Many factors such as performance status, IPI, B symptoms, and serum β2-microglobulin are indicating factors in the prognosis estimation of DLBCL. Recent studies indicated that bulky mass and high SUVmax could be prognostic parameters suggesting large tumor burden [14
]. These prognostic factors usually affect both nodal and extranodal DLBCL. However, unlike nodal disease, primary extranodal DLBCL had a separate genetic origin [5
]. Therefore, the present study evaluated whether these prognostic factors had an impact on survival outcome in primary extranodal disease.
It was reported that MTD had adverse prognostic value in young patients with good-prognosis DLBCL [14
]. In this previous study, the cut-off value of MTD was 10.0 cm, whereas in our study it was defined at 7.5 cm, considering the fact that the number of patients with MTD above 10.0 cm was limited in our study. However, adverse prognostic value still existed in both studies.
In the past, the imaging of initial evaluation and follow-up of lymphoma was based solely on the findings of contrast-enhanced CT. However, as contrast-enhanced CT has limited sensitivity in detecting involvement of normal-sized lymph nodes, bone marrow, spleen, and extranodal tissues, 18-FDG PET/CT has been widely used for staging of disease, detection of recurrence, and monitoring of treatment response in patients with Hodgkin disease and NHL [22
]. The intensity of FDG uptake in lymphoma is determined by many factors, including viable tumor cell fraction, tumor cell proliferation, upregulation of glucose metabolism, salvage and tumor-specific pathways, and the presence of hypoxia, and suggests large tumor burden [23
]. Consequently, initial intensity of FDG uptake was associated with survival outcome, and the cut-off point of SUVmax was considered a poor prognostic factor, which is also a finding of our study. Although there was some evidence that PET/CT is a valuable diagnostic, predictive, and prognostic tool in DLBCL, limitations of 18-FDG PET/CT still remain, including protocol variability by center, easily affected quantification of SUV depending on the time after FDG infusion and blood glucose level, and inconsistency of CT scanning.
Moller et al. showed differences between nodal and extranodal DLBCL [25
]. This study announced that patients with extranodal DLBCL in stage I disease were markedly older and had poorer performance status. However, extranodal disease itself was associated with poor survival irrespective of IPI. The relationship among IPI factors such as age and LDH level, sex, and prognosis was also evaluated in stage IE or stage IIE extranodal DLBCL. Only IPI was associated with an inferior survival outcome as a result.
It has been reported that the prognosis according to extranodal site of involvement was not different [19
]. However, other studies showed that lymphoma arising in 2 specific sites (Waldyer's ring and GI tract) showed very favorable features at diagnosis, whereas the DLBCL arising in the other areas presented with unfavorable characteristics [11
]. Our study indicated that specific site of extranodal involvement was not associated with significant survival outcome, and further studies are required to determine the impact of location or extranodal involvement.
The limitation of the present study was that it was performed retrospectively with small number of patients, and the treatment modalities after R-CHOP chemotherapy, such as radiotherapy and second-line chemotherapy were not analyzed. The 18-FDG PET/CT has some limitations of its own, as mentioned earlier. Further studies about newly emerging parameters such as mean SUVmax, metabolic tumor volume, and tumor glycolysis are needed.
In conclusion, SUVmax and MTD were significantly related to the survival outcome of patients with primary extranodal DLBCL, while high SUVmax (cut-off value 11.0) and MTD (cut-off value 7.5 cm) were poor prognostic factors. More intensive therapy should be considered in patients with high SUVmax and MTD in primary extranodal DLBCL.