Fluorodeoxyglucose positron emission tomography/computed tomography for evaluation of bone marrow involvement in lymphoma: when is it superior to biopsy?

Abstract

Bone marrow biopsy (BMB) is widely performed in patients with either Hodgkin lymphoma (HL) or non-Hodgkin lymphomas (NHLs) to provide diagnostic and prognostic information. Bone marrow involvement (BMI) upstages patients to stage IV disease and may direct more intensive therapeutic strategies. It is, however, an invasive procedure frequently associated with anxiety and pain, and has a small risk of hemorrhage or sedation-related complications [1,2]. It is also resource-intensive with the potential to delay commencement of therapy. It is performed blindly, usually in the posterior iliac crest, and assesses only a small portion of the entire marrow based on the assumption that tumor cells spread diff usely through marrow. Accordingly, it has high specifi city but potential for low sensitivity due to sampling error if BMI is focal and not diff use. Th is is highlighted by studies demonstrating signifi cant discordance of results in patients undergoing bilateral BMB, with discrepancy rates as high as 60%, or higher detection rates with longer trephine length [3 – 5]. Imaging is increasingly playing a central role in the management of patients with lymphoma. Its use has led to improved outcomes through more accurate staging and also reduced morbidity through minimization of invasive procedures. Use of computed tomography (CT) in the 1970s replaced the need for staging laparotomy and invasive lymphangiography for nodal staging [6]. Nuclear medicine with gallium-67 provided the template for functional imaging, particularly for restaging, as it allows diff erentiation of active lymphoma from residual fi brotic tissue, which is diffi cult with anatomical imaging [7]. Positron emission tomography (PET) with fl uorodeoxyglucose (FDG) emerged in the 1980s as a sensitive tumor-detecting radiopharmaceutical demonstrating high management impact in patients with lymphoma [8,9]. FDG PET has provided new insights into the extent and distribution of BMI by demonstrating focal marrow involvement in some patients, thereby highlighting the weakness of blind biopsy. Early studies suggested that FDG PET had inferior sensitivity for the detection of marrow involvement compared to BMB and, whilst complementary in some patients, could not replace BMB. Th ese studies were limited by the use of stand-alone PET technology and analysis of heterogeneous cohorts, including patients with low and high grade disease, some of whom had already undergone therapy [10]. Some early studies using blinded BMB as the gold-standard spuriously suggested false-positive PET results, but when directed biopsies of FDG-avid bone abnormalities were performed, all revealed lymphomatous infi ltration [11]. Hybrid PET/ CT improved accuracy by enabling precise anatomical characterization of any functional abnormality [12,13] and also enabled rapid attenuation correction, which is particularly valuable in the assessment of marrow. Even in the PET/CT era, there have been numerous advances, including use of newer-generation scintillation crystals, time-of-fl ight and improved reconstruction algorithms resulting in substantial improvement in image quality. With experience, improved recognition of diff erent patterns, such as the signifi cance of focal versus heterogeneous or homogeneously increased marrow activity within particular lymphoma subtypes, has also increased accuracy. Earlier studies need to be reconsidered in light of these multiple advances. In the current issue, Richardson et al . assessed the role of BMB in the FDG PET/CT era in a population of 50 patients with classical HL and also assessed current practice by surveying practitioners in 23 centers in the United Kingdom [14]. Th e cohort had a high risk of BMI, with an incidence of 20% compared to an overall incidence of 4 – 10% generally seen in HL [15]. All BMB-positive cases were identifi ed by FDG PET/ CT, and BMB did not identify involvement in any patient with normal marrow FDG uptake, suggesting the redundancy of BMB in patients staged with PET. Although PET identifi ed patients with marrow involvement not seen with BMB, in this study, these fi ndings did not result in treatment intensifi cation, as these patients already had stage IV disease on the