21 - Multiple Myeloma Flashcards
Multiple Myeloma
- Plasma cell malignancy
- Arises in bone marrow, causing destruction of bone, kidneys, heart
Key three classifications of multiple myeloma
- MGUS (Monoclonal Gammopathy of Uncertain Significance)
- Smouldering Multiple Myeloma
- Multiple Myeloma
Plasma Cell Dyscrasias
MGUS > SMM > Multiple Myeloma
RIsk factors
- Elderly
- Male
- Black
- Family history
- Radiation
- HIV
- MGUS
Risk of MGUS progressing to MM
1% per year
Pathogenesis
Increased number of abnormal plasma cells that infiltrate into bone marrow, express RANK ligand which activates osteoclasts, leading to bone destruction, anaemia, and hypercalcaemia leading to renal failure
Cytokines involved in MM
Increased IL-6 and TNF alpha
Mutations in MGUS
- (11;14q) translocation
- Ras mutation
- Myc overexpression
Mutations in MM
- NF-kB mutations
- Myc translocation
- p53 loss
Diagnosis of MM
- SLiM CRAB
- Blood tests (haemoglobin, calcium)
- Bone marrow biopsy
CRAB
- Increased calcium level
- Renal dysfunction
- Anemia
- Destructive bone lesions
SLiM
- S (Sixty % BM plasmacytosis)
- Li (Light chains >100)
- M (MRI)
Abnormal monoclonal paraprotein diagnosis
- Blood: Serum protein electrophoresis
- Urine: Bence Jones protein
Serum Protein Electrophoresis
- Measures different fractions of blood proteins (globulins) separated by an electric current
- Blood serum is applied to a buffered agarose gel matrix (pH ~8.6)
- Current applied and globulins are separated based on: charge (Determined by sum of charge of amino acids) and Size of globulin (endo-osmotic force)
Albumin
Most negatively charged and moves the furthest to the anode
γ-globulins
Rely on endo-osmotic forces and move towards Cathode (-)
Serum Protein Electrophoresis Myeloma
- Decreased Albumin, Alpha 1, 2 and beta globulins
- Increased gamma globulins (M spike, indicative of myeloma)
Immunofixation
- Once an abnormal M-spike is identified, it is important to identify the specific monoclonal paraprotein causing the spike
- Incubating agarose gel with antibodies against the different types of immunoglobulin by specific staining (chromogen) for antigen-antibody complexes
- The specific paraprotein is then both identified + quantified
What do antigen antibody complexes form
- IgG, A, M
- Light chains (kappa, lambda)
Location & Pattern of M-Spike
Can Help Predict Paraprotein Type
Types of paraprotein in myeloma
- IgG kappa
- IgG lambda
- IgA lambda
- Lambda light chain
- IgG kappa
Blood film diagnosis
- Anaemia
- Rouleaux formation
- Blush ish tinge to background
- Circulating plasma cells
Plasma cells
- Eccentric nucleus
- Clock Face chromatin
- Basophilic cytoplasm
- Perinuclear clearing
- Interstitial location
Aspirate
Liquid sample
Trephine
Solid bone component
Markers of poor prognosis in myeloma
- CD28
- CD45
CD138
- Detects syndecan-1 expression
- Membranous expression
- Exclusive to plasma cells → Most sensitive marker
MUM1
- Also called IRF4
- Nuclear expression
- Also stains germinal B-cells and activated T-cells
Most common is t(11;14)(q13;q32) translocation
- Involves CCND1 leading to overexpression of cyclin D1
- Associated with a good prognosis
- Can also identify hyperdiploidy, aneuploidy
Treatment options
- Combination chemo
- Monoclonal antibodies
- Autologous stem cell transplantation
- Radiotherapy
- Blood transfusion support
Autologous stem cell process
- Pre treatment to mobilise stem cells from bone marrow to peripheral blood
- collection of stem cells
- freezing stem cells for storage
- administer chemo to dampen immune system
- infusion of stem cells back into patient
- supportive therapy
