How to differentiate bone lesions between multiple myeloma and hyperparathyroidism?

Differentiating Bone Lesions: Multiple Myeloma vs Hyperparathyroidism

The key distinction is that multiple myeloma produces focal "punched-out" lytic lesions with suppressed parathyroid hormone (PTH) and elevated monoclonal protein, while hyperparathyroidism causes diffuse osteopenia/brown tumors with elevated PTH and normal protein electrophoresis. 1, 2, 3

Imaging Characteristics

Multiple Myeloma Bone Lesions

• Focal lytic "punched-out" lesions appear on skeletal survey, particularly in skull, spine, ribs, and pelvis with asymmetric distribution 3
• Whole-body low-dose CT or FDG-PET/CT detects 25.5% more lesions than plain radiographs and is now preferred over skeletal survey 3
• MRI shows focal or diffuse marrow replacement patterns 3
• Lesions appear as FDG-avid on PET/CT imaging 3

Hyperparathyroidism Bone Lesions

• Diffuse decreased bone density (osteopenia/osteoporosis) on DEXA scan with thinned cortices and decreased trabecular bone 3, 4
• Brown tumors (when present) appear as well-defined osteolytic lesions but represent only 3% of primary hyperparathyroidism cases 4
• No focal marrow abnormalities on MRI 3

Laboratory Algorithm for Differentiation

Initial Laboratory Screen (Order Simultaneously)

• Serum protein electrophoresis with immunofixation - positive M-protein indicates myeloma, absent in hyperparathyroidism 2, 3
• Serum free light chain assay with kappa/lambda ratio - abnormal ratio suggests myeloma 2, 3
• Intact parathyroid hormone (PTH) - elevated in hyperparathyroidism, suppressed or normal in myeloma 1, 5, 4
• Serum calcium and phosphate - both conditions cause hypercalcemia, but hypophosphatemia strongly suggests hyperparathyroidism 5, 4
• Complete blood count - anemia (hemoglobin <10 g/dL) present in 73% of myeloma cases, typically absent in hyperparathyroidism 2, 6
• Serum creatinine - renal insufficiency (>2 mg/dL) occurs in 19% of myeloma at diagnosis 2, 6

Diagnostic Pattern Recognition

Multiple Myeloma Pattern:

• M-protein present on electrophoresis 2
• Abnormal free light chain ratio 2
• PTH suppressed or inappropriately normal despite hypercalcemia 1, 5
• Anemia and/or renal dysfunction present 2, 6
• Elevated total protein with decreased albumin-to-globulin ratio 3

Hyperparathyroidism Pattern:

• No M-protein on electrophoresis 4
• Normal free light chain ratio 4
• PTH elevated (often >100 pg/mL, can exceed 1000 pg/mL) 4
• Hypophosphatemia (<2.5 mg/dL) 5, 4
• No anemia or renal dysfunction (unless severe chronic disease) 4

Confirmatory Testing

If Myeloma Pattern Identified

• Bone marrow aspiration and biopsy showing ≥10% clonal plasma cells with CD138 staining confirms diagnosis 2, 3
• Cytogenetic/FISH studies for risk stratification (del(17p), t(4;14), t(14;16)) 2
• 24-hour urine collection for Bence Jones protein 2, 3

If Hyperparathyroidism Pattern Identified

• Parathyroid imaging with technetium-99m sestamibi scintigraphy to localize adenoma 4
• Neck ultrasound and/or CT to identify parathyroid mass 4
• 25-hydroxyvitamin D level (often low in primary hyperparathyroidism) 4

Critical Diagnostic Pitfalls

Coexistence of Both Conditions

• Both diseases can occur simultaneously in the same patient, though rare 5, 7
• If hypercalcemia is refractory to bisphosphonates in confirmed myeloma, always measure PTH to exclude concurrent hyperparathyroidism 5, 7
• The presence of hypophosphatemia in a myeloma patient should trigger PTH measurement 5
• Approximately 20 case reports document this dual diagnosis, suggesting systematic evaluation with both PTH and protein electrophoresis in all hypercalcemia cases 5

Distinguishing from Severe Osteoporosis

• Do not confuse severe osteoporosis with myeloma - always check M-protein before assuming osteoporosis in patients with multiple vertebral fractures 3
• Progressive osteoporosis with long-standing history suggests benign disease, while sudden onset indicates active myeloma 1
• Osteoporosis lacks systemic symptoms (no anemia, renal dysfunction, or hypercalcemia) 3

Age and Clinical Context

• Mild, stable hypercalcemia without lytic lesions suggests hyperparathyroidism over myeloma 1
• Multiple myeloma typically presents with bone pain worsening at night or with movement 3
• Median age for myeloma diagnosis is 65-70 years, with 85% of patients >65 years 6

Management Implications

• Hyperparathyroidism requires surgical parathyroidectomy for definitive treatment, with medical management (cinacalcet, bisphosphonates) reserved for high surgical risk patients 7, 4
• Multiple myeloma requires systemic chemotherapy when CRAB criteria are met (hypercalcemia, renal insufficiency, anemia, bone lesions) 2
• Brown tumors from hyperparathyroidism resolve after parathyroidectomy without orthopedic intervention, avoiding unnecessary bone surgery 4