The cytological features of effusions with mesothelioma in situ: A report of 9 cases.

Abstract

The diagnosis of mesothelioma in situ (MIS) is now accepted by the WHO as a pre-invasive neoplastic mesothelial proliferation and considered a diagnosis based on histologic evaluation only. Although the definition of MIS includes recurrent effusions, little is known about the cytologic features of such effusions. Since mesothelioma is usually diagnosed at an advanced stage and has a poor prognosis, early detection of a neoplastic mesothelial population in such effusions can potentially have a positive impact on the management of such a dire disease. We reviewed a total of 18 pleural effusions from nine patients with recurrent effusions. Of these, five patients had follow-up biopsies diagnosed as MIS and the remaining four cases had negative radiology and malignant cytology proven by molecular markers (BAP1, MTAP or CDKN2A deletion) and at least 1 year follow-up with no overt mass identified by radiology. Initial effusions may mimic reactive mesothelial hyperplasia or exhibit atypia. As effusions recur, the cellularity and atypia increase and the mesothelial proliferation becomes morphologically indistinguishable from mesothelioma. Molecular alterations diagnostic of mesothelioma can be detected in these effusions, even in the initial-benign/reactive appearing ones. The cellularity and atypia detected in such effusions surpassed those noted on the biopsies, raising questions regarding the cause of such discrepancy. The diagnosis of MIS can be suspected based on malignant effusion cytology supported by molecular alterations. We propose that the proliferation of neoplastic mesothelial clones represent a clinically silent "liquid phase MIS stage" corresponding to in situ stage in other organs.