Multiple myeloma differential diagnosis

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

Overview

Multiple myeloma must be differentiated from monoclonal gammopathy of undetermined significance (MGUS), isolated plasmacytoma of the bone, and extramedullary plasmacytoma.

Differentiating Multiple Myeloma from other Diseases

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

Plasma Cell Neoplasm	M Protein Type	Pathology	Clinical Presentation
MGUS	IgG kappa or lambda; or IgA kappa or lambda	<10% plasma cells in bone marrow	Asymptomatic, with minimal evidence of disease (aside from the presence of an M protein)
Isolated plasmacytoma of bone	IgG kappa or lambda; or IgA kappa or gamma	Solitary lesion of bone; <10% plasma cells in marrow of uninvolved site	Asymptomatic or symptomatic
Extramedullary plasmacytoma	IgG kappa or lambda; or IgA kappa or gamma	Solitary lesion of soft tissue in the nasopharynx, tonsils, or sinuses	Asymptomatic or symptomatic
Multiple myeloma	IgG kappa or lambda; or IgA kappa or gamma	Often multiple lesions of bone	Symptomatic

• Another important differential diagnosis is that of widespread bony metastases. Findings that favor the diagnosis of bony metastases over that of multiple myeloma include:

• Bone metastases more commonly affect the vertebral pedicles rather than vertebral bodies.
• Bone metastases rarely involve mandible and distal axial skeleton.
• Although both entities have variable bone scan appearances (both hot and cold) unlike multiple myeloma, extensive bony metastases rarely have a normal appearance.

• Multiple myeloma must also be differentiated from other causes of bone pain and fatigue such as:

• Waldenstrom Hypergammaglobulinemia
• Bone fracture
• Fibrous dysplasia
• Enchondroma
• Eosinophilic granuloma
• Giant cell tumor
• Osteoblastoma
• Aneurysmal bone cyst
• Solitary bone cyst
• Hyperparathyroidism
• Infection
• Chondroblastoma
• Chondromyxoid Fibroma
• Reactive plasmacytosis
• Macroglobulinemia
• Osteoporosis (osteoporotic fracture)

Multiple myeloma must be differentiated from other diseases that cause decreasing in bone mineral density (BMD), such as idiopathic transient osteoporosis of hip, osteomalacia, scurvy, osteogenesis imperfecta, homocystinuria, and hypermetabolic resorptive osteoporosis.

Differential Diagnosis Similar Features Differentiating Features Osteoporosis On physical examination, demonstrates acute musculoskletal pain, if fracture happened On imaging studies, demonstrates severe decrease in BMD - Idiopathic transient osteoporosis of hip On physical examination, demonstrates acute hip pain On imaging studies, demonstrates sub-chondoral cortical loss and diffuse osteopenia of the femoral neck On history, demonstrates mostly involvement of pregnant women and young men On history, demonstrates to be self-limiting in 6-8 months Osteomalacia On physical examination, demonstrates diffuse bone pain, fatigue, and fractures are the common symptoms On imaging studies, demonstrates low bone mineral density (BMD) On imaging studies, demonstrate the brief bone mass loss in bones Scurvy On physical examination, demonstrates bone pain and frequent fractures due to brittle bone On imaging studies, demonstrates low bone mineral density (BMD) On physical examination, demonstrates other mucosal disruption symptoms, such as bleeding gums On imaging studies, demonstrates normal bone mineral density (BMD) Osteogenesis imperfecta On physical examination, demonstrates Short stature, scoliosis, and propensity for fractures On physical examination, demonstrates tooth defects, hearing defects, and blue sclera On laboratory studies, demonstrates near normal bone mineral density (BMD) Multiple myeloma On physical examination, demonstrates diffuse bone pain and tenderness On imaging studies, demonstrates osteolytic lesions in the bones On laboratory studies, demonstrates monoclonal IgM overload in electrophoresis, and also Bence-Jones protein in urine Homocystinuria On physical examination, demonstrates diffuse bone pain and musculoskeletal symptoms On physical examination, demonstrates visual impairment On laboratory studies, demonstrates high amounts of homocysteine in urine

References

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