SM_266b: Multiple Myeloma Flashcards
This is a ___
Plasma cell
Describe plasma cells
Plasma cell
- Perinuclear hof
- Fried egg appearance
- Clock face chromatin pattern in the nucleus
- Express bright CD38, CD138, and cytoplasmic immunoglobulins
B cells are antigen selected in the ___ and some differentiate into ___
B cells are antigen selected in the germinal center and some differentiate into plasma cells
- Plasma cells are terminally differentiated B cells
Normal plasma cells produce ___
Normal plasma cells produce immunoglobulins (antibodies) that are highly specific for antigen
Immunoglobulins consist of ____ and ____
Immunoglobulins consist of light chain and heavy chain
- Light chain: kappa or lambda
- Heavy chain: IgG, IgM, IgE, IgA, or IgD
B cells have ___ Ig while plasma cells have ___ Ig and ___ Ig
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
Each plasma cell expresses ___ light chains
Each plasma cell expresses kappa OR lambda light chains
In normal reactive plasma cell population, kappa:lambda ratio is about ___
In normal reactive plasma cell population, kappa:lambda ratio is about 2:1
____ can help identify a clonal plasma cell population
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
Plasma cell neoplasm is ___
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
Monoclonal gammopathy is ___
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
Describe serum protein electrophoresis
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
Monoclonal gammopathy of undetermined significance is ___ and ___
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
Multiple myeloma is ____ with ____
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
Multiple myeloma involves ___ with ___, ___, ___, and ___
Multiple myeloma involves evidence of end organ damage including hypercalcemia, renal insufficiency, anemia, and bone lesions
- CRAB
- Osteolytic lesions identified on radiographic imaging
Describe epidemiology and etiology of multiple myeloma
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
Smoldering myeloma is ___ with ___
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
Multiple myeloma is diagnosed via ___
Multiple myeloma is diagnosed via aspirate or core biopsy of bone marrow
This is bone marrow biopsy showing ___
Multiple myeloma
____ immunostain highlights plasma cells
CD138 immunostain highlights plasma cells
Antibodies against ___ can detect clonal plasma cell populations
Antibodies against light chains can detect clonal plasma cell populations
Bone marrow aspirate in multiple myeloma shows ___
Bone marrow aspirate in multiple myeloma shows increased plasma cells
Dutcher bodies and Russell bodies are characteristic of ____
Dutcher bodies and Russell bodies are characteristic of multiple myeloma
Plasma cells are identified with ___ and ___
Plasma cells are identified with CD138 and CD38
Normal plasma cells are ____, ____, and ____
Normal plasma cells are CD19+, CD56-, and polyclonal
Neoplastic plasma cells are ____, ____, and ____
Neoplastic plasma cells are CD19-, CD56+, and monoclonal
Myekoma cells produce factors that ___
Myekoma cells produce factors that drive bone destruction
- Expression of MIP1-alpha -> activation of RANKL -> activates osteoclasts (cells that resorb bone)
Myeloma cells produce ___
Myeloma cells produce IL-6
- Also dependent on IL-6 for growth, survival, and immunoglobulin
Multiple myeloma involves ____
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
Quantitative serum immunoglobulin analysis is useful for ___ and ___
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
Monoclonal light chains are smaller and can be excreted into the urine (_____)
Monoclonal light chains are smaller and can be excreted into the urine (Bence-Jones proteins)
Immunoglobulins and immunoglobulin components produced by myeloma cells are often ___ and can be ___
Immunoglobulins and immunoglobulin components produced by myeloma cells are often abnormal and can be nephrotoxic
Multiple myeloma involves misfolded ____ leading to ____
Multiple myeloma involves misfolded monoclonal light chains deposited in extracellular tissues (amyloid)
- Beta pleated sheat form from some clonal light chains
- Causes nephrotic syndrome
Congo red stain shows ___ under polarization in the presence of amyloid in multiple myeloma
Congo red stain shows apple green birefringence under polarization in the presence of amyloid in multiple myeloma
Multiple myeloma presents with ___ that appears as ___
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
Multiple myeloma presents with ____, ____, ____, ____, and ____
Multiple myeloma presents with anemia, hypercalcemia, lytic bone lesions, renal insufficiency, and amyloidosis
Describe clinial findings in multiple myeloma
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
Monoclonal immunoglobulins ___ against bacteria, so people with multiple myeloma most commonly die from ___
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
Survival in mutliple myeloma is ___
Survival in mutliple myeloma is variable
- Prognostic factors: stage (tumor burden), patient factors, tumor biology, response to therapy
Del(17p) in multiple myeloma predicts ___ prognosis
Del(17p) in multiple myeloma predicts poor prognosis
Multiple myeloma is treated with ___
Multiple myeloma is treated with high-dose combination chemo with autologous stem cell transplant
- Followed by maintenance therapy
Daratumumab is a ___ used to treat multiple myeloma
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
Describe solitary plasmacytoma
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
Primary amyloidosis (immunoglobulin light chain amyloidosis) is ___
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
Waldenstrom’s macroglobulinemia is ___
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
Neoplastic cells ___ like plasma cells
Neoplastic cells do NOT always look like plasma cells
