Cytologic examination of pleural fluid is often performed in order to detect malignancy.

The normal constituents of pleural fluid include varying proportions of mesothelial cells, histiocytes, and lymphocytes which are all typically seen as isolated cells. Benign mesothelial cells may also be seen in small clusters.

This sample demonstrates features compatible with adenocarcinoma. A large number of overlapping cells create a 3-dimensional cluster composed of pleomorphic cells with hyperchromatic nuclei, irregular chromatin, high N/C ratio, and prominent and often abnormally shaped nucleoli. Mitoses are visible within some of the clusters. Other features of adenocarcinoma which are not clearly seen in this sample may include cytoplasmic vacuolation, clusters of cells with smooth borders, and the presence of a "dual" cell population (of benign mesothelial cells and overtly malignant cells).

Immunohistochemistry performed on a cell block may be required to confirm the diagnosis, identify the site of origin, and exclude mimics such as mesothelioma. Regardless of the site of origin, metastatic adenocarcinoma within the pleural fluid signifies advanced stage disease.