Answer: Mesothelioma

Histology: The specimen is a pleural biopsy. The pleura shows focal marked chronic inflammation and some fibrosis. In addition, there is a proliferation of relatively bland appearing cells with abundance of pale pink cytoplasm. The nuclei are relatively round and regular with occasional nucleoli. Some of these cells seem to be lining the pleura and are typical mesothelial cells, but the striking feature is that these cells are infiltrating into the pleura and fibrous tissue. In some areas these cells infiltrate in almost a single file fashion and in other areas they proliferate in a more sheet-like pattern.

Discussion: The major differential diagnosis in this case is mesothelioma versus metastatic carcinoma. Although there is chronic inflammation, the cellular proliferation infiltrating into the soft tissue is more significant than one would see in a simple chronic pleural effusion. Although mesothelial proliferation can be quite florid in the pleura, the mesothelial cells in these settings rarely proliferate in such an infiltrative pattern. Based on this infiltrative pattern, we would consider this a tumor, and then the primary differential diagnosis rests between a tumor of mesothelial origin versus a metastatic tumor from an occult primary, such as lung or other sites. Immunoperoxidase staining can be extremely helpful in this differential diagnosis. In this case, the neoplastic cells were positive for CK7, CAM5.2 and cytokeratin AE1/AE3. Most importantly, the tumor cells also stained positively for calretinin. This latter stain is typically positive in mesothelial cells as well as mesotheliomas and is most helpful in establishing the diagnosis of mesothelioma. The neoplastic cells in this tumor were also negative for TTF, HMB45, and S-100 and thyroglobulin. These markers are helpful in ruling out a lung primary and melanoma.