Multiple Myeloma - Krafts & Johns

Question 1

What is the typical clinical presentation of mulitiple myeloma?

Answer 1

• Bone pain (80%)
  
  • lytic bone lesions
  • hypercalcemia
• Bruising or bleeding (low platelet count)
• Infections
• Renal failure (50% - plugged glomeruli)
• Hyperviscosity Syndrome

Question 2

What is the classic triad of symptoms for Multiple Myeloma?

Answer 2

1. Anemia
2. Bone pain
3. Renal failure

Question 3

What causes Hyperviscosity Syndrome (purpura, confusion, decreased vision)?

Answer 3

• non-differentiated Plasmablasts produce large amounts of immunoglobulins (IgG, IgA)
• normal cell death of plasma cells by apoptosis doesn’t occur

Question 4

What are the three key pathology features of Multiple Myeloma?

Answer 4

1. Monoclonal proliferation of plasma cells
2. Monoclonal gammopathy
3. Decreased levels of other, normal (polyclonal) immunoglobulins.

Question 5

What are typical lab findings in Multiple Myeloma?

Answer 5

• big monoclonal gammopathy in the blood, or urine, or both
• M-spike
  
  • due to big quantity of monoclonal immunoglobulin
• Type of IgG
  
  • IgG (60%)
  • IgA (20%)
• Bence-Jones protein in urine
  
  • malignant plasma cells secrete only light chains → filtered out by kidney
• Decreased normal Ig
  
  • cancer cells inhibiting normal plasma cell functioning

Question 6

What blood morphologies are seen in Multiple Myeloma?

Answer 6

• Anemia
• Rouleaux (stacked RBCs)
• rarely see Plasma cells

Question 7

What bone marrow morphologies are seen in Multiple Myeloma?

Answer 7

• Plasma cells
  
  • <20% (normal 3%)
  • varied stages of maturity
  • Russell bodies (small, reddish cytoplasmic blobs containing immunoglobulin)
  • Dutcher bodies (large, single, intranuclear pseudoinclusions that look like holes and contain immunoglobulin)
  • Flame cells
• Amyloid
  
  • due to over-production of immunoglobulin light chains

Question 8

How come you see rouleaux in myeloma?

Answer 8

• abundant amounts of immunoglobulin in the blood disrupts the normal repellant force between RBCs
  
  • Ig breaks the “zeta potential”

Question 9

What are some of the other plasma cell disorders?

Answer 9

• Solitary plasmacytoma
  
  • localized myeloma (one part of body)
• Plasma cell leukemia
  
  • presents de novo OR end result of MM
• Waldenström Macroglobulinemia
  
  • Lymphoplasmacytoid lymphoma
  • overproduces IgM
  • Hyperviscosity syndrome (retina)
• MGUS (Monoclonal gammopathy of undetermined significance)
  
  • small M-spike with no myeloma symptoms (not malignant)
  • occasionally transforms into myeloma (monitor condition)

Question 10

What are the three laboratory tests used to judge the severity of Multiple Myeloma as treatment progresses?

Answer 10

• Serum protein electrophoresis
• Serum immunoelectrophoresis
• Urine immunoelectrophoresis

Question 11

What is the treatment for Multiple Myeloma?

Answer 11

• Chemotherapy
  
  • Dexamethasone (steroid)
  • Melphalan (alkylating agent)
  • Cyclophosphamide (alkylating agent)
• Autologous Peripheral Blood Stem Cell Transplant (x2)
• Bone Marrow Transplant
• New Treatments: Thalidomide, Lenalidomide, Bortezomib

Question 12

What is the prognosis for patients with Multiple Myeloma?

Answer 12

• Prognosis without bone marrow transplantation is poor (median survival = 3 years).
• Conventional chemotherapy = 3-4 years

Question 13

What are the specific (underlying) causes of death in Multiple Myeloma?

Answer 13

• Pancytopenia post bone marrow transplant
• Renal failure
• Sepsis
• Acute leukemia