Myeloma Flashcards
What tests are used to assess immunoglobulin (Ab) - do these if suspect myeloma
Serum immunoglobulin total level Electrophoresis - urine and plasma Immunofixation Serum light chain Urinary bence jones protein - light chain part of Ab present in urine
What does electrophoresis do
Identify paraprotein - appears as spike
Separates Ig based on size and charge
What does immunofixation do
Identify class of paraprotein
What is a paraprotein and how do you identify type
Monoclonal immunoglobulin present in blood or urine
Should all be different
Do electrophoresis
What does presence of paraprotein tell you
Monoclonal proliferation of a B lymphocyte or matured plasma cell
What disease is associated with IgM paraprotein
Low grade Lymphoma
Can’ t get myeloma as IgM produced by B cell NOT plasma cell
What does IgA or IgG paraproteins suggest
Myeloma
Produced by plasma cells after isotope switching in secondary response
Will then have either light chain affected as well
Can have a situation whee only light chain affected
Do most cancers arise in B or T cell
B cells as germinal centre of LN where B cells proliferate and rearrange and Ab production starts
What is myeloma
Neoplastic disorder of plasma cells (mature B lymphocytes)
Due to single clone of plasma cell undergoing abnormal proliferation so secrete excessive amount of Ab / Ig (paraprotein or monoclonal Ab)
Results as B-lymphocytes differentiate into mature plasma cells in LN etc.
Step 1 = MGUS develops
- Clone of plasma producing same monoclonal Ab
- Usually inciting event during normal immune response
- Asymptomatic
Step 2 = MM develop
- Cytogenetic and bone marrow changes
- 1% of MGUS will develop each year
Subtype
- Classic
- Light chain only
- Non-secretoy = rare
What is myeloma common in
Elderly Black population Male FH Obesity
What are the features of myeloma / direct effect of plasma cells
CRAB High calcium Renal impairment Anaemia - Due to Bone marrow failure / infiltration - May have relative EPO deficiency Bone disease
Will also have increased infections - lack of normal Ig
What bone disease occurs
Due to proliferation of plasma cells in bone marrow
Lytic bone lesion = pain due to increased osteoclast and reduced osteoblast (due to cytokines)
Pathological fracture
Cord compression
Hypercalcaemia
Osteoporosis
How does hypercalcaemia occur
Increased osteoclast activity
Also could be due to impaired renal function / elevated PTH
Can present as oncologication emergency
Phosphate and ALP normal
What are main features of bone marrow failure
Anaemia = common - lethargy Thrombocytopenia = bruising / bleeding Neutropenia = infection
What effects does paraprotein have on body
Hyperviscosity -> stroke Hypogammaglobulinaemia Amyloidosis Neuropathy Paraesthesia - Due to hypo or hyperCa Spinal cord compression due to fracture / bone disease Carpal tunnel Night sweats/ cramping = Ix
Rarely HSM / LN / fever
- If present with this consider other malignancies
What causes renal failure (can be new AKI or CKD)
Cast nephropathy - light chain deposition which damages loop of Henle
Ig deposition - blockage of renal tubules = main
Multiple ways Hyperviscosity Hypercalcaemia Hyperuricaemia Dehydration Medication used to treat can be harmful e.g. biphosphoantes Amyloidosis NSAID Infection
What is hyper viscosity and how do you Rx
Syndrome caused by increased viscosity in blood
Leads to impaired microcirculation and hypo perfusion
Plasmapharesis to remove
What does it lead too
Bleeding as capillaries burst - retinal, oral, nasal, cutaneous Cardiac failure Pulmonary congestion Renal failure Confusion Stroke
What does hypogammaglobulinaemia suggest
Paraprotein is switching of production of other Ig
Leads to infection
What is Amyloidosis
Group of diseases characterised by deposition of fibrillary protein
What is AL amyloid
Amyloidosis caused by protein or light chain
Common cause
How does it present
Nephrotic syndrome Cardiac failure Carpal tunnel Autonomic neuropathy Cutaneous infiltration
How do you treat AL amyloid
Get rid of paraprotein by chemotherapy
High mortality as patient very ill
How do you investigate suspected myeloma
FBC+ film, U+E, LFT, ESR, LDH bone profile, PSA and urinanaylsis
Detect monoclonal AB - product of malignant plasma cells
- Myeloma screen
- Serum or urine protein electrophoresis + serum light chain to look for light chains = typical screen
- Can do other Ig tests
Assess bone marrow to look for malignant clone
- Bone marrow aspirate and trephine = diagnostic
Look for organ damage e.g. CRAB
- Bloods
- Whole body MRI = 1st line for bone
- CT if CI
- Skeletal survey 2nd line if no CT or MRI to look for lytic lesions
