Multiple myeloma Flashcards
MM is the malignant proliferation of….
Plasma cells in the bone marrow –> destroys bone and bone marrow
MM is characterised by high serum …
IL6 (plasma cell growth factor)
Stimulates plasma cell growth and immunoglobulin production
List clinical features (mostly investigation findings) of MM
Bone
- Bone pain + hypercalcaemia
- Lytic lesions especially on vertebrae and skull (don’t come up on bone scan)
- Pathological fractures
Elevated serum protein - neoplastic plasma cells produce immunoglobulin; M spike (in the gamma region) is present on SPEP, most commonly due to IgA or IgG
Infection - monoclonal ab lacks antigenic diversity; most common cause of death
Rouleaux formation of RBCs on blood film
Normo/macrocytic anaemia
High total protein but low albumin!
Primary amyloid light chain amyloidosis - free light chains are overproduced relative to heavy chains and deposit in tissues
Kidneys
Proteinuria - free light chains are excreted in the urine as bence jones proteins
Renal failure - deposition of free light chains in the kidney tubules lead to kidney failure
Hyperviscosity
- Confusion, headache, visual changes, mucosal haemorrhage, high output CCF
- Fundoscopy: flame haemorrhages
What’s monoclonal gammopathy of undetermined significance (MGUS)?
Pre-myeloma state
Increased serum protein with M spike on SPEP but no other features e.g. CRAB features of MM
What are the CRAB features of MM?
Hypercalcaemia
Renal failure (CrCl <40)
Anaemia (Hb <100)
Bone disease (1+ lytic lesions)
What % of MGUS becomes MM?
1% of MGUS develops into MM per year
Do we treat MGUS or smouldering myeloma?
No
Treatment is only offered to MM
What’s the difference between smouldering myeloma and MGUS?
Both don’t have CRAB features
MGUS has <10% clonal plasma cells in BM
Smouldering has 10-60% clonal plasma cells in BM
How does multiple myeloma differ to smouldering or MGUS?
Clonal BM plasma cells ≥10% or ≥1 biopsy-proven plasmacytoma AND 1 or more MM defining events:
- ≥ 1 crab feature
- ≥ 1 Biomarker of malignancy
- —> clonal plasma cell in BM ≥60%
- —> Serum FLC ratio ≥100 (either kappa or lambda)
- —> >1 MRI focal lesion ≥5mm on MRI
What will you see on fundoscopy in MM?
Flame haemorrhages due to hyperviscosity
Rx for hyperviscosity in MM
Plasmapharesis
If IgM >50g/L, IgA >70g/L, IgG >100g/L is a medical emergency
Which is the most viscous? IgM, IgA, IgG?
IgM > IgA > IgG
Hence Waldenstrom macroglobinemia is the most likely to produce hyperviscosity since it predominantly produces IgM antibodies
Standard investigations for MM
FBC, blood film
Biochem including creatinine and calcium
SPEP + immunofixation (more sensitive than SPEP at picking up small M proteins)
UPEP + immunofixation - Bence Jones proteins
BM biopsy and aspirate
Cytogenetics (metaphase karyotype & FISH)
Serum b2 microglobulin prognosis
LDH prognosos
Serum free light chains
- Measures free lambda & kappa light chains
- Measures kappa/lambda ratio
- sFLC may go up in renal failure or immune activation. If the ratio is abnormal, then its monoclonal polyclonal disorders
What would you expect to see in MM? 1) FBC 2) Film C) Biochem 4) LDH
1) normocytic/macrocytic anaemia, cytopenias
2) rouleaux, circulating plasma cells
3) Raised creatinine and calcium, raised total protein, low albumin
4) High LDH in aggressive disease
How does MM cause renal impairment?
1) myeloma cast nephropathy - light chains and paraprotein are filtered through glomerulus –> go through tubules where they complex with tamm-horsfall protein –> form casts –> block tubules
2) Light chain deposition disease
Light chains and paraproteins also trigger inflammatory cascade –> damaging to proximal tubule cells
3) Amyloidosis
4) Acquired fanconi
5) Hypercalcaemia
6) Hyperuricaemia
