W7 - plasma cell myeloma & amyloid & MGUS Flashcards
Name 2 haematological cancers causing massive hepatosplenomegaly with no lymphadenopathy
CML, myelofibrosis
Hb 140/L, WWC 120 x 10^9/L, platelets 300 x 10^9/L (PB neutrophils basophils and myelocytes) – BM 3% blasts
A) Accelerated phase CML
B) Blast crisis CML
C) chronic phase CML
D) CLL
Chronic phase CML – CML and not CLL b/c peripheral blood shows myeloid cells
Hb is up, platelets are preserved, and blast is only 3% = this is still in the chronic phase of CML
Ph translocation BCR-ABL1 rearrangement is oncogenic via novel __________ _______
fusion oncoprotein
What is MM? What is it a malignancy of?
multiple myeloma - malignancy of BM plasma cells
Myeloma plasma cells:
- home and infiltrate the ______ ______
- may form bone expansile or soft tissue tumours called _________
- produce serum monoclonal ____ or _____, called _________
- produce excess o monoclonal kappa or lambda ____ ___ ____
- urine monoclonal free light chains are called ____ ____ _____
- BM
- plasmacytomas
- IgG, IgA, paraprotein (M spike)
- serum free light chains
- Bence Jones protein
What is the 2nd most common haematological cancers?
Multiple myeloma
What is the median age of diagnosis of MM?
What is the distribution between sex/ethnicity?
67 years of age
men > women
Black (x2) > Caucasians and Asians
What is the aetiology of MM? What are the risk factors
aetiology = unknown
risk factors:
- obesity
- age
- genetics (Black)
- genetics (sporadic familial cases)
MM is always preceded by a premalignant condition called
Monoclonal Gammopathy of Uncertain Significant (MGUS)
What is MGUS?
presence of a monoclonal antibody in the serum
What are the diagnostic criteria for MGUS?
- Serum M-protein <30g/L
- BM clonal plasma cells <10%
- No lytic bone lesions
- No myeloma-related organ or tissue impairment
- No evidence of other B-cell proliferative disorder
What is the average risk of progression of MGUS to MM?
1% annually
Other than MM, what other things (3) is MGUS associated with?
- osteoporosis
- thrombosis
- bacterial infection
What are the 3 risk factors used in MGUS risk stratification for progression to MM?
Non-IgG M-spike
M spike >15g/L
abnormal serum free light chain (FLC) ratio
What is smouldering myeloma? Describe the criteria
another premalignant condition prior to MM, similar to MGUS
Diagnostic criteria:
- serum monoclonal protein (IgG or IgA) >30g/L
- absence of myeloma defining events
What are the 3 risk factors used in smouldering myeloma risk stratification for progression to MM?
- BM myeloma cells >20%
M spike >20 g/L
Serum FLC ratio >20
Which premalignant condition most commonly leads to MM?
smouldering myeloma
What is the most common primary genetic pathogenesis in MM? What is the other?
Do they cause MM by themselves?
- Hyperdiploidy (60%)
- Rearrangement in chromosome 14q32 which codes for Ig
No => other 2ndary events will happen which will lead to MM
The myeloma cells interact with BM microenvironment, causing… (4)
- inhibit osteoblasts = bone destruction
- angiogenesis
- anaemia
- Immunosuppression => hence infections
What is the diagnostic criteria for MM?
>10% plasma cells in BM or plasmacytoma + 1 CRAB or MDE
CRAB:
C = hypercalcaemia
R = renal disease (high creatinine, low eGFR)
A = anaemia
B = bone disease
Myeloma defining events (MDE):
- BM plasma cells >60%
- involved/uninvolved FLC ratio >100
- >1 focal lesion in MRI
How does MM present usually?
80% present with bone disease
- proximal skeleton (spine, chest wall, pelvic pain)
- osteolytic lesions
- osteopenia
- pathological fractures
- hypercalcaemia
- renal impairment
What imaging modalities is better than XR Films for MM?
- CT scans
- FDG-PET scan
- whole body diffusion-weighted MRI
What is one bone emergency caused in MM?
Cord compression => soft tissue compression onto cord OR spinal fracture
Management of cord compression (complication of MM)
DIAGNOSE AND TREAT within 24 hours
- Imaging => MRI scan
- Dexamethasone, radiotherapy, neurosurgery sometimes, stabilise unstable spine
