Plasma Cell Disorders

  1. Where do plasma cells come from?
    B cells
  2. What is the most common plasma cell malignancy?
    Multiple myeloma
  3. synthesize excess L or H chains or complete homogenous immunoglobulins
    Monoclonal plasma cells
  4. When is the peak incidence of plasma cell disorders?
    7th decade
  5. In a plasma cell disorder, how much of bone marrow consists of neoplastic cells?
  6. Describe pathological features of plasma cell disorders
    • Osteolytic lesions in ribs,skull, sternum, vertebrae
    • Bone marrow patchy, can have fibrosis
    • Morphology of plasma cells varies
  7. Describe malignant plasma cells
    • eccentricalyl located nucleus
    • chromatin is clumped like clock faced chromatin
    • perinuclear huff and pail area
  8. In multiple myeloma, describe bone destruction
    • Begins in medullary cavity and works its way outword
    • Pathology fx and punched out lesions occur and occasionally produce diffuse demineralization of the bone
  9. soft, red, gelatinous masses
  10. perinuclear clearing due to prominent Golgi apparatus, eccentrically placed nucleus
    neoplastic plasma cell associated with MM
  11. Dysregulated synthesis and secretion of immunoglobulin can lead to accumulation of intact or partially degraded Ig
  12. Fiery red cytoplasm
    Flame cell associated with MM
  13. multiple blue grapelike cytoplasmic droplets
    Mott cell associated with MM
  14. Russell and Dutcher bodies
    • Russell: cytoplasmic inclusions
    • Dutcher bodies: nuclear inclusions
    • Associated with MM
  15. What happens as MM progresses?
    Invades soft organs: kidneys, lung, lymph nodes
  16. Describe cells you might see in MM
    • Flame cells
    • Mott cells
    • Russell bodies
    • Dutcher bodies
  17. Peripheral red blood smears may cause rouleaux formation from high levels of M protein
  18. Neoplastic plasma cells may be seen in peripheral blood (making it look a little like leukemia)
  19. Myeloma kidney MOA
    Bence Jones proteins injure the kidney as some light chains are directly toxic to epithelial cells AND/OR BJ proteins combine with a urinary protein to produce tubular casts that obstruct the tubular luminal and induce an inflammatory reaction around the casts
  20. Clinical features of myeloma kidney
    • Hypercalcemia and hyperuricemia
    • Amyloidosis
    • Light chain deposition dz
    • Formation of concentric laminated casts which obstruct tubular lumen (By BJ proteins)
  21. What infections is a MM pt prone to?
    Strep pneumo, staph aureus, and e coli
  22. What type of anemia is associated with MM and why?
    normocytic normochromic as plasma cells crowd out RBC precursors
  23. What is the M component and where is it found?
    • Monoclonal immunoglobulin in blood
    • Comes from same clone
    • Have high molecular weights
    • Restricted to plasma and extracellular fluid because of
    • weight
    • Not typically in urine if the glomerulus is uninjured
  24. Light chains exreted in urine due to small size
    BJ proteins (will be high in blood in cases of renal failure or if kidneys can't excrete fast enough)
  25. Most common symptomatic monoclonal gammopathy
  26. Multiple nodules composed of abnormal plasma cells
  27. What is significant abuot IL-6 in MM
    IL-6 leads to proliferation and increased survival of plasma cells, therefore high levels are associated with a poor prognosis
  28. Which factors in MM are produce by neoplastic plasma cells? What do they do?
    • MIP-1 and RANKL
    • They activate osteoclasts, resorb the bone and break it down, giving rise to osteolytic lesions
    • They contribute to increased calcium in the blood
    • Calcium is ultimately filtered in the kidney
  29. What are karyotopic abnormalities with MM? What do they lead to?
    • Deletions of 13q
    • Translocation involving heavy IgH chain locus on 14
    • FGFR3
    • Cyclin D1: a cell regulatory gene on chromosome 11q13
    • Cyclin D3: on chromosome 6p21
    • cMAF: gene for transcription factor on chromosome 16q23
    • MUM1/IRF4: a gene for
    • an interferon regulatory factor
    • They lead to cell being transcribed more rapidly, going through the cell cycle more rapidly, and proliferating more rapidly
  30. Plasma cell disorder not associated with skeletal lesions but with diffuse infiltratesof neoplastic cells into various tissues
    Waldenstrom's macrolobulinemia
  31. Plasma cell disorder not associated with lytic lesions but with diffuse infiltratesof neoplastic cells into various tissues
    heavy chain dz
  32. What do you need with the criteria to dx MM?
    1 major or 3 minor
  33. What are the major criteria for MM?
    • Marrow plasmacytosis >30%
    • Plasmacytoma on bx
    • M component, serum IgG >3.5; IgA >2, Urine >1 g/24 of BJ protein
  34. What are the minor criteria for MM?
    • Marrow plasmacytosis of 10-30%
    • M component present but less than in major criteria
    • Lytic bone lesions
    • Reduced nl serum Igs (<50% of nl)
  35. What are the four features of a localize plasmacytoma?
    • single lesion
    • skeletal lesions (can be readily bx)
    • may have masses in the upper respiratory tract
    • extra osseous lesions rarely disseminate
  36. Plasma cell disorder involving multiple organs with progressive demyelinating polyneuropathy
    POEMS (osteosclerotic myeloma)
  37. What are clinical features of osterosclerotic myeloma?
    • Poly neuropathy
    • Organomegaly
    • Endocrinopathy
    • Skin changes
  38. What are the three major differences between MM and POEMS?
    • POEMs has sclerotic, not lytic lesions, and there is neurological involvement.
    • Onset is much younger than MM (51 opposed to 70s)
  39. Megakaryocytes may be large with hyperlobulated nuclei
  40. What is a plasmacytoma and how is it related to MM?
    • It is a solitary myeloma (single lesion of bone or soft tissue) associated with modest increase of proteins in the blood or urine
    • Can be osseous or extraosseous, but the osseous variety commonly progresses to MM (extraosseous less likely to progress)
  41. Sheets of abnl neoplastic plasma cells that are extremely heterogenous
  42. Describe MGUS
    • no evidence of plasma cell dyscraise and minimal to no Bence JOnes protein in the urine
    • Monoclonal protein <3g
    • NO bone lesion, renal impairment, or hypercalcemia
    • Bone marrow might be nl or have a slight increase in nl plasma cells
  43. What do you need to be careful of MGUS?
    It can smolder and lead to MM, therefore have periodic assessment of B-J proteins and serum M component spikes
  44. AKA Waldenstrom’s macroglobulinemia
    lymphoplasmacytic lymphoma
  45. B cell lymphoma of primarily males 60-70 yo
    Lymphoplasmacytic lymphoma
  46. Tumor cells undergo terminal differentiation to plasma cells
    Lymphoplasmacytic lymphoma
  47. H-S megaly with lymphadenopathy
    Lymphoplasmacytic lymphoma
  48. Russell and Dutcher bodies
    Inclusions associated with lymphoplasmacytic lymphoma
  49. Visual abnormalities due to hyperviscosity of RBCs (problems perfusing eyes and brain); neurologic abnl (HA, dizziness, stupor)
    Lymphoplasmacytic lymphoma
  50. Bleeding problems due to complexes between macroglobulins and platelets
    Lymphoplasmacytic lymphoma
  51. Plasma cell disorder involving BM, LN, liver and spleen but WITHOUT bony erosions
    Lymphoplasmic lymphoma
  52. Hemolysis by cold agglutinins : IgM Abs binding to RBC at temperatures below 37C
    Lymphoplasmacytic lymphoma
  53. Raynau'd phenomenon and cold urticaria
    Lymphoplasmacytic lymphoma
  54. BM sparse with plasma cells, lymphocytes, and plasmacytoid lymphocytes
    Lymphoplasmacytic lymphoma
  55. Hyperplasia of mast cells
    Lymphoplasmacytic lymphoma
  56. Prognosis of someone with Lymphoplasmacytic lymphoma
    Incurable progressive, median surviva is 4 years
  57. What is the difference between IgG and IgA in heavy chain dz?
    • IgG: diffuse, lymphadenopathy with h-s megaly
    • IgA: prediliction for SI, respiratory tract
  58. Monoclonal group of plasma cells secrete free L chains
    Immunocyte-associated amyloidosis
  59. L chains pressed and deposited as amyloid that can be deposited in a lot of different organs
    Immunocyte-associated amyloidosis
Card Set
Plasma Cell Disorders
For upcoming pathology exam