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Hematology 2 > Lecture 10 Plasma Cell Dyscrasias > Flashcards

Lecture 10 Plasma Cell Dyscrasias Flashcards

1
Q

What are Plasma Cell Dyscrasias?

A

Group of disorders representing the differentiated end cells of B Lymphocytes, namely plasma cells and plasmacytoid lymphocytes. Referred to as a group of monoclonal gammopathies.

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2
Q

What does the term “monoclonal gammopathies” mean?

A

Monoclonal because cells in this disorder represent a single clone arising from a single abnormal parent cell.

Gammopathies because these abnormal cells produce an increased amount of immunoglobulin in the serum with the appearance of a narrow peak or spike during serum protein electrophoresis.

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3
Q

What is the most common plasma cell dyscrasias?

A

Multiple Myeloma

General FYI Info:
Affects older people (50-75yrs of age) with slightly higher percentage in males.
African-Americans twice as likely as whites to be affected.
Causes unknown with links to genetics, radiation and chronic antigenic stimuli possible causes.

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4
Q

When is the transformation to malignant cell thought to occur for Multiple Myeloma?

A

Transformation of malignant cell probably at stem cell level as malignant cells shown to express Pre-B Cell antigen CALLA (CD10).

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5
Q

What general surface markers do the Multiple Myeloma malignant cells show?

A

Malignant cells demonstrate megakaryocytic, myelomonocytic and erythroid surface markers.

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6
Q

*Where does clonal proliferation occur in Multiple Myeloma? And the result?

A

Clonal proliferation occurs in the bone marrow. Increased number of plasma cells.

Note: Similar to other Leukemias Plasma Cell Dyscrasias occurs as a bone marrow malignant transformation at the stem or progenitor stage since they demonstrate markers from all 3 cell lines. The end result is an abnormal proliferation of B (plasma) cells and products of B cells.

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7
Q

What do the plasma cells in Multiple Myeloma release in the bone marrow and the result?

A

Release osteclastic activating factor increasing the number of osteoclasts.

Leads to increased bone resorption, lytic bone lesions and later on bone fractures and collapse of vertebrae. In extreme cases spontaneous bone fractures.

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8
Q

What chemistry marker is indicative of Multiple Myeloma?

A

High plasma calcium due to the breakdown of bone is one of the important diagnostic markers of Multiple Myeloma.

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9
Q

What symptoms occur as a result of plasma tumor cells proliferating in the marrow in MM?

A

Crowding out normal cells leading to symptoms of anemia, infection and bleeding.

Anemia, renal dysfunction causing weakness and fatigue.

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10
Q

Where else can plasma cells infiltrate in MM?

A

Plasma cells can also infiltrate lymph nodes, spleen, and other organs.

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11
Q

Why do Multiple Myeloma patients suffer from increased risk of infection?

A

Increased risk of infection because of marked decrease in normal immunoglobulins.

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12
Q

Why can Multiple Myeloma sufferers have kidney damage?

A

Large amounts of low molecular weight Light chains (Bence-Jones protein) filtered and reabsorbed by kidney eventually damage nephron of kidney with resulting kidney damage without timely intervention.

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13
Q

What problems does amyloid deposition that occurs in Multiple Myeloma patients cause?

A

Amyloid deposition: composed of L-chains fragments produce protein deposits throughout the body with subsequent loss of organ (kidney, heart, liver) function. Occurs in approx 15% of patients.

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14
Q

Why can some Multiple Myeloma patients have bleeding disorders?

A

Some monoclonal proteins interfere with platelets and coagulation factors producing bleeding disorders. Results in bleeding due to thrombocytopenia and coagulation abnormalities.

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15
Q

What is the main symptom that Multiple Myeloma patients complain about?

A

Main complaint is skeletal pain.
Initial back pain with progression to severe pain with possible spontaneous bone fracture.

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16
Q

What are the lab findings in patients with Multiple Myeloma?

A
  1. Normocytic, normochromic anemia.
  2. Increased ESR with rouleaux formation.
  3. Macroscopic appearance of stained blood smear shows bluish tinge due to immunoglobulins.
  4. Differential may show slight neutropenia.
  5. Little or no evidence of plasma cells in early stage with few plasma or plasmacytoid lymphs in later stage
  6. Pancytopenia with leukoerythroblastic picture.
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17
Q

What % of abnormal plasma cells in the bone marrow is diagnostic of Multiple Myeloma?

A

More than 10% abnormal plasma cells in bone marrow important diagnostic criteria

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18
Q

What is the morphology of the abnormal plasma cells in the bone marrow?

A
  1. Morphological variety of abnormal plasma cells from case to case.
  2. Cells may be large with immature chromatin or small with mature chromatin.
  3. Cytoplasm may be pale or dark.
  4. Multinucleated or lobulated nuclei may be present.
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19
Q

What factors are used for the classification of Multiple Myeloma?

A

For the proper classification of Multiple Myeloma:
1. Increased monoclonal protein,
2. Number of plasma cells and
3. Bone and organ involvement

See Table 34.6 on slide 12.

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20
Q

What are Dutcher bodies?

A

Cellular inclusions intranuclear bodies (Dutcher bodies)

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21
Q

What are Russell bodies?

A

Accumulation of immunoglobulins in the rough endoplasmic reticulum of the cytoplasm called Russell bodies.

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22
Q

What are Mott cells?

A

Cells with Russell bodies also called Mott cells.

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23
Q

What are flame cells?

A

Few IgA Myelomas demonstrate flame cells- so called because of reddish pink coloration in the cytoplasm of the cell. Ribosomal protein responsible for this appearance.

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24
Q

Why may routine urinalysis not detect increased globulins and L-chains?

A

Routine analysis may not detect the extent of proteinuria as sulfosalicyclic acid more sensitive to albumin than globulin and L-chains.

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25
Q

Is microscopic urine examination helpful to detect possible Multiple Myeloma?

A

Microscopic exam of urine may show hyaline casts and renal tubular epithelial cells in hyaline casts.

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26
Q

What are the best chemistry tests for detecting Multiple Myeloma?

A
  1. Protein electrophoresis in almost all cases demonstrates monoclonal immunoglobulin in both serum and urine.
  2. Bence-Jones protein present in urine only as glomerulus of kidney filters out serum.
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27
Q

What is the frequency in % of the various monoclonal bands seen in patients with Multiple Myeloma?

A

IgG: 50% of cases
IgA: 20% of cases
IgD and IgE: rare
L-chain only: 15% of cases
IgM: usually seen in Waldenstroms Macroglobulinemia although IgM myelomas have been described

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28
Q

What percentage of cases show light chains in urine for Multiple Myeloma patients? Which one is most typical?

A

80% of all cases of Multiple Myelomas show free Light chains in urine (more frequently kappa)

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29
Q

Why is hyperuricemia seen and increased serum calcium?

A
  1. Hyperuricemia from increase cell turnover. Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood.
  2. Increased serum calcium from increased osteclastic activity.
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30
Q

What can X-ray show in patients of Multiple Myeloma?

A

X-ray usually show evidence of osteoporosis and skeletal lytic bone lesions.

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31
Q

What are the treatment options and prognosis for Multiple Myeloma patients?

A
  1. Chemotherapy treatment is helpful but prognosis is variable. Previously patients responding to treatment (approx 40%) live 3-4yrs.
  2. Newer drugs offer improved outcomes
  3. Bone Marrow transplants and stem cell rescue offer options in some patients
  4. Non-responders live less than 1 year.
32
Q

What is non-secretory Multiple Myeloma?

A
  1. No abnormal immunoglobulin in blood or urine, <1% of MM cases.
  2. Number of plasma cells in marrow, elevated calcium and lytic lesions of bone still occur
  3. Infection complications are fewer.
  4. Renal function and survival is better than secretory MM.
33
Q

What are the laboratory findings for Plasma Cell Leukemia in the peripheral blood and bone marrow?

A
  1. Absolute blood count >2 x 10^9/L or >20% circulating plasma cells.
  2. Pancytopenia, leukoerythroblastic picture with elevated ESR common findings.
  3. Plasma cells can be small, abnormal cells or large blast like cells.
  4. Extensive diffuse bone marrow replacement is typical. Usually >45% plasma cells in marrow.
  5. High proportion associated with IgE.
34
Q

What is Solitary Plasmacytoma?

A

Solitary Plasmacytoma is a malignant growth of plasma cells (tumor), extramedullary (outside of bone marrow), that invade an area of tissue or bone without bone marrow involvement.

35
Q

What non-bone structures/organs do Plasmacytomas grow in?

A

Plasmacytomas of non-bone structures include tissues such as sinuses, G.I. tract, and skin..

36
Q

What disease can Plasmacytomas progress into?

A

Plasmacytomas can progress to Multiple Myeloma. Non-bone less likely to convert.

37
Q

What percentage of MM patients have tumors at other sites (other than bm)?

A

10-20% of MM cases show plasma cell tumors of other body sites.

38
Q

What are the clinical findings for Solitary Plasmacytoma?

A

Small serum monoclonal spike may be present but other signs of MM are absent.

39
Q

What is the main treatment for Solitary Plasmacytoma?

A

Radiation Treatment

40
Q

*What is the diagnostic criteria for Plasma Cell Leukemia?

A

Diagnosis requires an absolute plasma cell count of 2000/cubic millimeter (2 x 10^9/L) or 20% circulating plasma cells.

41
Q

What are the previous condition of people who get Plasma Cell Leukemia?

A

50% of cases are de novo arising as a separate discrete entity.
50% of cases occur as a late terminal manifestation of multiple myeloma

Note: Least common type of Plasma Cell Dyscrasia

42
Q

What are the clinical findings for Plasma Cell Leukemia?

A
  1. Patient usually younger with abrupt disease onset, poor response to therapy and short survival time (less than 1 year).
  2. More frequent high calcium levels, more kidney failure and much more anemia and thrombocytopenia
  3. Liver, spleen and lymph node enlargement are common
43
Q

What makes Plasma Cell Leukemia different from the other Plasma Cell Dyscrasias?

A

Plasma cell leukemia set itself apart by the higher # of plasma cells and also that immature forms of plasma cells such as plasmablasts and Proplasmacytes can be present .

44
Q

What is the maturation sequence of the Plasma Cell?

A

Antigen –> Med/Large Lymphocyte –> Plasmablast (Immunoblast) –> Proplasmacyte –> Plasma Cell –> Death

45
Q

*What is Waldenstrom’s Macroglobulinemia?

A

Lymphoproliferative disorder characterized by large concentration of monoclonal IgM, exceeding 15% of gamma globulin concentration. (normal 5-10%)

46
Q

What can abnormal B lymphocytes in Waldenstrom’s Macroglobulinemia differentiate into?

A

Abnormal B lymphoctes are transitional cells having the ability to differentiate into plasma cells, lymphocytes, or plasmacytoid lymphocytes.

47
Q

Can Waldenstrom’s Macroglobulinemia result in osteolytic lesions and renal involvement?

A

Yes, but rarely osteolytic lesions and renal involvement less common than Multiple Myeloma.

48
Q

What problem does the IgM complexes of amyloid cause in Waldenstrom’s Macroglobulinemia?

A

Glomerular lesions if present caused by IgM complexes of amyloid.

49
Q

*What is a significant problem in Waldenstrom’s Macroglobulinemia? What causes it?

A

Hyperviscosity: Blood more “sticky” and more resistant to flow.

Note: Hyperviscosity a significant problems with Waldenstrom’s due to the large amount of IgM, IgM as you know is a large molecule which contributes to the hyperviscosity.

50
Q

What are the clinical findings in Waldenstrom’s Macroglobulinemia?

A
  1. Predominates in men, middle-aged to elderly.
  2. Fatigue, weakness, weight loss, blurred vision, bleeding episodes (especially nosebleeds).
  3. Hepatosplenomegaly and lymphadenopathy more frequent than Multiple Myeloma
  4. Congestive heart failure, retinal complications including hemorrhage and neurological problems due to hyperviscosity.
  5. Hyperviscosity
51
Q

*What kind of anemia does Waldenstrom’s Macroglobulinemia typically result in and why?

A

Normocytic, normochromic anemia from hemorrhage and hypervolemia.

Some cases may produce autoimmune hemolytic anemia disorder associated with cold agglutinin disease (anti I).

52
Q

What cells are found in the bone marrow in Waldenstrom’s Macroglobulinemia?

A

Bone marrow shows increase and variety of lymphoid cells: small lymphocytes, plasmacytoid lymphocytes or plasma cells.

53
Q

What problems do the increase IgM macromolecules cause in Waldenstrom’s Macroglobulinemia?

A
  1. IgM macromolecules coat platelets, inhibit normal function causing increased Bleeding Time and platelet aggregation studies. In the patient this causes bleeding and neurological problems such as blurred vision and retinal problems.
  2. IgM can interfere with coagulation factors causing elevated coagulation results.
54
Q

What happens to the reticulocyte, leukocyte and platelet counts in Waldenstrom’s Macroglobulinemia? Lymphocyte count?

A
  1. Reticulocyte count normal or decreased.
  2. Leukocytes and platelet count usually normal.
  3. Relative or absolute lymphocytosis.
55
Q

What happens to the ESR in WM?

A

Increased ESR due to elevated IgM.

56
Q

What notable cells are seen in WM?

A

Wide variety of mature appearing or plasmacytoid lymphocytes.

57
Q

What are the chemistry findings for WM?

A
  1. Serum protein electrophoresis demonstrates presence of IgM spike.
  2. Approx 80% of patients produce small amount of free L chains ( Bence Jones proteins) in urine.
58
Q

What can be elevated that causes problems with the platelet or WBC count in WM?

A

Cryoglobulins test may be elevated.

Electronic cell counters may have problems with blood specimens from these patients counting cryoglobulins as platelets or leukocytes.

59
Q

What is the treatment for Waldenstrom’s Macroglobulinemia?

A
  1. Early stages may not require treatment.
  2. Immunoglobulin, monoclonal IgM and serum viscosity levels should be monitored.
  3. Progressive disease may require chemotherapy and plasmapheresis to reduce IgM and symptoms of hyperviscosity.
  4. Patients responding to therapy average 4 year survival.
60
Q

What is heavy chain disease?

A
  1. Rare lymphoproliferative disorder demonstrating excessive production of heavy-chain portion of antibody unit.
  2. Appears plasma cells have lost ability to synthesize light chain component.

Note: Cause - Abnormal cells lost ability to synthesize light chains with excessive production of heavy chain component.

61
Q

What the three classes of incomplete heavy chains in heavy chain disease?

A

Incomplete Heavy chains of the three major classes produced by tumor cells: Alpha, gamma, Mu

62
Q

What doe the tumor cells resemble in heavy chain disease?

A

Tumor cells resemble activated (reactive) lymphocytes and plasma cells

63
Q

What are the 3 types of heavy chain disease?

A

3 types of Heavy Chain Disease: Gamma (IgG), Alpha (IgA) and Mu (IgM).

See slide 40 for associated organ involvement and characteristics.

64
Q

What does Alpha HCD impact/involve in the body?

A

Alpha HCD does not usually involve the bone marrow. Peripheral blood findings reflect complications such as intestinal bleeding or malabsorption.

65
Q

Is serum protein electrophoresis helpful in Alpha HCD? What is a more helpful in diagnosing Alpha HCD?

A

Serum protein electrophoresis helpful in only 50% of cases.

Jejunal or respiratory secretion analysis by immunoelectrophoresis provides more reliable evidence of Alpha HCD.

66
Q

What can be seen that is notable in the peripheral blood and bone marrow in Heavy Chain Disease Gamma?

A
  1. Variant (atypical) lymphocytes and plasma cells can be seen on peripheral blood.
  2. Can be a variety of lymphocytes, plasma cell presursors and plasma cells in bone marrow similar to Waldenstrom’s Macroglobulinemia.
67
Q

What is seen in electrophoresis analysis of heavy chain disease gamma?

A
  1. Band or sharp peak can be see in beta-gamma portion of electrophoresis.
  2. Presence of gamma H chains is diagnostic.

Note: Serum protein electrophoresis very helpful for diagnosis.

68
Q

What kind of cell gives a clue that heavy chain disease - Mu is present?

A

Detection of mature vacuolated plasma cells in bone marrow provide clue to Mu which is present in two thirds of cases.

69
Q

Where are the mu chains found in heavy chain disease - Mu?

A

Free mu chains in the serum but not in the urine.

70
Q

What does HCD-Mu show in a serum protein electrophoresis analysis?

A

Serum protein electrophoresis show hypogammaglobulinemia, free mu chains in the serum but not in the urine.

71
Q

What type of chains are the Bence Jones Proteins found in the urine in HCD-Mu?

A

Only HCD in which Bence Jones Proteins usually kappa are secreted in urine.

72
Q

What two analysis are most helpful in the diagnosis of HCD-Mu?

A

Serum protein electrophoresis and Bence Jones proteins very helpful for detection and diagnosis.

73
Q

What is Monoclonal Gammopathy of Uncertain Significance (MGUS)?

A

Presence of monoclonal protein on electrophoresis but with no other clinical or laboratory evidence of plasma cell dyscrasia.

Surprising frequent finding especially with increasing age.

74
Q

*What is the percentage of people that have Monoclonal Gammopathy of Uncertain Significance (MGUS)?

A

1% of those older than 25 and 3% of those older than 70 found to have MGUS.

75
Q

*What can happen with those that have MGUS?

A

The Monoclonal concentration remains stable for many years.

Must be followed as 25% will develop one of the malignant disorders (plasma cell dyscrasias).

Hematology 2 (25 decks)

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