Malignant mesothelioma: cytologic diagnosis with histologic, immunohistochemical, and ultrastructural correlation

The differential diagnoses of malignant mesothelioma in serous effusions include adenocarcinoma and reactive mesothelial cells. While several cytologic features are of predictive value in separating these entities, immunostaining and ultrastructural examination are important adjuncts that increase the diagnostic yield. Many of the cytomorphologic features can be correlated with immunohistochemical and ultrastructural findings. Most important among these is the ultrastructural demonstration of long, often branching microvillous processes in malignant mesothelial cells. Corresponding microvilli can be visualized by immunostaining for epithelial membrane antigen in both cell block preparations from effusions and biopsy specimens, allowing the identification of malignant mesothelioma. In addition, the circumferential distribution of these immunostained microvilli in cells dispersed in stromal connective tissue identifies them as malignant mesothelial cells, corresponding to the ultrastructural appearance of aberrant microvilli, which project through deficiencies in the basal lamina. These microvilli show interdigitation with stromal collagen fibers, a phenomena not observed in adenocarcinoma.