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Haematology > Myeloma > Flashcards

Myeloma Flashcards

1
Q

What are B cells derived from?

A

Derived from pluripotent haematopoietic stem cells in the bone marrow

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2
Q

What system are B cells part of?

A

The adaptive immune system

‘think AB’

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3
Q

B cells have a _____ role.

A

Dural

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4
Q

What is the dual role of B cells?

A
  1. Antibody production.

2. Acting as antigen presenting cells.

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5
Q

What are immunoglobulins?

A

Antibodies produced by B cells and plasma cells

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6
Q

Describe the structure of immunoglobulins.

A

Proteins made up of (κ or λ) 2 heavy (μ, α, δ, γ, ε) and 2 light chains

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7
Q

What does each antibody in the body do?

A

Recognises a specific antigen

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8
Q

The type of antibody is determined by the type of ______ chain used

A

Heavy

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9
Q

Of the 5 types of immunoglobulins, which are:

i) monomers
ii) dimers
iii) pentamers?

A

i) IgD, IgE, IgG.
ii) IgA.
ii) IgM.

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10
Q

Name the 5 immunoglobulins found in the body.

A

IgD, IgE, IgG, IgA, IgM

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11
Q

What differentiates immunoglobulins?

A

The type of heavy chain used

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12
Q

Where does initial production and development of B cells occur?

A

In the bone marrow

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13
Q

What is B cell development under the control/influence of?

A

The microenvironment

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14
Q

What is the Ig variable element generated from?

A

V-D-J region recombination early in development

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15
Q

What are removed during B cell development?

A

Self-reactive cells

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16
Q

What do immature B cells have on their surface?

A

Immunoglobulin (Ig).

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17
Q

What happens to immunoglobulins when they leave the surface of B cells?

A

They exit bone marrow, ready to meet their target

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18
Q

What can B cells undergo once they have left the bone marrow?

A

Class switching by switching heavy chains

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19
Q

Once B cells leave the bone marrow, and travel tot the periphery, where do they go?

A

The follicle germinal centre of the lymph node

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20
Q

What do B cells do in the follicle germinal centre of the lymph node?

A

They identify the antigen and improve the fit by somatic mutation, or be deleted

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21
Q

Lymph nodes are the site where …

A

Immature B cells are exposed to antigens

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22
Q

Once B cells have been exposed to antigens in the lymph node, what do they do?

A

Either return to the marrow as a plasma cell, or circulate as a memory cell.

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23
Q

What is a plasma cell also known as?

A

A factory cell

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24
Q

What do plasma cells do?

A

Pump out antibodies

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25
Q

Describe the characteristic features on microscopy, of plasma cells pumping out antibodies.

A
  • Eccentric ‘clock face nucleus’ on H+E.

* Open chromatin

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26
Q

Why does plasma cells pumping out antibodies look like an eccentric clock face nucleus on microscopy?

A
  • Plentiful blue cytoplasm.
  • Laden with protein.
  • Pale perinuclear area.
  • Golgi apparatus.
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27
Q

Describe the appearance of a bone marrow aspirate in multiple myeloma.

A

Typical ‘fried egg’ appearance, with nucleus off to one side and large, pale cytoplasm.

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28
Q

Healthy individuals will have a POLYCLONAL appearance

A

T

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29
Q

Malignancy reveals a monoclonal appearance

A

T

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30
Q

If a polyclonal increase of immunoglobulins is seen, what does this tell us about how the immunoglobulins were produced?

A

Many different plasma cells

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31
Q

Polyclonal means that many different plasma cells have many immunoglobulins

A

T

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32
Q

What is polyclonal immunoglobulins usually indicative of?

A

A reactive problem

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33
Q

Give examples of reactive problems which could cause polyclonal immunoglobulins.

A
  • Infection.
  • Autoimmune.
  • Malignancy – reaction of the host to the malignant clone.
  • Liver disease.
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34
Q

What are ALL immunoglobulins derived from when a monoclonal rise in immunoglobulins is seen?

A

Clonal expansion of a single B-cell

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35
Q

Describe the antibodies produced by clonal expansion of a single B cell.

A

They are identical in structure and specificity (size and charge

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36
Q

What other name is used for ‘monoclonal immunoglobulin’?

A

Paraprotein

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37
Q

What is a monoclonal rise in immunoglobulins a marker of?

A

Underlying clonal B cell disorder

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38
Q

What method is used to detect immunoglobulins?

A

Serum electrophoresis

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39
Q

What does serum electrophoresis do?

A

Separates proteins into distinct bands or zones

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40
Q

Proteins move at different rates, determined by …

A

Their size and charge

41
Q

What molecule is closest to the anode? Why?

A

Albumin – it is the most negatively charged molecule.

42
Q

If electrophoresis looks suspicious for a paraprotein, what should you do?

A

Serum immunofixation

43
Q

Why is serum immunofixation done?

A

To classify the abnormal protein band

44
Q

What are Bence Jones proteins?

A

Immunoglobulin light chains

45
Q

How are Bence Jones proteins detected?

A

Urine electrophoresis

46
Q

Why is it only immunoglobulin light chains (BJP’s) that are detected in urine electrophoresis?

A

Intact antibodies are too big to get through the kidney, but light chains can

47
Q

What is the normal free light chain production by plasma cells?

A

0.5g/day

48
Q

What happens if free light chains are produced in excess?

A

Excess can leak into the urine as BJP

49
Q

There is always a little bit of light chain over-production, but this isn’t usually detectable.

A

T

50
Q

What is the i) 1st ii) 2nd most common cause of paraproteinaemia?

A

i) Monoclonal Gammopathy of Uncertain Significance (MGUS).

ii) Myeloma.

51
Q

What can the effects of myeloma on the body be grouped into?

A
  • Direct tumour effects

* Paraprotein effects

52
Q

What are the direct tumour effects in Myeloma?

A
  1. Bone lesions.
  2. Increased calcium.
  3. Bone pain.
  4. Replace normal bone marrow - marrow failure.
53
Q

What are the paraprotein-mediated effects in myeloma?

A
  1. Renal failure.
  2. Immune suppression.
  3. Hyperviscosity.
  4. Amyloid.
54
Q

How is myeloma classified?

A

By the type of immunoglobulin produced

55
Q

What is the i) 1st ii) 2nd iii) 3rd most common classification of myeloma?

A
  1. IgG
  2. IgA
  3. Bence Jones - free light chains
56
Q

Describe the appearance of lytic bone disease seen in multiple myeloma.

A

Multiple ‘punched-out’ lytic lesions in the skull in myeloma

57
Q

Why do people with myeloma get lytic bone disease?

A

Myeloma cells produce cytokines which activate osteoclasts (bone destruction) and inhibit osteoblasts (bone construction)

The balance between bone production and construction is skewed.

58
Q

Why does hypercalacaemia occur?

A

Because of breakdown of bone in lytic bone disease

59
Q

What are the common manifestations of hypercalcaemia?

A
  • Stones.
  • Bones.
  • Abdominal groans.
  • Psychiatric moans.
  • Thirst.
  • Dehydration.
  • Renal impairment.
60
Q

What % of myeloma patients have renal failure at diagnosis?

A

30%

61
Q

List the causes of renal failure in myeloma paitients.

A
  • Tubular cell damage by light chains.
  • Light chain deposition - cast nephropathy.
  • Sepsis.
  • Hypercalcaemia and dehydration.
  • Drugs – NSAIDs.
  • Amyloid.
  • Hyperuricaemia.
62
Q

Light chains can cause renal failure by tubular cell damage and cast nephropathy. Explain this.

A
  • Free light chains are small enough to be filtered through the glomerular pores.
  • They do not simply pass into the urine however, because a specific function of the kidneys is to prevent the loss of small proteins such as light chains.
  • If the proximal tubules are overwhelmed by large amounts of light chain or damaged in some other way, then light chains can pass through into the loop of Henle.
  • In the thick ascending limb of the loop of Henle, Tamm-Horsfall protein is produced and this can combine with free light chains to produce insoluble casts which block the nephron.
  • Renal failure is a frequent feature of multiple myeloma and cast nephropathy is the most common cause in these patients.
63
Q

What is the most common cause of renal failure in multiple myeloma patients?

A

Cast nephropathy

64
Q

Is cast nephropathy damage reversible?

A

Possibly, with prompt treatment

65
Q

What is the treatment for cast nephropathy?

A

Steroids/chemo to switch off light chain production.

66
Q

What is the median age of diagnosis of multiple myeloma?

A

65

67
Q

What is the survival like of someone with multiple myeloma?

A

5-8 years for younger pts, with more effective therapy.

68
Q

Give examples of drugs/methods used to treat myeloma.

A
  • Corticosteroids; dexamethasone or prednisolone (high dose = toxic to plasma cells)
  • Alkylating agents eg cyclophosphamide, melphalan
  • ‘Novel agents’ like thalidomide, bortezomib and lenalidomide
  • Many more becoming available even monoclonal antibodies against plasma cells!
  • High dose chemo/autologous stem cell transplant in fit patients
69
Q

What is used to monitor response to treatment in multiple myeloma patients?

A

Paraprotein level

70
Q

What drug is used to manage pain in multiple myeloma patients?

A

Opiates

71
Q

What should NOT be used to manage pain in multiple myeloma patients?

A

NSAID’s

72
Q

What is used to manage pain and spinal cord compression in multiple myeloma patients?

A

Local radiotherapy

73
Q

What is used to manage hypercalcaemia and bone pain in multiple myeloma patients?

A

Bisphosphonates

74
Q

What is vertebroplasty?

A

Inject sterile cement into a fractured bone to stabilise it

75
Q

What is Monoclonal Gammopathy of Uncertain Significance (MGUS)?

A

Patient who has paraproteins but not myeloma

76
Q

MGUS becomes more common as people get older

A

T

77
Q

Outline the features which define MGUS.

A
  • Paraprotein <30g/l
  • Bone marrow plasma cells <10%
  • No evidence of myeloma end organ damage;
  • Normal calcium
  • Normal renal function
  • Normal Hb
  • No lytic lesions
  • No increase in infections
78
Q

What is AL amyloidosis?

A

Immunoglobulin light chain amyloidosis

79
Q

AL amyloidosis is common/rare

A

Rare

80
Q

Describe the pathology of AL amyloidosis.

A
  • A small plasma cell clone.
  • Mutation in the light chain leads to altered structure.
  • And precipitates arise in tissues as an insoluble beta pleated sheet.
81
Q

Is AL amyloidosis a cancer?

A

NO

82
Q

Why can AL amyloidosis result in problems?

A

Because accumulation of the insoluble beta pleated sheet in tissues can cause organ damage.

83
Q

AL amyloidosis is a …..

A

SLOWLY PROGRESSIVE, MULTISYSTEM DISEASE.

84
Q

What is the prognosis of AL amyloidosis like?

A

Poor – especially if cardiac amyloid

85
Q

Outline the organ damage which may occur in AL amyloidosis.

A
  • Kidney – nephrotic syndrome.
  • Heart – cardiomyopathy.
  • Liver – organomegaly, deranged LFT’s.
  • Neuropathy – autonomic, peripheral.
  • GI tract – malabsorption.
86
Q

What is the gold standard diagnostic test for AL amyloidosis?

A

Organ biopsy, confirming Al amyloid deposition.

Congo red stain !!! - +ve result

87
Q

What may be done if there is a HIGH clinical suspicion of AL amyloidosis?

A

Rectal or fat biopsy – less invasive

88
Q

What is also looked for when diagnosing someone with AL amyloidosis? How?

A

Evidence of deposition of amyloid in other organs:

  • SAP scan.
  • Echocardiogram.
  • Heavy proteinuria.
89
Q

What stain is used to show amyloid deposition in AL amyloidosis?

A

Congo red

90
Q

How does amyloid deposition appear in a congo red stain under polarised light?

A

‘apple-green’ birefringence

91
Q

What is Waldenstrom’s Macroglobulinaemia?

A

IgM paraprotein

think the ‘W’ in Waldenstrom’s is an upside down M

92
Q

Is Waldenstrom’s Macroglobulinaemia a neoplasm?

A

Yes

93
Q

What type of neoplasm is Waldenstrom’s Macroglobulinaemia?

A

LYMPHOPLASMACYTOID neoplasm.

  • Clonal disorder of cells intermediate between a lymphocyte and a plasma cell.
  • Characteristic IgM paraprotein.
94
Q

What are the TUMOUR EFFECTS in Waldenstrom’s Macroglobulinaemia?

A
  • Lymphadenopathy.
  • Splenomegaly.
  • Marrow failure.
95
Q

What are the PARAPROTEIN EFFECTS in Waldenstrom’s Macroglobulinaemia?

A
  • Hyperviscosity.

* Neuropathy.

96
Q

Why are the problems in Waldenstrom’s Macroglobulinaemia different to in Myeloma?

A

Because IgM is a pentamer, so is 5x the size of IgG.

97
Q

What are the clinical features of WM?

A
  • Hyperviscosity Syndrome*
  • Fatigue, visual disturbance, confusion, coma.
  • Bleeding.
  • Cardiac failure.

B symptoms; night sweats; weight lossLOT

98
Q

Lots of IgM makes the blood more viscous

A

T

99
Q

How is WM treated?

A
  • Chemotherapy.

* Plasmapheresis – removes the patients IgM paraprotein from the circulation and replace with donor plasma

Haematology (26 decks)

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