Plasma Cell Dyscrasias Flashcards

1
Q

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

A

Derived from stem cells in the bone marrow

- produce antibodies

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2
Q

What are antibodies and how are they structured?

A

Immunoglobulins

  • -> proteins made of 2 heavy chains + 2 light chains
  • monomers = IgD, IgE + IgG
  • dimer = IgA
  • pentamer = IgM
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3
Q

Describe the progression of a stem cell into a plasma cell

A

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)

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4
Q

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

A

Factory cell –> pumps out antibody

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

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5
Q

What might cause a polyclonal rise in Ig?

A

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

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6
Q

What would cause a monoclonal rise in Ig?

A

Underlying clonal B cell disorder

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7
Q

What is another term for monoclonal Ig?

A

Paraprotein

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8
Q

Which investigations defect monoclonal Ig?

A

Serum electrophoresis –> detects abnormal protein bands

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

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9
Q

What is Bence Jones protein and how is it detected?

A

Excess Ig light chains in urine

–> detected by urine electrophoresis

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10
Q

What are the possible causes of paraproteinaemia?

A
MGUS (monoclonal gammaopathy of uncertain significance)
Myeloma
Amyloidosis
Lymphoma
Plasmacytoma
CLL
Waldenstrom's
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11
Q

What is myeloma?

A

Malignant proliferation of plasma cells in bone marrow

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

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12
Q

How is myeloma classified?

A

By Ig class:

  • 2/3 are IgG
  • 1/3 are IgA
  • rest are IgM or IgD
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13
Q

What happens to the other classes of Ig in myeloma?

A

Other classes will be low –> immunoparesis

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14
Q

What are the key features of myeloma?

A
Osteolytic bone lesions --> fractures + bone pain --> HYPERCALCAEMIA
Pancytopenia (marrow infiltration)
Infection (immunoparesis)
Renal disease
Hyperviscosity
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15
Q

What is the mechanism of kidney injury in myeloma?

A

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

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16
Q

What are the features of hypercalcaemia?

A
Stones
Bones
Abdo groans
Psychiatric moans
Thirst
Dehydration
Renal impairment
17
Q

What would be seen on bloods in myeloma?

A

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

18
Q

What would be seen on the blood film in myeloma?

A

Rouleaux formation (stacked RBCs)

19
Q

Which investigations should be done for myeloma?

A

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

20
Q

What is diagnostic criteria for myeloma?

A

Both:

  1. marrow aspirate/biopsy showing clonal plasma cells >10%
  2. 1 or more organ dysfunction –> CRAB (Calcium, renal, anaemia, bone)
21
Q

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

A

Electrophoresis + ESR

22
Q

What is the symptomatic treatment for myeloma?

A

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

23
Q

What is the specific treatment for myeloma?

A

Combination chemotherapy

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

24
Q

How is response to treatment monitored in myeloma?

A

Paraprotein level

25
Q

What are some of the complications of myeloma?

A

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

26
Q

What is hyperviscosity syndrome?

A

Increase in PV usually due to raised Ig/paraproteins, RBCs or WBCs

(note: raised PV is also an inflammatory marker)

27
Q

What are the causes of hyperviscosity syndrome?

A

Myeloma
Waldenstrom’s macroglobulinaemia
Polycythaemia vera
Leukaemia

28
Q

What are the clinical features of hyperviscosity syndrome?

A

Classic triad:

  • neuro symptoms: impaired cognition, headaches, seizures
  • visual changes from retinopathy
  • mucosal bleeding
29
Q

How is hyperviscosity syndrome managed?

A

Plasmapharesis

30
Q

When would a patient be considered to have MGUS?

A

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

31
Q

What is AL amyloidosis?

A

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

32
Q

How is AL amyloidosis diagnosed?

A
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
33
Q

How is AL amyloidosis treated?

A

Chemotherapy similar to myeloma (switch off light chain supply)

34
Q

How is Waldenstrom’s macroglobulinaemia characterised?

A

IgM paraprotein

35
Q

What are the clinical features of Waldenstrom’s?

A
Lymphadenopathy
Splenomegaly
Marrow failure
Hyperviscosity syndrome
Night sweats, weight loss
36
Q

How is Waldenstrom’s treated?

A
Chemotherapy
Plasmapheresis (removes paraprotein from circulation)