HAEM: Multiple myeloma, amyloid and MGUS Flashcards
Define multiple myeloma.
Malignancy of bone marrow plasma cells, the terminally differentiated and immunoglobulin (Ig) secreting B cells
Features of myeloma plasma cells:
- Where do they home?
- What tumours do they form?
- What happens to Ig and free light chains?
- What is found in urine?
- Home and infiltrate the bone marrow
- Plasmacytomas - expansile bone or soft tissue tumours
- Excess monoclonal IgG and IgA (paraprotein or M-spike) AND excess monoclonal kappa or lambda serum free light chains
- Urine shows monoclonal free light chains called Bence Jones protein
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Which types of B cells are implicated in myeloma? What about Waldenstrom’s lymphoplasmacytic lymphoma?
Myeloma = IgG or IgA producing long-lived plasma cells
Waldenstrom’s = IgM producing short-lived plama cells
How common is myeloma in terms of other haematological cancers? What is the median age of diagnosis? Which ethnicities/sex?
- Second most common haematological malignancy, prevalence increasing
- 67years median age
- males > females
- black > caucasian
What are the risk factors for myeloma?
Aetiology unknown but RF include:
- obesity
- age
- genetics - black ethnicity, sporadic cases of familial myeloma
- MGUS (this premalignant condition ALWAYS precedes myeloma)
What does MGUS stand for?
Monoclonal gammopathy of uncertain significance
How common is MGUS?
- most common premalignant condition
- 1-3% of elderly affected
- increases with age
Which type of MGUS must the patient have for progression to myeloma or lymphoma?
IgG or IgA - myeloma
IgM - lymphoma
What is the WHO diagnostic criteria for MGUS diagnosis?
- Serum M-protein <30g/L
- BM clonal plasma cells <10%
AND
- No lytic bone lesions
- No myeloma-related organ or tissue impairment
- No evidence of other B-cell proliferative disorder
Which criteria is used for risk stratification of MGUS? Describe the 3 risk factors used.
Mayo criteria
Risk factors include:
- non-IgG M spike
- M-spike >15g/L
- abnormal serum free light chain (FLC) ratio
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Define smouldering multiple myeloma.
Both criteria must be met:
- Serum monoclonal protein (IgG/A) >30g/L OR urinary >500mg/24hr AND/OR clonal BM plasma celsl 10-60%
- Absence of myeloma defining events or amyloidosis
What is the use of risk stratification in smouldering multiple myeloma?
If score is 0 or 1 then observation used; if >2 then ?treatment.
Risk factors for points:
- BM myeloma cells >20%
- M-spike >20g/L
- Serum FLD ratio >20
(2019 IMWG updated risk stratification model)
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What does MGRS stand for?
monoclonal gammopathy of renal significance
Describe the clinical spectrum of myeloma and related plasma cell disorders.
Usual progression is….
- MGUS
- smouldering myeloma
- symptomatic myeloma
- remitting relapsing
- refractory
- plasma cell leukaema
…with increases in % plasma cell in BM, M-spike, organ damage and symptoms and appearance of PC in circulation and extramedullary disease.
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What are the primary and secondary events in multiple myeloma?
Primary:
- Hyperploidy (60%) - additional odd number Chr
- IGH rearrangement (Chr 14q32)
- t(11,14) - IGH/CCND1
- t(4;14) IGH/FGFR3
- t(14;16) IGH/MAF
Secondary:
- Copy number abnormalities
- DNA hypomethylation
- Acquired mutations
- KRAS, NRAS
- t(8;14) IGH/MYC
- 1q gain/1p del
- del 17p (TP53)
- 13-/del 13q
What is the diagnostic criteria for multiple myeloma?
CRAB
- Calcium >2.75mmol/L
- Renal disease - Cr >177micromol/L or EGFR <40min/min
- Anaemia - Hb <100g/L or drop by 20g/L
- Bone disease - 1 or more lytic bone lesions on imaging
What are MDE (myeloma defining events)?
- BM plasma cells >60%
- Invovled:uninvolved FLC ratio >100
- >1 focal lesion on MRI (>5mm)
Where do bone lesions usually present in MM? Give some examples of bone disease in MM. What is the calcium level?
80% - usually in proximal skeleton, spine, chest wall and pelvic regions.
- OsteoLYTIC lesions (never osteoblastic)
- Osteopenia
- Pathological fractures
- Bloods show hypercalcaemia