Diagnosing Multiple Myeloma: Key Tests and Clinical Evaluations
Multiple myeloma is a complex blood cancer that affects plasma cells in the bone marrow. Early and accurate diagnosis is crucial for effective treatment planning and improved patient outcomes. Because symptoms can be subtle or mimic other conditions, a comprehensive diagnostic approach combining clinical evaluation, laboratory tests, and advanced imaging is essential.
Recognizing Common Clinical Symptoms
Most patients with multiple myeloma initially present with a range of systemic symptoms. Bone pain—particularly in the back or ribs—is one of the most frequent complaints, often worsening with movement or at night. This results from the infiltration of malignant plasma cells into the bone marrow, leading to lytic lesions and increased fracture risk.
Fatigue and weakness are also prevalent, primarily due to anemia caused by impaired red blood cell production. In more advanced cases, patients may develop signs of kidney dysfunction, including proteinuria (excess protein in urine) or hematuria (blood in urine). Some individuals progress to renal failure or even end-stage renal disease requiring dialysis.
Essential Laboratory Blood and Urine Tests
Blood tests play a foundational role in identifying abnormalities associated with multiple myeloma. A complete blood count (CBC) typically reveals normocytic, normochromic anemia. While white blood cell and platelet counts may remain normal early in the disease, they often decline as the condition progresses.
Serum protein electrophoresis (SPEP) and immunofixation electrophoresis are critical for detecting monoclonal (M) proteins—abnormal antibodies produced by cancerous plasma cells. These tests help classify the subtype of myeloma, such as IgG, IgA, light chain-only, or non-secretory types.
Additional key biomarkers include:
- Serum free light chains (kappa and lambda)
- Quantitative immunoglobulins (IgG, IgA, IgM)
- Beta-2 microglobulin (β2-M), which correlates with tumor burden and prognosis
- Lactate dehydrogenase (LDH), an indicator of disease aggressiveness
Urine protein electrophoresis (UPEP) and 24-hour urine collection for Bence Jones proteins (free light chains) further support diagnosis, especially in light-chain myeloma.
Imaging Techniques to Detect Bone and Extramedullary Involvement
Imaging studies are vital for assessing the extent of skeletal damage and guiding staging. The choice of modality depends on the suspected location and severity of disease.
Conventional X-ray surveys (skeletal survey) are often used initially to detect osteolytic lesions, especially in the skull, pelvis, spine, and long bones. However, they may miss early or small lesions.
Magnetic resonance imaging (MRI) is highly sensitive for evaluating spinal involvement and detecting marrow infiltration before bone destruction becomes visible on X-rays. It's particularly useful when neurological symptoms suggest spinal cord compression.
PET-CT scans offer a powerful advantage: They combine metabolic and structural imaging to identify active myeloma sites throughout the body, including extramedullary plasmacytomas—tumors outside the bone marrow. PET-CT is also valuable for monitoring treatment response and detecting relapse.
Confirming Diagnosis with Bone Marrow Examination
A bone marrow aspiration and biopsy remain the gold standard for confirming multiple myeloma. The procedure assesses the percentage of plasma cells in the marrow. According to diagnostic criteria, the presence of clonal plasma cells exceeding 10% is considered significant.
Flow cytometry is then used to characterize these cells immunophenotypically, distinguishing malignant plasma cells from reactive ones. Cytogenetic analysis and fluorescence in situ hybridization (FISH) may also be performed to detect high-risk genetic abnormalities such as del(17p), t(4;14), or 1q amplification, which influence prognosis and treatment choices.
Comprehensive Evaluation for Staging and Prognosis
Once initial tests confirm the diagnosis, clinicians integrate findings to stage the disease using systems like the International Staging System (ISS) or Revised ISS (R-ISS). This helps predict survival and tailor therapy accordingly.
Early and thorough assessment—including symptom review, lab testing, imaging, and bone marrow analysis—enables precise diagnosis, accurate risk stratification, and personalized treatment strategies, ultimately improving long-term outcomes for patients with multiple myeloma.