Multiple Myeloma Flashcards
What is myeloma?
Malignancy of plasma cells leading to progressive bone marrow failure. It is associated with production of characteristic paraprotein, bone disease and renal failure.
Antibody produced = monoclonal paraprotein!! - KNOW THIS
What cell line is affected by multiple myeloma?
Plasma cells - malignant clonal expansion - produce excessive amounts of one type of Ig/Ig fragment (monoclonal element) in the serum or urine.
Explain the pathophysiology of myeloma.
- Genetic mutation of a specific type of plasma cell, causing it to rapidly and uncontrollably multiply.
- One of the types of Ig will be significantly high
(More than 50% of the time this is IgG). - This single type of antibody that is produced by all the identical cancerous plasma cells can be called a monoclonal paraprotein. This means a single type of abnormal protein.
- The “Bence Jones protein” that can be found in the urine of many patients with myeloma is actually a part (subunit) of the antibody called the light chains.
Give 3 symptoms of myeloma.
- Tiredness.
- Bone/back pain.
- Infections.
Give 4 signs of myeloma.
CRAB!
- Calcium is elevated.
- Renal failure.
- Anaemia.
- Bone lesions.
Why is calcium elevated in myeloma?
There is increased bone resorption and decreased formation meaning there is more calcium in the blood.
What kind of anaemia is seen in patients with multiple myeloma?
Normochromic normocytic.
Why might someone with myeloma have anaemia?
The bone marrow is infiltrated with plasma cells. Consequences of this are anaemia, infections and bleeding.
Why are patients with myeloma susceptible to recurrent infections?
There is a reduction in polyclonal immunoglobulin levels.
Why might someone with myeloma have renal failure?
Due to light chain deposition.
How is multiple myeloma classified?
On a spectrum, according to M protein (a monoclonal component) and presence of tissue/organ involvement:
- MGUS (monoclonal gammopathy of unknown significance)
- M-protein <30g/dL
- BM clonal cells <10% - Smouldering (asymptomatic) myeloma
- M-protein >30
- BM cloncal cells >10%
- BUT no tissue/organ involvement - Active (symptomatic) myeloma
- M-protein >30
- BM cloncal cells >30%
- And CRAB features.
What are the 3 main associations of multiple myeloma?
1) Osteolytic bone disease + hypercalcaemia
2) Anaemia (due to accumulation of plasma cells in BM)
3) Renal disease
Most common haematological malignancy!
Mean age 60yrs
What disease often precedes myeloma?
Monoclonal gammopathy of undetermined significance (MGUS).
What is MGUS?
A common disease with paraprotein present in the serum but no myeloma. Often asymptomatic. <10% plasma cells in the bone marrow.
Give an example of smouldering myeloma.
Waldenstrom’s macroglobulinemia is a type of smouldering myeloma where there is excessive IgM specifically.
In extreme cases, patients with myeloma can present with blurred vision, gangrene and bleeding. What is the pathology behind this?
Paraproteins form aggregates in the blood and change the viscosity.
What are the diagnostic criteria for myeloma?
1) Monoclonal protein band on serum/urine electrophoresis
2) Increased plasma cells on bone marrow biopsy
3) Evidence of end organ damage (hypercalcaemia, renal failure, anaemia)
In order to make a diagnosis of myeloma, there must be evidence of mono-clonality. What is mono-clonality?
Abnormal proliferation of a single clone of plasma cell leading to immunoglobulin secretion and causing organ dysfunction especially to the kidney.
What initial investigations might you do in suspected myeloma?
- FBC (low white blood cell count in myeloma)
- Calcium (raised in myeloma)
- ESR (raised in myeloma)
- Plasma viscosity (raised in myeloma)
If any of these are positive or myeloma is still suspected, do an urgent serum protein electrophoresis and a urine Bence-Jones protein test.
What investigations might you do to diagnose myeloma?
- Blood film.
- Bone marrow aspirate and trephine biopsy.
- Serum Urine/Protein Electrophoresis (Gold standard!!)
- Whole body MRI
- Whole body CT
- Skeletal survey (X-ray images of the full skeleton)
- Chromosomal abnormalities.
BLIP:
Bence-Jones protein urine electrophoresis
Serum free Light chain assay
Serum Ig’s
Protein electrophoresis
How is myeloma bone disease usually assessed?
X-ray.
In approximately 2/3 of people with myeloma, what might their urine contain?
Immunoglobulin light chains with kappa or lamda lineage.
What would you expect to see on the blood film taken from someone with myeloma?
Rouleaux formation (aggregations of RBC’s).
What are you looking for on a bone marrow biopsy taken from someone with myeloma?
Increased plasma cells.
Plasma cells infiltrate >10% (minor) or >30% (major)
