An Updated Contextual Approach to Mesothelial Proliferations in Pleural Effusion Cytology Leveraging Morphology, Ancillary Studies, and Novel Biomarkers

Context.— Pleural effusions are common cytologic specimens that can be leveraged to make diagnoses of malignancy that drive appropriate patient management. However, the overlap in morphologic features of reactive mesothelial proliferations, mesotheliomas, and adenocarcinomas can create diagnostic pitfalls in the cytologic evaluation of pleural fluids. Objective.— To review the morphologic spectrum of benign and malignant mesothelial proliferations in pleural effusions, as well as relevant clinicoradiologic contexts and ancillary tests. Data Sources.— Existing scientific and clinical literature as of January 2023. Conclusions.— We can leverage the knowledge of several overlapping morphologic features, clinicoradiologic scenarios, and immunohistochemical studies to enhance the diagnostic accuracy of pleural effusion cytology to appropriately delineate cases of adenocarcinoma, reactive mesothelial proliferation, and mesothelioma. Earlier diagnosis through cytology, particularly in cases of mesothelioma, may positively impact patient treatment options and prognosis.