EZH2 and POU2F3 Can Aid in the Distinction of Thymic Carcinoma from Thymoma

Thymic carcinoma is an aggressive malignancy that can be challenging to distinguish from thymoma using histomorphology. We assessed two emerging markers for these entities, EZH2 and POU2F3, and compared them with conventional immunostains. Whole slide sections of 37 thymic carcinomas, 23 type A thymomas, 13 type B3 thymomas, and 8 micronodular thymomas with lymphoid stroma (MNTLS) were immunostained for EZH2, POU2F3, CD117, CD5, TdT, BAP1, and MTAP. POU2F3 (≥10% hotspot staining), CD117, and CD5 showed 100% specificity for thymic carcinoma versus thymoma with 51%, 86%, and 35% sensitivity, respectively, for thymic carcinoma. All POU2F3 positive cases were also positive for CD117. All thymic carcinomas showed >10% EZH2 staining. EZH2 (≥80% staining) had a sensitivity of 81% for thymic carcinoma and a specificity of 100% for thymic carcinoma versus type A thymoma and MNTLS but had poor specificity (46%) for thymic carcinoma versus B3 thymoma. Adding EZH2 to a panel of CD117, TdT, BAP1, and MTAP increased cases with informative results from 67/81 (83%) to 77/81 (95%). Overall, absent EZH2 staining may be useful for excluding thymic carcinoma, diffuse EZH2 staining may help to exclude type A thymoma and MNTLS, and ≥10% POU2F3 staining has excellent specificity for thymic carcinoma versus thymoma.