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Haematology Path Year 5 > Myeloma and amyloid and monoclonal gammopathy of uncertain significance > Flashcards

Myeloma and amyloid and monoclonal gammopathy of uncertain significance Flashcards

1
Q

What is Multiple myeloma?

A

Malignancy of mature bone marrow plasma cell.
the terminally differentiated and immunoglobulin (Ig) secreting B Cells

The long-lived IgG/IgA plasma cells are those that form Multiple Myeloma’s

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2
Q

What is the median age of diagnosis? and which group of people is it more common in?

A
  1. Median age 67 years

2. More common in men and afrocarribeans

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3
Q

What are the main risk factors for multiple myeloma?

A
  1. Age
  2. Obesity
  3. Genetics (afrocarribean or FHx)
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4
Q

Which 2 condiitions is multiple myeloma preceded by? What are their diagnostic criteria?

A
  1. Monoclonal Gammopathy of Uncertain Significance (MGUS).
  • > Serum M Protein <30g/L (M protein = Monoclonal Protein)
  • > Bone marrow clonal plasma cells <10%
  1. Smouldering Myeloma (next step after MGUS basically)

-> Serum M Protein > 30g/L OR Urinary Monoclonal Protein >500mg
OR
-> Bone marrow clonal plasma cells 10-60%

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5
Q

What are patients with MGUS at an increased risk of?

A
  • > Osteoporosis
  • > Thrombosis
  • > Bacterial Infection
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6
Q

What percentage of patients with MGUS develop myeloma?

A

around 1%

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7
Q

What are 3 characteristics of cells in multiple myeloma?

A

These cells hone in and infiltrate the bone marrow
These cells may also form tumours at bone or soft tissue i.e. plasmacytomas
They also release;
-> Monocloncal IgG or IgA -> i.e. paraprotein/ M-spike
-> Serum free light chains (Kappa or Lambda), when found in the urine this is a Bence Jones Protein

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8
Q

What are the consequences of multiple myeloma cells interacting with bone?

A
  1. Bone destruction (osteoclast activation, results in high Ca2+)
  2. Angiogenesis
  3. Pancytopenia (mostly anaemia)
  4. Immunosuppression
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9
Q

How do you diagnose multiple myeloma?

A
  1. > 10% plasma cells in bone marrow OR plasmacytoma

+

  1. 1 CRAB or 1 MDE
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10
Q

What is CRAB and MDE?

A 
CRAB:
hyperCalcaemia
Renal disease
Anaemia
Bone disease

MDE (myeloma defining events)
bone marrow plasma cells >60%
>1 focal lesion in MRI

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11
Q

What is the clinical presentation of a patient with multiple myeloma bone disease?

A

80% present with bone disease

  1. Proximal skeleton involvement
  2. Spine, chest wall and pelvic pain
  3. Osteolytic lesions
  4. Osteopenia
  5. Pathalogical fractures
  6. Hypercalcaemia
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12
Q

What kind of imaging is used for multiple myeloma?

A
  1. Whole body CT
  2. CT / FDG-PET scan
  3. Whole body diffusion weighted MRI
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13
Q

What are 2 emergencies to do with myeloma?

A
  1. Cord compression
    MRI
    Dexamethsone + Radiotherapy
  2. Hypercalcaemia
    Fluids, steroids and zolendronic acid
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14
Q

How are the kidneys affected in the patient with multiple myeloma?

A

Physiologically, B Cells produce more Light Chains than Heavy chains, as a result their tends to be some Serum Free Circulating Light Chains i.e. Kappa or Lambda.
-> These are filtered by the glomeruli and reabsorbed by the proximal tubule to which they are recycled into the body.

In Multiple Myeloma, the sheer amount of Serum Free Light Chains overwhelms the reabsoptive capabilities of the proximal tubule.

  • > The light chains enter the distal tubule where they bind to THP (Tamm Horsfall Protein) o.e. Uromodulin
  • > Here they form gel like materials which destroy the nephron
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15
Q

What is a good marker of prognosis and outcome of multiple myeloma?

A

Kidney Disease

  • > Those with severe kidney disease i.e. eGFR<30ml/min have a worse outcome.
  • > If the Myeloma Kidney Disease can be overturned, patient outcome improves dramatically.
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16
Q

What is the key histopathological myeloma marker?

A

CD138 on plasma cells

17
Q

What are the diagnostic tests for multiple myeloma?

A
  1. Immunoglobulin studies
  2. Bone marrow aspirate and biopsy
  3. FISH analysis
18
Q

What is the aetiology of AL amyloidosis?

A
  1. Background of MGUS or myeloma

2. Free light chains released misfold and aggregate into amyloid fibrils in organs

19
Q

Which stain is used for amyloid fibrils?

20
Q

What are common target organs for AL amyloidosis?

A
  1. Kidney
  2. Heart
  3. Liver
  4. Neuropathy
21
Q

What is Monoclonal Gammopathy of renal significance (MGRS)?

A

B cell clonal lymphoproliferation where there are:

  1. one or more kidney lesions caused by monoclonal immunoglobulin
    AND
  2. b cell clone does not cause tumour complications for immediate specific therapy
22
Q

What is the treatment for multiple myeloma?

A
  1. Steroids (dex and pred)
  2. Immunomodulatory Drugs (lenalidomide)
  3. Therapeutic monoclonal antibodies

Haematology Path Year 5 (5 decks)

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