Immunohistochemical distinction between mesothelial and adenocarcinoma cells in serous effusions: A combination panel-based approach with a brief review of the literature

Abstract

The prognostic and therapeutic significance of differentiating adenocarcinoma (AC) from reactive mesothelium (RM) in effusions cannot be overemphasized. To avoid diagnostic errors, ancillary techniques like immunohistochemistry are employed. However, results vary and no universal standard has been accepted so far. To study the combined diagnostic efficacy of epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), E-cadherin (EC), calretinin (CAL), desmin (DES) and vimentin (VIM) in distinguishing RM from AC cells in serous effusions. Unequivocally diagnosed cases of 39 adenocarcinomatous and 38 RM populations were studied using sections from 49 formalin-fixed, paraffin-embedded cell blocks. The immunomarkers were applied on cell block sections using the avidin-biotin peroxidase technique. The distribution/intensity of immunostaining in mesothelial and AC cells were graded semiquantitatively. Fischer's exact test was used to calculate the efficacy of individual markers and their combinations. EMA was the best single marker for AC, with 100% sensitivity and 97.37% specificity. For the mesothelial cells, CAL exhibited 100% sensitivity and 92.31% specificity. DES was more specific than CAL but had a poor sensitivity of 55.26%. EC, CEA and VIM had unsatisfactory predictive values precluding their use as individual diagnostic markers. Among the combinations, two panels--EMA+ AND (CAL- OR DES-) for ACs and CAL+ AND (EMA- OR CEA-) for RM had 100% specificities and sensitivities. Most panel studies on fluid cytology are based on the arbitrary use of individual markers with the best statistical values, leading to a less than accurate diagnostic assessment. We believe that statistical parameters calculated in combination provide for a more practical and objective evaluation as well as allowing for meaningful comparative studies.