Multiple Myeloma

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  1. Monoclonal Gammopathies are disorders associated with production of a monoclonal immunoglobulin protein. What is the most common of these? What is the second most common?
    • Monoclonal Gammopathy of Undetermined Significance (MGUS)
    • Multiple Myeloma
  2. What is the most common clinically significant monoclonal gammopathy?
    Multiple Myeloma: MGUS is most common overall, but is not clinically significant
  3. What are the three main characteristics of Multiple Myeloma (the Triad)?
    • Accumulation of plasma cells in bone marrow
    • Bone lesions
    • Monoclonal immunoglobulin protein in serum and/or urine
  4. What is the second most common malignancy of lymphoid cells overall, and the most common in african americans? In what age population does this predominantly occur in?
    • Multiple Myeloma
    • Older -- 70s
  5. What is the etiology of Multiple Myeloma?
    • Most cases idiopathic
    • Possible occupational exposure -- increased in farmers, petroleum workers, wood & leather industries
    • Ionizing Radiation -- radiologists, nuclear plant workers, etc
  6. What three characteristics are used to make a diagnosis of Multiple Myeloma?
    • Monoclonal protein in serum and/or urine
    • Increased plasma cells in marrow
    • Presence of end-organ or tissue damage due to plasma cell proliferation or monoclonal immunoglobulin
  7. What is the key to the diagnosis of symptomatic mulitple myeloma?
    The presence of myeloma-related organ damage or tissue infiltration
  8. What are the indicators of Multiple Myeloma End-Organ Damage?
    • C: hyperCalcemia
    • R: Renal abnormalities
    • A: Anemia
    • B: Bone Lesions
  9. What is the main indicator of symptomatic versus asymptomatic multiple myeloma?
    Symptomatic: presence of end-organ damage (not seen in asymptomatic)
  10. What are the common lab findings associated with Multiple Myeloma?
    • Anemia
    • Hypercalcemia
    • Renal Insufficiency
    • Elevated total serum protein with normal or decreased serum albumin
  11. What is the diagnosis based on the bone marrow biopsy below? What is the indicator?
    Image Upload 1
    • Multiple Myeloma
    • Increased plasma cell presence & presence of nucleoli in the plasma cells
  12. What is the diagnosis based on the bone marrow biopsy below?
    Image Upload 2
    • Multiple Myeloma
    • Sheet of Plasma Cells -- Plasmacytoma
  13. What are the two types of bone lesions seen in Multiple Myeloma?
    • "Punched Out" Osteolytic Lesions: vertebrae, skull, ribs, pelvis, others
    • Diffuse Osteopenia
  14. Myeloma cell produce factors which stimulate osteoclasts to resorb bone. What are these called?
    Osteoclast Activating Factor (OAF)
  15. Liberation of calcium from bone causes __________?
  16. What should be an important diagnostic consideration in any elderly patient with back pain plus anemia, renal insufficiency, or elevated serum protein?
    Multiple Myeloma
  17. In most cases of multiple myeloma there is production of an intact immunoglobulin (both heavy and light chains), sometimes with production of excess light chain. In some cases, however, there is production of a _______ chain only. What is the most common immunoglobulin that this happens with? Second most common?
    • Light
    • IgG
    • IgA
  18. What tests are used for the detection of monoclonal proteins in Multiple Myeloma?
    • Serum Protein Electrophoresis (SPEP)
    • Immunofixation
    • Free Light Chain Assay
  19. Free light chains are relatively small; therefore, they are filtered through the glomerulus and do not accumulate in large quantities in teh serum. This is why a negative serum protein electrophoresis does not exclude myeloma. Where else must you look for it?
  20. Free light chains cleared by the kidney are often called "_________ _________" protein.
    "Bence Jones"
  21. What are the two main types of cytogenetic abnormalities in multiple myeloma?
    • Abnormalities of chromosome number (Aneuploidy)
    • Reciprocal Translocations (usually involving 14q32 -- IgH gene)
  22. What is one of the most important prognostic factors in myeloma patients?
    Presence of Cytogenetics
  23. What is the most common translocation in multiple myeloma?
  24. What complications are related to multiple myeloma?
    • Bone pain and fractures
    • Infection
    • Renal failure
    • Hypercalcemia
  25. What is the most common cause of death in multiple myeloma? What is the second most common?
    • Infections
    • Renal Insufficiency
  26. What is the most common cause of renal damage in multiple myeloma, pictured below?
    Image Upload 3
    Myeloma Cast Nephropathy: precipitation of the monoclonal immunoglobulin in large casts in the renal tubules, which elicit a cellular reaction and plug up the renal tubules
  27. No conventional therapy for multiple myeloma is curative. What typically happens with treatment?
    Patients respond for months-years; eventually resistance develops -- survival thereafter is poor
  28. What are the treatment options (drugs) for Multiple Myeloma?
    • Thalidomide, with or without dexamethason
    • Dexamethasone alone
    • Preteosome Inhibitors (Velcade)
    • Bisphophonates (Pamidronate)
  29. What type of stem cell transplant is widely used for Multiple Myeloma? What type is potentially curative?
    • Autologous -- myeloma almost always recurs
    • Allogenic -- most myeloma patients are too old to undergo this type
  30. This is a plasma cell tumor outside of bone. It is usually solitary. Where is the most common site for this? Local therapy may be curative. What must be excluded?
    • Extramedullary Plasmacytoma
    • Upper Respiratory Tract
    • Disseminated Disease -- bone marrow involvement
  31. This is characterized by the presence of a monoclonal protein in absence of signs or symptoms of multiple myeloma. There are no lytic bone lesions; <10% plasma cells in marrow; low level of M-protein (<3g/dL in serum; minimal in urine). This is common in elderly populations.
    There is no clinical significance associated with this.
    Monoclonal Gammopathy of Undetermined Significance (MGUS)
  32. About 25% of MGUS patients transform to what? This occurs in a median time of about 8 years after diagnosis. What makes patients more susceptible to this transformation?
    • Overt Myeloma
    • Higher M-protein levels at higher risk
  33. This is the presence of a monoclonal IgM protein in a patient with a histologic type of non-Hodgkin lymphoma designated lymphoplasmacytic lymphoma, which is a proliferation of cells intermediate between lymphocytes and plasma cells. The clinical behavior of this resembles typical myeloma.
    Waldenstrom's Macroglobulinemia (WM)
  34. Are the following symptoms seen in Lymphoma?

    Liver/Spleen Involvement?
    Blood Involvement?
    Lytic Bone Lesions?
    • Lymphadenopathy: Common
    • Liver/Spleen Involvement: Occasional
    • Blood Involvement: Occasional
    • Lytic Bone Lesions: No
    • M-Protein: Rare
  35. Are the following symptoms seen in Myeloma?

    Liver/Spleen Involvement?
    Blood Involvement?
    Lytic Bone Lessions?
    • Lymphadenopathy: Rare
    • Liver/Spleen Involvement: Rare
    • Blood Involvement: Rare
    • Lytic Bone Lesions: Yes
    • M-Protein: Yes; not IgM
  36. Are the following symptoms seen in Waldenstrom's Macroglobulinema (WM)?

    Liver/Spleen Involvement?
    Blood Involvement?
    Lytic Bone Lesions?
    • Lymphadenopathy: Sometimes
    • Liver/Spleen Involvement: Occasional
    • Blood Involvement: Occasional
    • Lytic Bone Lesions: No
    • M-Protein: Yes; IgM
  37. What syndrome is associated with Waldenstrom's Macroglobulinemia? This is due to high levels of IgM protein, which increases blood viscosity. What are the symptoms associated with this? What is seen on exam?
    • Hyperviscosity Syndrome
    • Fatigue, dizziness, blurred vision, SOB
    • Dilated, "sausage-shaped" retinal veins
  38. How is Waldenstrom's Macroglobulinema (WM) treated?
    • Plasmaphoresis for hyperviscosity
    • Chemotherapy needed to prevent reaccumulation
  39. This is the deposition of protein with beta-pleated sheet configuration in tissues. A variety of proteins can cause it, including Ig light chains or fragments, SAA, prealbumin, and a variety of hormones. All of these look alike: they look like amorphous pink material on H&E stain
  40. Identify the phenomenon seen in the slide below. What type of stain is used to identify this?
    Image Upload 4
    • Amyloidosis
    • Congo Red: "apple green" birefringence under polarized light
  41. This is a slide of Amyloid viewed under polarized light. What stain makes the "apple green" birefringence appear?
    Image Upload 5
    Congo Red Stain
  42. What is the most common type of Amyloidosis in the US? This is caused by the deposition of immunoglobulin light chain or fragments. In this, lambda > kappa (reverse of normal and of multiple myeloma). This may or may not be associated with overt myeloma.
    What complications are associated with this?
    • AL ("Primary") Amyloidosis
    • Heart (congestive failure, arrhythmias), Kidney (renal failure, nephrotic syndrome), Skin (purpura), others
  43. This type of Amyloidosis is due to a primary illness -- typically chronic inflammation. The most common cause of this in the US is RA. It is due to the deposition of amyloid-associated protein in tissue; derived from serum amyloid-associated protein (SSA).
    AA (secondary) Amyloidosis
  44. What two factors, required in AA Amyloidosis, combine, resulting in increased AA protein which deposits in tissues as beta-pleated sheets.
    • Chronic increase in SAA protein
    • Defective macrophage processing or breakdown of SSA
  45. What is the treatment for AA Amyloidosis?
    Treat primary condition
  46. This type of Amyloidosis is characterized by the deposition of prealbumin fragments; due to a mutation in prealbumin protein. This may present as a peripheral neuropathy -- better prognosis. What is the procedure of choice for diagnosis of this type?
    • Familial (AF) Amyloidosis
    • Abdominal Fat Pad Aspiration
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Multiple Myeloma

Multiple Myeloma
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