Myeloma and other plasma cell disorders

Question 1

Where in the lymph node does B cell encounter antigens?

Answer 1

Follicle germinal centre

Question 2

What do plasma cells look like on cytology?

Answer 2

open chromosome
blue laden cytoplasma cells
a bit lighter in perinuclear region for golgi apparatus

Question 3

Increased polyclonal production of Igs is always reactive. but reactive to what?

Answer 3

• infection
• malignancy (body’s reaction to the malignant clone)
• liver disease

Question 4

What tests are used to determine immunoglobulin types?

Answer 4

Serum electrophoresis and immunofixation

There is always small amount of excess of light chains in blood

Question 5

Paraprotein

Answer 5

Monoclonal antibodies/Igs

Question 6

What causes paraproteinaemia?

Question 7

What is myeloma?

Answer 7

a cancer of plasma cells

Premalignant state: MGUS clone
Asymptomatic myeloma
Myeloma

Question 8

What is MGUS?

Answer 8

Monoclonal gammanopathy of undertermined significanc

Bone marrow plasma cells is very small
No evidence of clinical presentation

Question 9

How does myeloma affect the body?

Answer 9

1. Direct tumour cell effects from clonal plasma cells
   - bone lesions
   - increase calcium concentration in blood?
   - bone pain
   - replace normal bone marrow (marrow failure –> pancytopenia)
2. Paraprotein mediated effects
   - renal

Question 10

How are myelomas classified?

Answer 10

by isotype of antibody produced
IgA
IgE
IgG
Non-secretory (plasma cells so faulty they don’t produce Igs)
BJP (just light chains)

Question 11

How does myeloma lead to lytic bone disease?

Answer 11

Osteoblasts suppressed
Osteoclasts activated
Bone matrix under these send signals to activate myeloma cells (positive feedback loop)

Question 12

How does myeloma lead to kidney damage (multiple ways)?

Answer 12

Cast nephropathy (can be due to light chain accumulation or intake of nephrotoxic drugs that relieve pain in myeloma)

Question 13

How to treat myeloma?

Answer 13

Combination novel agent chemotherapy
- corticosteroids: dexamethasone
- new agents: bortezomib, lenalidomide
- monoclonal antibodies, daratumumab

• transplant in younger patients (autologous HSC transplant) –> reinstate immune system after chemo

Monitor via paraprotein level

Question 14

How to control symptoms of myeloma?

Answer 14

Opiates for analgesia
Bisphosphonates to correct bone destruction

Question 15

What is amyloidosis?

Answer 15

amyloid aggregates that make them insoluble
Many different types of amyloid, depends on type of misfolded protein

Haematology => AL amyloid (produced from faulty light chain aggregation) - can accumulate in heart muscles

Question 16

Amyloidosis diagnosis and staging

Answer 16

biopsy - staining
echo
SAP scan

Question 17

what is waldenstrom’s macroglobulinaemia?

Answer 17

Faulty cells are half-way between lymphocytes and plasma cells
IgM paraprotein

Tumour effects - lymphadenopathy, splenomegaly, marrow failure

IgM effects - hyperviscosity (huge IgM antibodies!), neuropathy

Hyperviscosity syndrome - chemo, plasmapheresis