Pathology of Mesothelioma, Subtypes, and Rare Variants: What Is the Role of Immunohistochemical Markers in Differential Diagnosis?

Malignant pleural mesothelioma (MPM) is an asbestos-related aggressive tumor arising from mesothelial cells on the pleural surface. The definitive diagnosis of MPM is made histopathologically, supported by clinical and radiological findings, but morphological discrimination between MPM and other malignant tumors and that between MPM and non-neoplastic reactive mesothelial hyperplasia (RMH) are often difficult. In such cases, ancillary diagnostic techniques, fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), are effective to diagnose MPM. Immunohistochemical markers, mesothelial-related positive and negative markers, are especially essential for discrimination between MPM and other malignant tumors. Immunohistochemical detection of BRCA1-associated protein 1 (BAP1) protein loss and that of methylthioadenosine phosphorylase (MTAP) protein loss are also useful for differentiating MPM from RMH similar to detection of CDKN2A (p16) homozygous deletion by FISH. Moreover, BAP1 IHC and MTAP IHC, as well as CDKN2A (p16) FISH, are effective for diagnosing early-stage MPM and assessing malignancy of mesothelial cells in pleural effusion. In this chapter, we focus on the pathological approach including auxiliary diagnostic techniques, particularly IHC, in the differential diagnosis of MPM.