Cytologic differential diagnosis among reactive mesothelial cells, malignant mesothelioma, and adenocarcinoma: utility of combined E-cadherin and calretinin immunostaining.

BACKGROUND

The differential diagnosis between reactive mesothelial cells (RMs), malignant mesotheliomas (MMs), and adenocarcinomas (ACs) is often difficult in cytologic specimens, and the utility of various immunohistochemical markers have been explored. Because recent immunohistologic studies have suggested that E-cadherin (E-cad) and calretinin (Cal) may be useful markers for epithelial and mesothelial differentiations, respectively, the authors investigated their utility in cytologic diagnosis.

METHODS

In this retrospective study, immunostaining was performed on smears retrieved from Papanicolaou-stained slides of effusions using the labeled streptavidin-biotin method. Sixteen cases of RM, 9 cases of MM, and 52 cases of AC from various sites, including 13 pulmonary primaries, were examined with primary antibodies against E-cad and Cal.

RESULTS

The positive rates for E-cad and Cal, respectively, were as follows: RM, 0/16 (0%) and 16/16 (100%); MM, 9/9 (100%) and 8/8 (100%); and AC, 45/52 (86.5%) and 0/51 (0%). The E-cad expression by neoplastic cells was strongest in the intercellular junctions, and poorly differentiated neoplastic cells in the single cell form showed the weakest expression.

CONCLUSIONS

In contrast to the results of previous immunohistochemical studies, the current study indicates that MMs constantly express E-cad, whereas RMs lack its expression in cytologic specimens, which would be useful in the differential diagnosis between the two. On the other hand, E-cad expression is not reliable for distinguishing AC from MM. The Cal expression can be a very useful marker for the distinction between AC and the mesothelial lineage. The combined immunostaining for E-cad and Cal has utility in differential diagnosis among RM, MM, and AC.