18F-FDG PET/CT in patients with post-transplant lymphoproliferative disorders: so far so good
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Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of lymphoproliferative diseases occurring after solid organ transplant (SOT) or allogeneic hematopoietic cell transplant (HCT). Epstein-Barr virus (EBV) serology mismatch among recipient and donor, type of transplanted organ, and intensity and type of immunosuppression are considered as established risk factors for developing PTLD. The risk is also higher among children compared with adults .
According to the recent update of the WHO classification of tumors of hematopoietic and lymphoid tissues, PTLD are classified in early lesions (non-destructive PTLD), monomorphic PTLD (B cell, T cell, and NK cell subtype), polymorphic PTLD, and classical Hodgkin lymphoma PTLD. Monomorphic PTLD (in particular diffuse large B cell lymphoma) is the most frequent PTLD subtype . Notably, PTLD is characterized by a high incidence of extranodal disease .
As PTLD are serious post-transplant complications associated with significant morbidity and mortality, a timely and accurate diagnosis of these disorders is needed. The diagnosis of PTLD can be challenging due to the nonspecific clinical presentation and heterogeneity in histopathologic and immunophenotypic presentation; therefore, histopathology and adequate immunophenotyping are essential to confirm the diagnosis of PTLD .
About the imaging methods, current National Comprehensive Cancer Network (NCCN) guidelines recommend chest/abdomen/pelvis contrast-enhanced computed tomography (CECT) and/or whole-body fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) as part of initial diagnostic workup for PTLD . According to the recent evidence-based guidelines from the American Society of Transplantation, 18F-FDG PET/CT may provide additional useful information for staging and end of treatment response assessment in adults and children with PTLD .
The article of Montes de Jesus et al. recently published in EJNMMI provides further evidence on the usefulness of 18F-FDG PET/CT in the management of patients with PTLD . In this retrospective study, the authors evaluated the diagnostic performance of 18F-FDG PET/CT in a significant population (n = 91) of patients with suspected PTLD examining the factors affecting the diagnostic yield of 18F-FDG PET/CT. Sensitivity, specificity, positive and negative predictive value, and accuracy of 18F-FDG PET/CT for the diagnosis of PTLD were 85%, 90%, 83%, 92%, and 89%, respectively, with good inter-observer agreement (k = 0.78). Among the main clinical features, only increased lactate dehydrogenase levels seemed to be correlated with a true positive 18F-FDG PET/CT scan in PTLD patients. EBV-DNA load and timing of 18F-FDG PET/CT after transplantation did not affect the diagnostic performance of 18F-FDG PET/CT in PTLD . The good diagnostic performance reported in this study suggests that 18F-FDG PET/CT is a valuable imaging modality for detecting PTLD. These findings are in agreement with the results of previous published studies on the same topic [6, 7, 8] that, however, presented a different methodology compared to the study of Montes de Jesus et al.
A recent evidence-based article reported that 18F-FDG PET/CT is currently the most frequently investigated imaging modality for the diagnosis and staging of PTLD . In this setting, 18F-FDG PET/CT may contribute to confirm the clinical suspicion of PTLD identifying hypermetabolic targets for possible diagnostic biopsy. Moreover, 18F-FDG PET/CT may detect additional PTLD lesions compared to conventional imaging modalities in about 28% of cases, mainly in extranodal sites, resulting in possible disease upstaging . Nevertheless, false-negative results (due to PTLD lesions located in anatomical regions with high physiological background activity and early PTLD lesions) and false-positive results (mainly due to inflammatory conditions or other tumors) of 18F-FDG PET/CT should be taken into account . However, it should be underlined that some false-positive findings for PTLD at 18F-FDG PET/CT, such as infections or other tumors, represent common complications after SOT or HCT; the detection of these findings in the post-transplant period by 18F-FDG PET/CT is usually clinically relevant .
Beyond diagnosis and staging of PTLD, 18F-FDG PET/CT is emerging as a useful imaging modality to evaluate the treatment response in patients with PTLD. In this setting, 18F-FDG PET/CT findings may alter or provide additional treatment guidance in 29% of cases . Recent published data demonstrated that negative interim and/or negative end of treatment 18F-FDG PET/CT may identify PTLD patients with low risk of disease recurrence, due to its high negative predictive value, providing clinically relevant information, in particular in patients with partial response based on conventional imaging evaluation [11, 12].
In conclusion, 18F-FDG PET/CT is emerging as a useful imaging modality for diagnosis, staging and treatment response assessment in the heterogeneous spectrum of patients with PTLD. However, additional validation of its utility in these settings is required; in particular, prospective and multicenter studies including larger populations to better characterize the diagnostic performance of 18F-FDG PET/CT in the different subtypes of this heterogeneous pathological entity are needed.
A comparative analysis among different imaging modalities in different patient population (pediatric or adult patients) with PTLD would also be recommended. In particular, 18F-FDG PET/MRI could be a valid alternative to the 18F-FDG PET/CT in children to obtain metabolic information with a significant reduction in ionizing radiation, but to date, published reports on the use of 18F-FDG PET/MRI in PTLD patients are lacking.
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Conflict of interest
The authors declare that they have no competing interests.
This article does not contain any study with human participants or animals performed by any of the authors.
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