What is the next step in evaluating lytic bony lesions to rule out multiple myeloma, sarcoidosis, and ankylosing spondylitis?

Comprehensive Evaluation of Lytic Bone Lesions to Rule Out Multiple Myeloma and Other Conditions

The next step in evaluating lytic bone lesions should be a combination of bone marrow assessment with aspiration and biopsy, along with whole-body low-dose CT imaging. 1, 2

Initial Diagnostic Workup

Bone Marrow Assessment

• Bone marrow aspiration and biopsy are essential first-line tests for all patients with suspected lytic bone lesions 1
  • Evaluate plasma cell morphology and quantify total plasma cell infiltration
  • Determine clonal plasma cell infiltration using flow cytometry or kappa/lambda labeling
  • Assess for >10% bone marrow plasma cells (which would support MM diagnosis)
  • Perform cytogenetic/FISH studies to identify prognostic abnormalities (del(13), t(4;14), del(17p)) 1

Advanced Imaging

• Whole-body low-dose CT (WBLDCT) is the preferred imaging method 2

  • Can detect lesions when only 30% of trabecular bone is lost (vs. 50% for conventional X-rays)
  • Provides high-resolution images of cortical and trabecular bone
  • Can detect small (<5mm) lytic lesions 1
  • Significantly impacts disease staging and treatment decisions

• MRI should be performed if WBLDCT shows no definitive lesions but clinical suspicion remains high 2

  • Gold standard for detecting bone marrow involvement and spinal cord compression
  • Superior for detecting infiltrative patterns in the spine that may be missed on CT 3
  • Particularly valuable for evaluating the spine and pelvis

Laboratory Evaluation

Monoclonal Protein Assessment

• Serum protein electrophoresis and immunofixation
• Quantification of immunoglobulins (IgG, IgA, IgM)
• 24-hour urine protein electrophoresis and immunofixation
• Serum free light chain assay 1

Additional Laboratory Tests

• Complete blood count with differential
• Serum calcium and creatinine levels
• Beta-2 microglobulin and albumin (for staging if MM is confirmed) 1

Differential Diagnosis Considerations

Multiple Myeloma

• Diagnostic criteria include ≥10% clonal plasma cells on bone marrow examination or biopsy-proven plasmacytoma, plus evidence of end-organ damage (CRAB criteria: hypercalcemia, renal insufficiency, anemia, or bone lesions) 1

Smoldering Multiple Myeloma

• ≥3 g/dL serum monoclonal protein and/or ≥10% clonal bone marrow plasma cells without end-organ damage 1
• Progresses to symptomatic MM at a rate of 10% per year over the first 5 years 1

Sarcoidosis with Bone Involvement

• Consider this diagnosis particularly if there is evidence of pulmonary involvement
• Bone marrow biopsy may show noncaseating granulomas 4
• Note that sarcoidosis and multiple myeloma can coexist, with sarcoidosis typically preceding MM development 4

Ankylosing Spondylitis

• Primarily affects the spine and sacroiliac joints
• MRI is particularly useful for detecting early inflammatory changes

Important Considerations and Pitfalls

• Do not rely solely on conventional radiography as it can miss significant bone disease, potentially delaying appropriate treatment 2
• Flow cytometry on bone marrow samples can detect minimal residual disease and has prognostic significance - patients with aberrant plasma cells by flow cytometry have higher risk of progression to symptomatic MM 1
• PET/CT may be valuable in selected cases to evaluate treatment response and detect extramedullary disease 2, 3
• Consider that multiple myeloma bone disease differs from other metastatic bone lesions - MM shows increased osteoclastic bone destruction with suppressed osteoblast activity 5, 6

By following this systematic approach to evaluating lytic bone lesions, you can efficiently rule out or confirm multiple myeloma and other conditions, leading to appropriate management decisions based on the definitive diagnosis.