Myeloma + paraproteinaemia

Question 1

Define paraprotein

Answer 1

monoclonal antibody arising from a clone of lymphocytes or plasma cells

Question 2

What produces antibodies?

Answer 2

mature B-cells (mainly plasma cells)

Question 3

How are paraproteins detected?

Answer 3

appears as additional abnormal band on serum protein electrophoresis

Question 4

Describe serum protein electrophoresis

Answer 4

drop of patient plasma put on gel strip with electric current along it
proteins with different charges separate

Question 5

What are serum free light chains?

Answer 5

light chains of antibody not connected to a heavy chain
detected by immunoassay

Question 6

Describe how immunoassay is used

Answer 6

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

Question 7

Describe myeloma

Answer 7

form of bone marrow cancer
malignant proliferation of plasma cells
variable clinical spectrum (asymptomatic to quick death)
60-65 years = median

Question 8

Cardinal features of myeloma

Answer 8

increased bone marrow plasma cells (>10%)
bone destruction –> lytic lesions
paraprotein band in blood

Question 9

Clinical feature of myeloma

Answer 9

end organ damage (CRAB):
- hypercalcaemia
- renal failure
- anaemia
- bone lesions

Also:
- infections
- spinal cord compression (plasmocytomas/fractures)

Question 10

What is the mechanism of bone disease in myeloma?

Answer 10

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

Question 11

Describe which serum paraproteins are present in myeloma

Answer 11

IgG (53% patients)
IgA (25% patients)
light chains only = free kappa/lambda (17% patients)

IgM = associated with lymphoma NOT myeloma

Question 12

What are light chains found in urine called?

Answer 12

Bence-Jones protein
superseded by serum free light chains

Question 13

Myeloma investigations

Answer 13

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)

Question 14

Myeloma treatment

Answer 14

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

Question 15

Other causes of a paraprotein

Answer 15

other B-cell/plasma cell neoplasms:
- MGUS
- plasmocytoma
- lymphoma
- primary amyloidosis

Question 16

Describe MGUS

Answer 16

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

Question 17

Describe plasmocytoma

Answer 17

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

Question 18

Describe low grade lymphoma (relating to paraproteinaemia)

Answer 18

lymphoma cells can make a paraprotein
usually IgM paraprotein
clinical behaviour = low grade lymphoma, NOT myeloma
increased risk hyperviscosity (pentameric IgM = large)

Question 19

What is primary amyloidosis?

Answer 19

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

Question 20

How can primary amyloidosis manifest in different organ systems? (heart, kidneys, nerves, liver, gut, skin)

Answer 20

heart = congestive cardiomyopathy
kidneys = nephrotic syndrome +/- renal insufficiency
nerves = peripheral neuropathy
liver = hepatomegaly
gut = macroglossia, malabsorption
skin = deposity

Question 21

How is primary amyloidosis diagnosed?

Answer 21

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

Question 22

Primary amyloidosis treatment

Answer 22

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

Question 23

Hypercalcaemia treatment

Answer 23

fluids –> bisphosphonates –> denosumab