myeloma and other Causes of Paraproteinaemia

Question 1

what is a paraprotein

Answer 1

a monoclonal antibody arising from a clone of lymphocytes or plasma cells

Question 2

what are the components of an antibody

Answer 2

heavy chains + light chains

Question 3

what happens to antibody levels in infection/inflammation

Answer 3

a polyclonal increase

Question 4

when do paraproteins arise

Answer 4

when there is a clone of cells all making the same antibody -> monoclonal globulin produced

Question 5

what will electrophoresis show if paraproteins are present

Answer 5

an additional abnormal band on serum protein electrophoresis

Question 6

how are serum free light chains detected

Answer 6

immunoassays - use of antibodies against the surface of the light chains (usually hidden when bound) and so will detect light chains free in the serum

Question 7

what are the 2 types of light chains

Answer 7

serum free lambda and serum free kappa

Question 8

why is the ratio of lamba:kappa chains useful to detect

Answer 8

useful in detecting clonality - a clone of cells will make only one type of light chain while in infection both kappa and lamba will be similarly raised

Question 9

what cells are affected in malignant myeolma

Answer 9

bone marrow plasma cells

Question 10

3 cardinal features of myeloma

Answer 10

1. increased bone marrow plasma cells (>10%);
2. bone destruction (lytic lesions produced);
3. paraprotein band in blood (81%) of patients

Question 11

how can the plasma cell percentage be determined

Answer 11

calculations using bone marrow aspirate (liquid biopsy) or bone marrow trephine (solid core of tissue)

Question 12

what is light chain myeloma

Answer 12

a myeloma where the plasma chains only secrete light chains into the blood

Question 13

when is a protein band not seen in myeloma

Answer 13

in light chain myeloma or non-secretory myeloma

Question 14

what is non-secretary myeloma

Answer 14

myeloma where neither paraprotein nor light chains are detected - diagnosis made by plamsa cell conc

Question 15

what do plasma cells look like on a blood film

Answer 15

oval, round eccentric nucleus, deep blue cytoplasm (with stain - basophilic), perinuclear hof (pale area next to the nucleus - the golgi zone where proteins are made)

Question 16

what are the 4 key clinical features of end-organ damage myeloma and why

Answer 16

CRAB
hyperCalcaemia - due to bone remodelling;
Renal failure - tubular damage from light chain deposition or from drug toxicity to treat the other symptoms;
Anaemia - bone marrow replaement + renal damage (decr. epo);
Bone lesions - bone remodelling

Question 17

what other symptoms might myeloma present with (2)

Answer 17

infections (due to immunosuppression);
spinal chord compression (plamactyomas - lumps of plasma cells - pressing on the spine or pathological fractures)

Question 18

how does myeloma affect bone homeostasis

Answer 18

factors produced by plasma cells (RANKL, OPG etc) trigger bone resorption and inhibit bone production:
1. activation of osteoclasts (incr resoption);
2. inhibition of osteoblasts (decr production)

Question 19

what can be seen on an x-ray of a myeloma pt

Answer 19

lytic lesions on bones, vertebral collapse (leading to loss of height), pathological fracture

Question 20

what types of paraportiens are usually seen in myeloma

Answer 20

IgG or IgA

Question 21

what chains are more rapidly cleared from the body

Answer 21

light chains - half life of 2 days compare to 30

Question 22

what is an autologous stem cell transplant

Answer 22

a stem cell transplant that uses healthy blood stem cells from your own body to replace your diseased or damaged bone marrow

Question 23

B cell/plasma causes of paraproteinaemia (4)

Answer 23

1. monoclonal gammopathy of undertemined significance (MGUS);
2. plamacytoma;
3. lymphoma;
4. primary amyloidosis;

Question 24

4 non-B cell causes of paraproteinaemia

Answer 24

1. infections (hep C, HIV etc.);
2. connective tissue disorders;
3. carcinomas;
4. transplant-related

Question 25

MGUS vs myeloma

Answer 25

lower paraprotein conc (<10g/L); lower plasma cell conc (<10%); no end organ damage (no CRAB criteria)

Question 26

what demographic is MGUS associated with

Answer 26

> 80yro

Question 27

MGUS manageent

Answer 27

watch and wait - rate of progression to myeloma is low

Question 28

when should myeloma be suspected

Answer 28

elevated paraprotein levels + any CRAB symptom

Question 29

2 types of plasmacytomas

Answer 29

1. solitary plasmacytoma of bone;
2. solitary extramedullary plasmacytoma

Question 30

treatment of plasmacytomas

Answer 30

high dose RT if there is no underlying myeloma - cure achieved in 50% of pts

Question 31

why is there an increased risk of hyperviscocity in low grade lymphoma

Answer 31

due to IgM paraproteins being present - they are large pentemeric molecules

Question 32

what is amyloidosis

Answer 32

a group of rare conditions caused by deposition of insoluble protein (amyloid)

Question 33

primary amyloidosis (AL amyloidosis) pathophys

Answer 33

protein conformation disorder - light chain fragments are deposited in organ as insoluble amyloid protein -> causes damage

Question 34

what are the 6 most prequently affects organs by primary amyloidosis

Answer 34

1. heart - congestive cardio myopathy;
2. kidneys - nephrotic syndrome/renal insufficency;
3. nerves - peripheral neuropathy;
4. liver - hepatomegaly;
5. gut - macroglossia, malabsorption;
6. skin - deposits;

Question 35

how is primary amyloidosis diagnosed

Answer 35

tissue biopsy;
subcutaneous fat aspiration - commonly deposited here;
evaluation of plasma cell abnormality (same as for myeloma e.g. serum electrophoresis, bone marrow biopsy etc.)

Question 36

treatment for primary amyloidosis

Answer 36

organ specific e.g. renal transplant, maximise cardiac function, minimise fluid retention;
treat underlying cause - chem for underlying plasma clone cell rather than the amyloid itself

Question 37

prognosis for primary amyloid

Answer 37

life expectancy 1 yr, particularly poor if cardiac amyloid