What is the recommended workup and treatment for multiple myeloma in a patient with chronic cervical spondylosis?

Workup for Multiple Myeloma in a Patient with Chronic Cervical Spondylosis

In a patient with chronic cervical spondylosis being evaluated for multiple myeloma, proceed with the standard multiple myeloma diagnostic workup while recognizing that MRI of the cervical spine is particularly critical in this case—both to assess for myeloma-related spinal involvement and to differentiate myelomatous lesions from pre-existing degenerative changes. 1

Initial Laboratory Assessment

The diagnostic workup should include the following blood tests:

• Complete blood count (CBC) with differential and peripheral blood smear to assess for anemia (present in 73% of myeloma patients at diagnosis), leukopenia, and thrombocytopenia 2, 3
• Comprehensive metabolic panel including serum creatinine (to evaluate renal function, as 19% present with acute kidney injury), serum calcium (to detect hypercalcemia), and serum albumin (for prognostic staging) 2, 3
• Serum protein electrophoresis (SPEP) with immunofixation electrophoresis to detect and characterize the monoclonal protein 1, 2
• Quantitative immunoglobulins (IgG, IgA, IgM) to track disease burden 1, 2
• Serum free light chain (FLC) assay with kappa/lambda ratio for diagnosis and monitoring 1, 2
• Beta-2 microglobulin and lactate dehydrogenase (LDH) for prognostic assessment via the Revised International Staging System 1, 2, 3

Urine Studies

• 24-hour urine collection for total protein, urine protein electrophoresis (UPEP), and urine immunofixation electrophoresis—this cannot be replaced by random or morning urine samples 1, 4

Critical pitfall: Do not use random urine samples corrected for creatinine concentration, as this has not been validated for myeloma diagnosis. 1

Bone Marrow Evaluation

• Unilateral bone marrow aspirate and/or biopsy to confirm ≥10% clonal plasma cells, which establishes the diagnosis 1, 2
• CD138 immunoperoxidase staining should be used to accurately determine plasma cell percentage 1
• Cytogenetics including metaphase karyotype and FISH to detect high-risk features: del(17p), t(4;14), t(14;16), t(14;20), gain 1q, and p53 mutation 1, 2, 3

The highest plasma cell percentage from either aspirate or biopsy should be recorded for diagnostic purposes. 1

Imaging Studies: Special Considerations for Cervical Spondylosis

This is where your patient's pre-existing cervical spondylosis creates a unique diagnostic challenge:

Standard Skeletal Survey

• Complete skeletal survey including posteroanterior chest, anteroposterior and lateral views of cervical/thoracic/lumbar spine, skull (AP and lateral), humeri, femora, and pelvis 1
• This remains the standard screening method and can detect 79% of patients with osteolytic bone disease at presentation 1, 3

MRI of the Spine—Mandatory in Your Case

MRI of the spine and pelvis is mandatory in this patient because: 1

1. Differentiation of pathology: The patient's known cervical spondylosis will show degenerative changes on plain films, making it difficult to distinguish new myelomatous lesions from chronic degenerative disease 1
2. Detection of cord compression: MRI can identify unsuspected spinal cord compression from myeloma (distinct from spondylotic myelopathy), which would require urgent intervention 1
3. Assessment of bone marrow involvement: MRI reveals focal, diffuse, or variegated patterns of marrow infiltration that are not visible on plain radiographs 1
4. Soft tissue evaluation: MRI detects extramedullary plasmacytomas arising from bone lesions 1

Important distinction: While the ESMO guidelines state MRI is "optional" for general myeloma diagnosis, they explicitly recommend MRI when spinal cord compression is suspected—which is a legitimate concern in any patient with pre-existing cervical spine disease. 1

Additional Imaging Considerations

• PET/CT scan may help distinguish between active myeloma and smoldering disease, and can refine staging beyond what skeletal survey provides 1

Diagnostic Confirmation

The diagnosis requires:

• ≥10% clonal plasma cells in bone marrow (confirmed by CD138 staining and immunoperoxidase/immunofluorescence for monoclonal immunoglobulin) 1
• Monoclonal protein detected in serum or urine by electrophoresis and immunofixation 1
• Evidence of end-organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions) or biomarkers of malignancy 3

Staging and Prognostic Assessment

Once diagnosis is confirmed:

• Revised International Staging System combines beta-2 microglobulin, albumin, LDH, and high-risk cytogenetic features [del(17p), t(4;14), t(14;16)] to stratify patients 2, 3
• Stage I patients (28% at diagnosis) have a median 5-year survival of 82% 3

Critical Pitfalls in This Clinical Scenario

1. Do not attribute all cervical spine abnormalities to pre-existing spondylosis without MRI confirmation—new lytic lesions or pathologic fractures may be myelomatous 1
2. Do not rely solely on skeletal survey in patients with known degenerative spine disease, as it has limited sensitivity for early marrow involvement 1
3. Do not use random urine samples instead of 24-hour collections, as this will miss light chain disease 1, 4
4. Do not skip serum free light chain testing even if SPEP shows a monoclonal protein, as FLC ratio provides additional prognostic information 1, 2

Referral and Next Steps

Once the workup confirms multiple myeloma:

• Immediate referral to hematology/oncology for treatment planning, including assessment for autologous stem cell transplantation eligibility 5
• Neurosurgical consultation if MRI reveals spinal cord compression requiring decompression (this would be urgent/emergent) 1
• Orthopedic oncology evaluation if pathologic fractures or impending fractures are identified on imaging 1

Standard first-line therapy consists of a proteasome inhibitor (bortezomib), immunomodulatory agent (lenalidomide), and dexamethasone, with median progression-free survival of 41 months. 3