Multiple Myeloma and Related Flashcards
plasma cell neoplasms
unregulated proliferation of a clonal plasma cell population
clinical manifestations caused by:
- expansion of neoplastic cells in bone marrow
- immunoglobin secretion
- suppression of normal immune function
multiple myeloma
clonal population of neoplastic plasma cells (terminally differentiated B cells), >10% of bone marrow
production of monoclonal immunoglobin referred to as “M” protein - any one of 5 isotypes, sometimes only light chains are produced
which cytokine is an important mediator of proliferation in multiple myeloma?
IL-6 (inflammatory)
associated with worse prognosis
what are the “M proteins” produced in multiple myeloma?
single isotype Ig - usually IgG, sometimes IgA (but can be any isotype)
complete antibodies confined to blood and excluded from urine
in some cases, only light chains (kappa or lambda) produced - small, can enter kidney and damage tubules
what is the clinical presentation of multiple myeloma?
CRAB:
Calcium disorders (hypercalcemia)
Renal insufficiency
Anemia (normocytic)
Bone pain
Bacterial infection
describe the bone pain associated with multiple myeloma (what causes it?)
bone pain is most common presenting symptom
tumor expansion in bone marrow, hyperactive osteoclasts (via increased RANKL activity) cause bone destruction —> increased risk of pathological fractures
multiple myeloma cells suppress osteoblast activity
bone lesions appear radiographically as “punched out” defects
myeloma in vertebrae can cause acute spinal cord compression
explain how bone disease and hypercalcemia observed in patients with multiple myeloma are related
increased osteoclasts activity (via increased RANKL activity) causes increased bone resorption —> increased serum calcium —> hypercalcemia and renal injury
half of patients with multiple myeloma will have renal insufficiency at diagnosis
how does this occur?
major causes of renal insufficiency:
1. light chains in urine (toxic to kidney PCT) - “Bence-Jones proteins”
2. hypercalcemia (remember this is related to bone destruction)
increased creatinine observed
what kind of anemia develops in patients with multiple myeloma?
normoctyic anemia with low reticulocytes
due to replacement of marrow by expanding tumor, renal dysfunction (low EPO), EPO unresponsiveness (because of myeloma cell cytokines)
*note that bone marrow infiltration can lead to pancytopenia
what would you see on a peripheral smear of a patient with multiple myeloma?
Rouleaux formation: RBC stick together and looked like stacked coins
occurs due to evaluated plasma globulins
what kind of immunity is impaired in patients with multiple myeloma? what does this lead to?
humoral immunity is impaired! (B cells)
patients have large amount of monoclonal antibodies - not super helpful !
—> hypogammaglobinemia: suppression of normal antibody synthesis and destruction of normal antibodies
how is multiple myeloma diagnosed? (3)
- presence of serum “M protein”
- presence of urine free light chains (some cases)
- clonal expansion of neoplasticism plasma cells in bone marrow (>10%)
what is the first clue of multiple myeloma?
increase in TOTAL serum protein levels, due to increased immunoglobulin
follow up with serum protein electrophoresis (SPEP) - will see “M spike” (narrow band, since it is monoclonal population)
*note that urine dipstick will be negative for protein because it is specific for albumin!
what is immunofixation used for?
determines isotype of monoclonal protein, as in multiple myeloma
in multiple myeloma you will see sharp bands and single light chain type (normal should be diffuse with both light chains present)
in patients with multiple myeloma, renal failure is higher for those with:
a. intact antibodies
b. light chains
light chains - more at risk for renal failure
