MULTIPLE MYELOMA OF THE SPINE
IMWG Criteria | MRI Patterns | Bone Disease | Orthopaedic Management
MRI INFILTRATION PATTERNS
Critical Must-Knows
- IMWG 2014 criteria: 2 or more focal lesions on MRI (5mm+) = symptomatic myeloma
- Pure lytic lesions - myeloma NEVER produces blastic/sclerotic response
- Radiosensitive tumor - radiation highly effective for local control
- Pathological fracture risk - vertebroplasty/kyphoplasty effective for pain
- Spinal cord compression - emergency requiring urgent decompression
Examiner's Pearls
- "CRAB criteria: Calcium elevated, Renal insufficiency, Anemia, Bone lesions
- "MRI more sensitive than CT for detecting bone marrow infiltration
- "Whole-body low-dose CT has replaced skeletal survey
- "Myeloma is radiosensitive - responds well to radiation therapy
Critical Multiple Myeloma Exam Points
CRAB Criteria
Symptomatic myeloma definition: C=Calcium elevated (over 11 mg/dL), R=Renal insufficiency (creatinine over 2), A=Anemia (Hb under 10), B=Bone lesions. Any one of these with clonal plasma cells = requires treatment.
IMWG Imaging
2014 IMWG criteria include MRI: 2 or more focal lesions (5mm or greater) on MRI OR one or more osteolytic lesions on CT = symptomatic myeloma. Single MRI lesion is NOT diagnostic but warrants investigation.
Lytic Only
Myeloma produces ONLY lytic lesions - never blastic. If you see sclerotic response, consider POEMS syndrome (rare) or other diagnosis. The "punched out" lytic lesions are pathognomonic.
Radiosensitive
Myeloma is radiosensitive - unlike many solid tumor metastases. Radiation provides excellent local control. Surgery reserved for mechanical instability or decompression needs.
Multiple Myeloma vs Metastatic Carcinoma
| Feature | Multiple Myeloma | Metastatic Carcinoma |
|---|---|---|
| Lesion type | PURE LYTIC only | Lytic, blastic, or mixed |
| Primary site | Bone marrow (plasma cells) | Breast, prostate, lung, kidney, thyroid |
| Bone scan | Often NEGATIVE (no osteoblastic) | Usually positive |
| MRI sensitivity | Very high (marrow infiltration) | High for lytic lesions |
| Radiosensitivity | Highly radiosensitive | Variable by histology |
| Systemic markers | M-protein, free light chains | Tumor markers (PSA, CEA, etc) |
At a Glance
Multiple myeloma is a plasma cell malignancy with 80% having bone disease at diagnosis, with the spine being the most common site (49%). It produces only pure lytic lesions (never blastic) - the classic "punched out" appearance. Symptomatic disease is defined by CRAB criteria (Calcium elevation, Renal insufficiency, Anaemia, Bone lesions). The 2014 IMWG criteria include imaging: ≥2 focal lesions (≥5mm) on MRI is diagnostic. Myeloma is highly radiosensitive, so radiation provides excellent local control. Surgery is reserved for mechanical instability (SINS score) or spinal cord decompression; vertebroplasty/kyphoplasty effectively manages painful vertebral lesions.
CRAB Criteria for Symptomatic Myeloma
Memory Hook:CRAB criteria define end-organ damage requiring treatment
SLiM Criteria - New IMWG Biomarkers
Memory Hook:SLiM criteria added in 2014 - can diagnose myeloma WITHOUT CRAB symptoms
MRI Infiltration Patterns
Memory Hook:FDMVN patterns - Diffuse pattern has worst prognosis
Overview and Epidemiology
Multiple myeloma is a plasma cell neoplasm characterized by clonal proliferation of malignant plasma cells in the bone marrow, monoclonal protein in blood/urine, and end-organ damage including bone disease.
Epidemiology:
- Second most common hematologic malignancy (after NHL)
- Approximately 10% of all hematologic cancers
- Median age at diagnosis: 65-70 years
- Male to female ratio: 1.4:1
- Higher incidence in African Americans (2-3x)
Bone Disease Distribution:
| Site | Frequency | Clinical Significance |
|---|---|---|
| Vertebrae | 49% | Most common - compression fractures |
| Skull | 35% | "Pepper pot" appearance |
| Pelvis | 34% | May cause pathological fractures |
| Ribs | 33% | Pain, fracture risk |
| Proximal femur/humerus | 20% | Impending fracture concern |
Pathogenesis of Bone Disease:
Myeloma cells activate osteoclasts and suppress osteoblasts through:
- RANKL upregulation
- DKK1 (Dickkopf-1) inhibits Wnt signaling
- MIP-1alpha (macrophage inflammatory protein)
- IL-6, IL-1beta, TNF-alpha secretion
Why Pure Lytic?
Myeloma causes ONLY lytic lesions because it suppresses osteoblast activity through DKK1. Without osteoblastic response, bone scans are often negative (no radioisotope uptake). This is why MRI and CT are preferred over bone scan for myeloma.
Pathophysiology
Disease Spectrum
Monoclonal Gammopathy of Undetermined Significance
Precursor condition with low risk of progression:
- M-protein under 3 g/dL
- Clonal plasma cells under 10% in marrow
- No CRAB features or myeloma-defining events
- 1% per year progression to myeloma
- No treatment required - observation only
MRI typically normal or minimal abnormality in MGUS.
Bone Marrow Infiltration
The pattern of bone marrow infiltration on MRI correlates with prognosis:
| Pattern | Description | Prognosis | Treatment Response |
|---|---|---|---|
| Normal | No signal abnormality | Best | N/A (MGUS/early) |
| Focal | Discrete lesions, normal background | Good | Generally favorable |
| Diffuse | Homogeneous marrow replacement | Worst | Higher tumor burden |
| Mixed | Focal + diffuse changes | Intermediate | Variable |
| Variegated | Salt-and-pepper heterogeneous | Variable | Depends on extent |
Diffuse Pattern Significance
Diffuse bone marrow infiltration on MRI indicates high tumor burden and correlates with worse prognosis and higher ISS stage. These patients often have more severe cytopenias and higher beta-2 microglobulin levels.
Classification and Staging
International Staging System (ISS)
| Stage | Criteria | Median Survival |
|---|---|---|
| I | Beta-2 microglobulin under 3.5 mg/L AND Albumin 3.5 g/dL or more | 62 months |
| II | Neither I nor III | 44 months |
| III | Beta-2 microglobulin 5.5 mg/L or more | 29 months |
ISS is based on two readily available serum markers. Beta-2 microglobulin reflects tumor burden while albumin reflects performance status.
Single MRI Lesion
A single focal lesion on MRI does NOT meet IMWG criteria for myeloma diagnosis. However, it should prompt further investigation with CT (one lytic lesion on CT IS diagnostic) or biopsy.
Clinical Presentation
Presenting Features
Bone Pain (70% at presentation):
- Most common symptom
- Often back pain from vertebral involvement
- Worse with movement, may improve at rest
- Pathological fractures common
Systemic Symptoms:
- Fatigue (anemia)
- Weight loss
- Recurrent infections (immunoparesis)
- Hyperviscosity symptoms (rare)
Spinal Manifestations
Vertebral Compression Fractures:
- Present in 55-70% at diagnosis
- May be presenting feature
- Multiple levels common
- Thoracolumbar junction most common
Spinal Cord Compression:
- Emergency presentation
- From vertebral collapse or extraosseous extension
- Requires urgent assessment and treatment
- Good prognosis if treated promptly (radiosensitive)
Radiculopathy:
- Neural foraminal narrowing
- Extraosseous tumor extension
- May present before diagnosis
Red Flags
- Age over 50 with new back pain
- Pathological fracture (minimal trauma)
- Anemia, renal insufficiency
- Hypercalcemia
- Elevated ESR/plasma viscosity
- Recurrent infections
Investigations
Laboratory Studies
Essential Panel:
- FBC (anemia, rouleaux formation)
- Renal function, electrolytes
- Calcium (hypercalcemia)
- Total protein, albumin (AG ratio)
- LDH, beta-2 microglobulin
Myeloma-Specific Tests:
- Serum protein electrophoresis (SPEP) - M-spike
- Urine protein electrophoresis (UPEP) - Bence-Jones protein
- Serum free light chains (kappa/lambda ratio)
- Immunofixation (identifies M-protein type)
Bone Marrow:
- Aspirate and trephine biopsy
- Plasma cell percentage
- Cytogenetics/FISH for prognostic markers
Imaging
Whole-Body Low-Dose CT (WBLDCT)
Now preferred first-line imaging (replaced skeletal survey):
- Sensitivity: 78% vs skeletal survey 50%
- One lytic lesion on CT = diagnostic criterion
- Better detection of rib/pelvic lesions
- Can assess fracture risk
Findings:
- Punched-out lytic lesions
- NO sclerotic rim (unlike metastases)
- Pathological fractures
- Osteopenia
WBLDCT is first-line imaging for initial staging per IMWG.
Management
Systemic Treatment
First-Line Therapy (Haematology):
Orthopaedic surgeons should understand systemic treatment:
- Triplet therapy: VRd (Bortezomib, Lenalidomide, Dexamethasone)
- Quadruplet therapy: Adding daratumumab for fit patients
- Autologous stem cell transplant: For eligible patients under 70
Bone-Targeted Therapy:
- Bisphosphonates: Zoledronic acid monthly
- Denosumab: Alternative if renal impairment
- Reduces skeletal events by 40%
Orthopaedic Management
Conservative Measures
Most patients managed non-operatively:
- Analgesia (WHO ladder)
- Bracing for vertebral fractures
- Activity modification
- Physiotherapy
Vertebral Augmentation:
- Kyphoplasty/Vertebroplasty highly effective
- 80-90% pain relief
- Can be done under local anesthesia
- Multiple levels in single session
- Good option for pathological compression fractures
Vertebral augmentation is first-line for painful compression fractures.
Spinal Cord Compression
Oncological Emergency in Myeloma:
Unlike metastatic carcinoma, myeloma cord compression has excellent prognosis if treated promptly:
Management:
- Dexamethasone 10mg IV bolus then 4mg q6h
- MRI whole spine (skip lesions common)
- Assessment for surgery:
- If mechanically unstable = surgery + radiation
- If stable = radiation alone effective
- Radiation highly effective (radiosensitive)
Outcomes:
- Ambulatory patients: 90%+ maintain ambulation
- Non-ambulatory: 50-70% recover ambulation (better than carcinoma)
Myeloma vs Carcinoma Cord Compression
Unlike metastatic carcinoma, myeloma is highly radiosensitive. If the spine is mechanically stable (SINS under 7), radiation alone is often sufficient for cord compression. Surgery is not automatically required as in radioresistant tumors.
Complications
Skeletal Complications
Pathological Fractures:
- Vertebral compression fractures (55-70%)
- Long bone fractures (less common)
- Rib fractures
Spinal Cord Compression:
- 5-10% of myeloma patients
- Usually from vertebral collapse
- Extraosseous extension less common
Hypercalcemia:
- Present in 25-30% at diagnosis
- From osteoclast activation
- Medical emergency if severe
Treatment-Related Complications
Bisphosphonate Therapy:
- Osteonecrosis of jaw (ONJ) - 1-10%
- Renal toxicity (especially zoledronic acid)
- Atypical femoral fractures (rare)
Surgical Complications:
- Wound healing issues (immunosuppression)
- Hardware failure (poor bone quality)
- Infection risk (hypogammaglobulinemia)
Disease Progression
Extramedullary Disease:
- Occurs in 10-20% during disease course
- More aggressive biology
- Requires modified treatment approach
Evidence Base
IMWG 2014 Diagnostic Criteria Update
- Added SLiM biomarkers to CRAB criteria
- 2 or more focal lesions on MRI = myeloma-defining
- 60% or more plasma cells = myeloma-defining
- FLC ratio 100 or more = myeloma-defining
Vertebroplasty in Myeloma
- 65 patients with myeloma compression fractures
- Pain relief in 86% at 6 months
- No serious complications
- Multiple levels safely treated
WBLDCT vs Skeletal Survey
- WBLDCT sensitivity 78% vs skeletal survey 50%
- WBLDCT detects more osteolytic lesions
- Lower radiation than conventional CT
- Now recommended as first-line imaging
MRI Patterns and Prognosis
- Diffuse MRI pattern predicts worse survival
- Focal pattern has better prognosis
- MRI patterns correlate with ISS stage
- Treatment response assessable on MRI
Exam Viva Scenarios
Practice these scenarios to excel in your viva examination
New Diagnosis with Back Pain
"A 68-year-old man presents with 3 months of progressive thoracic back pain. Blood tests show Hb 9.5, creatinine 1.8, calcium 2.8 mmol/L. SPEP shows M-protein 45 g/L. MRI shows multiple T1-hypointense vertebral lesions."
Cord Compression from Myeloma
"A 72-year-old woman with known myeloma presents with 48-hour history of progressive leg weakness. Examination shows 3/5 bilateral LE power. MRI shows T8 vertebral collapse with Bilsky grade 2 epidural compression."
Painful Compression Fractures
"A 65-year-old woman with myeloma in remission presents with severe L1 and L3 compression fractures (50% and 40% collapse). SINS 7. She has severe mechanical pain limiting mobility."
Solitary Plasmacytoma
"A 55-year-old man presents with a single T12 lytic lesion. Biopsy confirms plasmacytoma. Bone marrow shows 5% plasma cells. SPEP shows small M-protein 8 g/L. No CRAB features. Whole-body imaging shows no other lesions."
MULTIPLE MYELOMA SPINE
High-Yield Exam Summary
CRAB Criteria
- •C: Calcium over 11 mg/dL
- •R: Renal - Creatinine over 2 mg/dL
- •A: Anemia - Hb under 10 g/dL
- •B: Bone - 1 or more lytic lesions
- •Any CRAB + clonal plasma cells = symptomatic myeloma
SLiM Biomarkers (IMWG 2014)
- •S: Sixty percent or more plasma cells in marrow
- •Li: Light chain ratio 100 or more
- •M: MRI - 2 or more focal lesions (5mm+)
- •Any SLiM = myeloma WITHOUT needing CRAB
Key Imaging Points
- •WBLDCT replaced skeletal survey (first-line)
- •MRI most sensitive for marrow infiltration
- •2 or more MRI lesions = diagnostic criterion
- •Bone scan often NEGATIVE (no blastic response)
- •Pure LYTIC - never blastic in myeloma
MRI Patterns
- •Focal: Best prognosis, discrete lesions
- •Diffuse: Worst prognosis, homogeneous replacement
- •Mixed: Focal + diffuse
- •Variegated: Salt-and-pepper heterogeneous
- •Normal: MGUS or early disease
Treatment Pearls
- •Myeloma is RADIOSENSITIVE - radiation very effective
- •Vertebroplasty/kyphoplasty for painful fractures
- •Surgery only if unstable (SINS 13+) or failed RT
- •Cord compression: If stable = RT alone effective
- •Bisphosphonates reduce skeletal events by 40%
vs Metastatic Carcinoma
- •Myeloma: Pure lytic, radiosensitive, bone scan negative
- •Carcinoma: May be blastic/mixed, variable sensitivity
- •Myeloma cord compression: RT alone often sufficient
- •Carcinoma cord compression: Usually needs surgery
MCQ Practice Points
Exam Pearl
Q: What is the SINS score and its role in myeloma spine management?
A: Spinal Instability Neoplastic Score (SINS): Evaluates tumor-related spinal instability. Components: Location, pain, bone quality, radiographic alignment, vertebral body collapse, posterolateral involvement. Score 0-6: Stable. 7-12: Potentially unstable (surgical consultation). 13-18: Unstable (surgical stabilization indicated).
Exam Pearl
Q: What are the indications for surgical intervention in spinal myeloma?
A: Neurological deficit from cord compression, spinal instability (SINS greater than 12), intractable pain unresponsive to radiation/chemotherapy, pathological fracture with deformity, need for tissue diagnosis when uncertain. Surgery typically combined with radiation and systemic chemotherapy. Goal is palliation and function preservation.
Exam Pearl
Q: What is the role of vertebroplasty/kyphoplasty in spinal myeloma?
A: Percutaneous cement augmentation provides pain relief and mechanical stability for compression fractures without cord compression. Can be performed under local anesthesia in frail patients. Contraindicated if: posterior wall breach with epidural extension, neurological deficit, coagulopathy. May be combined with radiation.
Exam Pearl
Q: Why do myeloma lesions not appear on bone scan?
A: Myeloma cells secrete osteoclast-activating factors (RANKL, IL-6) causing pure bone resorption while suppressing osteoblast activity (via DKK1). Bone scan relies on osteoblastic activity for tracer uptake. No osteoblast response = no bone scan uptake. Use skeletal survey, whole-body low-dose CT, or MRI for myeloma staging.
Exam Pearl
Q: What is the typical surgical approach for myeloma cord compression?
A: Posterior decompression and stabilization most common - allows access to most vertebral levels, provides immediate stability. Circumferential approach (anterior + posterior) for significant anterior compression or vertebral body destruction. Separation surgery concept: Decompression to create space, then radiation for tumor control.
Australian Context
Multiple myeloma management in Australia follows IMWG international guidelines with treatment coordinated through haematology services. The Myeloma Australia organization provides patient support and education resources.
Bone-targeted therapy with bisphosphonates (zoledronic acid) or denosumab is PBS-listed for myeloma patients with bone disease. Treatment is typically administered monthly for 2 years and then can be de-escalated based on response.
Vertebral augmentation procedures including kyphoplasty and vertebroplasty are available through public and private hospitals, providing effective pain relief for pathological compression fractures. Coordination between haematology, radiation oncology, and orthopaedic/neurosurgery teams is essential for optimal outcomes.
References
- Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-48.
- Hillengass J, Usmani S, Rajkumar SV, et al. International myeloma working group consensus recommendations on imaging in monoclonal plasma cell disorders. Lancet Oncol. 2019;20(6):e302-12.
- Moulopoulos LA, Dimopoulos MA, Kastritis E, et al. Diffuse pattern of bone marrow involvement on magnetic resonance imaging is associated with high risk cytogenetics and poor outcome in newly diagnosed, symptomatic patients with multiple myeloma. Leukemia. 2012;26(4):683-9.
- Chew C, Craig L, Edwards R, et al. Safety and efficacy of percutaneous vertebroplasty in malignancy: a systematic review. Clin Radiol. 2011;66(1):63-72.
- Terpos E, Zamagni E, Lentzsch S, et al. Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group. Lancet Oncol. 2021;22(3):e119-30.