POU2F3 beyond thymic carcinomas: expression across the spectrum of thymomas hints to medullary differentiation in type A thymoma

The thymic medulla comprises various cell types, including tuft cells that are involved in innate immunity. We recently reported that in Western cohorts of patients, most thymic squamous cell carcinomas (TSQCCs), in contrast to thymomas, exhibit strong and extensive expression of tuft cell markers, including the tuft cell master regulator, POU2F3. On closer inspection of 94 thymomas that cover the full spectrum of thymoma histotypes, we now find by immunohistochemistry that approximately half of types A, AB, and B1 thymomas contain small numbers (< 10%) of cells expressing POU2F3, while most types B2 and B3 thymomas do not (p < 0.05). Further, in rarer types A and AB thymomas with adenoid growth pattern, POU2F3( +) cells formed aggregates and co-expressed KIT, as did the tumor cells in 100% (9/9) of TSQCCs expressing POU2F3. However, the expression of another tuft cell marker, L1CAM, still distinguished TSQCC from the spectrum of thymomas that were all L1CAM-negative. This study is the first to demonstrate the high frequency of POU2F3 expression in an Asian cohort of TSQCCs. The common occurrence of scattered POU2F3( +) cells in types A and AB thymomas hints at their variable degree of medullary differentiation and supports the historical hypothesis of the medullary nature of type A thymomas. Immunohistochemistry of L1CAM may be a valuable tool to differentiate TSQCCs from thymomas.