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Multiple Myeloma

Topic updated on 06/30/14 10:56am
  
Introduction
  • neoplastic proliferation of plasma cells that presents with skeletal lesions
    • neoplastic plasma cells produces immunoglobulins
      • heavy chains: IgG (52%), IgA (21%), IgM (12%)
      • light chains: kappa or lambda 
        • aka Bence Jones proteins
  • Disease forms 
    • disease takes multiple forms that vary in treatment and prognosis and includes
      • multiple myeloma (see below)
      • solitary plasmacytoma
      • osteosclerotic myeloma
  • Epidemiology
    • incidence
      • most common primary bone malignancy
    • demographics
      • patients > 40 years of age
      • affects males more than females
      • twice as common in African-americans
  • Prognosis
    • prognosis is variable
    • data suggests 5 year survival of 30% and 10 year survival of 11%
      • overall survival is related to stage of disease and secondary factors like renal failure or hypercalcemia
      • median survival is 3 years from diagnosis
      • shortest survival is seen in patients with renal failure
    • poor prognostic factors in multiple myeloma
      • chromosome 13 deletion or translocation (t4;14), 4(14;16)
      • circulating plasma cells
      • increased beta 2 microgloblulin (indicates elevated tumor burden)
      • decreased serum albumin
      • increased marrow microvessels
    • solitary plasmacytoma has best prognosis
Classification
  • Multiple Myeloma 
    • most common form
    • requires one major and one minor (or three minor) criteria for diagnosis
      • major criteria
        • biopsy confirmation of plasmacytoma
        • >30% plasma cells on bone marrow biopsy
        • serum IgG > 3.5g/dL, IgA > 2g/dL 
        • urine IgA > 1g/24hr or presence of Bence Jones proteins
      • minor criteria
        • 10-30% plasma cells on bone marrow biopsy
        • serum or urine protein levels below those listed for major criteria
        • presence of multiple lytic bone lesions ("punched out" lesions without evidence of surrounding sclerosis)
        • decreased serum IgG levels
  • Solitary Plasmacytoma
    • plasma cell tumor occurring in a single skeletal location and lacking appropriate criteria for diagnosis of multiple myeloma
    • sensitive to radiation
    • progress to multiple myeloma in over 50% of patients
    • diagnostic criteria
      • solitary lesion on skeletal survey
      • histologic biopsy confirmation of plasmacytoma
      • negative bone marrow biopsy (i.e. no plasma cells in bone marrow)
  • Osteosclerotic Myeloma
    • a rare syndrome characterized by POEMS: Polyneuropathy,  Organomegaly, Endocrinopathy, M protein, Skin changes
    • neurologic symptoms are symmetric and begin distal and migrate proximally
      • sensory symptoms manifest first and then are followed by motor weakness
      • neurological symptoms usually do not improve
    • skin lesions are characteristic and occur predominantly in the trunk
      • up to 25-50% of skin lesions occur in the extremities
    • sclerotic bone lesions occur in both the axial and appendicular skeleton
Presentation
  • Symptoms
    • usually present with localized bone pain (usually spine or ribs) or pathologic fracture 
    • fatigue secondary to anemia, renal insufficiency, hypercalcemia
Imaging
  • Radiographic 
    • show multiple "punched-out" lytic lesions 
      • lytic lesions caused by osteoclastic bone resorption via RANKL, IL-6 and MIP-1alpha 
      • lack of osteoblastic activity in myeloma cause the "punched out lesions" on radiographs which lack a sclerotic border
    • skeletal survey
      • if there is a suspicion for multiple myeloma obtain a skeletal survey as bone scans are cold in 30%
  • MRI
    • shows multiple lesions that are bright on T2 and dark on T1 
  • Bone scans
    •  are cold in 30% so obtain a skeletal survey
    • bone scans are "hot" due to radio-tracer integration into the inorganic phase of bone caused by osteoblastic activity
    • multiple myeloma often lacks osteoblastic activity
Labs
  • Serum labs
    • anemia
    • elevated creatinine
    • hypercalcemia
      • present in 30% of patients due to excessive resorption of bone
    • ESR often elevated
    • SPEP (serum protein electrophoresis)
      • M spike present (50% IgG, 25% IgA)
  • Urine
    • proteinuria
    • UPEP (urine protein electrophoresis) 
      • may show Bence Jones proteins (secreted immunoglobulin kappa and lambda light chains)
Histology
  • Distinctive histology
    • round plasma cells with an eccentric nucleus, prominent nucleolus, and clock face organization of chromatin  
    • characteristic clear area (Hoffa clear zone) next to the nucleus represents the prominent Golgi apparatus involved in immunoglobulin (protein) production  
  • Bone marrow aspirate
    • percentage of plasma cells on bone marrow aspirate is one major criteria used to distinguish plasmacytoma (10-30% plasma cells) vs. multiple myeloma (>30% plasma cells) 
    • normal amount of plasma cells on bone marrow aspirate is < 2%
  • Immunohistochemical stains
    • CD38+
Treatment
  • Multiple myeloma
    • nonoperative
      • multiagent chemotherapy
        • indications
          • is the mainstay of treatment
        • cytotoxic chemotherapy combined with steroids
      • bisphosphonates 
        • help reduce number of skeletal events in multiple myeloma patients
    • operative
      • surgical stabilization and irradiation
        • indications
          • for complete or impending fractures
          • vertebral compression fractures with instability or neural compression resistant to radiation
        • technique
          • kyphoplasty an option for painful vertebral compression fractures
  • Solitary plasmacytoma
    • nonoperative
      • external beam irradiation alone (45 - 50 Gy)
        • indications
          • is the mainstay of treatment
    • operative
      • surgical stabilization
        • indications
          • for complete or impending fractures
  • Osteosclerotic myeloma
    • nonoperative
      • chemotherapy, radiotherapy, and plasmapheresis
        • indications
          • is the mainstay of treatment
        • outcomes
          • neurologic changes usually do not improve with treatment 


Differential & Groups
 
 
Bone lesion in older patient(1)
 
Multiple lesion in older patient(1)
     
Benefits from Bisphonate therapy
 
Treatment is chemotherapy and radiotherapy(2)
Myeloma
 
     
   
Metastatic bone disease
 
     
 
 
Lymphoma
 
         
Chondrosarcoma
               
MFH
               
Secondary sarcoma
               
Pagets disease    
     
 
 
Fibrous dysplasia            
 
 
Synovial sarcoma                
 
Hyperparathyroidism    
           
Gomus tumor                  
ASSUMPTIONS: (1) Older patient is > 40 yrs; (2) assuming no impending fracture
 
IBank
  Location
Xray
Xray
CT
B. Scan
MRI
MRI
Histo(1)
Case A femur
 
 
Case B radius
 
 
Case B femur
 
 
Case C radius
 
 
 
Case D femur
 
 
 
Case E humerus
 
 
 
Case F spine
 
 
 
Case F skull
 
 
 

 


 

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Qbank (4 Questions)

TAG
(OBQ12.190) A 61-year-old male has a 6 month history of low back pain with increasing left sciatic leg pain for 5 weeks. On examination, he has bone tenderness in the lumbar and thoracic spine. Neurological examination shows 4/5 weakness in the L5 distribution in the left leg. MRI images of the thoracic and lumbar spine are shown in Figures A. Follow-up laboratory studies show anemia associated with the presence of a serum monoclonal protein. What would be the next most appropriate investigation in the diagnostic work-up of this patient? Topic Review Topic
FIGURES: A          

1. CT scan of head
2. Urine electrophoresis
3. Lower extremity electromyelography
4. Lumbar puncture
5. Bone marrow aspiration and biopsy

PREFERRED RESPONSE ▶
TAG
(OBQ11.64) Lytic bone lesions, commonly seen in metastatic bone disease or multiple myeloma, are due to which of the following mechanisms? Topic Review Topic

1. RANK ligand action on neoplastic cells
2. RANK action on neoplastic cells
3. Osteoprotegrin action on osteoclastic cells
4. RANK ligand action on osteoclastic cells
5. RANK action on osteoclastic cells

PREFERRED RESPONSE ▶
TAG
(OBQ08.136) A 55-year-old male with chronic low grade back pain, intermittent fevers, and anemia underwent a bone biopsy for a lytic lesion in the spine. The biopsy is seen in Figure A. A urine protein electrophoresis is likely to show which of the following? Topic Review Topic
FIGURES: A          

1. Bacteria
2. Leukemia
3. Monoclonal heavy chain immunoglobin
4. Monoclonal light chain immunoglobin
5. Decreased urine albumin

PREFERRED RESPONSE ▶
TAG
(OBQ08.142) A 55-year-old male has chronic thoracic back pain and undergoes a biopsy of a suspicious lesion in the T6 vertebral body seen in Figure A. The asterisk in Figure B represents what type of cell seen by the pathologist? Topic Review Topic
FIGURES: A   B        

1. Osteoblasts
2. Spindle Cells
3. Giant Cells
4. Plasma Cells
5. Eosinophils

PREFERRED RESPONSE ▶



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