What are the common lab abnormalities associated with multiple myeloma?

Laboratory Abnormalities of Multiple Myeloma

Multiple myeloma presents with a characteristic constellation of laboratory abnormalities including anemia, elevated serum protein with monoclonal paraprotein, hypercalcemia, renal dysfunction, and elevated beta-2 microglobulin, which together form the diagnostic and prognostic foundation for this disease. 1

Hematologic Abnormalities

Anemia

• Anemia is present in approximately 73% of patients at diagnosis, typically defined as hemoglobin <10 g/dL or >2 g/dL below normal 1, 2
• The anemia is characteristically normocytic normochromic in most cases 3
• Complete blood count with differential and peripheral blood smear evaluation is essential for initial assessment 1

Other Blood Cell Abnormalities

• Lymphopenia occurs in 94% of patients, with Grade 3-4 severity in 71% 4
• Neutropenia is present in 60% of patients, with Grade 3-4 severity in 20% 4
• Thrombocytopenia affects 48-75% of patients, with Grade 3-4 severity in 10-20% 4
• Elevated erythrocyte sedimentation rate (ESR) is seen in 65.3% of cases 3
• Increased neutrophil-to-lymphocyte ratio occurs in approximately 30% of patients 3

Protein Abnormalities

Monoclonal Protein (M-Protein)

• Serum protein electrophoresis (SPEP) reveals a localized monoclonal band in 70.8% of patients 3
• Of those with M-bands, 78% migrate to the γ-region and 18% to the β-region of the electrophoretogram 3
• Serum immunofixation electrophoresis (SIFE) provides specific identification of the abnormal antibody type 5
• IgG is the most common paraprotein type, followed by IgA, then light chain only 3

Serum Free Light Chains

• The serum free light chain (FLC) assay is essential for diagnosis and has high sensitivity when combined with SPEP and SIFE 5
• An abnormal FLC ratio has prognostic value and is required for documenting stringent complete response 5
• The FLC assay allows quantitative monitoring in light chain myeloma and oligosecretory disease 5

Immunoglobulin Abnormalities

• Hypogammaglobulinemia is detected in 32.8% of patients 3
• Hypergammaglobulinemia occurs in 49.2% of patients, with 18.1% showing polyclonal patterns 3
• Quantitative immunoglobulin levels are crucial for baseline assessment 1

Urine Protein Abnormalities

• Bence Jones protein is positive in 50% of cases 3
• 20% of patients have measurable urinary M-proteins requiring 24-hour urine collection 5
• 24-hour urine protein electrophoresis (UPEP) and urine immunofixation electrophoresis (UIFE) are necessary for complete assessment 1
• 3% of patients have nonsecretory myeloma with neither serum nor urine M-proteins 5

Chemistry Abnormalities

Calcium

• Hypercalcemia occurs in 11.3% of patients at presentation 3
• Serum calcium measurement is a critical component of the initial diagnostic workup 1

Renal Function

• Serum creatinine >2.0 mg/dL is present in 27.2% of cases at diagnosis 3
• Approximately 19% of patients have acute kidney injury at presentation 2
• Renal dysfunction can be multifactorial, related to hyperuricemia, hypercalcemia, or elevated neutrophil-to-lymphocyte ratio 3
• Renal impairment can artificially elevate beta-2 microglobulin levels independent of tumor burden 6

Albumin

• Low albumin/globulin (A/G) ratio is present in 54.2% of patients 3
• Serum albumin is incorporated into the Revised International Staging System for prognostication 2
• The presence of high ESR and low A/G ratio in elderly patients should prompt investigation for multiple myeloma 3

Other Chemistry Parameters

• Hyperproteinemia occurs in 30% of patients 3
• Lactate dehydrogenase (LDH) measurement provides prognostic information and is part of the Revised International Staging System 5, 2

Prognostic Markers

Beta-2 Microglobulin

• Beta-2 microglobulin is elevated in 67% of patients and represents one of the most important prognostic parameters 6, 3
• It is a standard measure of tumor burden in multiple myeloma 6
• Higher levels (>5.5 mg/L) are associated with advanced disease and poorer survival outcomes 6
• Beta-2 microglobulin combined with serum albumin forms the International Staging System prognostic index 6

Bone Marrow Findings

Plasma Cell Infiltration

• Diagnosis requires ≥10% clonal plasma cells in bone marrow 1
• Bone marrow aspiration and biopsy are essential for quantitative and qualitative assessment 5
• CD138 staining and immunohistochemistry/flow cytometry establish clonality by demonstrating predominance of either kappa or lambda light chains 5

Cytogenetic Abnormalities

• FISH panel should examine for del(17p), t(4;14), t(14;16), t(14;20), del(13q), t(11;14), 1q21 gain/amplification, and 1p deletion 5
• Deletion of 17p13 (p53 locus) is a high-risk feature 5
• t(4;14), t(14;16), and t(14;20) confer poor prognosis 5
• Gains/amplification of 1q21 and 1p deletion increase progression risk 5
• del(13q) on metaphase cytogenetics (not FISH alone) is a negative prognostic factor 5

Clinical Pitfalls

• Absence of paraprotein in blood does not exclude multiple myeloma—always check urine studies and consider serum FLC assay for nonsecretory disease 3
• Light chain multiple myeloma patients may have high α2 globulin concentration and normal A/G ratio, potentially masking the diagnosis 3
• The serum FLC assay cannot replace 24-hour urine protein electrophoresis for monitoring patients with measurable urinary M-proteins 5
• Renal dysfunction can artificially elevate beta-2 microglobulin independent of tumor burden 6
• Use the same test (SPEP or quantitative immunoglobulins) for serial monitoring to ensure accurate relative quantification 5