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Heme / Onc > SM_266b: Multiple Myeloma > Flashcards

SM_266b: Multiple Myeloma Flashcards

1
Q

This is a ___

A

Plasma cell

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2
Q

Describe plasma cells

A

Plasma cell

  • Perinuclear hof
  • Fried egg appearance
  • Clock face chromatin pattern in the nucleus
  • Express bright CD38, CD138, and cytoplasmic immunoglobulins
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3
Q

B cells are antigen selected in the ___ and some differentiate into ___

A

B cells are antigen selected in the germinal center and some differentiate into plasma cells

  • Plasma cells are terminally differentiated B cells
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4
Q

Normal plasma cells produce ___

A

Normal plasma cells produce immunoglobulins (antibodies) that are highly specific for antigen

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5
Q

Immunoglobulins consist of ____ and ____

A

Immunoglobulins consist of light chain and heavy chain

  • Light chain: kappa or lambda
  • Heavy chain: IgG, IgM, IgE, IgA, or IgD
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6
Q

B cells have ___ Ig while plasma cells have ___ Ig and ___ Ig

A

B cells have surface Ig while plasma cells have cytoplasmic Ig and secreted Ig

  • Plasma cells are responsible for producing immunoglobulins
  • Immunoglobulins are critical for immunity
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7
Q

Each plasma cell expresses ___ light chains

A

Each plasma cell expresses kappa OR lambda light chains

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8
Q

In normal reactive plasma cell population, kappa:lambda ratio is about ___

A

In normal reactive plasma cell population, kappa:lambda ratio is about 2:1

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9
Q

____ can help identify a clonal plasma cell population

A

Skewing of the kappa:lambda ratio can help identify a clonal plasma cell population

  • Flow cytometry and immunohistochemistry can be used to evaluate light chains
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10
Q

Plasma cell neoplasm is ___

A

Plasma cell neoplasm is uncontrolled growth and expansion of a single clone of plasma cells

  • Clonal plasma cells typically produce clonal immunoglobulin
  • Presence of clonal plasma cells is NOT sufficient for diagnosis of multiple myeloma
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11
Q

Monoclonal gammopathy is ___

A

Monoclonal gammopathy is a monoclonal immunoglobulin in the blood or urine identified by serum or urine protein electrophoresis or immunofixation

  • Also called paraprotein, M protein, M component, M spike
  • Not always IgM
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12
Q

Describe serum protein electrophoresis

A

Serum protein electrophoresis

  • Serum proteins separated by running on a gel electrophoresis
  • Bands on gel are quantified (peaks)
  • Immunofixation used to identify heavy and light chain
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13
Q

Monoclonal gammopathy of undetermined significance is ___ and ___

A

Monoclonal gammopathy of undetermined significance is most common plasma cell disorder and is asymptomatic

  • Monoclonal expansion of plasma cells with associated monoclonal gammopathy
  • < 10% of clonal plasma cells in the bone marrow
  • No evidence of end organ damage
  • 1-2% progress to multiple myeloma per year
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14
Q

Multiple myeloma is ____ with ____

A

Multiple myeloma is bone marrow-based malignant proliferation of plasma cells (10-60%) with evidence of organ or tissue damage

  • Production of a monoclonal immunoglobulin
  • If plasma cells > 60% of bone marrow, other findings not necessary for diagnosis
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15
Q

Multiple myeloma involves ___ with ___, ___, ___, and ___

A

Multiple myeloma involves evidence of end organ damage including hypercalcemia, renal insufficiency, anemia, and bone lesions

  • CRAB
  • Osteolytic lesions identified on radiographic imaging
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16
Q

Describe epidemiology and etiology of multiple myeloma

A

Multiple myeloma

  • Peak incidence at 65-70 years old
  • Etiology unknown
  • Predisposing factors: family history of myeloma or monoclonal gammopathy of undetermined significance, decreased immunity, or radiation
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17
Q

Smoldering myeloma is ___ with ___

A

Smoldering myeloma is bone marrow-based malignant proliferation of plasma cells (10-60%) with no evidence of organ or tissue damage

  • Production of a monoclonal immunoglobulin
  • 75% progress to symptomatic myeloma
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18
Q

Multiple myeloma is diagnosed via ___

A

Multiple myeloma is diagnosed via aspirate or core biopsy of bone marrow

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19
Q

This is bone marrow biopsy showing ___

A

Multiple myeloma

20
Q

____ immunostain highlights plasma cells

A

CD138 immunostain highlights plasma cells

21
Q

Antibodies against ___ can detect clonal plasma cell populations

A

Antibodies against light chains can detect clonal plasma cell populations

22
Q

Bone marrow aspirate in multiple myeloma shows ___

A

Bone marrow aspirate in multiple myeloma shows increased plasma cells

23
Q

Dutcher bodies and Russell bodies are characteristic of ____

A

Dutcher bodies and Russell bodies are characteristic of multiple myeloma

24
Q

Plasma cells are identified with ___ and ___

A

Plasma cells are identified with CD138 and CD38

25
Q

Normal plasma cells are ____, ____, and ____

A

Normal plasma cells are CD19+, CD56-, and polyclonal

26
Q

Neoplastic plasma cells are ____, ____, and ____

A

Neoplastic plasma cells are CD19-, CD56+, and monoclonal

27
Q

Myekoma cells produce factors that ___

A

Myekoma cells produce factors that drive bone destruction

  • Expression of MIP1-alpha -> activation of RANKL -> activates osteoclasts (cells that resorb bone)
28
Q

Myeloma cells produce ___

A

Myeloma cells produce IL-6

  • Also dependent on IL-6 for growth, survival, and immunoglobulin
29
Q

Multiple myeloma involves ____

A

Multiple myeloma involves massive production of immunoglobulins

  • Contributes to pathology of disease
  • IgG is 55%, IgA is 25%
  • Clonal plasma cells often produce light chains in excess of whole Ig molecule
  • 20% only produce light chains
30
Q

Quantitative serum immunoglobulin analysis is useful for ___ and ___

A

Quantitative serum immunoglobulin analysis is useful for diagnosis and disease monitoring of plasma cell neoplasms

  • IgG: 800-1600 mg/dL
  • IgA: 200-400 mg/dL
  • IgM: 100-200 mg/dL
31
Q

Monoclonal light chains are smaller and can be excreted into the urine (_____)

A

Monoclonal light chains are smaller and can be excreted into the urine (Bence-Jones proteins)

32
Q

Immunoglobulins and immunoglobulin components produced by myeloma cells are often ___ and can be ___

A

Immunoglobulins and immunoglobulin components produced by myeloma cells are often abnormal and can be nephrotoxic

33
Q

Multiple myeloma involves misfolded ____ leading to ____

A

Multiple myeloma involves misfolded monoclonal light chains deposited in extracellular tissues (amyloid)

  • Beta pleated sheat form from some clonal light chains
  • Causes nephrotic syndrome
34
Q

Congo red stain shows ___ under polarization in the presence of amyloid in multiple myeloma

A

Congo red stain shows apple green birefringence under polarization in the presence of amyloid in multiple myeloma

35
Q

Multiple myeloma presents with ___ that appears as ___

A

Multiple myeloma presents with anemia that appears as Rouleaux formation

  • Anemia secondary to bone marrow suppression and renal failure
  • Rouleaux: RBCs stacking like coins, results from alteration of negative charge of RBCs by immunoglobulins in serum
36
Q

Multiple myeloma presents with ____, ____, ____, ____, and ____

A

Multiple myeloma presents with anemia, hypercalcemia, lytic bone lesions, renal insufficiency, and amyloidosis

37
Q

Describe clinial findings in multiple myeloma

A

Multiple myeloma

  • Anemia
  • Hypercalcemia (corrected serum Ca > 11.5 mg/dL): secondary to bone destruction
  • Bone lytic lesions (punched out): axial skeleton, pathological fractures
  • Renal insufficiency (elevated serum Cr): secondary to light chain deposition in kidney
  • Amyloidosis: certain monoclonal light chains can deposit in beta-pleated sheets in tissue, contribute to renal failure and cause multi-organ failure
38
Q

Monoclonal immunoglobulins ___ against bacteria, so people with multiple myeloma most commonly die from ___

A

Monoclonal immunoglobulins are NOT protective against bacteria, so people with multiple myeloma most commonly die from infection

  • Production of other normal immunoglobulins is suppressed: hypogammaglobulinemia
39
Q

Survival in mutliple myeloma is ___

A

Survival in mutliple myeloma is variable

  • Prognostic factors: stage (tumor burden), patient factors, tumor biology, response to therapy
40
Q

Del(17p) in multiple myeloma predicts ___ prognosis

A

Del(17p) in multiple myeloma predicts poor prognosis

41
Q

Multiple myeloma is treated with ___

A

Multiple myeloma is treated with high-dose combination chemo with autologous stem cell transplant

  • Followed by maintenance therapy
42
Q

Daratumumab is a ___ used to treat multiple myeloma

A

Daratumumab is a monoclonal antibody targeting CD38 which binds to plasma cells used to treat multiple myeloma

  • Kills cells directly and helps immune system attack the cells
43
Q

Describe solitary plasmacytoma

A

Solitary plasmacytoma

  • Solitary plasmacytoma of bone: 50% have monoclonal gammopathy, 2/3 develop multiple myeloma
  • Extramedullary (outside of bone): upper respiratory site, cured often, progression to multiple myeloma rare
44
Q

Primary amyloidosis (immunoglobulin light chain amyloidosis) is ___

A

Primary amyloidosis (immunoglobulin light chain amyloidosis) is deposition of immunoglobulin light chains (kappa or lambda) which form a beta-pleated sheet in various tissues

  • Can be seen with or without multiple myeloma
45
Q

Waldenstrom’s macroglobulinemia is ___

A

Waldenstrom’s macroglobulinemia is IgM monoclonal gammopathy in the presence of lymphoplasmocytic lymphoma

  • Serum hyperviscosity caused by IgM pentamers
  • Bleeding due to platelet dysfunction
  • Lytic bone lesions are absent
  • MYD88 gene mutation
46
Q

Neoplastic cells ___ like plasma cells

A

Neoplastic cells do NOT always look like plasma cells

Heme / Onc (41 decks)

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