Haematology 12: Myeloma And Amyloid, Monocloncal Gammopathy Flashcards
What is monoclonal gammopathy of uncertain significance (MGUS) ?
- IgG/IgA < 30G/L
- <10% clonal plasma cells
- No symptoms (CRAB)
- Genetic errors occur in plasma cell due to infection, inflammation or chromosomal instability.
- This causes monoclonal accumulation of the plasma cells
- This is considered harmless but pre-malignant
- If further mutation, can become multiple myeloma
Which mutation can trigger transformation of MGUS to multiple myeloma ?
K-RAS
What are the clinical features of Multiple myeloma ?
Calcium - elevated
Renal impairment
Anaemia
Bone lesions
Monoclonal paraprotein (gammaglobulins) Bence jones protein in urine (immunoglobulin light chains)
What are some of the characteristic features of Multiple myeloma on histology ?
Overcrowding of plasma cells in bone marrow
Plasmacytic cells: Nucleus on one side (eccentric nucleus), dense chromatin, low nuclear to cytoplasmic ratio
Plasmablastic cells: prominent nucleoli, reticular chromatin, less cytoplasm than mature cells
Red cell rouleaux
List 3 characteristic finding of multiple myeloma on Immunohistochemistry ?
CD138
CD38
light chain restricted Ig
What is fanconi syndrome ?
Renal tubule acidosis with light chain Chrystal depositions
What are the 4 main types of treatment for multiple myeloma ?
Cytostatic drug - Melphalan
Steroids
Immuno modulators- Thalidomide
Proteasome inhibitors
List the 3 features required to diagnose Multiple myeloma ?
- Clonal plasma cells on bone marrow biopsy
- Paraprotein in blood or urine
- Evidence of end-organ damage - CRAB
List the 3 features that are required to diagnose Smouldering myeloma ?
- Serum paraprotein > 30 g/L
- Clonal plasma cell > 10 % on bone marrow biopsy
- No evidence of end organ damage (CRAB)
(This is basically asymptomatic MM)
List 3 features required to diagnose MGUS ?
- Serum paraprotein < 30g/l
- Clonal plasma cells < 10 % on bone marrow biopsy
- No signs of end organ damage (CRAB)
List 3 features of waldenstrom macroglobinaemia ?
- Low grade NHL (lymphoplasmacytoid)
- Monoclonal IgM
- Hyperviscosity symptoms (visual problems, CCF, weakness, confusion)
list some key features of myeloma plasma cells
infiltrate bone marrow
can form expansile or soft tissue tumours - plasmacytomas
produce a serym monoclonal IgG or IgA - paraprotein or M spike
produce excess of monoclonal kappa or lambda free light chains
BJ protein in urine - urine monoclonal free light chains
define multiple myeloma
cancer of transformed plasma cells, terminally differentiated B cells, that secrete immunoglobulins and are effector cells of the specific humoural response
describe B cell development
common lymphoid progenitor … mature B cell (bone marrow)
mature B cell… short lived plasma cell (marginal zone)
mature B cell … memory cell/ long lived plasma cell (germinal centre)
RF for myeloma
obesity
age
genetics
always preceded by a premalignany condition = MGUS
what is MGUS
most common (known) premalignant condition incidence increases with age average risk of progression 1% annually IgG or IgA MGUS --> myeloma IgM --> lymphoma