264 - Multiple Myeloma Flashcards
What is the therapy for myeloma?
- High dose combination therapy with autologous stem cell transplant
- Prognosis variable
- Do more chemo if pt not elligible for stem cell transplant
What is the significance of Ig light chains in multiple myeloma?
- Myeloma cells produce more light chain than heavy chain–> extra light chains floating around
- light chains excreted in urine as Bence-Jones proteins
- Can be nephrotoxic
- Misfolded light chains -> can form amyloid -> Nephrotic syndrome
What is the normal kappa:lamba ratio in plasma cells?
What is the significance of a deviation from this ratio?
Kappa:Lambda = 2:1
Deviation => Clonal population (possible malignancy, cannot diagnosis without consistent clinical features)
Note: Dr. Gao’s lecutre (264) says ~1:1, and Dr. Wolniak’s lecture (266) says ~2:1
What hematologic malignancy arises from plasma cells?
Multiple myeloma
What cytokine drives myeloma cell growth, survival, and Ig production?
IL-6
- myeloma cells will produce IL-6 and are also dependent on it for growth, survival, and immunoglobin production
What is the most frequent cause of death in multiple myeloma?
Infection
- Malignant plasma cells
- -> no healthy/functional plasma cells
- -> not enough working antibody
- -> cannot protect against infection
What testing method do we use to find monoclonal gammopathies?
Serum Protein Electrophoresis (SPEP)
- serum proteins separated when running on a gel, can quantify
- If <10% clonal plasma cells = monoclonal gammopathy of undetermined significance (MGUS)
- If >10% clonal plasma cells = may be multiple myeloma (need to have consistent clinical features though)
What are the characteristics of plasma cells?
(2 morphologic features, 2 markers)
Morphologic Features:
- Fried egg appearance w/ perinuclear hof (pale region alongside the nucleus)
- Clock-face chromatin (rare to see)
Markers:
- CD38+
- CD138+
- Markers are cytoplasmic => detected on immunostain, not flow cytommetry
What do plasma cells produce in abundance that can have pathologic effects on organs (especially the kidney)?
Immunoglobulins (antibodies) -> deposition -> tissue damage
Ig Light chains can also form amyloid -> tissue damage
What finding on peripheral blood smear may be concerning for multiple myeloma?
Roleaux formation (stack of coins)
- Immunoglobulins in serum alter normal (-) charge of RBCs -> they stick together
- Not specific, but warrants further screening*
What is the diagnosis if a patient has 10-60% monotypic plasma cells but no clinical signs of myeloma?
Smoldering myeloma
- bone marrow based malignant proliferation of plasma cells (10-60%)
- production of monoclonal immunoglobin but no evidence of organ/tissue damage
75% chance of turning into myeloma
What will plasma cells look like on flow cytometry?
CD 19+
CD56-
If CD19- and CD56+, likely a neoplastic plasma cell
Immunostain will show CD138+, CD38+ (but these are cytoplasmic markers so won’t show on flow cytometry)
What are the diagnostic criteria for multiple myeloma?
≥ 10% clonal plasma cells in the bone marrow, in the setting of myeloma-defining clinical criteria
- Myeloma-defining criteria: CRAB
- HyperCalcemia
- Renal insufficiency
- Anemia
- Bone lesions
Monoclonal gammopathy is not sufficient to diagnose - need clinical criteria
What do Bence Jones proteins in the urine indicate?
Multiple myeloma
If consistent clinical picture (ex: lytic bone lesions, hypercalcemia)
Ig Light Chains enter the urine -> Bence Jones proteins
How does the presentation of Waldenstrom’s macroglobulinemia differ from that of myeloma?
= IgM monoclonal gammopathy in the presence of lymphoplasmacytic lymphoma
Waldenstrom will have:
- Hyperviscosity syndrome caused by IgM pentamers
- Bleeding due to platelet dysfunction
- No lytic bone lesions
- MYD88 gene mutation
Waldenstrom is an IgM monoclonal gammopathy
