scholarly journals Analyzing Longitudinal wb-MRI Data and Clinical Course in a Cohort of Former Smoldering Multiple Myeloma Patients: Connections between MRI Findings and Clinical Progression Patterns

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 961
Author(s):  
Markus Wennmann ◽  
Thomas Hielscher ◽  
Laurent Kintzelé ◽  
Bjoern H. Menze ◽  
Georg Langs ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Destruction ◽  
Growth Dynamics ◽  
Whole Body ◽  
Mri Findings ◽  
Diffuse Infiltration ◽  
Smoldering Multiple Myeloma ◽  
Local Bone ◽  
Mri Features ◽  
Progression Patterns

The purpose of this study was to analyze size and growth dynamics of focal lesions (FL) as well as to quantify diffuse infiltration (DI) in untreated smoldering multiple myeloma (SMM) patients and correlate those MRI features with timepoint and cause of progression. We investigated 199 whole-body magnetic resonance imaging (wb-MRI) scans originating from longitudinal imaging of 60 SMM patients and 39 computed tomography (CT) scans for corresponding osteolytic lesions (OL) in 17 patients. All FLs >5 mm were manually segmented to quantify volume and growth dynamics, and DI was scored, rating four compartments separately in T1- and fat-saturated T2-weighted images. The majority of patients with at least two FLs showed substantial spatial heterogeneity in growth dynamics. The volume of the largest FL (p = 0.001, c-index 0.72), the speed of growth of the fastest growing FL (p = 0.003, c-index 0.75), the DI score (DIS, p = 0.014, c-index 0.67), and its dynamic over time (DIS dynamic, p < 0.001, c-index 0.67) all significantly correlated with the time to progression. Size and growth dynamics of FLs correlated significantly with presence/appearance of OL in CT within 2 years after the respective MRI assessment (p = 0.016 and p = 0.022). DIS correlated with decrease of hemoglobin (p < 0.001). In conclusion, size and growth dynamics of FLs correlate with prognosis and local bone destruction. Connections between MRI findings and progression patterns (fast growing FL—OL; DIS—hemoglobin decrease) might enable more precise diagnostic and therapeutic approaches for SMM patients in the future.

scholarly journals MULTIPLE MYELOMA AS A FORM OF LEUKEMIA

Blood ◽  
1949 ◽  
Vol 4 (9) ◽  
pp. 1049-1067 ◽  
Author(s):  
MICHAEL A. RUBINSTEIN
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Bone Destruction ◽  
Tumor Formation ◽  
Diffuse Infiltration ◽  
Skeletal Involvement ◽  
The Difference ◽  
Distinguishing Features ◽  
Osseous System

Abstract The conventional points in the differential diagnosis between myeloma and leukemia have been discussed. Evidence has been brought to show that these points of distinction cannot be regarded as being of fundamental nature. Instances are abstracted where cases of multiple myeloma show the various characteristics of leukemia and vice versa. 1. Leukemic features in myeloma have been shown in: a. diffuse infiltration in multiple myeloma without circumscribed tumor formation and without any gross bone destruction; b. extraskeletal visceral myelomatous spread involving the kidney, spleen, lymph nodes, etc.; c. invasion of peripheral blood in myeloma—occasional myeloma cells (corresponding to the aleukemic forms of leukemia) may frequently be found in concentrated smears, even though they may be missed on routine examination; however, massive invasion of peripheral blood is rare; d. increased uric acid content of the blood and elevated basal metabolism, characteristic of leukemia, frequently seen also in myeloma; e. occurrence of myeloma in youth; f. symptomatology of multiple myeloma at times not referable to the osseous system. 2. Myeloma features in leukemia have been shown in: a. skeletal involvement in leukemia; b. very rare medullary forms of leukemia (without visceral involvement); c. occurrence of Bence-Jones proteinuria or d. hyperproteinemia with hyperglobulinemia in rare cases of leukemia; e. instances when the symptomatology of leukemia was referable to the osseous system. 3. Coexistence of multiple myeloma and leukemia is reviewed from the literature, and a case is reported of extensive mixed lymphocytic and plasma cell infiltration. In conclusion, the difference between myeloma and leukemia, as far as the listed conventional distinguishing features are concerned, is merely one of incidence: what is rare in one disease, is common in the other, and vice versa. Multiple myeloma is in all probability a leukemia of plasma cells.

scholarly journals The value of MRI examination on bilateral hands including proximal interphalangeal joints for disease assessment in patients with early rheumatoid arthritis: a cross-sectional cohort study

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying-Qian Mo ◽  
Ze-Hong Yang ◽  
Jun-Wei Wang ◽  
Qian-Hua Li ◽  
Xin-Yun Du ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Erosion ◽  
Whole Body ◽  
Disease Assessment ◽  
Mri Findings ◽  
Cross Sectional ◽  
Early Ra ◽  
Mri Examination ◽  
Mri Features ◽  
High Prevalence

Abstract Background Bilateral hands including proximal interphalangeal joints (PIPJs) are recommended on physical, X-ray radiographic, or ultrasonographic examination by clinical guidelines of rheumatoid arthritis (RA), but MRI still tends to examine unilateral wrists and/or MCPJs. We aimed to demonstrate the advantages of MRI examination on bilateral hands including PIPJs for disease assessment in early RA patients. Methods Active early RA patients received 3.0T whole-body MRI examination with contrast-enhanced imaging on bilateral wrists, MCPJs, and PIPJs. MRI features were scored referring to the updated RAMRIS. Clinical assessments were conducted on the day of MRI examination. Results The mean time of MRI examination was 24 ± 3 min. MRI bone erosion in MCPJs would be missed-diagnosed in 23% of patients if non-dominant MCPJs were scanned unilaterally, while osteitis in MCPJs would be missed-diagnosed in 16% of patients if dominant MCPJs were scanned unilaterally. MRI synovitis severity was also asymmetric: 21% of patients showing severe synovitis unilaterally in non-dominant MCPJs/PIPJs and other 20% showing severe synovitis unilaterally in dominant MCPJs/PIPJs. Among these early RA patients, MRI tenosynovitis occurred the most frequently in wrist extensor compartment I, while MRI examination on bilateral hands demonstrated no overuse influence present. However, overuse should be considered in dominant PIPJ2, PIPJ4, and IPJ of thumb of which MRI tenosynovitis prevalence was respectively 18%, 17%, or 16% higher than the non-dominant counterparts. Early MRI abnormality of nervus medianus secondary to severe tenosynovitis occurred either in dominant or non-dominant wrists; MRI of unilateral hands would take a risk of missed-diagnosis. Common MRI findings in PIPJs were synovitis and tenosynovitis, respectively in 87% and 69% of patients. MRI tenosynovitis prevalence in IPJ of thumb or PIPJ5 was much higher than the continued wrist flexor compartments. MRI synovitis or tenosynovitis in PIPJs independently increased more than twice probability of joint tenderness (OR = 2.09 or 2.83, both p < 0.001). Conclusions In consideration of asymmetric MRI features in early RA, potential overuse influence for certain tenosynovitis in dominant hands, and high prevalence of MRI findings in PIPJs, MRI examination on bilateral hands including PIPJs is deserved for disease assessment in early RA patients.

scholarly journals Role of Magnetic Resonance Imaging in the Management of Patients With Multiple Myeloma: A Consensus Statement

2015 ◽  
Vol 33 (6) ◽  
pp. 657-664 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Jens Hillengass ◽  
Saad Usmani ◽  
Elena Zamagni ◽  
Suzanne Lentzsch ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Myeloma ◽  
Magnetic Resonance ◽  
Bone Destruction ◽  
Whole Body ◽  
Focal Lesion ◽  
Resonance Imaging ◽  
Pelvic Mri ◽  
Symptomatic Disease ◽  
Osteoporotic Vertebral Fractures

Purpose The aim of International Myeloma Working Group was to develop practical recommendations for the use of magnetic resonance imaging (MRI) in multiple myeloma (MM). Methods An interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations for the value of MRI based on data published through March 2014. Recommendations MRI has high sensitivity for the early detection of marrow infiltration by myeloma cells compared with other radiographic methods. Thus, MRI detects bone involvement in patients with myeloma much earlier than the myeloma-related bone destruction, with no radiation exposure. It is the gold standard for the imaging of axial skeleton, for the evaluation of painful lesions, and for distinguishing benign versus malignant osteoporotic vertebral fractures. MRI has the ability to detect spinal cord or nerve compression and presence of soft tissue masses, and it is recommended for the workup of solitary bone plasmacytoma. Regarding smoldering or asymptomatic myeloma, all patients should undergo whole-body MRI (WB-MRI; or spine and pelvic MRI if WB-MRI is not available), and if they have > one focal lesion of a diameter > 5 mm, they should be considered to have symptomatic disease that requires therapy. In cases of equivocal small lesions, a second MRI should be performed after 3 to 6 months, and if there is progression on MRI, the patient should be treated as having symptomatic myeloma. MRI at diagnosis of symptomatic patients and after treatment (mainly after autologous stem-cell transplantation) provides prognostic information; however, to date, this does not change treatment selection.

scholarly journals Whole Body Diffusion Weighted MRI (WB DWI) for the Management of Multiple Myeloma: High Concordance between MRI Diffuse Pattern and BONE Marrow Plasma CELL Infiltration RATE

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5495-5495
Author(s):  
Silvia Mangiacavalli ◽  
Zacchino Michela ◽  
Virginia Valeria Ferretti ◽  
Claudio Salvatore Cartia ◽  
Giovanni Savietto ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Progressive Disease ◽  
Infiltration Rate ◽  
Whole Body ◽  
Radiological Findings ◽  
Focal Lesions ◽  
Diffuse Infiltration ◽  
Diffusion Weighted ◽  
Weighted Sequences

Background: Diffusion-weighted whole body MRI (WB-DWI) is a new functional imaging technique comprising anatomical and functional sequences with an emerging role in the management of multiple myeloma (MM) patients (pts) since it allows highly sensitive detection of diffuse bone marrow (BM) infiltration pattern and focal lesions, avoiding intravenous injections and radiation exposure. The aims of our study were 1) to test the correlation between plasma cells infiltration (BMPC) rate at BM biopsy and the presence of diffuse infiltration pattern at WB-DWI. 2) to compare response according to IMWG criteria and WB-DWI response and to establish the rate of discordancy (WB-DWI progression with increased focal lesions and at least a partial response according to IMWG criteria) Methods: We reviewed data regarding 45 MM patients (pts) observed in our Centre between September 2018 and July 2019 for whom quantification of serum and urine monoclonal component (MC), free light chains value (FLC), BM biopsy, whole body CT scan and WB-DWI data were available at the same time point. Sequential assessment of WB-DWI and laboratory data was available in 20 pts. Patients performed a WB-DWI (Magnetom Area, 1.5T, Siemens Enlarged Germany) for head to knee. The protocol included anatomical sequences T1 and T2 weighted with fat suppression on the sagittal plane specifically for the spine. Coronal T2 weighted fat suppression sequences are performed for the study of femural bone. Axial Dixon T1 weighted sequences of the whole scan region, in breath-old. The functional part is formed by diffusion weighted sequences in the axial plane. MM diagnosis and response were assessed by IMWG criteria. Response were categorized as follows: responsive patients if ≥PR, progressive disease if <PR. BM infiltration rate was used as a continuous variable. WB-DWI findings at first evaluation were categorized as follows: presence/absence of focal lesions, presence/absence of diffuse pattern of BM infiltration. Radiological re-assessment of both focal lesions and diffuse pattern was categorized as follows: reduced/stable/increased. Discordant pattern of progression was defined as: ≥PR + diffuse pattern stable/reduced + focal lesions increased. Association between two categorical variables was evaluated by Fisher's exact test. Mann-Whitney test was used to compare a quantitative variable among two independent groups of patients. P-values<0.05 were considered significant. Results: Table 1 summarizes the clinical and radiological data of the population on study. Median age was 64 years (range 38-86), median number of previous lines of therapy at time of evaluation was 0 (range 0-)2; 47% pts were at the onset, 31% were in follow-up after treatment completion, 22% had progressive disease. WB-DWI showed a diffuse pattern in 22 pts (49%); in 23 patients without a diffuse pattern, 7 (30%) had PBMC >10%; BMPC infiltration rate was significantly higher in pts with presence of diffuse pattern at WB-DWI (p<0.001; Figure 1). WB-DWI showed focal lesions in 35 pts (78%): 19 of them were at onset of disease. Most of the patients performing sequential assessment of WB-DWI were responsive according to IMWG criteria at time of WB-DWI re-evaluation (17 pts with ≥PR, 85%). Table 2 shows radiological findings according to IMWG response. Focusing on patients with ≥PR, WB-DWI diffuse pattern was reduced in 13 pts (76.5%) and stable in 4 pts (23.5%) with complete concordance between hematological and radiological findings (increased diffuse pattern in no pt with ≥PR); focal lesions were reduced in 76.5% and increased in 23.5%; a discordant pattern of progression was found in 4 patients (20%). Conclusions: Our study findsa significant correlation between presence of WB-DWI diffuse infiltration patter and BMPC rate, highlighting the possible future use of this radiological technique for monitoring BM residual disease. In addition, this study shows the possible not negligible emergence of discordant pattern of progression, probably deriving from the spatial heterogeneity of MM clones and their different sensitivity to therapy. Disclosures Mangiacavalli: celgene: Consultancy; Janssen cilag: Consultancy; Amgen: Consultancy. Varettoni:Gilead: Other: travel expenses; ABBVIE: Other: travel expenses; Roche: Consultancy; Janssen: Consultancy. Arcaini:Celgene: Speakers Bureau; Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses; Gilead Sciences: Research Funding; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy.

scholarly journals Imaging of Monoclonal Gammapathy of Undetermined Significance and Smoldering Multiple Myeloma

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 486 ◽  
Author(s):  
Bastien Jamet ◽  
Clément Bailly ◽  
Thomas Carlier ◽  
Cyrille Touzeau ◽  
Anne-Victoire Michaud ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Multiple Myeloma ◽  
Fdg Pet ◽  
Whole Body ◽  
Bone Lesions ◽  
Rapid Progression ◽  
Smoldering Multiple Myeloma ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
Undetermined Significance

Multiple myeloma (MM) is always preceded by an initial monoclonal gammopathy of undetermined significance (MGUS) that then develops into asymptomatic or smoldering multiple myeloma (SMM), which constitutes an intermediate clinical stage between MGUS and MM. According to a recent study, risk factors for faster MGUS to MM progression include an M protein of 1.5 g/dL or more and an abnormal free light chain ratio in patients with non-IgM MGUS. Therefore, the International Myeloma Working Group (IMWG) decided to recommend whole-body computed tomography (WBCT) for patients with high-risk MGUS in order to exclude early bone destruction. Studies evaluating magnetic resonance imaging (MRI) in SMM found an optimal cutoff of two or more focal lesions to be of prognostic significance for fast progression into symptomatic disease and considered this biomarker as a myeloma-defining event (MDE) needing to start therapy with the aim to avoid progression to harmful bone lesions. Moreover, studies assessing positron emission tomography (PET) with computed tomography (CT) using 18F-deoxyglucose (FDG) (FDG-PET/CT) in SMM showed that presence of focal bone lesion without underlying osteolysis is associated with a rapid progression to symptomatic MM. Latest IMWG guidelines recommended to perform WBCT (either CT alone or as part of an FDG-PET/CT protocol) as the first imaging technique at suspected SMM and, if these images are negative or inconclusive, to perform whole-body MRI. The goal of this paper is to clarify the role of different imaging modalities in MGUS and SMM workups.

scholarly journals Intramedullary Nailing for Pathological Fractures of the Proximal Humerus Caused by Multiple Myeloma: A Case Report and Literature Review

2021 ◽  
Author(s):  
guoqiang xu ◽  
gang wang ◽  
xiaodong bai ◽  
zhenyu liu ◽  
xinjia wang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Proximal Humeral Fracture ◽  
Pathological Fracture ◽  
Proximal Humerus ◽  
Combined Treatment ◽  
Bone Destruction ◽  
Humeral Fracture ◽  
Whole Body ◽  
Left Shoulder ◽  
Im Nailing

Abstract Background: Multiple myeloma bone disease(MMBD) is indicative of multiple myeloma (MM), and it will reduce patient life quality. In addition to oncological, antineoplastic systemic therapy, surgical therapy in patients with MM represents an essential treatment pillar within the framework of supportive therapy measures and is the task of orthopedic tumor surgery. Nevertheless, there are few reports about applying intramedullary (IM) nailing in treating MM-induced proximal humeral fracture to prevent fixation loss. This paper aims to describe a case of pathological fracture of the proximal humerus caused by multiple myeloma effectively treated with IM nailing without removal of tumors and review the current literature.Case presentation: This study reported a 64-year-old male patient complaining of serious left shoulder pain and limited movement. X-ray films showed left proximal humeral fracture accompanying with osteoporosis and bone destruction. During the preoperative examinations, tumor markers, whole-body bone imaging and bone marrow biopsy were performed. The patient was finally diagnosed with multiple myeloma (IgAλ, IIIA/II). After the treatment of pathological fracture with IM nailing, the patient's function recovered and the pain was relieved rapidly. The visual analogue scale (VAS) reduced by 7 points to 2 points postoperatively compared with that preoperatively. Histopathological examination results presented plasma cell myeloma. Next, the patient received chemotherapy in the hematology department. Humeral fracture displayed good union in the 40-month follow-up, with complete healing of fracture, and the clinical outcome was still satisfactory.Conclusion: The pathological fracture of proximal humerus caused by multiple myeloma should be treated by surgery early. IM nail can be used for this kind of fracture without removal of tumors, bone cement augmentation for bone defect or local adjuvant therapy was also employed. Under the combined treatment, the proximal humerus fracture can eventually heal.

Correlation of Serological and MRI-Based Treatment Response to Systemic Chemotherapy In 100 Patients with Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2977-2977
Author(s):  
Jens Hillengass ◽  
Sofia Ayyaz ◽  
Kerstin Kilk ◽  
Marc-André Weber ◽  
Thomas Hielscher ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Systemic Chemotherapy ◽  
Whole Body ◽  
P Value ◽  
Serological Response ◽  
Focal Lesions ◽  
Diffuse Infiltration ◽  
Weighted Sequences ◽  
Total Disappearance

Abstract Abstract 2977 Findings of magnetic resonance imaging (MRI) are increasingly being applied to assess disease activity and tumor mass in patients with multiple myeloma (MM), since it has been shown that this technique is the most sensitive to detect bone marrow infiltration in monoclonal plasma cell disease. However, the correlation of serological response to systemic treatment with alterations in MRI has not been investigated. We therefore analyzed changes in diffuse infiltration and in number and size of focal lesions (FL) in whole body-MRI (wb-MRI) in 100 patients after systemic therapy in order to learn whether the degree of remission would differ for morphological, MRI-based and serological criteria. Median age of patients was 59 years (range 28–74 years). Autologous stem cell transplantation was performed in 93, and conventional chemotherapy including novel agents in 7 patients. MRI protocol included T1 and T2 weighted sequences in coronal orientation of the whole body (excluding T2 of the lower legs to maintain acceptable examination time) as well as T1 and T2 weighted sequences of the whole spine in sagittal orientation. MRI-remission was assessed by two experienced radiologists in consensus for focal and diffuse infiltration separately and in combination. Definitions of MRI-response were determined with focal complete remission (fCR) indicating total disappearance of focal lesions, focal partial remission (fPR) being defined as reduction of the number of FL of 50% or more, focal stable disease (fSD) as unchanged number of FL and focal progressive disease (fPD) as any increase in number of focal lesions after therapy. For diffuse infiltration dCR was defined as total disappearance of diffuse infiltration. If diffuse infiltration was reduced after therapy but was still detectable in MRI it was defined as dPR. Constancy of diffuse infiltration was defined as dSD and increase in diffuse infiltration as dPD. Serological remission was determined summarizing near CR and CR as seroCR and VGPR and PR as seroPR to simplify statistical analysis. A weak but significant correlation of MRI-derived with serological remission was found for focal response with a correlation coefficient (CC) of 0.26 and a p-value of 0.003 and for diffuse response with a CC of 0.27 and a p-value of 0.003 respectively. In diffuse infiltration the remission stage would be more favorable if determined with MRI than with serological criteria, whereas in focal or multifocal disease patterns serological criteria would indicate a better response than would MRI changes. However, these differences were not significant. In contrary to a recent publication of the Arkansas group no better progression free survival (PFS) was seen for patients with more favorable MRI-response. Comparison of the 8 out of 40 patients in serological CR or near CR who also achieved a MRI-CR showed no significantly better PFS compared to patients in whom serological CR was achieved but residual infiltration was detected in MRI. We conclude that serological response to chemotherapy goes along with a similar trend of changes in MRI after systemic chemotherapy. The fact that the correlation in our study was rather weak and no survival benefit was found for MRI-CR, may be at least in part due to the inability of conventional MRI to differentiate between vital lesions and residual changes after treatment as well as between plasma cell infiltration and increased cellularity because of bone marrow regeneration after chemotherapy. Furthermore, residual lesions may consist of hyposecretory myeloma cells which can eventually lead to relapse of disease. Functional imaging methods such as positron emission tomography and new MRI techniques e.g. dynamic contrast-enhanced MRI and diffusion weighted imaging may contribute to solve these questions. If treatment of residual changes in MRI for example by local irradiation leads to a better outcome by deepening remission is another issue arising from our results. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Spatial Distribution of Focal Lesions in Whole-Body MRI and Influence of MRI Protocol on Staging in Patients with Smoldering Multiple Myeloma According to the New SLiM-CRAB-Criteria

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2537
Author(s):  
Markus Wennmann ◽  
Thomas Hielscher ◽  
Laurent Kintzelé ◽  
Bjoern H. Menze ◽  
Georg Langs ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Spatial Distribution ◽  
Whole Body ◽  
Focal Lesion ◽  
Focal Lesions ◽  
Whole Body Mri ◽  
Smoldering Multiple Myeloma ◽  
Mri Protocol ◽  
Prognostic Data

The purpose of this study was to assess how different MRI protocols (spinal vs. spinal plus pelvic vs. whole-body (wb)-MRI) affect staging in patients with smoldering multiple myeloma (SMM), according to the SLiM-CRAB-criterion ‘>1 focal lesion (FL) in MRI’. In this retrospective study, a baseline cohort of 147 SMM patients with wb-MRI at initial diagnosis was investigated, including prognostic data regarding development of CRAB-criteria. Fifty-two patients formed a follow-up cohort with a median of three wb-MRIs. The locations of all FLs were determined and it was calculated how staging decisions regarding the criterion ‘>1 FL in MRI’ would have been made if only a limited anatomic area (spine vs. spine plus pelvis) would have been covered by the MRI protocol. Furthermore, subgroups of patients selected by different cutoff-protocol-combinations were compared regarding their prognosis for development of CRAB-criteria. With an MRI protocol limited to spine/spine plus pelvis, only 28%/64% of patients who actually had >1 FL in wb-MRI would have been rated correctly as having ‘>1 FL in MRI’. Fifty-four percent/36% of patients with exactly 1 FL in spine/spine plus pelvis revealed >1 FL when the entire wb-MRI was analyzed. During follow-up, four more patients developed >1 FL in wb-MRI; both limited MRI protocols would have detected only one of these four patients as having >1 FL at the correct timepoint. Having >1 FL in spine/in spine plus pelvis/in the whole body was associated with a 43%/57%/49% probability of developing CRAB-criteria within 2 years. Patients with >3 FL in spine plus pelvis and patients with >4 FL in the whole body had an 80% probability to develop CRAB-criteria within 2 years. MRI protocols limited to the spine or to spine plus pelvis lead to substantial underdiagnoses of patients who actually have >1 FL in wb-MRI at baseline and during follow-up, which influences staging and treatment decisions according to the current SLiM-CRAB criteria. However, given the spatial distribution of FLs and the analysis on clinical course of patients indicates that the cutoff for the number of FLs should be adopted according to the MRI protocol when using MRI for staging in SMM.

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