Plasma cell myeloma Flashcards
what is multiple myeloma?
we have been learning in haem about blood malignancies, and these are mainly of blasts (right at beginning of the chain)
multiple myeloma is blood malignancy affecting plasma B cells (right at end of the differentiation chain - even after b cells themselves as plasma cells make antibodies)
Multiple myeloma (MM) is a hematologic neoplastic disease in which uncontrolled proliferation of clonal plasma cells’ leads to end-organ damage
what are the features of multiple myeloma on ivx?
Physical:
may form bone expansile or soft tissue tumours: plasmacytomas
Bloods:
- produce serum monoclonal immunoglobulins IgG or IgA:
paraprotein or M-spike
- excess monoclonal (κ or λ) serum free light chains
Urine:
Bence Jones protein: urine monoclonal free light chains
what is the epidemiology of MM?
2nd most common blood cancer
Median age 67 years
Incidence increases with age
Only 1% of patients are younger than 40 years
Men > women
Black > Caucasian and Asians
what is Waldenstrom’s - Lymphoplasmacytic lymphoma?
a cancer of 2 types of B cells;
plasma cells and lympho-plasmacy-toid cells.
is similar to NHL clinically - indolent. it is not multiplee myeloma but can predispose to MM.
aetiology: genetic mutations
myeloma is always preceded by a which premalignant condition?
Monoclonal Gammopathy of Uncertain Significance (MGUS)
average risk for progression : 1% annually
IgG or IgA MGUS -> _____ ?
IgM -> ____ ?
IgG or IgA MGUS -> myeloma
IgM -> lymphoma
what is the Diagnostic criteria for MGUS (WHO)?
Serum M-protein (monoclonal immunoglobulins) <30g/L
Bone marrow clonal plasma cells <10%
No lytic bone lesions
No myeloma-related organ or tissue impairment
No evidence of other B-cell proliferative disorder
how is the risk of MGUS progression to MM determined on an individual basis?
Mayo criteria:
Non-IgG M-spike (so IgA spike)
M-spike >15g/L
Abnormal serum free light chain (FLC) ratio
above are the 3 risk factors, the more the gr8 your risk of progression 3 = 27% risk.
what is the intermediate condition between MGUS and MM?
what are its diagnostic criteria
smouldering myeloma
diagnostics: above MGUS criteria but below MM criteria:
≥10% Plasma cells
+/-
M-spike ≥30g/L
no organ damage or symptoms
which events are involved in the pathogenesis of multiple myeloma ? which are more common
primary & secondary genetic events
primary happens first then secondary occur after primary
Primary events:
- Hyperdiploidy - MOST common
- IgH rearrangement
Secondary events:
Gene abberations eg
KRAS, NRAS
t(8;14) IGH/MYC
what is the role of primary & secondary genetic events in disease progression in Myeloma?
Having primary events is generally only associated with early stage disease (MGUS)
as secondary geneetic abberations are added, the disease progresses on to SM –> MM and at the worst of the spectrum is relpase.
what is the association between genes and outcome in MM?
Increased genetic heterogeneity is linked to poor prognosis
because treatment has a bottleneck effect driving clonal selection
heterogeneity means that is is hard to devleop targetted therapy in MM
what is the diagnostic criteria for MM?
≥10% plasma cells in bone marrow or plasmacytoma + ≥1 CRAB or MDE
Myeloma defining events:
Bone marrow plasma cells ≥60%
Involved : uninvolved FLC ratio >100
> 1 focal lesion in MRI (>5mm)
C: Hypercalcaemia calcium >2.75mmol/L R: Renal disease creatinine >177μmol/L or eGFR <40ml/min A: Anaemia Hb <100g/L or drop by 20g/L B: Bone disease One or more bone lytic lesions in imaging
what is the normal plasma cell response to infection (in terms of gammopathy)?
polyclonal gammaopathy - so it makes loads of antibodies - alpha, beta AND gamma globulins ; IgG, IgA1, IgA2 etc
what are the 2 histological subtypes of MM?
Mature Plasmacytic Cells
Immature Plasmablastic Cells -
- Less abundant cytoplasm
- poorer prognosis
On immunoHISTOchemistry, what would you find for MM?
*yes so it is staining histology
§ CD138 mainly!!
§ CD38
§ CD56 - very important differentiator
note: so not your typical B cell antigens
§ Monotypic cytoplasmic immunoglobulin
§ Light chain restriction (either kappa or lambda positive)
80-90% of MM patients have what?
lytic bone lesions + bone PAIN
less present with fractures though
which imaging modalities are used in MM?
○ MRI
§ High sensitivity for bone marrow infiltration
§ Rx Response monitoring
○ CT Scans
§ Better at detecting very small lytic lesions
§ Good for radiotherapy planning
§ low dose used radiation dose
○ PET Scans
§ Detects active disease
§ Often combined with MRI
patient presents with drowsiness, constipation, fatigue, muscle weakness, AKI.
what is happening and rx?
hypercalcaemia
rx: Fluids, steroids, zolendronic acid
list the emergencies in MM?
CORD COMPRESSION - must treat within 24hrs!!
Hypercalcaemia
Kidney disease - as associated w poor outcome: - renal calculi, amyloidosis, pyelonephritis, casts - renal tubular acidosis -> fanconi syndrome #Save the kidneys
how is cord compression managed in MM?
MRI scan
Ig and FLC studies +/- biopsy
Dexamethasone
Radiotherapy
high serum free light chains (FLC) levels and Bence Jone proteinuria results in?
cast nephorpathy:
the formation of plugs (urinary casts) in the kidney tubules from free immunoglobulin light chains leading to kidney failure (envisage a pipe blocked up with a ball)
what is the diagnostic work up for MM?
Immunoglobulin studies:
Serum protein electrophoresis
Serum free light chain levels
24h Bence Jones protein
Bone marrow aspirate and biopsy:
IHC for CD138!! CD56
FISH analysis:
looks for translocations
Flow cytometry immunophenotyping
for diagnosis and resdiaul diseasee monitoring
how do we identify AL amyloid?
Amyloid fibrils stain with Congo Red, are solid, non-branching and randomly arranged with a diameter of 7 – 12 nm
