Plasma Cell Dyscrasias

Question 1

Where do B cells come from and what is their function?

Answer 1

Derived from stem cells in the bone marrow

- produce antibodies

Question 2

What are antibodies and how are they structured?

Answer 2

Immunoglobulins

• -> proteins made of 2 heavy chains + 2 light chains
• monomers = IgD, IgE + IgG
• dimer = IgA
• pentamer = IgM

Question 3

Describe the progression of a stem cell into a plasma cell

Answer 3

Stem cell –> lymphoid progenitor –> pro B cell –> pre B cell –> (leaves marrow) –> IgM B cell –> IgM plasma cell

(may return to marrow as plasma cell or circulate as memory B cell)

Question 4

What is the function of a plasma cell and what does it look like?

Answer 4

Factory cell –> pumps out antibody

Clock-face nucleus, plentiful blue cytoplasm, pale patch next to nucleus

Question 5

What might cause a polyclonal rise in Ig?

Answer 5

Reactive to –> infection, AI, malignancy, liver disease

Question 6

What would cause a monoclonal rise in Ig?

Answer 6

Underlying clonal B cell disorder

Question 7

What is another term for monoclonal Ig?

Answer 7

Paraprotein

Question 8

Which investigations defect monoclonal Ig?

Answer 8

Serum electrophoresis –> detects abnormal protein bands

Serum immunofixation –> classifies abnormal band e.g. IgG, IgM

Question 9

What is Bence Jones protein and how is it detected?

Answer 9

Excess Ig light chains in urine

–> detected by urine electrophoresis

Question 10

What are the possible causes of paraproteinaemia?

Answer 10

MGUS (monoclonal gammaopathy of uncertain significance)
Myeloma
Amyloidosis
Lymphoma
Plasmacytoma
CLL
Waldenstrom's

Question 11

What is myeloma?

Answer 11

Malignant proliferation of plasma cells in bone marrow

–> large amount of identical Ig (paraprotein) + free light chains (Bence Jones proteins if in urine)

Question 12

How is myeloma classified?

Answer 12

By Ig class:

• 2/3 are IgG
• 1/3 are IgA
• rest are IgM or IgD

Question 13

What happens to the other classes of Ig in myeloma?

Answer 13

Other classes will be low –> immunoparesis

Question 14

What are the key features of myeloma?

Answer 14

Osteolytic bone lesions --> fractures + bone pain --> HYPERCALCAEMIA
Pancytopenia (marrow infiltration)
Infection (immunoparesis)
Renal disease
Hyperviscosity

Question 15

What is the mechanism of kidney injury in myeloma?

Answer 15

Light chains (BJPs) deposit in kidneys –> tubular obstruction + kidney failure = cast nephropathy

Question 16

What are the features of hypercalcaemia?

Answer 16

Stones
Bones
Abdo groans
Psychiatric moans
Thirst
Dehydration
Renal impairment

Question 17

What would be seen on bloods in myeloma?

Answer 17

Normocytic anaemia
Raised ESR + plasma viscosity
Raised urea + creatinine
Bone profile: hypercalcaemia + normal ALP

Question 18

What would be seen on the blood film in myeloma?

Answer 18

Rouleaux formation (stacked RBCs)

Question 19

Which investigations should be done for myeloma?

Answer 19

Bloods + film
Serum + urine electrophoresis
Imaging to detect bony lesions (whole body MRI)

Question 20

What is diagnostic criteria for myeloma?

Answer 20

Both:

1. marrow aspirate/biopsy showing clonal plasma cells >10%
2. 1 or more organ dysfunction –> CRAB (Calcium, renal, anaemia, bone)

Question 21

How should myeloma be screened for in a patient > 50 with new back pain?

Answer 21

Electrophoresis + ESR

Question 22

What is the symptomatic treatment for myeloma?

Answer 22

Bisphosphonates + analgesia (NOT NSAIDs) for bone
- RT +/- surgery if fractures or high risk
Transfusions +/- Epo for anaemia
Fluids +/- bisphosphonates for hypercalcaemia
Antibiotic prophylaxis, vaccines, Ig

Question 23

What is the specific treatment for myeloma?

Answer 23

Combination chemotherapy

- high dose chemo + autologous stem cell transplant in fit patients

Question 24

How is response to treatment monitored in myeloma?

Answer 24

Paraprotein level

Question 25

What are some of the complications of myeloma?

Answer 25

Hyperviscosity syndrome Spinal cord compression Death usually due to infection or kidney failure

Question 26

What is hyperviscosity syndrome?

Answer 26

Increase in PV usually due to raised Ig/paraproteins, RBCs or WBCs (note: raised PV is also an inflammatory marker)

Question 27

What are the causes of hyperviscosity syndrome?

Answer 27

Myeloma Waldenstrom's macroglobulinaemia Polycythaemia vera Leukaemia

Question 28

What are the clinical features of hyperviscosity syndrome?

Answer 28

Classic triad: - neuro symptoms: impaired cognition, headaches, seizures - visual changes from retinopathy - mucosal bleeding

Question 29

How is hyperviscosity syndrome managed?

Answer 29

Plasmapharesis

Question 30

When would a patient be considered to have MGUS?

Answer 30

Paraprotein < 30g/l, bone marrow plasma cells < 10% No evidence of myeloma end organ damage - normal calcium, renal function, Hb, bones - no increase in infections

Question 31

What is AL amyloidosis?

Answer 31

Rare disorder Mutation in light chain --> altered structure Precipitates in tissues as an insoluble beta pleated sheet --> organ damage

Question 32

How is AL amyloidosis diagnosed?

Answer 32

``` Organ biopsy showing amyloid deposition: - congo red stain --> apple green birefringence under polarised light Evidence of deposition in other organs: - SAP scan (serum amyloid P) - echo/cardiac MRI - nephrotic range proteinuria ```

Question 33

How is AL amyloidosis treated?

Answer 33

Chemotherapy similar to myeloma (switch off light chain supply)

Question 34

How is Waldenstrom's macroglobulinaemia characterised?

Answer 34

IgM paraprotein

Question 35

What are the clinical features of Waldenstrom's?

Answer 35

``` Lymphadenopathy Splenomegaly Marrow failure Hyperviscosity syndrome Night sweats, weight loss ```

Question 36

How is Waldenstrom's treated?

Answer 36

``` Chemotherapy Plasmapheresis (removes paraprotein from circulation) ```