Multiple myeloma differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2] Haytham Allaham, M.D. [3] Shyam Patel [4]

Overview

Multiple myeloma must be differentiated from other causes of bone lesions such as osteoporosis, osteomalacia, scurvy, osteogenesis imperfecta, and homocystinuria. Each condition has unique causes, features, and treatment.

Differentiating Multiple Myeloma from other Diseases

• The table below summarizes how to differentiate multiple myeloma from other conditions that have a similar presentation:

Differential Diagnosis	Causes	Features	Therapy
Multiple myeloma	Chromosomal aberrations or other genetic insults Malignant transformation of plasma cells Clonal plasma cell proliferation	Diffuse bone pain and tenderness with osteolytic lesions Renal failure Hypercalcemia Anemia	Induction chemotherapy with bortezomib, lenalidomide, and dexamethasone Bisphosphonates RANK ligand inhibitors (denosumab) Autologous stem cell transplantation
Monoclonal gammopathy of undetermined significance (MGUS)	Chromosomal aberrations or other genetic insults Clonal plasma cell proliferation	Asymptomatic Serum M protein of <30 g/L Fewer than 10% plasma cells in the bone marrow No evidence of bone or organ damage	Observation
Asymptomatic Plasma Cell Myeloma (Smoldering and Indolent plasma cell myeloma)	Chromosomal aberrations or other genetic insults Malignant transformation of plasma cells Clonal plasma cell proliferation	Asymptomatic Serum M protein of >30 g/L Greater than 10% plasma cells in the bone marrow No evidence of bone or organ damage	Observation
Plasma Cell Leukemia	Chromosomal aberrations or other genetic insults Malignant transformation of plasma cells	Renal failure Hypercalcemia Cytopenias No bone lesions	Chemotherapy
Plasmacytoma	Chromosomal aberrations or other genetic insults Malignant transformation of plasma cells	Solitary bone plasmacytoma (bone) Extramedullary plasmacytoma (soft tissues) Clinical manifestations related to tumor mass and compression symptoms	Surgery
Osteoporosis	Imbalance between bone resorption and bone formation Preceded by osteopenia Decreased bone mineral density	Acute musculoskletal pain if fractures develop Severe decrease in BMD on dual-energy X-ray absorptiometry (DEXA) test T score less than -2.5 on DEXA scan	Calcium and vitamin D supplementation Bisphosphonates Weight-bearing exercise Teriparatide RANK ligand inhibitors (denosumab)
Osteomalacia	Inadequate mineralization of bone Deficiency of vitamin D calcium, or phosphorus Renal tubular acidosis Malabsorption	Diffuse bone pain, fatigue, and fractures Low bone mineral density (BMD) Hypocalcemia	Vitamin D3 supplementation
Scurvy	Vitamin C deficiency Malabsorption Hemodialysis	Gum disease such as gum bleeding Loose teeth Easy bruising Impaired immune response Impaired wound healing	Vitamin C supplementation Citrus fruits
Osteogenesis imperfecta	Mutations in COL1A1 or COL1A2 Impaired type I collagen synthesis	Short stature, scoliosis, and propensity for fractures Blue discoloration of sclera	Bisphosphonates Physical therapy Surgical fixation of brittle bones Genetic counseling for offspring
Homocystinuria	Deficiency of cystathionine beta synthase Deficiency of folate, vitamin B12, or vitamin B6	Diffuse bone pain and musculoskeletal symptoms	High-dose vitamin B6 supplementation Betaine supplementation