Myeloma + paraproteinaemia Flashcards
(23 cards)
Define paraprotein
monoclonal antibody arising from a clone of lymphocytes or plasma cells
What produces antibodies?
mature B-cells (mainly plasma cells)
How are paraproteins detected?
appears as additional abnormal band on serum protein electrophoresis
Describe serum protein electrophoresis
drop of patient plasma put on gel strip with electric current along it
proteins with different charges separate
What are serum free light chains?
light chains of antibody not connected to a heavy chain
detected by immunoassay
Describe how immunoassay is used
detects serum free light chains
detects surface usually hidden where light chains bind to heavy chains
light chains bound to heavy chains not measured
2 assays = lambda + kappa
ratio useful to detect clonality:
- clone of cells will make only one type of light chain
- polyclonal increase in cells (eg. infection) = kappa + lambda light chains increase
Describe myeloma
form of bone marrow cancer
malignant proliferation of plasma cells
variable clinical spectrum (asymptomatic to quick death)
60-65 years = median
Cardinal features of myeloma
increased bone marrow plasma cells (>10%)
bone destruction –> lytic lesions
paraprotein band in blood
Clinical feature of myeloma
end organ damage (CRAB):
- hypercalcaemia
- renal failure
- anaemia
- bone lesions
Also:
- infections
- spinal cord compression (plasmocytomas/fractures)
What is the mechanism of bone disease in myeloma?
myeloma cells produce factors (eg. osteoprotegerin, Rank-L) which result in:
- osteoclast activation (increased resorption)
- osteoblast inhibition (decreased production)
net result = bone resorption
lytic lesions present
vertebral collapse (pain, kyphosis, decreased height)
pathological fractures
Describe which serum paraproteins are present in myeloma
IgG (53% patients)
IgA (25% patients)
light chains only = free kappa/lambda (17% patients)
IgM = associated with lymphoma NOT myeloma
What are light chains found in urine called?
Bence-Jones protein
superseded by serum free light chains
Myeloma investigations
FBC + blood film
renal function
serum Ca
serum protein electrophoresis
serum free light chains
bone marrow biopsy
skeletal survey (CT/MRI/PET of whole skeleton)
Myeloma treatment
renal failure = IV fluids, ?dialysis
hypercalcaemia = IV fluids, bisphosphonates
pain = analgesia, radiotherapy
fractures = radiotherapy, surgery
spinal cord compression = steroids, radiotherapy
anaemia = transfusion, EPO
infection = antibiotics
hyperviscosity = plasma exchange, urgent chemotherapy
psychological distress = psych support
Other causes of a paraprotein
other B-cell/plasma cell neoplasms:
- MGUS
- plasmocytoma
- lymphoma
- primary amyloidosis
Describe MGUS
monoclonal gammopathy of undetermined significance
- paraprotein (lower than myeloma)
- bone marrow plasma cells <10%
- no CRAB criteria
- management = watch + wait
- 1% evolve to myeloma
- suspect myeloma if CRAB present
Describe plasmocytoma
tumoural mass of plasma cells
- clonal proliferation of plasma cells identical to myeloma but manifest as localised mass in bone/soft tissue
- solitary plasmocytoma of bone/solitaryextramedullary plasmocytoma
- treatment = high dose radiotherapy
Describe low grade lymphoma (relating to paraproteinaemia)
lymphoma cells can make a paraprotein
usually IgM paraprotein
clinical behaviour = low grade lymphoma, NOT myeloma
increased risk hyperviscosity (pentameric IgM = large)
What is primary amyloidosis?
insoluble protein deposits in organs
irreversible
protein conformation disorder associated with clonal plasma cells
clonal plasma cells make light chain fragments which are deposited into organs as insoluble amyloid protein resulting in damage to affected organs
How can primary amyloidosis manifest in different organ systems? (heart, kidneys, nerves, liver, gut, skin)
heart = congestive cardiomyopathy
kidneys = nephrotic syndrome +/- renal insufficiency
nerves = peripheral neuropathy
liver = hepatomegaly
gut = macroglossia, malabsorption
skin = deposity
How is primary amyloidosis diagnosed?
tissue biopsy:
- biopsy affected organ
- SC fat aspirate
evaluation of plasma cell abnormality:
- FBC, U+E, Ca
- serum protein electrophoresis
- serum free light chains
- bone marrow biopsy
- skeletal imaging
Primary amyloidosis treatment
supportive treatment–> organ specific:
- renal transplants
- increase cardiac function
- decrease fluid retention
treat underlying cause:
- chemotherapy
- treats plasma cell clone rather than amyloid itself
- gradual regression of amyloid burden
Hypercalcaemia treatment
fluids –> bisphosphonates –> denosumab
