Cytologic Malignancy Versus Benignancy: How Useful Are the “Newer” Markers in Body Fluid Cytology?

Abstract Context.—Differentiating reactive effusion, malignant mesothelioma, and metastatic adenocarcinoma in body cavity fluids can be challenging. Interpreting immunohistochemical markers in cell block preparations can be difficult because of nonspecific staining, focal staining, or poor staining quality. We selected a panel of conventional and newer markers to assess their utility in evaluating effusions. Objective.—To evaluate the efficacy of 5 immunohistochemical markers in the differential diagnosis of reactive mesothelial proliferation, malignant mesothelioma, and metastatic adenocarcinoma in body cavity fluids. Design.—A total of 72 formalin-fixed, paraffin-embedded cell block specimens from pleural and peritoneal effusions, including 5 mesotheliomas, 48 adenocarcinomas, and 19 benign effusions were stained with antibodies against calretinin, D2-40, XIAP, MOC-31, and WT1. Results.—All benign effusions and mesotheliomas demonstrated diffuse membranous staining with D2-40. All mesotheliomas displayed calretinin positivity, whereas only 58% of benign effusions stained focally with calretinin. MOC-31 was positive in all cases of adenocarcinoma, whereas all benign effusions and mesotheliomas were negative. All cases of the metastatic adenocarcinoma were negative for calretinin and D2-40. However, background reactive mesothelial cells were positive for calretinin and D2-40. Overall, D2-40 highlighted more mesothelial cells than calretinin. WT1 was positive in 50% of benign effusions, 60% of mesotheliomas, and 27% of adenocarcinomas. XIAP stained most mesotheliomas (80%), some adenocarcinomas (51%), and rare benign effusions (11%). Conclusions.—MOC-31 and D2-40 were very sensitive and specific markers of epithelial and mesothelial cells, respectively. Compared with calretinin, D2-40 was a more sensitive marker of mesothelial cells. WT1 proved to be nonspecific. XIAP was not a sensitive marker for malignancy and had a limited value in cytology. We recommend using a panel to include MOC-31 and D2-40 to improve diagnostic accuracy in body cavity effusions.