What tests should be ordered for a suspected myeloma workup in an orthopedic outpatient department (OPD)?

Myeloma Workup in Orthopedic OPD

When evaluating a patient with suspected myeloma in the orthopedic outpatient setting, order a comprehensive laboratory panel including complete blood count, chemistry screen with calcium and creatinine, serum protein electrophoresis with immunofixation, serum free light chains, 24-hour urine collection for protein electrophoresis and immunofixation, and arrange for bone marrow biopsy with cytogenetics, along with skeletal imaging. 1, 2

Essential Laboratory Tests

Blood Tests - First Priority

• Complete blood count with differential to assess for anemia (hemoglobin <10 g/dL or ≥2 g/dL below normal), which occurs in approximately 73% of myeloma patients at presentation 1, 2, 3
• Chemistry screen including:
  • Serum calcium (≥11.5 mg/dL indicates hypercalcemia) 1, 2
  • Serum creatinine (≥2 mg/dL indicates renal insufficiency) 1, 2
  • Serum albumin for prognostic staging 1, 2
  • Lactate dehydrogenase (LDH) for prognosis 1, 2
  • Serum beta-2 microglobulin for staging 1, 2

Protein Studies - Critical for Diagnosis

• Serum protein electrophoresis (SPEP) with immunofixation to detect and quantify monoclonal protein 1, 4, 2
• Nephelometric quantification of serum immunoglobulins (IgG, IgA, IgM) - these two methods are complementary and both should be performed 1
• Serum free light chain assay to screen for myeloma and monitor disease, particularly important in nonsecretory cases 1, 2

Urine Studies - Cannot Be Omitted

• 24-hour urine collection for total protein, electrophoresis, and immunofixation - this is mandatory as relying solely on serum testing misses 20% of patients with secretory urinary proteins only 1, 4, 2
• A random urine sample cannot replace the 24-hour collection 1, 2

Bone Marrow Evaluation

• Unilateral bone marrow aspirate and/or biopsy to confirm ≥10% clonal plasma cells required for diagnosis 1, 2
• Cytogenetics including:
  • Standard metaphase karyotype 1, 2
  • FISH studies with probes for chromosome 17p13, t(4;14), and t(14;16) for prognostic information 1, 2

Imaging Studies - Orthopedic Focus

• Skeletal survey including spine, pelvis, skull, humeri, and femurs to detect lytic lesions, severe osteopenia, or pathologic fractures, which occur in approximately 79% of patients at presentation 1, 2, 3
• MRI of spine and pelvis is mandatory if solitary plasmacytoma is suspected, and should be considered in smoldering myeloma to detect occult lesions 1
• CT or PET/CT may be performed as clinically indicated for better detection of bone lesions 2, 3

Critical Pitfalls in Orthopedic Setting

Warning Signs That Should Trigger Myeloma Workup

• Back pain independent of movement (occurs in 85% of myeloma patients with skeletal involvement) 5
• Night pain (present in 69% of cases) 5
• Pain at multiple skeletal locations (30% of patients) 5
• Substantial change in pain characteristics in patients with preexisting skeletal disease (63% of cases) 5
• Back pain is the most frequent complaint (81%), mainly thoracic and/or lumbar 5

Common Diagnostic Errors to Avoid

• Do not skip the 24-hour urine collection - approximately 20% of patients have urinary-only monoclonal proteins that would be missed by serum testing alone 4
• Do not perform urine-free light chain assay - this test is not recommended 1, 2
• Ensure adequate urine concentration - incomplete collection and inadequate concentration lead to false negatives 4
• Be aware that approximately 3% of patients have nonsecretory myeloma with neither serum nor urine proteins, making serum free light chains essential 2

Timing Considerations

• Median time to diagnosis in orthopedic patients is 7 months, highlighting the importance of early recognition 5
• Consider MM as a differential diagnosis whenever warning signs are present, particularly skeletal pain independent from movement, at night, at various locations, accompanied by fatigue 5