FDG PET/CT versus Bone Marrow Biopsy for Diagnosis of Bone Marrow Involvement in Non-Hodgkin Lymphoma: A Systematic Review  
[PERSON]  
1 Leeds Institute of Cardiovascular & Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9 JT, UK; m119 [EMAIL_ADDRESS] (J.A. ); [EMAIL_ADDRESS] (C.T. ); [PERSON]S] (R.F)  
[PERSON]  
1 Leeds Institute of Cardiovascular & Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9 JT, UK; m119 [EMAIL_ADDRESS] (J.A. ); [EMAIL_ADDRESS] (C.T. ); [PERSON]S] (R.F)  
[PERSON]  
1 Leeds Institute of Cardiovascular & Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9 JT, UK; m119 [EMAIL_ADDRESS] (J.A. ); [EMAIL_ADDRESS] (C.T. ); [PERSON]S] (R.F)  
[PERSON]  
3 Department of Health Sciences, European University Cyprus, Nicosia 2404, Cyprus 3*  
T-cell lymphoma (PTCL) accounts for about 6% of NHILs and mantle cell lymphoma (MCL), which is considered a rare B-cell lymphoma, accounts for around 6% of NHL cases [3]. Other rare subtypes, such as primary mediastinal large B-cell lymphoma (PMBCL) and Burkitt lymphoma (BL) account for approximately 2% of the cases. In NHL, the accurate detection of the BMI is crucial, as its presence indicates advanced stages and affects the prognosis, clinical management and treatment process [6]. Regarding the Ann Arbor staging system, BMI leads to the transition of the lymphoma to stage IV, as a result of which a more aggressive treatment is required [7]. BMI has also been found to be an indicator of the occurrence of an infusion-related reaction following rituximab administration in patients with B cell non-Hodgkin lymphoma and special care should be taken with regard to patients who have BMI during rituximab treatment [8]. The reference standard method for assessing BMI in NHL patients is the bone marrow biopsy (BMB) in the unilateral or bilateral iliac crest [9]. BMB only investigates a limited section of the bone marrow in the iliac crest, but it has nevertheless been routinely used for many decades as the standard method. This remains the case despite several studies concluding that due to its small sample size and sample error, BMB may have low sensitivity and may miss patchy or focal bone marrow lymphoma outside the iliac crest area. Additionally, complications might occur during BMB, as it is an invasive procedure and can cause bleeding and infection, although the risk is small but nevertheless it is not negligible. Finally, BMB logistics (i.e., decalcification) proves to be time consuming and the waiting period to receive a result may cause treatment delay. Imaging with [18]Fluoro-2-deoxy-D-glucose ([18]F]FDG positron emission tomography (PET), combined with computed tomography (CT) (PET/CT), has revolutionized the staging of lymphoma patients. PET/CT is a non-invasive technique that has been established as an important tool for staging of FDG-avid lymphomas such as Hodgkin lymphoma and DLBCL [10]. Several studies have shown that PET/CT may be used as complementary to, or may even replace, BMB, as it provides information from the entire bone marrow compared to BMB, which is limited to the iliac crest area, thus avoiding sampling errors [11; 12]. Most of the NHL histopathologic subtypes have shown the presence of high [18]F]FDG avidity [13], which justifies the investigation of the usefulness of [18]FDG PET/CT for the management of NHL patients. Whilst [18]F]FDG PET/CT produces non-invasive visualizations of the whole bone marrow, it lacks histological information and not all the FDG avid lesions are lymphomas. A previous systematic review, conducted in 2005, and meta-analysis by [PERSON] et al. [14] showed that [18]FDG PET has low sensitivity for the detection of BMI in NHL patients (i.e., sensitivity and specificity equal to 43% and 88%, respectively). The authors attributed the low sensitivity to the use of studies that included a mixed population of FDG high- and low-avidity NHL histologic subtypes.