Utility of Bone Marrow Biopsy in the Staging of Diffuse Large B-Cell Lymphoma in the Era of PET-CT
Authors: Vishnu Prakash , Wingerson Andrew , Aboulafia David M 
Published: October 2019

Abstract
BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL). Recent advances in imaging, use of prognostic indices and molecular profiling has improved our ability to characterize disease and predict outcomes in DLBCL. About one-third of patients with DLBCL have bone marrow involvement at the time of diagnosis, and bone marrow aspirate/biopsy (BMAB) is considered gold standard to detect such involvement. 18 F-fluro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (PET-CT), has become standard pre-treatment imaging in DLBCL and may be a non-invasive alternative to BMAB. Prior studies have suggested that PET-CT scan may obviate the need for BMAB as a component for staging patients with newly-diagnosed DLBCL, but owing to a variety of reasons this is not yet a standard of practice. We investigated whether FDG uptake-based bone marrow assessment can replace BMAB in newly-diagnosed DLBCL.
METHODS
This study is a single institution retrospective medical records' review. All patients with newly-diagnosed DLBCL at Virginia Mason Medical Center between January 2003 to December 2013 who underwent pre-treatment PET-CT and BMAB were included. FDG-PET/CT images were visually assessed for bone marrow involvement in posterior iliac crest. Patients with primary mediastinal DLBCL, previous history or coexistence of another lymphoma subtype and those with a non-diagnostic BMAB, and in whom the PET-CT did not show marrow signal abnormality were excluded from the analysis. Ann Arbor stage was determined using PET-CT with and without the contribution of BMAB, and the proportion of stage IV cases by each method was measured.
RESULTS
105 eligible patients were identified. The median age was 62 years (range, 24-88), 62 (59%) were male, 53 (50%) had elevated LDH and 17 (16%) had an ECOG performance status of >2. Thirteen (12%) patients had > 1 extra-nodal site of lymphoma involvement. R-IPI score was 0-1 in 39 (37%), 2 in 42 (40%), 3 in 20 (19%), and 4 in 4 (4%) patients. A total of 38 (36%) patients had bone marrow involvement established by either PET-CT (n=24, 19%), BMAB (n=14, 13%), or both (n=12, 11%). 12 of the 24 patients (50%) with positive PET-CT had marrow involvement by DLBCL, while only 2 of the 81 patients (2%) with negative PET/CT showed marrow involvement. BMAB upstaged 1 of the 53 (2%) stage I/II patients to stage IV. The sensitivity of PET-CT scan to detect marrow involvement by DLBCL was 86% while the specificity was 87%. The positive predictive value of PET-CT was only 50% while the negative predictive value was 98%.
CONCLUSIONS
In patients with newly diagnosed DLBCL, PET-CT is complementary to BMAB in detecting marrow involvement by lymphoma. Although PET-CT has a high negative predictive value for bone marrow involvement, it overestimates the number of cases with marrow involvement by lymphoma. In clinical practice, routine BMAB may no longer be necessary for all patients with DLBCL, who are staged by PET-CT, unless the results would change both staging and therapy. The prognostic implication of marrow involvement identified by PET-CT compared to BMAB remains unknown.

Disclosures
No relevant conflicts of interest to declare.