Myeloma

Question 1

What is myeloma?

Answer 1

a plasma cell malignancy

due to abnormal proliferation of single clone of plasma cells (secrete immunoglobulin)

Question 2

In myeloma, is there a polyclonal or monoclonal increase in Ig?

Answer 2

monoclonal - as there is abnormal proliferation of a single clone producing a single antibody
overproduction of single antibody

Question 3

What is a paraprotein?

Answer 3

monoclonal Ig

Question 4

How is Ig detected?

Answer 4

serum electrophoresis

Question 5

How does Ig appear on serum electrophoresis in myeloma?

Answer 5

monoclonal bands

Question 6

How does myeloma affect the body?

Answer 6

direct tumour cell effects: 
bone pain, bone lesions, hypercalcaemia, bone marrow failure (when malignant cells overwhelm normal marrow)
paraprotein effects:
renal failure 
hyper viscosity 
immune suppression

Question 7

How are myelomas classified?

Answer 7

by the Ig they secrete

Question 8

What Ig do the majority of myelomas secrete?

Answer 8

IgG (60%)

IgA (30%)

Question 9

What are Bence Jones proteins?

Answer 9

appear in 2/3rds of myelomas
free Ig light chains of kappa or lambda
in urine

Question 10

What are the symptoms of myeloma?

Answer 10

bone pain
anaemia, infection, bleeding
renal impairment

Question 11

What is lytic bone disease?

Answer 11

focal bone destruction

bone pain, pathological fractures, wedge compression fracture in spine

Question 12

Why do you get lytic bone disease in myeloma?

Answer 12

myeloma cells produce cytokines
over activation of osteoclasts
suppression of osteoblasts

Question 13

What does lytic bone disease look like in the skull?

Answer 13

‘punched out’ lesions

Question 14

What are the symptoms of hypercalcaemia?

Answer 14

thirst 
psychiatric moans
stones 
bones - bone pain 
abdominal groans

Question 15

Why do you get renal impairment in myeloma?

Answer 15

1 - free light chains small enough to be filtered by glomerulus
2 - kidney stops loss of small proteins e.g. light chains - proximal tubule reabsorbs
3 - if overwhelmed by high number of light chains e.g. in myeloma, can pass into loop of Henle
4 - in thick ascending loop - Tamm Horsfall proteins produced and combines with free light chains –> insoluble casts that block the nephron

Question 16

What do free light chains combine with to form insoluble casts in cast nephropathy?

Answer 16

Tamm Horsfall proteins

Question 17

What is the treatment of myeloma?

Answer 17

supportive 
- bone pain: analgesia (avoid NSAIDs)
- bisphosphonate 
- local radiotherapy - focal disease 
chemotherapy and steroids

Question 18

What is MGUS?

Answer 18

monoclonal gammopathy of uncertain significance
have paraprotein but don’t have myeloma (no evidence of end organ damage)
no treatment necessary

Question 19

What is Waldenstrom’s macroglobinaemia?

Answer 19

IgM paraprotein (rarely get IgM myeloma)
clonal disorder of cells halfway between lymphocytes and plasma cells (lymphoplasmacytoid neoplasm)

Question 20

What are the paraprotein effects and tumour effects in Waldentroms macroglobinaemia?

Answer 20

paraprotein effects:
- hyper viscosity (thrombosis, fatigue, cardiac failure)
- B symptoms
- neuropathy 
tumour effects: 
- lymphadenopathy
- splenomegaly 
- marrow failure

Question 21

What is the treatment of Waldenstrom’s macroglobinaemia?

Answer 21

chemo

plasmapheresis

Question 22

What is AL Amyloidosis?

Answer 22

rare disorder
small plasma cell clone
mutation in light chain - alters structure: large insoluble sheets, build up in tissue

Question 23

How is AL amyloidosis diagnosed?

Answer 23

organ biopsy and congo red stain

Question 24

What can happen to organs in AL amyloidosis?

Answer 24

organ damage

• neuropathy
• nephrotic syndrome
• cardiomyopathy
• hepatomegaly, deranged LFTs
• malabsorption