Bone marrow abnormalities and early bone lesions in multiple myeloma and its precursor disease: a prospective study using functional and morphologic imaging

Abstract

The incidence and importance of bone marrow involvement and/or early bone lesions in multiple myeloma (MM) precursor diseases is largely unknown. This study prospectively compared the sensitivity of several imaging modalities in monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and MM. Thirty patients (10 each with MGUS, SMM and MM) were evaluated with skeletal survey, [18F]FDG-PET/CT, [18F]NaF-PET/CT and morphologic dynamic contrast enhanced (DCE)-MRI. An additional 16 SMM patients had skeletal surveys and FDG-PET/CT. Among MGUS patients, DCE-MRI found only one focal marrow abnormality; other evaluations were negative. Among 26 SMM patients, five (19%) were re-classified as MM based on lytic bone lesions on CT and six had unifocal or diffuse marrow abnormality. Among MM, marrow abnormalities were observed on FDG-PET/CT in 8/10 patients and on DCE-MRI in nine evaluable patients. Abnormal NaF uptake was observed only in MM patients with lytic lesions on CT, providing no additional clinical information.

Trial registration: ClinicalTrials.gov NCT01237054 NCT01572480.

Keywords: DCE-MRI; FDG; MGUS; NaF; PET/CT; functional imaging; multiple myeloma; smoldering myeloma.

Conflict of interest statement

Disclosure of Conflicts of Interest: The authors report no potential conflicts of interest.

Figures

Figure 1

1 A. 48-year-old male with smoldering multiple myeloma. Axial 18F-FDG PET image shows increased tracer uptake within the left clavicle (arrow) (A). Corresponding axial CT image demonstrates a lytic bone lesion within the left clavicle (arrow) (B), This lytic bone lesion is likely within the trabecular bone as cortical bone seems intact, and was retrospectively identified with the help of 18F-FDG PET. The lytic bone lesion shows no significant uptake on the axial 18F-NaF PET (arrow) (C). This lytic bone lesion was biopsied under guidance of CT and the histopathology was consistent with myeloma involvement. 1B. 79-year-old male with monoclonocal gammopathy of undetermined significance (MGUS). Coronal T2W SPAIR MR image demonstrates a focal abnormal signal within the bone marrow in the posterior part of the L3 vertebral body (arrow) (A). The focal bone marrow abnormality shows no uptake on the coronal 18F-NaF PET (arrow) (B), and on 18F-FDG PET (arrow) (C). Corresponding CT from 18F-FDG PET demonstrates no lytic bone lesion (arrow) (D). 1C. 55-year-old male with multiple myeloma. Coronal T2W SPAIR MR image demonstrates a lytic bone lesion within the L3 vertebral body, which affects almost the whole vertebral body (arrow) (A). The lytic bone lesion shows uptake on the coronal 18F-NaF PET (arrow) (B), and on 18F-FDG PET (arrow) (C). Corresponding CT from 18F-FDG PET demonstrates a mixed blastic and lytic bone lesion within the L3 vertebral body (arrow) (D).

Figure 1

1 A. 48-year-old male with smoldering multiple myeloma. Axial 18F-FDG PET image shows increased tracer uptake within the left clavicle (arrow) (A). Corresponding axial CT image demonstrates a lytic bone lesion within the left clavicle (arrow) (B), This lytic bone lesion is likely within the trabecular bone as cortical bone seems intact, and was retrospectively identified with the help of 18F-FDG PET. The lytic bone lesion shows no significant uptake on the axial 18F-NaF PET (arrow) (C). This lytic bone lesion was biopsied under guidance of CT and the histopathology was consistent with myeloma involvement. 1B. 79-year-old male with monoclonocal gammopathy of undetermined significance (MGUS). Coronal T2W SPAIR MR image demonstrates a focal abnormal signal within the bone marrow in the posterior part of the L3 vertebral body (arrow) (A). The focal bone marrow abnormality shows no uptake on the coronal 18F-NaF PET (arrow) (B), and on 18F-FDG PET (arrow) (C). Corresponding CT from 18F-FDG PET demonstrates no lytic bone lesion (arrow) (D). 1C. 55-year-old male with multiple myeloma. Coronal T2W SPAIR MR image demonstrates a lytic bone lesion within the L3 vertebral body, which affects almost the whole vertebral body (arrow) (A). The lytic bone lesion shows uptake on the coronal 18F-NaF PET (arrow) (B), and on 18F-FDG PET (arrow) (C). Corresponding CT from 18F-FDG PET demonstrates a mixed blastic and lytic bone lesion within the L3 vertebral body (arrow) (D).

Figure 2. Illustrative representation of overall imaging findings (lytic bone lesions and bone marrow abnormalities) for every patient with high risk smoldering multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma

Each column represents a patient. Rows represent the image specific bone marrow and bone findings. 2A and 2B, from top: Row 1: FDG-avid bone marrow abnormalities and lytic bone lesions; coded as green (no activity), or gray (focal or diffuse bone marrow abnormalities, possibly representative of myelomatous infiltration, but not biopsy proven), or red (FDG-avid lytic bone lesion, either biopsy proven, one patient or unproven, one patient). Row 2: CT (*CT component of FDG-PET) detected lytic bone lesions coded as red (present) or green (absent). Row 3: NaF activity in lytic bone lesions; coded as green (absent) and white (if test was not done). Row 4: MRI detected focal bone marrow abnormalities; coded as green (absent) or gray (present, but of unclear significance in the absence of biopsy). Row 5: lytic bone lesions on skeletal survey coded as negative (green). Overall, among evaluable patients, bone marrow abnormalities were seen in 6 patients with smoldering multiple myeloma, and 1 patient with MGUS. Lytic bone lesions were detected on PET/CT in 5 patients with smoldering multiple myeloma; these patients were upstaged. 2C, from top: Row 1: FDG-avid focal bone marrow abnormalities with or without a CT correlate of lytic bone lesions; coded as green (no activity), or red (positive activity, indicated by number of lesions for that patient). Row 2: FDG-PET detected diffuse bone marrow abnormalities; coded as red (present) and green (absent). Row 3: CT (*CT component of FDG-PET) detected lytic bone lesions; coded as red (present, indicated by number of lesions for that patient). Row 4: NaF-avid lytic bone lesions; coded as green (absent) and white (test was not done). Row 5: MRI detected bone marrow abnormalities; coded as green (absent) or white (test was not done). Row 6: skeletal survey detected bone lytic lesions; coded as green (absent), red (present, indicated by number of lesions for that patient), and white (missing data). For the purpose of counting bone lytic lesions and bone marrow abnormalities we took into account 13 most important skeletal regions at risk for myeloma invasion: vertebral column (cervical, thoracic and lumbar), sternum and ribs, clavicles and scapulae, humeri, skull, pelvis and femora