Applications and limitations of immunohistochemistry in the diagnosis of malignant mesothelioma

Malignant mesothelioma is an uncommon malignant epithelial neoplasm originating from the serosal surface of body cavities. Because serosal surfaces are a common site of metastatic spread for a variety of malignant neoplasms originating from internal organs, separating malignant mesothelioma from metastatic tumors is of clinical importance. The diagnosis of malignant mesothelioma is complex and usually requires a multimodal approach that includes careful clinical history and physical examination, imaging studies, and tissue sampling for multimodal evaluation including routine histology, histochemistry, electron microscopy, and immunohistochemical tests. Of these, immunohistochemistry has emerged as the most valuable and readily available modality for the routine evaluation of these tumors. Unfortunately, no specific antibodies have yet been developed that can be accepted as exclusive for these tumors. The immunohistochemical diagnosis of malignant mesothelioma therefore depends on the use of a panel of stains that includes markers that are commonly expected to react with these tumors ("positive" markers) and markers that are not commonly expected to react with these tumors ("negative" markers). Additionally, the selection and utility of these various markers can vary considerably based on a constellation of circumstances, including patient sex, histologic appearance of the tumor (ie, epithelioid vs. sarcomatoid, etc), and various other clinical circumstances. Herein, we will review the currently available immunohistochemical markers used for the diagnosis of malignant mesothelioma and offer suggestions for the use of appropriate panels of stains based on specific morphologic types and clinical circumstances.