Background Rebound thymic hyperplasia (RTH) is a common phenomenon caused by stress factors such as chemo- (CTX) or radiotherapy with an incidence of up to 40%. Misinterpretation of RTH and thymic lymphoma relapse (LR) may lead to unnecessary diagnostic procedures including invasive biopsies or treatment intensification. The aim of this study was to identify parameters that differentiate between RTH and thymic LR in the anterior mediastinum. Methods After completion of CTX, we analyzed CTs and MRIs of 291 patients with classical Hodgkin lymphoma (CHL) and adequate imaging available from the European Network for Pediatric Hodgkin lymphoma C1-trial. In all patients with biopsy proven LR an additional FDG-PET-CT was assessed. Structure and morphologic configuration in addition to calcifications and presence of multiple masses in the thymic region and signs of extrathymic LR were evaluated. Results After CTX, a significant volume increase of a new or growing mass in the thymic space occurred in 133 of 291 patients. Without biopsy only 100 patients could be identified as RTH or LR. No single finding related to thymic regrowth allowed differentiation between RTH and LR. However, the vast majority of cases with thymic LR presented with additional increasing tumor masses (34/35). All RTH patients (65/65) presented with isolated thymic growth. Conclusion Isolated thymic LR is very uncommon. CHL relapse should be suspected when increasing tumor masses are present in distant sites outside of the thymic area. Conversely, if regrowth of lymphoma in other sites can be excluded, an isolated thymic mass after CTX likely represents RTH.

Immunohistochemical markers are associated with treatment outcome in adults with classical Hodgkin Lymphoma (cHL). Studies in children are scarce and inconsistent. We investigated in 67 children with cHL, whether the expression of CD15, CD30, PAX5, PD-1, PD-L1, CD68, CD163 and TARC is associated with the event-free survival (EFS) and the interim remission status. Low expression of PD-L1 was significantly associated with complete remission at interim PET-scan. There was no association between marker expression and EFS. Our data suggest a difference between pediatric and adult cHL. This underlies the importance of future research into specific molecular drivers in pediatric cHL.