Myeloma and amyloid and monoclonal gammopathy of uncertain significance Flashcards
What is Multiple myeloma?
Malignancy of mature bone marrow plasma cell.
the terminally differentiated and immunoglobulin (Ig) secreting B Cells
The long-lived IgG/IgA plasma cells are those that form Multiple Myeloma’s
What is the median age of diagnosis? and which group of people is it more common in?
- Median age 67 years
2. More common in men and afrocarribeans
What are the main risk factors for multiple myeloma?
- Age
- Obesity
- Genetics (afrocarribean or FHx)
Which 2 condiitions is multiple myeloma preceded by? What are their diagnostic criteria?
- Monoclonal Gammopathy of Uncertain Significance (MGUS).
- > Serum M Protein <30g/L (M protein = Monoclonal Protein)
- > Bone marrow clonal plasma cells <10%
- Smouldering Myeloma (next step after MGUS basically)
-> Serum M Protein > 30g/L OR Urinary Monoclonal Protein >500mg
OR
-> Bone marrow clonal plasma cells 10-60%
What are patients with MGUS at an increased risk of?
- > Osteoporosis
- > Thrombosis
- > Bacterial Infection
What percentage of patients with MGUS develop myeloma?
around 1%
What are 3 characteristics of cells in multiple myeloma?
These cells hone in and infiltrate the bone marrow
These cells may also form tumours at bone or soft tissue i.e. plasmacytomas
They also release;
-> Monocloncal IgG or IgA -> i.e. paraprotein/ M-spike
-> Serum free light chains (Kappa or Lambda), when found in the urine this is a Bence Jones Protein
What are the consequences of multiple myeloma cells interacting with bone?
- Bone destruction (osteoclast activation, results in high Ca2+)
- Angiogenesis
- Pancytopenia (mostly anaemia)
- Immunosuppression
How do you diagnose multiple myeloma?
- > 10% plasma cells in bone marrow OR plasmacytoma
+
- 1 CRAB or 1 MDE
What is CRAB and MDE?
CRAB: hyperCalcaemia Renal disease Anaemia Bone disease
MDE (myeloma defining events)
bone marrow plasma cells >60%
>1 focal lesion in MRI
What is the clinical presentation of a patient with multiple myeloma bone disease?
80% present with bone disease
- Proximal skeleton involvement
- Spine, chest wall and pelvic pain
- Osteolytic lesions
- Osteopenia
- Pathalogical fractures
- Hypercalcaemia
What kind of imaging is used for multiple myeloma?
- Whole body CT
- CT / FDG-PET scan
- Whole body diffusion weighted MRI
What are 2 emergencies to do with myeloma?
- Cord compression
MRI
Dexamethsone + Radiotherapy - Hypercalcaemia
Fluids, steroids and zolendronic acid
How are the kidneys affected in the patient with multiple myeloma?
Physiologically, B Cells produce more Light Chains than Heavy chains, as a result their tends to be some Serum Free Circulating Light Chains i.e. Kappa or Lambda.
-> These are filtered by the glomeruli and reabsorbed by the proximal tubule to which they are recycled into the body.
In Multiple Myeloma, the sheer amount of Serum Free Light Chains overwhelms the reabsoptive capabilities of the proximal tubule.
- > The light chains enter the distal tubule where they bind to THP (Tamm Horsfall Protein) o.e. Uromodulin
- > Here they form gel like materials which destroy the nephron
What is a good marker of prognosis and outcome of multiple myeloma?
Kidney Disease
- > Those with severe kidney disease i.e. eGFR<30ml/min have a worse outcome.
- > If the Myeloma Kidney Disease can be overturned, patient outcome improves dramatically.
