Issues and Their Resolution in the Pathological Diagnosis of Malignant Pleural Mesothelioma in the Early Stage

Objectives. Differential diagnosis of pleural mesothelioma in the early stage and reactive mesothelial hyperplasia is important to determine therapeutic strategy, but the morphological discrimination between them is very difficult. It has been reported that the p16INK4A and NF2 genes are frequently deleted in malignant pleural mesothelioma in the advanced stage. In this study, we examined whether these gene abnormalities are useful to discriminate between pleural mesothelioma in the early stage and reactive mesothelial hyperplasia. Method. Cases of malignant pleural mesothelioma in the advanced stage (16), pleural mesothelioma in the early stage (2), and reactive mesothelial hyperplasia (3) were selected based on morphological and immunohistochemical examinations and their tissues were analyzed for the p16INK4A and NF2 genes by real-time PCR. Results. The p16INK4A gene was deleted in all cases (16/16) and the NF2 gene was deleted in most cases (15/16) of advanced stage malignant pleural mesothelioma, whereas all cases (3/3) of reactive mesothelial hyperplasia retained these genes. As for early stage pleural mesothelioma, the p16INK4A gene was deleted in both cases (2/2), one of which (1/2) showed the deletion of the NF2 gene. Conclusion. The gene diagnosis of p16INK4A and NF2 locus may be useful for the discrimination of early stage pleural mesothelioma and reactive mesothelial hyperplasia.