To the Editor:
Post-transplant lymphoproliferative disease (PTLD) is a rare, but serious and potentially lethal complication of solid organ transplantation. It encompasses a heterogeneous group of diseases, ranging from Epstein–Barr virus driven polyclonal proliferations resembling infectious mononucleosis, to highly aggressive monomorphic proliferations indistinguishable from aggressive types of lymphoma (1). At diagnosis, patients are usually staged according to conventional diagnostic methods routinely applied for malignant lymphoma, including whole body computer tomography (CT) scanning and bone marrow biopsy (2). Although PTLD characteristically involves extranodal sites, these localizations may not always be visualized by CT scanning (3). Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is a whole body imaging technique allowing functional characterization of hypermetabolic tissues by showing increased uptake of FDG at these sites. It has already been shown that FDG-PET provides significant additional information for the detection and staging of malignant lymphoma (4). We wondered whether FDG-PET would be as useful in PTLD as it is in aggressive lymphoma, and evaluated its value in the staging and treatment evaluation of histologically confirmed PTLD in 12 kidney transplant recipients observed between January 2000 and June 2004.
At PTLD diagnosis, all patients were fully staged, including whole body CT and bone marrow biopsy. FDG-PET scans were available in 10 patients at diagnosis; 5 patients also had follow-up scans after treatment. In two additional patients, FDG-PET scans were available only after treatment. To compare CT with FDG-PET, all scans were re-evaluated (blinded) by a radiologist and an expert in nuclear medicine, respectively.
FDG-PET scans at diagnosis could readily be interpreted and showed high-FDG uptake at the primary sites of histologically confirmed PTLD. At staging, FDG-PET-positive hot spots were found in concordance with lesions found with conventional CT scanning, and also at additional extranodal sites not readily visualized by routine CT scanning (Figure 1) in 5 out of 10 patients (50%). These findings are in concordance with the observation in other types of aggressive lymphoma that FDG-PET is superior to conventional diagnostic methods for the detection of extranodal localizations (3).
In patients with aggressive lymphoma, FDG-PET performed after treatment may provide a more accurate response classification and prediction of prognosis as compared to CT-based assessment because of its ability to distinguish between viable tumor and necrosis or fibrosis in residual mass(es) following treatment (5). This report might extend these findings for PTLD, as FDG-PET also turned out to be an excellent predictor of progression-free survival in our patients. Five patients reached complete remission confirmed by both CT and FDG-PET and remained progression-free with a median follow-up of 37 months (range 3–46 months). Discordant findings after treatment with Rituximab were observed in two patients. In patient 10, CT revealed no abnormal sites after treatment, whereas FDG-PET showed pronounced focal accumulation of FDG in the stomach. Progressive disease with extensive stomach involvement was observed 1 month later, and this patient ultimately died of PTLD 6 months later. In patient 2, CT scanning revealed the liver and spleen as well as the allograft and left kidney as possible sites of persistent involvement after treatment, whereas FDG-PET showed no pathological uptake. Based on FDG-PET findings, no further treatment was given. At 58 months of follow-up no PTLD recurrence was observed.
In conclusion, our findings demonstrate that FDG-PET can visualize PTLD and is an excellent tool for staging and treatment evaluation. The ability of FDG-PET to visualize extranodal localizations of PTLD, often present but not readily detectable by routine conventional diagnostic methods, is of additional value.