Recent Advances in the Diagnosis of Malignant Mesothelioma: Focus on Approach in Challenging Cases and in Limited Tissue and Cytologic Samples

Mesothelial proliferations can be diagnostically challenging in small specimens, such as body fluid cytology and small tissue biopsies. A great morphologic challenge for pathologists is the separation of benign reactive mesothelial proliferations from malignant mesotheliomas. Reactive mesothelial proliferations may have histologic features that resemble malignancy including increased cellularity, cytologic atypia, and mitoses. Recent advances in mesothelioma genetics resulted in identification of BAP1 mutations and p16 deletions as features of malignant mesotheliomas. Hence, BAP1 immunohistochemistry and fluorescence in situ hybridization for p16 emerged as 2 most common diagnostically helpful ancillary studies used on limited samples when the question is whether the proliferation is malignant or benign. In contrast, separation of mesothelioma from other malignancies is relatively straight forward using morphology and immunohistochemical stains. The choice of antibody panel to be applied in an individual case is driven by morphology, either epithelioid or sarcomatoid. This brief review will focus on morphology and ancillary testing of mainly pleural mesothelial proliferations.

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