Plasma cell myeloma Flashcards
(47 cards)
Definition of multiple myeloma
malignancy of terminally differentiated plasma cells - Ig secreting B cells
Histology of plasma cells
Blue cytoplasm
pale area - golgi apparatus
Summarise features of myeloma plasma cells
home and infiltrate in bone marrow
can form bone expansile or soft tissue tumours - plasmacytomas
produce serum monoclonal IgG or IgA- paraprotein or M spike
make excess monoclonal (K/Lambda) serum free light chains
Bence jones protein - urine monoclonal free light chains
Summarise B cell development in the context of myeloma
Normal counterpart for myeloma cells is - terminally differentiated long-lived plasma cells in bone marrow
ie have been through whole path of B cell development:
been mature B Cell -> lymphoid organ -> if receptor recognise epitope either become:
1. short lived plasma cells produce IgM counterpart for lymphoma
2. go through germinal centre
* 3. Somatic hypermutation - increases affinity of Ab to epitope
* class switch recombination form IgM -> IgG or IgA
3. then either memory cell or long lived plasma cell
epidemiology of myeloma
Older age
>men
>black
prevalence increasing - 2nd most common haematological malignancy
Aetiology of myeloma
Unknown
RF
* obesity
* age
* genetics - suggested by FHx, ethnicity
Always preceded by monoclonal gammopathy of uncertain significance
Summarise monoclonal gammopathy of uncertain significance
Presence of monoclonal Ig in blood or urine
Commonly find in elderly - risk increases with age
Bone marrow plasma clonal cells <10%
No sx or organ damage
progresses to multiple myeloma -1% risk of progression/yr
Higher risk of osteoporosis, thrombosis, bacterial infection etc
MGUS risk stratification and mx
Mayo criteria
RF
1. non-IgG M spike
2. M spike >15g/L
3. abnormal serum fre light chain ration (kappa and lambda)
more RF = more risk of progression
What is smouldering myeloma
both:
1. serum monoclonal protein (IgG or IgA) >= 30g, or urine >=500mg/24hr and/or clonal bone marrow plasma cells 10-60%
2. absence of myeloma defining events or amyloidosis
*no sx *
Risk stratification for smouldering myeloma
IMWG model
No evidence that beneficial to rx high risk disease
Clinical spectrum of myeloma
Clonal cells get more mutations with time -> malignancy
Microenv in immune system - immune system in equilibrium with plasma cells in bone marrow - if lost - then the plasma cells escape - get sx disease
Cycle of remission and relapse - until run out of treatment options - when become refractrory - proliferative disease
Pathogenesis of multiple myeloma
primary - can see at MGUS
either have hyperdiploidy or rearrangement of the locus of the heavy Ig gene - bring genes close to powerful enhancer
secondary - additional genetic event contribute to progression and refractory to rx later
clonal cells** interact with microenvironment -**>
1. All of the sx and organ damage either due to this or the high level of Hb in blood
1. Stimulate osteoclasts to destroy bones - get hyperca, fractures, bone pain
1. Osteoblasts support the growth and proliferation of plasma cells
suppress bone marrow cells -> anaemia, immunocompromised
**Myeloma paralyses immune system - **and escapes immunological control - this process happens in relapse
Diagnostic criteria for multiple myeloma
> =10% plasma cells in marrow/plasmacytoma and at least 1 CRAB feature
bone disease - pain/lytic lesion/fracture
What is myeloma defining events
bone marrow plasma cells >=60%
involved:uninvolved FLC ratio >100
1 focal lesion in MRI >5mm
*Don’t have CRAB or other sx
In next few mo - they will devlelop the disease
So consider them the asx myeloma *
Bone disease in multiple myeloma
Involves the prox skeleton
Skull, spine, ribs, pelvis
Can cause fractures - lesions are always osteolytic
Can cause osteopenia
High ca
Pathological fractures
Ix for bone disease in multiple myeloma
Whole body CT scan low dose
CT/FDG-PET
Whole body diffusion weighted MRI - bone marrow cellularity, active/residual vs treated disease
Bone disease and emergencies in myeloma
cord compression
hypercalcaemia
cord compression in myeloma
Fracture/soft tissue -> spinal canal -> paralysing from that level down, back pain
dx in 24hrs - MRI
Ig and free light chanin studies +/- biopsy
dexamethasone
radiotherapy
neurosurgery - rarely
stablise unstable spine
MDT
Hypercalcaemia and myeloma
present: drowsy, constipation, fatigue, muscle weakness, AKI
Mx
1. fluids
2. steroids
3. zolendronic acid
definition of myeloma kidney disease
serum creatinine >177umol (>2mg/dL) or eGFR <40
acute kidney injury as result of myeloma
common
Pathophysiology of myeloma kidney disease
- Light chains - pass glomerulus in filtrate
- In prox tubules - cell detect the light chains - capture - endocytose and reabsorb
- When levels increase - cells go into stress - most light chains not resorbed
- Bind to uromodulin - form casts - block the passage in renal tubules
hyperca, loop diuretics, infection, dehydration and nephrotoxics also contribute
effect of myeloma kidney disease on Px
Kidney disease have a major impact on outcome - early death, prolonged stay, lethal injections
nephrotoxic/renally excreted myeloma drugs - zoledronic acid, lenalidomide
Has to be mx as medical emergency - try to redyuce the free light chains - stop kidnye injury - and hope kiudneys recover
Most effective rx - bortezomib
Why does myeloma predispose to infection
immunoparesis - low serum normal Igs
myeloid, T cells and NK cell impairment
chemo impairs immune response
myeloma immune invasion
Susceptable to gram +ve first - then -ve and viruses
Myeloma and covid
High mortality
RF - age, high risk disease, progressive/active disease, renal failure, non-white patients
reduced response to vaccination
