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Differentiating malignant pleural mesothelioma (MPM) cells morphologically from reactive mesothelial hyperplasia cells is problematic. Homozygous deletion (HD) of  p16  ( CDKN2A ), detected by FISH, is a good marker of malignancy and is useful to differentiate between these cells. However, the correlation between the  p16  status of effusion smears and that of the underlying MPM tissues has not been investigated. We used  p16 ‐specific FISH to investigate 20 cases of MPM from which both effusion cytologic smears and histologic specimens were available. In five cases, histologic specimens included both an invasive component and surface mesothelial proliferation. In 14 cases (70%), MPM cells in both tissue sections and effusion smears were  p16  HD‐positive. Conversely, MPM cells in the remaining six tumors (30%) were  p16  HD‐negative in both tissue sections and effusion smears. For all five MPM cases with surface mesothelial proliferations and invasive components, the effusion smears, surface mesothelial proliferations, and invasive MPM components all displayed  p16  deletion. Moreover, the extent to which  p16  was deleted in smears highly correlated with the extent of  p16  deletion in tissues. The  p16  deletion percentages were also similar among smears, tissue surface proliferations, and invasive components. In cases with clinical and radiologic evidence of a diffuse pleural tumor, detection of  p16  deletion in cytologic smear samples may permit MPM diagnosis without additional tissue examination. However, the absence of  p16  deletion in cytologic smear samples does not preclude MPM.

Deletion status of p16 in effusion smear preparation correlates with that of underlying malignant pleural mesothelioma tissue