Myeloma and Other Plasma Cell Dyscrasias

Question 1

Describe B cells

Answer 1

Derived in bone marrow from pluripotent haemopoietic stem cells
Part of the adaptive immune system

Question 2

What are the roles of B cells?

Answer 2

Antibody production

Antigen presenting cells

Question 3

What are immunoglobulins?

Answer 3

Antibodies produced by B cells and plasma cells

Proteins made up of 2 heavy and 2 light chains

Question 4

What do antibodies recognise?

Answer 4

A specific antigen

Question 5

What do B cells do regarding the periphery?

Answer 5

travel to the follicle germinal centre of the lymph node
Identify antigen and improve the fit by somatic mutation or be deleted
May return to the marrow as plasma cell or circulate as memory cell

Question 6

Describe a plasma cell

Answer 6

A factory cell
Pumps out antibody
Open chromatin
Plentiful blue cytoplasm (laden with protein)
Pale perinuclear area (golgi apparatus)

Question 7

What is paraprotein?

Answer 7

Monoclonal immunoglobulin

Question 8

What does electrophoresis detect?

Answer 8

Abnormal protein bands

Question 9

What 2 light chains are present on antibodies?

Answer 9

Kappa

Lambda

Question 10

What is the free light chain production by plasma cells?

Answer 10

0.5g/day

Question 11

What are causes of paraproteinaemia?

Answer 11

Myeloma
Amyloidosis
Lymphoma
Asymptomatic myeloma
Loads more

Question 12

What is a myeloma?

Answer 12

A plasma cell malignancy

Question 13

What are the direct tumour effects of myeloma?

Answer 13

Bone lesions
Increased calcium
Bone pain
Replace normal bone marrow = marrow failure

Question 14

What other type of effects can occur from myeloma and what are they?

Answer 14

Paraprotein effects

• renal failure
• Immune suppression
• Hyperviscosity
• Amyloid

Question 15

How is myeloma classified?

Answer 15

By the type of antibody produced

Question 16

What are features of hypercalcaemia?

Answer 16

Stones
Bones
Abdo groans
Psychiatric moans
Thirst
Dehydration
Renal impairement

Question 17

What effects can myeloma have on the kidney?

Answer 17

Tubular damage by light chains
Light chain deposition - cast nephropathy
Sepsis
Hypercalcaemia and dehydration
Amyloid
Hyperuricaemia
Drugs (NSAIDs)

Question 18

How can you stop light chain production to help with cast nephropathy?

Answer 18

Steroids/chemo

Question 19

How can you treat myeloma?

Answer 19

Corticosteroids
Alkylating agents (cyclophosphamide)
Novel agents (thalidomide)

Question 20

How do you measure the response to treatment for myeloma?

Answer 20

Paraprotein level

Question 21

How do you control the symptoms of myeloma?

Answer 21

Analgesia (not NSAIDs)
Local radiotherapy
Bisphosphonates
Vertebroplasty (inject cement into fractured bone to stabilise)

Question 22

What is MGUS?

Answer 22

Monoclonal Gammopathy of Uncertain Significance

Question 23

Describe MGUS?

Answer 23

Paraprotein <30g/l
Bone marrow plasma cells <10%
No evidence of myeloma or end organ damage

Question 24

What is AL Amyloidosis?

Answer 24

Rare
Small plasma cell clone
Mutation in the light chain > altered structure
Precipitates in tissues as an insoluble beta pleated sheet

Question 25

Describe AL Amyloidosis

Answer 25

Accumulation in tissue causes organ damage Slowly progressive Multisystem Different protein to SAA amyloidosis and familial amyloidosis Poor prognosis espeically if cardiac amyloid

Question 26

What organ damage can be caused by AL amyloid?

Answer 26

``` Kidney - Nephrotic syndrome Heart - Cardiomyopathy Liver - Organomegaly deranged LFT's Neuropathy - Autonomic and peripheral GI - Malabsorption ```

Question 27

How do you diagnose AL amyloidosis?

Answer 27

Organ biopsy for AL amyloid deposition Congo red stain Rectal or fat biopsy

Question 28

How do you test for deposition in other organs?

Answer 28

SAP can Echocardiogram Heavy proteinuria

Question 29

How does AL amyloid look under polarised light?

Answer 29

Apple-green birefringence

Question 30

What is Waldenstrom's Macroglobinaemia?

Answer 30

IgM paraprotein Lymphoplasmocytoid neoplasm Clonal disorder of cells intermediate between a lymphocyte and a plasma cell Characteristic IgM paraprotein

Question 31

What are the effects of Waldenstrom's Macroglobinaemia?

Answer 31

``` Tumour - Lymohadenopathy - Splenomegaly - Marrow failure Paraprotein - Hyperviscosity - Neuropathy ```

Question 32

Describe the IgM antibody?

Answer 32

Pentameric

Question 33

What are clinical features of Waldenstrom's Macroglobinaemia?

Answer 33

``` Hyperviscosity syndrome - Fatigue - Bleeding - Cardiac failure Night sweats and weight loss ```

Question 34

How do you treat Waldenstrom's Macroglobinaemia?

Answer 34

``` Chemo Plasmapheresis (removes protein from the circulation) ```