapy, and (3) advances in the pathological diagnosis of cytology specimens, small biopsy tissue, and early-stage lesions. This review article outlines (i) the WHO 2021 classification, which for the first time introduced the category of "benign and preinvasive mesothelial tumors" including mesothelioma in situ, (ii) the morphological ancillary assays based on genetic alterations of mesotheliomas that enabled the diagnosis of the new disease category, and (iii) its application to cytology, followed by (iv) an overview of the genetic alterations in mesothelial tumors and mesothelioma subtypes. Given that over 80% of pleural mesotheliomas initially present with pleural effusions, the role of cytology is expected to become more important. However, there are caveats and pitfalls associated with the application of ancillary assays, and the careful management and evaluation are desirable. Furthermore, diagnosing mesothelioma is challenging for pathologists alone, so it is essential that the results of histology and ancillary assays always be assessed and interpreted together with clinical and imaging findings.