Thymic 18F-FDG PET/CT Findings in Pediatric Malignant Lymphoma after Chemotherapy: Differentiation of Long-Lasting Thymic Hyperplasia from Lymphoma Recurrence
Authors: Fujiki Toshihiro , Maeba Hideaki , Araki Raita , Ikawa Yasuhiro , Kuroda Rie , Mase Shintaro , Fukuda Masaki , Koizumi Shoichi , Yachie Akihiro , Nishimura Ryosei 
Published: October 2019

Abstract
Background
Thymic FDG uptake due to rebound thymic hyperplasia after chemotherapy for cancers including malignant lymphoma (ML) is relatively widely-recognized phenomenon, especially in children. However, its occurrence rate based on ages and intensity of chemotherapy for various cancers has not really investigated. Therefore, to make clear distinction between thymic hyperplasia and lymphoma recurrence would be often difficult. To avoid misdiagnosis or unnecessary biopsies, recent report emphasized the importance to be aware of the possibility of thymic hyperplasia after chemotherapy. Another group suggested that SUV alone could be sufficient for differential diagnosis. However the duration showing rebound thymic hyperplasia after chemotherapy has never been studied so far, and there are no reports about the difference between rebound thymic hyperplasia and malignancy from the aspect of the morphological thymic uptake pattern. In this study, we investigated: 1) how long rebound thymic hyperplasia could last and 2) whether SUV alone would be sufficient or using additional findings such as the pattern of uptake (diffuse or nodular) would become much easier to distinguish them.
Method
From 2010 to 2014, eleven pediatric patients with ML were enrolled (ALCL 3, T-LBL 3, B-LBL 1, Burkitt lymphoma 2, DLBCL 2). PET/CT findings before and after completion of chemotherapy or autologous/allogeneic hematopoietic stem cell transplantation (HSCT) were reviewed retrospectively.
Results
Diffuse thymic FDG uptake before chemotherapy was seen in 3 patients with T-LBL (mean SUV 7.9, range 5.5-12.5). Seven cases showed diffuse uptake in thymus after completion of therapy with relatively low SUV (mean SUV 3.4, range 2.2-5.2). We eventually considered all of them as rebound thymic hyperplasia and they are alive. On the other hand, one patient with nodular uptake in thymus (SUV 6.4) accompanied with high sIL-2R was finally diagnosed lymphoma recurrence by biopsy. The timing appearing thymic uptake after chemotherapy alone and high-dose chemotherapy with autologous HSCT were 2.8 months (range 1-7 months) and 8.0 months (range 6-10 months), respectively. In contrast, two patients receiving allogeneic HSCT did not show thymic hyperplasia anymore. Interestingly rebound thymic hyperplasia was persistently observed once it occurred and even in some cases the SUV increased slowly during follow period. The longest case in our cohort is 4.5 years at present time.
Conclusion
Diffuse thymic uptake with low SUV after chemotherapy could be rebound thymic hyperplasia unless relapse was suspected by any symptoms or abnormal laboratory findings. Rebound hyperplasia was frequently observed in pediatric patients, and once it occurs, it could last at least couple of years. More importantly, in case of nodular uptake, thymic recurrence should be strongly considered especially when accompanied with high SUV.

Disclosures
No relevant conflicts of interest to declare.