What is the appropriate workup for a patient with back pain found to have multiple lytic bone lesions on CT?

Workup for Multiple Lytic Bone Lesions on CT

Obtain whole-body low-dose CT as the preferred imaging modality, followed by serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), serum free light chains, complete blood count, comprehensive metabolic panel including calcium and creatinine, and bone marrow biopsy to establish diagnosis 1, 2.

Initial Laboratory Evaluation

The laboratory workup must prioritize identifying multiple myeloma, which is the most common cause of multiple lytic bone lesions in adults:

• Serum protein electrophoresis (SPEP) with immunofixation
• Urine protein electrophoresis (UPEP) with immunofixation (24-hour collection)
• Serum free light chain assay - critical as some patients have light chain-only disease
• Complete blood count - assess for anemia, thrombocytopenia
• Comprehensive metabolic panel - evaluate calcium (hypercalcemia common), creatinine (renal involvement), albumin
• Lactate dehydrogenase (LDH) and beta-2 microglobulin - prognostic markers

Important Caveat

Be aware that negative SPEP/UPEP does not exclude plasma cell dyscrasia - approximately 2-3% of myeloma cases are truly non-secretory, and serum free light chains may be the only abnormality 3. If clinical suspicion remains high despite negative initial screening, proceed directly to bone marrow biopsy.

Advanced Imaging Strategy

Whole-body low-dose CT is superior to traditional skeletal survey and should be the standard imaging approach 1, 2. The guidelines are clear on this hierarchy:

• Whole-body low-dose CT detects 25.5% more lesions than skeletal survey and identifies up to 60% more relevant findings, leading to treatment changes in 20% of patients 2
• FDG-PET/CT is an acceptable alternative and particularly useful for:
  • Evaluating extramedullary disease
  • Assessing non-secretory or oligosecretory disease
  • Risk-stratifying equivocal lesions
  • Note: The CT component must be diagnostic quality, not just for attenuation correction 2
• MRI has equivalent sensitivity to PET/CT for spine and pelvis, useful for detecting marrow infiltration 1

Imaging Pitfall

Plain radiographs require 30% trabecular bone loss before lytic lesions become visible 4. Do not rely on skeletal survey alone - it will miss early disease and underestimate disease burden.

Tissue Diagnosis

Bone marrow biopsy with aspirate is essential for definitive diagnosis and should include:

• Morphologic assessment for plasma cells (≥10% defines myeloma)
• Flow cytometry for clonality
• Cytogenetics and FISH panel for risk stratification (del 17p, t(4;14), t(14;16), gain 1q, del 13)
• Consider CT-guided biopsy of an accessible lytic lesion if bone marrow is non-diagnostic, though be aware that sclerotic lesions have a 24% false-negative rate 5

Differential Diagnosis Considerations

While multiple myeloma is most likely, the workup must exclude:

• Metastatic carcinoma - check PSA (men), mammography (women), chest CT for lung primary
• Lymphoma - particularly diffuse large B-cell lymphoma can present with lytic lesions and hypercalcemia 6
• Hyperparathyroidism - check intact PTH; brown tumors can mimic malignancy 7
• Sarcoidosis - rare but can present with multiple lytic lesions; consider if ACE level elevated and biopsy shows non-caseating granulomas 8, 9

Critical Clinical Point

If imaging suggests malignancy but myeloma screening is negative and bone marrow biopsy is non-diagnostic, obtain tissue biopsy of an accessible lesion 10, 3. Multiple case reports demonstrate that atypical presentations of benign conditions (sarcoidosis, hyperparathyroidism) can masquerade as metastatic disease.

Algorithmic Approach

1. Immediate labs: SPEP/UPEP, serum free light chains, CBC, CMP with calcium
2. Imaging: Whole-body low-dose CT (if not already done) or FDG-PET/CT
3. If myeloma screening positive: Bone marrow biopsy with cytogenetics
4. If myeloma screening negative:
   • Check PTH, consider age-appropriate cancer screening
   • Proceed to bone marrow biopsy if high clinical suspicion
   • If bone marrow negative, obtain CT-guided biopsy of accessible lesion
5. Assess for complications: Spinal cord compression (MRI if neurologic symptoms), pathologic fracture risk, renal function

The key is not to delay tissue diagnosis when imaging and laboratory studies are discordant - atypical presentations are well-documented and require histologic confirmation before initiating therapy 3, 6.