When should myeloma be suspected in a patient?

When to Suspect Multiple Myeloma

Multiple myeloma should be suspected in patients with unexplained anemia, renal failure, hypercalcemia, or bone pain/lesions (CRAB features), especially in those over 60 years of age with elevated ESR, low albumin/globulin ratio, or unexplained back pain. 1, 2

Clinical Presentations That Should Trigger Suspicion

Key Clinical Features

• Bone pain: Particularly back pain or pathologic fractures
• Recurrent infections: Due to immune dysfunction
• Fatigue and weakness: Related to anemia
• Renal impairment: Often presenting as elevated creatinine
• Neurological symptoms: Including spinal cord compression

Laboratory Abnormalities That Should Raise Suspicion

• Complete blood count:

  • Anemia (present in approximately 50% of cases) 3
  • Elevated ESR (seen in 65.3% of cases) 3
  • Increased neutrophil-to-lymphocyte ratio (29.7% of cases) 3

• Blood chemistry:

  • Hypercalcemia (>11.5 mg/dL) 1
  • Elevated creatinine (>2 mg/dL) 1, 3
  • Hyperproteinemia (30% of cases) 3
  • Low albumin/globulin ratio (54.2% of cases) 3
  • Elevated β2-microglobulin (67% of cases) 3

High-Risk Populations

• Age: Most common in those over 60 years (mean age 61) 3
• Previous conditions:
  • Monoclonal gammopathy of undetermined significance (MGUS)
  • Smoldering multiple myeloma
• Family history: First-degree relatives of patients with multiple myeloma

Diagnostic Algorithm

Step 1: Initial Screening Tests

When multiple myeloma is suspected, order:

• Complete blood count with differential
• Comprehensive metabolic panel (including calcium, creatinine)
• Serum protein electrophoresis (SPEP) and immunofixation (SIFE)
• Quantitative immunoglobulins (IgG, IgA, IgM)
• Serum free light chain assay
• 24-hour urine for total protein, urine protein electrophoresis (UPEP), and urine immunofixation (UIFE) 1, 2

Step 2: Imaging

• Skeletal survey (plain radiographs including chest, spine, skull, humeri, femora, and pelvis)
• Consider advanced imaging:
  • MRI of spine and pelvis (especially if suspecting solitary plasmacytoma)
  • CT scan (particularly valuable when radiographs are normal or nonspecific but bone pain is present) 1, 4

Step 3: Confirmatory Testing

If initial tests suggest myeloma:

• Bone marrow aspiration and biopsy (diagnosis confirmed with ≥10% clonal plasma cells) 1, 2, 5
• Cytogenetic studies including FISH for high-risk features (del(17p), t(4;14), t(14;16)) 1, 5

Diagnostic Criteria

Multiple myeloma is diagnosed when there are:

1. ≥10% clonal plasma cells in bone marrow or biopsy-proven plasmacytoma, AND
2. One or more myeloma defining events:
   • CRAB features (hypercalcemia, renal failure, anemia, bone lesions)
   • Bone marrow clonal plasmacytosis ≥60%
   • Serum involved/uninvolved free light chain ratio ≥100 (provided involved FLC is ≥100 mg/L)

   • 1 focal lesion on MRI 6, 5

Common Pitfalls to Avoid

• Overlooking myeloma in elderly patients with back pain: Back pain is common in older adults but can be the first sign of myeloma
• Attributing anemia to other causes: Normocytic normochromic anemia is common in myeloma 3
• Missing non-secretory myeloma: Absence of paraprotein does not exclude myeloma (occurs in ~1% of cases) 3
• Delayed diagnosis: Myeloma has one of the longest diagnostic delays among cancers due to non-specific symptoms 7
• Incomplete laboratory workup: Both serum and urine studies are necessary, as some patients may only have light chain disease detectable in urine 1

Key Points for Earlier Detection

• Consider myeloma in patients over 60 with unexplained anemia, renal dysfunction, or bone pain
• The combination of high ESR, anemia, and low albumin/globulin ratio should prompt investigation for myeloma 3
• Utilize both serum and urine protein studies, as relying on serum studies alone may miss light chain myeloma
• When clinical suspicion is high but radiographs are normal, consider advanced imaging such as CT or MRI 4

By maintaining a high index of suspicion in patients with these features, clinicians can help reduce the often significant delay in diagnosing multiple myeloma, potentially improving outcomes through earlier intervention.