Plasma Cell Dyscrasias

Question 1

What are the two main functions of a B cell?

Answer 1

Antibody production

Antigen presenting cells

Question 2

What part of immunity are B cells?

Answer 2

Active immune system

Question 3

Where are B cells made?

Answer 3

Bone marrow from haematopoietic stem cells

Question 4

Which immunoglobulin is the largest and what is its shape?

Answer 4

IgM

Pentamer

Question 5

Which immunoglobulins are monomers?

Answer 5

IgD
IgE
IgG

Question 6

Where do B cells go to identify antigens when released from the marrow?

Answer 6

Follicle germinal centre of the lymph node

Question 7

Circulating B cells are referred to as?

Answer 7

Memory B cell

Question 8

B cells which return to the bone marrow are referred to as?

Answer 8

Plasma cells

Question 9

List some of the features of a plasma cell?

Answer 9

Blue cytoplasm
Pale perinuclear area
Open chromatin
Eccentric clock face nucleus

Question 10

What is another name for a monoclonal immunoglobulin?

Answer 10

Paraprotein

Question 11

What are paraproteins an indicator of?

Answer 11

Underlying clonal disorder of the B cells e.g. myeloma

Question 12

How are immunoglobulins detected?

Answer 12

Serum electrophoresis

Question 13

What is used to classify the abnormal protein band?

Answer 13

Serum immunofixation

Question 14

What are Bence Jones proteins?

Answer 14

Immunoglobulin light chains

Question 15

How do we detect Bence Jones proteins

Answer 15

Urine electrophoresis

Question 16

List some of the main causes of paraproteinaemia:

Answer 16

MGUS
Myeloma
Amyloidosis
Lymphoma
Waldenstrom's macroglobulinaemia

Question 17

How does myeloma occur?

Answer 17

Normal plasma cells take a ‘genetic hit’ which causes them to form an MGUS clone (premalignant)
Patients may be asymptomatic for a while but then as it progresses symptoms will occur

Question 18

What direct tumor cell effects occur in myeloma?

Answer 18

Bone lesions
Increased calcium
Bone pain
Replacement of normal bone marrow leading to marrow failure

Question 19

What effects will the paraproteins released in myeloma cause?

Answer 19

Renal failure (cast nephropathy)
Immune suppression
Hyperviscosity
Amyloid

Question 20

How is myeloma classified?

Answer 20

By the type of antibody produced e.g. IgG myeloma (most common)

Question 21

How does myeloma cause lytic bone disease?

Answer 21

Increase of myeloma cells leads to increased IL-6 which leads to an increased activation of osteoclasts and suppression of osteoblasts

Question 22

What is the median age of diagnosis of myeloma?

Answer 22

65 y/o

Question 23

What supportive treatments are given for myeloma?

Answer 23

Analgesia for bone pain (avoid NSAIDs)
Bisphosphonates (reduce fracture risk)
Anaemia treatment (epo / transfusion)
Dialysis 
Vertebroplasty 
Anti-coagulation 
Broad spectrum antibiotics in infections

Question 24

What chemotherapy approach is used in fitter patients with myeloma?

Answer 24

VAD
Vincristine Adriamycin & Dexamethasone
Then autologous stem cell transplant

Question 25

What "novel agents" may be added in the treatment of more resistant myeloma?

Answer 25

Thalidomide Bortezomib Lenalidomide

Question 26

What is the survival for myeloma?

Answer 26

5 - 10 years (especially in younger/fitter patients) | Relapse is inevitable

Question 27

What are some of the complications of myeloma?

Answer 27

Hypercalcaemia Spinal cord compression Hyperviscosity AKI

Question 28

What is MGUS?

Answer 28

Monoclonal gammopathy of undetermined significance

Question 29

How is MGUS clinically defined?

Answer 29

Para-protein levels <30g/l Bone marrow plasma cells <10% No evidence of myeloma end organ damage

Question 30

What is amyloidosis?

Answer 30

Rare disorder of a small plasma cell clone leading to a mutation in the light chain. This forms a precipitate in tissues as an insoluble beta pleated sheet

Question 31

How is amyloidosis diagnosed?

Answer 31

Congo red stain from an organ biopsy | also apple green birefringence under polarized light

Question 32

What is Waldenstrom's Macroglobulinaemia?

Answer 32

Lymphoplasmacytoid neoplasm | Clonal disorder of intermediate cells between a lymphocyte and plasma cell

Question 33

What type of immunoglobulin is characteristic in Waldenstrom's Macroglobulinaemia?

Answer 33

IgM para-protein

Question 34

What are some of the clinical features of Waldenstrom's Macroglobulinaemia?

Answer 34

Hyperviscosity syndrome | B symptoms

Question 35

What are "B symptoms"?

Answer 35

Night sweats Weight loss Fever

Question 36

What are some features of hyper-viscosity syndrome?

Answer 36

``` Fatigue Visual disturbances Confusion Coma Bleeding Cardiac failure ```

Question 37

How is Waldenstrom's treated?

Answer 37

Chemotherapy | Plasmapharesis to remove the paraprotein

Question 38

List some symptoms of myeloma:

Answer 38

``` Backache Pathological fractures Recurrent infections Anaemia / neutropaenia Moans / groans / bones / stones ```