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Haematology > Myeloma and other plasma cell dyscrasias > Flashcards

Myeloma and other plasma cell dyscrasias Flashcards

1
Q

Where are B cells developed from?

A

Bone marrow from pluripotent haematopoietic stem cell

Part of adaptive immune system

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2
Q

What is the dual function of B cells?

A

Antibody production

Acts as antigen presenting cells

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3
Q

What are immunoglobulins?

A

Antibodies produced by B cells and plasma cells
Proteins made up of 2 heavy and 2 light chains
Each antibody recognizes a SPECIFIC antigen

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4
Q

Describe the different shapes of immunoglobulins

A

Monomer; IgD, IgE, IgG
Dimer; IgA
Pentamer; IgM

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5
Q

What generates the variable region of Ig?

A

V-D-J region recombination early in development

Self reactive cells removed

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6
Q

Describe the development of B cells within the bone marrow

A

Stem cells
Common lymphoid progenitor
Pro B cells
Pre B cells

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7
Q

Where will B cells travel to once they reach the circulation?

A

Follicle germinal centre of the lymph node

Identify antigens and improves the fit by somatic mutation or deletion

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8
Q

How can B cells return to the circulation once they have passed through the germinal center?

A

Plasma cells; production antibodies

Memory B cell

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9
Q

What is a plasma cell?

A

Production of antibodies

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10
Q

Describe the appearance of a plasma cell?

A

Eccentric clock face nucleus on H+E
Open chromatin; synthesising mRNA
Plentiful blud cytoplasm laden with protein
Pale perinuclear area; golgi apparatus

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11
Q

What does a polyclonal increase in Ig suggest?

A 
Produced by many different plasma cells 
Reactive; 
Infection 
Autoimmune
Malignancy; reaction of host to malignant clone
Liver dx
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12
Q

What does a monoclonal rie in Ig suggest?

A

All derived from clonal expansion of single B-cell

Identical antibody structure and specificity

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13
Q

What is a monoclonal immunoglobulin?

A

Paraprotein

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14
Q

What is a monoclonal Ig an maker of?

A

Underlying clonal B cell disorder

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15
Q

How can immunoglobulins be detected?

A

Electrophoresis

The separated proteins appear as distinct bands or zones

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16
Q

What determines how far proteins move on electrophoresis?

A

Size

Charge

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17
Q

What will electrophoresis detect?

A

ABNORMAL protein bands

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18
Q

What is the purpose of serum immunofixation?

A

Classify abnormal protein band

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19
Q

What is a bence jones protein?

A

Immunoglobulin light chain

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20
Q

How are bence jones proteins identified?

A

Urine electrophoresis

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21
Q

How much free light chain is produced by normal plasma cells?

A

0.5g/ day

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22
Q

What are the different light chains?

A

Kappa - monomer

Lambda - dimeric

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23
Q

What can cause an increase in light chain immunoglobulin production?

A

Polyclonal increase; infection

Monoclonal increased; multiple myeloma

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24
Q

What are the commonest causes for paraproteinaemia?

A 
MGUS (monoclonal gammopathy of unknown significance) (56%)
Myeloma (18%)
Amyloidosis (10%) 
Lymphoma (5%) 
Asymptomatic myeloma (4%) 
Solitary or extramedullary plasmacytoma (3%) 
Chronic lymphocytic leukaemia (2%) 
Waldenstrom's macroglobulinemia (2%)
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25
Q

What is myeloma?

A

A plasma cell malignancy

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26
Q

How does myeloma occur?

A 
Normal plasma cells 
Genetic "hit" 
MGUS (benign/ premalignant) 
Genetic "hit"
Asymptomatic myeloma (malignant but no organ damage) 
Genetic "hit" 
Myelom (overtly malignant)
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27
Q

How will myeloma affect the body?

A

Direct tumour cell effects

Paraprotein mediated effects

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28
Q

What are the direct tumour cell effects of myeloma?

A

Bone lesions
Increased calcium
Bone pain
Replace normal bone marrow (marrow failure)

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29
Q

What are the paraprotein mediated effects of myeloma?

A

Renal failure
Immunosuppression
Hyperviscosity
Amyloid

30
Q

How is myeloma classified?

A

On the type of monoclonal protein they produce
Majority (60%) produce IgG
Then IgA
Then free light chains (bence jones myeloma)

31
Q

What is the characteristic skull x-ray appearance in myeloma?

A

Multiple “punched out” lytic lesions in skull

32
Q

What are the bony abnormalities seen in multiple myeloma?

A

Lytic skull lesions

Wedge compression fracture of thoracic vertebrae

33
Q

Which cytokines are upregulated in multiple myeloma?

A

IL-6

TGF beta

34
Q

What is the pathogenesis of myeloma lytic bone disease?

A

Myeloma cells increased IL-6
This activated osteoclasts and suppressed osteoblasts
Increased calcium

35
Q

What are the symptoms of hypercalcaemia?

A 
Stones
Bones
Abdominal groans
Psychiatric moans
Thirst
Dehydration 
Renal impairment
36
Q

What is the commonest consequence of myeloma on organ damage?

A

KIDNEY

30% will have renal impairment at diagnosis

37
Q

What are the different types of renal damage that myeloma can cause?

A 
Tubular cell damage via light chains
Light chain deposition - cast nephropathy
Sepsis
Hypercalcaemia and dehydration 
Drugs; NSAIDs
Hyperuricemia 
Amyloid
38
Q

What is the half life of free light chains?

A

2-6 hours
Can filter through the glomerular pores
Proximal tubules will attempt to reabsorb these proteins but if overwhelmed the protein will pass into the thick ascending loop of henle where it will combine with tamm horsfall proteins to produce insoluble casts

39
Q

What are the casts made from in cast nephropathy?

A

Free immunoglobulin light chains and Tamm Horsfall protein

40
Q

Where will casts form in cast nephropathy?

A

Thick ascending loop of henle

41
Q

Is cast nephropathy reversible?

A

Can be with prompt treatment
Hydration
STOP nephrotoxic drugs
Switch off light chain production via steroids/ chemo

42
Q

What is the treatment of myeloma?

A

Corticosteroids; dexa or pred
Alkylating agents; cyclophosphamide
Novel agents; thalidomide, bortezomib and lenalidomide

43
Q

What is the gold standard treatment for myeloma in fit patient?

A

High dose chemo

Autologous stem cell transplant

44
Q

How is response monitored in myeloma treatment?

A

Paraprotein (monoclonal immunoglobulin) levels

45
Q

What is autologous haematopoietic stem cell transplant?

A

Administer pre-treatment to release blood stem cells from bone marrow into blood stream
Collect blood stem cells
Freeze
Administer chemo to remove or partially remove immune system
Return thawed stem cells by infusion via vein

46
Q

What CD marker is present on B cells?

A

CD 20

47
Q

What CD marker is present on plasma cells?

A

CD 38

48
Q

What antibody can be used to target plasma cells in myeloma?

A

Daratumumab - targets CD38 surface receptor

49
Q

What is the symptom control management in multiple myeloma?

A

Opiate analgesia (avoid NSAIDs)
Local radiotherapy
Bisphosphonates (corrects hypercalcaemia and bone pain)
Vertebroplasty (inject sterile cement into fractured bone to stabilise)

50
Q

What is MGUS?

A

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

51
Q

What are the signs of myeloma end organ damage?

A 
Raised calcium
Reduced renal function 
Reduced Hb
Lytic lesions
Increase in infection
52
Q

Can MGUS progress to myeloma?

A

Yes - risk is 1% per year

53
Q

What is AL amyloidosis?

A

Small plasma cell clone mutation in light chain; altered structure

54
Q

What will AL amyloidosis precipitate as?

A

Insoluble beta pleated sheet

55
Q

What are the consequences of AL amyloidosis?

A

Accumulation in tissues = organ damage
Multisystem
Poor prognosis if cardiac amyloid

56
Q

What is the treatment of AL amyloidosis?

A

Chemo similar to myeloma to switch off light chain supply

57
Q

What organ damage will occur in AL amyloidosis?

A 
Kidney; nephrotic syndrome 
Heart; cardiomyopathy 
Liver; organomegaly - deranged LFTs
Neuropathy; autonomic, peripheral 
GI; malabsorption
58
Q

How is amyloid diagnosed?

A

Organ biopsy
Congo red stain with apple green birefringence under polarised light
Rectal or fat biopsy if high clinical suspicion

59
Q

How is amyloid staged?

A

SAP scan
Echo/ cardiac MRI
Nephrotic range proteinura

60
Q

What is a SAP scan?

A

Amyloid labelled scintigraphy to monitor disease burden and response
Localises rapidly and specifically to amyloid deposits in proportion to quantity of amyloid present

61
Q

What is waldenstrom’s macroglobulinaemia?

A

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

62
Q

What is the characteristic sign of waldenstrom’s macroglobulinemia?

A

IgM paraprptein

63
Q

What are the tumour effects of waldenstrom’s macroglobulinemia?

A

Lymphadenopathy
Splenomegaly
Marrow failure

64
Q

What are the paraprotein effects of waldenstrom’s macroglobulinemia?

A

Hyperviscosity

Neuropathy

65
Q

What is the structure of an IgM antibody?

A

Pentamer

900 KDa

66
Q

What is hyperviscosity syndrome?

A 
Fatigue
Visual disturbance
Confusion 
Coma
Bleeding 
Cardiac failure
67
Q

What is the treatment of waldenstrom’s macroglobulinemia?

A 
Chemo 
Plasmapheresis (removes paraprotein from circulation)
68
Q

What is a bence jones protein?

A

Free Ig light chain of kappa or lamba type filtered by the kidney

69
Q

How is myeloma diagnosed?

A

Monoclonal protein band in serum of urine electrophoresis
Increased plasma cells on marrow biopsy
Evidence of end-organ damage from myeloma; hypercalcaemia, renal insufficiency, anaemia
Bone lesions; skeletal survey after diagnosis detected bone diseae
+/- Tc-99m MIBI and PET

70
Q

What can be seen on the blood film in multiple myeloma?

A

Rouleaux formation

Haematology (31 decks)

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