An immunohistochemical panel consisting of EZH2, C-KIT, and CD205 is useful for distinguishing thymic squamous cell carcinoma from type B3 thymoma

Type B3 thymoma and thymic squamous cell carcinoma (SqCC) often cause a diagnostic problem due to their histological similarities. The aim of this study is to identify EZH2 as a novel and powerful biomarker that can effectively distinguish thymic SqCC from type B3 thymoma, and find optimal combinations among 11 markers. A total of 53 patients, comprising 26 with type B3 thymoma and 27 with thymic SqCC, were allocated to the discovery or validation cohorts, and immunohistochemical staining was performed and analyzed. The expression level of each marker was scored, and receiver-operator characteristic curve analysis was performed to evaluate their diagnostic accuracies. This analysis identified EZH2, C-KIT, and CD205 as useful markers for distinguishing thymic SqCC, and a combined panel approach using them further improved diagnostic accuracy in both the discovery and validation cohorts. In the combined cohorts analysis, EZH2 was the single best marker with 88.9% sensitivity and 100% specificity [area under the curve (AUC) = 0.967]. The sensitivity and specificity were 85.2% and 100% (AUC = 0.962) for C-KIT, and 100% and 73.1% (AUC = 0.844) for CD205. The combined panel had the highest sensitivity and specificity at 96.3% and 100%, which was significantly or marginally higher than those of EZH2, C-KIT, and CD205 alone (P = 0.071, 0.034, and 0.005, respectively). The present findings indicate that EZH2 is useful as a novel diagnostic marker for distinguishing thymic SqCC and that the panel approach can be used as an effective differential diagnostic tool in daily practice.