Multiple myeloma (MM) is the most common primary bone malignancy, characterized by uncontrolled proliferation of clonal plasma cells in the bone marrow. It accounts for approximately 10% of all hematologic malignancies with an annual incidence of 4-5 per 100,000. The median age at diagnosis is 65-70 years with slight male predominance. The disease localizes to the axial skeleton (spine, pelvis, skull, ribs, proximal long bones) — regions with the richest red bone marrow. The most classic radiologic finding is 'punched-out' lytic lesions without sclerotic rim — this feature is critical for differentiation from metastasis. 'Raindrop' pattern in the skull, diffuse osteopenia and compression fractures in vertebrae are common. Bone scintigraphy is usually negative because myeloma does not stimulate osteoblastic activity — therefore whole-body low-dose CT or PET-CT is preferred for staging. MRI is the most sensitive modality for demonstrating bone marrow infiltration; three infiltration patterns are defined: focal, diffuse, and variegated (salt-and-pepper). Diagnosis is based on CRAB criteria: Calcium elevation, Renal insufficiency, Anemia, and Bone lesions. Serum and urine protein electrophoresis, immunofixation, free light chains, and bone marrow biopsy confirm the diagnosis.
Age Range
50-80
Peak Age
65
Gender
Male predominant
Prevalence
Common
In multiple myeloma, clonal plasma cells proliferate uncontrollably in the bone marrow, suppressing normal hematopoiesis and disrupting the bone microenvironment. Myeloma cells secrete cytokines including RANKL (Receptor Activator of Nuclear Factor Kappa-B Ligand), MIP-1α (Macrophage Inflammatory Protein-1α), DKK1 (Dickkopf-1), and IL-6, dramatically increasing osteoclast activation; simultaneously, they suppress osteoblast activity through DKK1 and sclerostin-mediated Wnt pathway inhibition — this 'uncoupled bone remodeling' leads to bone destruction without new bone formation. This pathophysiological mechanism directly determines the radiologic findings: (1) Due to osteoblast suppression, lytic lesions do not form sclerotic rim — 'punched-out' appearance; (2) Bone scintigraphy cannot demonstrate involvement because there is no osteoblastic activity — false-negative result; (3) On CT, lytic lesions appear as low-density bone destruction without reactive sclerosis. On MRI, tumor cells replace normal fatty bone marrow, resulting in low T1 signal (loss of fat signal), high T2/STIR signal (increased water content + cellularity). DWI restriction reflects the high cellularity and reduced extracellular space of plasma cells. FDG uptake on PET-CT reflects the increased glycolysis of malignant plasma cells (Warburg effect) and indicates active disease.
The pathognomonic radiologic signature of myeloma is the presence of multiple sharply defined punched-out lytic lesions in the axial skeleton WITHOUT sclerotic rim around them. The absence of sclerotic rim is due to myeloma cells suppressing osteoblast activity via DKK1 and sclerostin — bone is destroyed but new bone cannot form. This same mechanism explains why bone scintigraphy is negative: 99mTc-MDP bisphosphonate agents bind to osteoblastic activity, and since osteoblasts are suppressed in myeloma, there is no uptake — this false-negative result is paradoxically a diagnostic clue for myeloma. The combination of lytic lesions + negative bone scintigraphy is virtually pathognomonic for myeloma and is the most important distinguishing finding from metastasis.
Whole-body low-dose CT is the gold standard for myeloma staging and is far more sensitive than conventional radiographs (radiographs cannot detect lesions until >30-50% bone loss). Lytic lesions are sharply defined, round/oval, low-density areas of bone destruction with NO sclerotic rim (no reactive bone formation) — this is the most distinguishing feature of myeloma. In the skull, numerous small (5-20 mm) punched-out lesions create the 'raindrop' or 'salt-and-pepper' pattern; both inner and outer tables are involved. In vertebrae, multiple lytic lesions and compression fractures are seen on a background of diffuse osteopenia. Lytic lesions are also common in the pelvis, ribs, and proximal long bones. In advanced disease, widespread bone destruction and pathologic fractures develop. Rarely (1-3%), sclerotic lesions may be seen — this is associated with POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes).
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Multiple sharply defined punched-out lytic lesions without sclerotic rim are seen in the [skull/spine/pelvis], consistent with multiple myeloma. An accompanying [compression fracture / pathologic fracture] is noted at the level of [vertebra].
T1-weighted sequences are the most sensitive for demonstrating bone marrow infiltration in myeloma, capable of detecting pathologic changes before CT. Normal adult fatty bone marrow's high T1 signal is replaced by low T1 signal tissue from myeloma plasma cells. Three distinct infiltration patterns are defined: (1) Focal pattern — discrete nodules/lesions with markedly low T1 signal, contrasting with surrounding normal fatty marrow's high signal; this is the most common pattern (60-70%). (2) Diffuse pattern — homogeneous widespread T1 signal decrease throughout the bone marrow, indicating complete marrow infiltration; signal is lower than disc and muscle; seen in advanced disease. (3) Variegated (salt-and-pepper) pattern — heterogeneous mixture of low and high signal areas, reflecting partial infiltration. In vertebrae, widespread low signal replacing the expected high T1 signal of normal fatty marrow is diagnostic. Marrow signal lower than disc or muscle on T1 is pathologic.
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On MRI T1-weighted sequences, [focal/diffuse/variegated pattern] low signal areas are seen in the bone marrow of [spine/pelvis/proximal femur], consistent with bone marrow infiltration. [Vertebral marrow shows lower signal than intervertebral disc — pathologic.]
STIR (Short Tau Inversion Recovery) is the most sensitive fat-suppressed sequence for demonstrating bone marrow infiltration in myeloma and forms the backbone of whole-body MRI protocols. Normal fatty bone marrow signal is suppressed on STIR appearing as low signal (dark). In areas with myeloma infiltration, tumor cells replace fat signal, so these areas are not affected by fat suppression and show markedly high signal (bright) — bright lesions against the dark normal marrow background create striking contrast. Focal lesions appear as bright nodules, diffuse infiltration as widespread bright marrow, and variegated pattern as heterogeneous bright-dark mixture. STIR is also very valuable in treatment response assessment: after successful treatment, STIR signal of lesions decreases (fatty marrow regeneration). Whole-body STIR-MRI is used as an alternative to PET-CT for staging and treatment response monitoring.
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On STIR sequences, [multiple focal / diffuse / variegated pattern] high signal areas are seen in the bone marrow of [spine/pelvis/skull/long bones], consistent with active bone marrow infiltration.
DWI (Diffusion-Weighted Imaging) shows high signal (restricted diffusion) in myeloma lesions and is a very valuable sequence for treatment response assessment. Dense packing of myeloma plasma cells (high cellularity) and increased nuclear-to-cytoplasmic ratio restrict free movement of water molecules in the extracellular space — this manifests as high signal on DWI and low value on ADC maps. At high b-values (b=800-1000 s/mm²), lesions appear conspicuously bright. The most important advantage of DWI is treatment response monitoring: after successful treatment, cell death reduces cellularity, diffusion restriction resolves, DWI signal decreases, and ADC value increases — these changes can be detected before anatomic size reduction. Whole-body DWI-MRI is a functional imaging method competing with PET-CT, and the absence of radiation is a significant advantage.
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On DWI sequences (b=800-1000), [marked/mild] diffusion restriction is seen in bone marrow lesions with low values on ADC maps — consistent with high cellularity.
18F-FDG PET-CT is one of the first-line imaging modalities for staging, prognostic assessment, and treatment response monitoring in myeloma. Myeloma plasma cells demonstrate increased glycolysis and avidly accumulate FDG. Multiple FDG-avid focal lesions in the axial skeleton are typical findings. Advantages of PET-CT: (1) Shows metabolic activity — can distinguish active disease vs inactive residual; (2) Can detect extramedullary disease (soft tissue plasmacytomas); (3) Metabolic response precedes anatomic response in treatment — complete metabolic response (CMR) is an important prognostic marker. FDG uptake intensity (SUVmax) correlates with prognosis: SUVmax >4.2 indicates poor prognosis. An important advantage of PET-CT is that it is not dependent on osteoblastic activity unlike bone scintigraphy — it directly demonstrates myeloma lesions.
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On PET-CT, [number] FDG-avid focal bone lesions are seen in the axial skeleton at the level of [spine/pelvis/skull/ribs] (highest SUVmax: [value]). [Extramedullary plasmacytoma is present/absent.] Findings are consistent with multiple myeloma.
The skull 'raindrop' pattern is one of the most recognizable and classic radiologic findings of myeloma. Numerous small (usually 5-20 mm), round, sharply defined punched-out lytic lesions are seen in the calvarial skull — these lesions involve both inner and outer tables and expand the diploic space. Lesions are uniform in size and distribution, without sclerotic rim. On CT bone window, lesions appear as distinctly low-density defects. This pattern is highly characteristic of myeloma but requires differential diagnosis from eosinophilic granuloma (Langerhans cell histiocytosis), metastasis, and hyperparathyroidism (brown tumors). In myeloma, lesions are typically more uniform in size and distribution, have no sclerotic rim, and may involve the mandible (rare in metastasis).
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Numerous small sharply defined punched-out lytic lesions involving both tables without sclerotic rim are seen in the calvarial skull, with 'raindrop' pattern consistent with multiple myeloma.
On contrast-enhanced MRI, myeloma lesions typically show homogeneous or heterogeneous enhancement. Focal lesions are distinguished from surrounding normal fatty marrow's low enhancement by their conspicuous enhancement. In diffuse infiltration, increased enhancement is seen throughout the bone marrow. Enhancement pattern is related to tumor vascularity and VEGF-mediated neoangiogenesis. Dynamic contrast-enhanced MRI (DCE-MRI) provides additional information in treatment response assessment. Contrast-enhanced sequences are especially valuable for detecting soft tissue plasmacytomas, evaluating spinal cord compression, and identifying epidural disease. Gadolinium-based contrast agents are used; in patients with renal insufficiency (common in myeloma), dosage and NSF risk must be evaluated.
Report Sentence
On contrast-enhanced T1-weighted sequences, [homogeneous/heterogeneous] enhancement is seen in bone marrow lesions. [Epidural / paravertebral soft tissue extension shows enhancement.]
Criteria
Most common pattern (60-70%). Appears as discrete focal lesions in the bone marrow. Multiple punched-out lytic lesions on CT, focal nodules with low T1 / high STIR signal on MRI. Durie-Salmon PLUS staging system is based on focal lesion count.
Distinct Features
Discrete focal lesions with potentially preserved normal marrow in between. On MRI, conspicuous contrast between surrounding normal fatty marrow's high T1 signal and lesions' low T1 signal. Multiple FDG-avid focal foci on PET-CT.
Criteria
Seen in advanced disease or high tumor burden (20-25%). On MRI, diffuse low T1 signal throughout bone marrow — vertebral marrow signal lower than intervertebral disc (pathologic). On CT, diffuse osteopenia + multiple compression fractures; focal lytic lesions may not be conspicuous.
Distinct Features
Widespread homogeneous marrow infiltration — diffuse change predominates. May be misinterpreted as osteopenia on CT (confused with osteoporosis in elderly). Vertebral marrow < disc signal on MRI T1 is diagnostic.
Criteria
Combination of focal and diffuse patterns (5-10%). On MRI, heterogeneous mixture of low and high signal areas in bone marrow — 'salt-and-pepper' appearance. May be seen in partial infiltration or post-treatment partial response. Also observed in early disease or during MGUS to myeloma progression.
Distinct Features
Heterogeneous marrow signal — neither fully focal nor fully diffuse. 'Salt-and-pepper' appearance conspicuous on MRI T1. Pattern change during treatment response monitoring has prognostic significance.
Criteria
Presents as a single bone lesion without systemic myeloma (bone marrow biopsy <10% plasma cells, M-protein low or absent). Accounts for 5-10% of bone plasmacytomas. Vertebra is most common location. Solitary lytic expansile lesion on CT, low T1 / high T2 signal on MRI. Treatment: local radiotherapy (40-50 Gy). 50-70% progress to systemic myeloma within 10 years.
Distinct Features
Single lesion without additional skeletal involvement. Single focus must be confirmed on whole-body MRI or PET-CT. May have soft tissue extension. No systemic disease criteria (CRAB).
Distinguishing Feature
Bone metastases typically show sclerotic rim around lytic lesions — myeloma has NO sclerotic rim (osteoblast suppression). Metastasis may show blastic or mixed pattern — myeloma is almost always purely lytic. Bone scintigraphy usually POSITIVE in metastasis, usually NEGATIVE in myeloma. Metastatic lesions vary in size — myeloma more uniform. Known primary malignancy favors metastasis; M-protein/free light chain abnormality favors myeloma.
Distinguishing Feature
LCH occurs in children and young adults (myeloma >50 years). LCH skull lesions show 'beveled edge' — inner and outer tables erode at different rates. In myeloma, both tables erode equally, symmetric punched-out. LCH usually solitary/few lesions, myeloma numerous. LCH may show periosteal reaction, rare in myeloma. M-protein/free light chains normal in LCH.
Distinguishing Feature
Vertebral hemangioma shows high T1 signal (fat content) — myeloma shows low T1 signal. Hemangioma has characteristic thick vertical trabeculae on CT ('polka-dot' axial, 'corduroy' sagittal). Hemangioma usually single/few, asymptomatic, incidental. Myeloma has multiple vertebral involvement + compression fractures.
Distinguishing Feature
Osteomyelitis usually involves single bone segment, myeloma multiple axial sites. Periosteal reaction prominent in osteomyelitis with surrounding soft tissue inflammation — rare in myeloma. Disc space involvement (diskospondylodiscitis) typical in osteomyelitis — myeloma preserves disc space. Clinical: fever/CRP/ESR in osteomyelitis, anemia/M-protein/hypercalcemia in myeloma.
Urgency
urgentManagement
medicalBiopsy
NeededFollow-up
specialist-referralMultiple myeloma diagnosis is confirmed by demonstrating ≥10% clonal plasma cells on bone marrow biopsy in the presence of CRAB criteria. Hematology consultation is urgent when myeloma is radiologically suspected. SPEP, immunofixation, free light chain ratio, CBC, calcium, creatinine, β2-microglobulin, and LDH are ordered. Staging: R-ISS + whole-body low-dose CT or PET-CT. Treatment: proteasome inhibitors (bortezomib), immunomodulators (lenalidomide), anti-CD38 monoclonal antibodies (daratumumab), autologous stem cell transplantation. Response monitoring: serum/urine M-protein, free light chains, and PET-CT/MRI. Compression fracture or spinal cord compression requires emergent intervention. Bisphosphonate or denosumab for skeletal event prevention.
Diagnosis is confirmed by serum and urine protein electrophoresis, bone marrow biopsy. Treatment includes chemotherapy, autologous stem cell transplantation, and supportive care (bisphosphonates, radiotherapy). Staging (Durie-Salmon PLUS) is performed with WBLDCT or PET-CT. Solitary plasmacytoma responds well to radiotherapy.