Awareness of Partial Loss is Essential in Interpreting Merlin Immunohistochemistry When Diagnosing Pleural...

Ancillary assays, including BAP1 (BRCA-1-associated protein 1), MTAP (methylthioadenosine phosphorylase), and Merlin immunohistochemistry (IHC), are effective in discriminating pleural mesothelioma (PM) from reactive mesothelial proliferations (RMP). IHC of Merlin, a protein product of the neurofibromin 2 gene, was most recently developed. Our previous study suggested uneven occurrence of Merlin loss within PM tissues. This was further investigated here in a total of 41 tissues of PM obtained from seven institutions. Partial or diffuse Merlin loss was detected with excellent interobserver agreement (kappa: 0.82). Of the 34 PM cases with interobserver consensus, partial and diffuse loss of Merlin expression were each observed in 13 cases (38%). PM with partial Merlin loss exhibited either discrete or intermingled spatial distribution of Merlin-lost cells. BAP1 or MTAP showed partial loss in none or only 5% of PM cases, respectively. The diagnostic sensitivity for PM was enhanced to 91% with addition of diffuse and partial Merlin loss to a combination of BAP1 and MTAP loss while maintaining 100% specificity. Although detection of Merlin loss as well as BAP1 and MTAP losses is effective for distinguishing PM from RMP, pathologists should be familiar with partial Merlin loss when interpreting Merlin IHC results.