Interest of Diffusion Weighted Magnetic Resonance Imaging for the Evaluation of Bone Marrow Infiltration in Multiple Myeloma, Smoldering Myeloma and Monoclonal Gammopathy of Undetermined Significance.

Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM) are two asymptomatic early stages of multiple myeloma, and are characterized by the absence of bone involvement. In contrast, bone lytic lesions are common complications of multiple myeloma. Magnetic resonance imaging (MRI) has improved the evaluation of bone involvement in multiple myeloma. Moreover MRI allows visualization of the medullary cavity and a direct assessment of the degree of myeloma cell infiltration before bone destruction becomes visible on plain radiographs. Diffusion weighted magnetic resonance imaging (DWI) probes the diffusion of water in the body. This sequence yields qualitative and quantitative information that reflects the tissue cellularity and cell membrane intregrity and thus complements morphological information obtained by conventional MRI. It shows considerable promise for detecting and characterizing tumors and evaluating treatment response.

Our objective was to study the potential interest of diffusion weighted MRI for the evaluation of bone marrow infiltration in multiple myeloma, SMM and MGUS. Diagnostic criteria used were those defined by the International Myeloma Working Group.

This retrospective study was conducted over a period of 8 months (November 2008 - June 2009) in Internal Medicine and Hematology departments of our institution. All patients who had a whole body MRI for evaluation of multiple myeloma, SMM or MGUS were included. We choose to study simultaneously 3 complementary sequences: T1 weighted, short time inversion recovery (STIR) and diffusion weighted.

Seventy patients were included in this study: 9 MGUS, 19 SMM and 42 symptomatic multiple myeloma (16 at diagnosis and 27 at relapse). They were 30 men and 40 women. The median age was 64 years (36 - 89 years). Thirty one of the 42 multiple myeloma patients have focal bone lesions. Focal lesions were observed in the 3 MRI sequences and diffusion did not detect new lesions. Regarding bone marrow infiltration assessment by MRI, four groups of patients could be identified: - Group 1 (20 patients – 28.6%): normal signal in T1, STIR, and diffusion. - Group 2 (19 patients – 27.1%): abnormal signal involving the whole spine on the STIR or diffusion weighted sequences and with a normal signal of the spine on T1.- Group 3 (25 patients – 35.7%): abnormal signal involving the whole spine on the STIR and diffusion weighted sequences and with a normal signal of the spine on T1.- Group 4 (6 patients – 8.6%): abnormal signal involving the whole spine on the 3 sequences. For the 28 patients with either MGUS or SMM, the distribution in the 4 groups was respectively 13 patients (46.4%), 7 patients (25.0%), 7 patients (25.0%) and 1 patient (3.6%) for group 1,2 3 and 4. Regarding the 42 cases of symptomatic multiple myeloma, 7 patients (16.7%) were classified in group 1, 12 (28.6%) in group 2, 18 (42.9%) in group 3 and 5 (11.9%) in group 4. There was no correlation between number of focal lesions and degree of diffuse infiltration. The degree of bone marrow infiltration evaluated by MRI was not correlated with Durie and Salmon stage, ISS, monoclonal component concentration or bone marrow plasmocytosis.

Diffusion weighted magnetic resonance imaging combined with conventional sequences (T1 and STIR) can distinguish 4 groups of patients with different aspects of bone marrow infiltration. Fifteen patients (53.6%) with either MGUS or SMM had various degree of bone marrow infiltration without any focal lesions. A prospective study on a large population of MGUS and SMM is needed to assess the impact of these asymptomatic infiltrations on the risk of malignant transformation. The degree of bone marrow infiltration evaluated by MRI is very heterogeneous between patients with multiple myeloma and not correlated with classical prognostic factors. Further prospective studies are necessary to investigate the possible prognostic impact of these different groups on the evolution of myeloma.

No relevant conflicts of interest to declare.