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YEAR 4 CANCER CARE > Haem Malignancy- Myeloma > Flashcards

Haem Malignancy- Myeloma Flashcards

1
Q

What is myeloma?

A
  • Haem malignancy characterised by plasma cell proliferation
  • Arises due to genetic muttions which occur as B-lymphocytes differentiate into mature plasma cells
  • Occurs for around 1% of all cancers
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2
Q

What is myeloma?

A
  • Haem malignancy characterised by plasma cells proliferation- results in large quantities of a single type of antibody being produced
  • Arises due to genetic mutataion which occur as B-lymphocytes differentiate into mature plama cells
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3
Q

What is Monoclonal gammopathy of undetermined significance?

A
  • Excess of a single type of antibody or antibody components without other features of myeloma or cancer
  • Often incidental finding in otherwise healthy person
  • May progress to myeloma and pts often followed up routinely to monitor for progression
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4
Q

Pathophysiology of Myeloma?

A
  • Plasma cells genetically mutated so they multiply rapidly and uncontrollably
  • These plasma cells produce one type of antibody/ immunoglobulins
  • When you measure immunoglobulins in a pt w myeloma one type of antibody (A,G,M,D,E) will be significantly abundant
  • More than 50% of the time it is IgG
  • This single type of antibody that is produced by all the identical plasma cells can be called monoclonal paraprotein
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5
Q

What are Bence Jones protein?

A
  • Found in urine of many pts with myeloma
  • subunit of the antibody-light chains
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6
Q

What is the monoclonal paraprotein in myeloma?

A
  • The single type of antibody that is produced by all the identical cancerous plasma cells
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7
Q

What age does myeloma present?

A
  • Median age is 70 years old
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8
Q

What are the clinical features of myeloma?

Just state them, will go into more detail in later q;s

A

Mnemoic CRABBI

  • Calcium- hypercalcaemia
  • Renal- Renal damage/failure
  • Anaemia- causing fatigue and pallor
  • Bleeding
  • Bones- bone pain and increased risk of pathological fractures
  • Infection- more susceptible
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9
Q

Cause and presentation of hypercalcaemia in myeloma?

A
  • primary factor: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells- leads to osteolytic lesions
  • much less common contributing factors: impaired renal function, increased renal tubular calcium reabsorption and elevated PTH-rP levels
  • this leads to constipation, nausea, anorexia and confusion
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10
Q

Cause and presentation of renal damage in myeloma?

A
  • monoclonal production of immunoglobulins results in light chain deposition within the renal tubules
  • this causes renal damage which presents as dehydration and increasing thirst
  • other causes of renal impairment in myeloma include amyloidosis, nephrocalcinosis, nephrolithiasis
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11
Q

Cause and presentation of anaemia in myeloma?

A
  • bone marrow crowding suppresses erythropoiesis leading to anaemia
  • this causes fatigue and pallor
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12
Q

Cause and presentation of bleeding in myeloma?

A
  • bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising
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13
Q

Cause and presentation of bone pain in myeloma?

A
  • bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates lytic bone lesions
  • this may present as pain (especially in the back) and increases the risk of pathological fractures
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14
Q

Cause of increased infection risk in myeloma?

A

a reduction in the production of normal immunoglobulins results in increased susceptibility to infection
The most common infections are respiratory and urinary.
* * Patients are also more susceptible to viral infections. These infections need to be recognised and treated quickly, as they can often progress rapidly.
* * Some patients with particularly low levels of immunoglobulins can have intravenous immunoglobul

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15
Q

Other features of myeloma?

NOT CRABBI

A
  • Amyloidosis
  • Carpal tunnel syndrome
  • Neuropathy
  • Hyperviscosity
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16
Q

What are the symptoms of hyperviscosity?

A
  • Easy bruising
  • Easy bleeding
  • Reduced or loss of sight due to vascular disease in the eye
  • Purple discolouration to the extremities (purplish palmar erythema)
  • Heart failure
17
Q

RF for myeloma?

A
  • older age
  • Male
  • Black african
  • family hx
  • obesity
18
Q

When should you consider myeloma?

A
  • Anyone over 60 with persistent bone pain, particularly back pain, or unexplained fractures
19
Q

What initial invesigations would you perform to rule out/in myeloma?

A
  • FBC- low WCC in myeloma
  • Calcium- raised in myeloma
  • ESR- raised in myeloma
  • Plasma viscosity- raise in myeloma
  • Blood film – rouleaux formation (red cells stacked on top of each other)

IF any of these are positive or myeloma is still suspected- do an URGENT SERUM PROTEIN ELECTROPHORESIS AND URINE BENCE-JONES PROTEIN

20
Q

What specific lab investigations (following the initial ones) would you do if you suspected myeloma?

A

Mnemonic BLIP

  • B- Bence Jones Protein (request urine electrophoresis)
  • L-Serum-free Light chain assay
  • I-Serum Immunoglobulins
  • P-Serum protein electrophoresis

Bone marrow biopsy is necessary to confirm the diagnosis of myeloma and get more info on the disease

21
Q

What imaging do you do for myeloma?

A

Required to assess for bone lesions
* Whole body MRI
* Whole body CT
* Skeletal survey

Patients only require one investigation but may not tolerate or be suita

above is order of preference

22
Q

What are the criteria for myeloma diagnosis?

A

Diagnostic criteria for multiple myeloma requires one major and one minor criteria or three minor criteria in an individual who has signs or symptoms of multiple myeloma.

Major criteria
* Plasmacytoma (as demonstrated on evaluation of biopsy specimen)
* 30% plasma cells in a bone marrow sample
* Elevated levels of M protein in the blood or urine

Minor criteria
* 10% to 30% plasma cells in a bone marrow sample.
* Minor elevations in the level of M protein in the blood or urine.
* Osteolytic lesions (as demonstrated on imaging studies).
* Low levels of antibodies (not produced by the cancer cells) in the blood.
*

23
Q

What is plasmacytoma?

A
  • Individual tumours made up of the cancerous plasma cells
  • Can occur in bones, replacing normal bone tissue or can occur outside bones in the soft tisue of the body
24
Q

Xray signs in myeloma?

A
  • Punched out lesions
  • Lytic lesions
  • “Raindrop skull” caused by many punched out (lytic) lesions throughout the skull that give the appearance of raindrops splashing on a surface
25
Q

What is the aim of treatment in Myeloma?

A
  • Control disease
  • Usually takes relapsing and remitting course
  • Aim to improve quality and quantity of life
  • MDT approach
26
Q

What is the first line treatment of myeloma?

A
  • Combination of chemotherapy with:
  • Bortezomid
  • Thalidomide
  • Dexamethsone
27
Q

Side effects of steroids

A
  • Weight gain
  • Insulin resistance
  • Cushings
  • Hirsuitism
  • Thin skin
  • Easy bruising
  • Insomnia
  • Bone weakness/osteoporosis
28
Q

Aside from chemotherapy, what adjuncts to treatment are there in myeloma?

A
  • Stem cell transplanatation can be used as part of clinical trial where pts are suitable
  • VTE prophylaxis
  • Manage myeloma bone disease following:
    Bisphosphonates- these suppress osteoclast activity
    Radiotherapy- to bone lesions can improve bone pain
    Orthopaedic surgery- can stabilise bones
    Cement augmentation- invovled injecting cement into vertebral fractures or lesions- can improve spine stability and pain
29
Q

Complications of myeloma?

A
  • Infection
  • Pain
  • Renal failure
  • Anaemia
  • Hypercalcaemia
  • Peripheral neuropathy
  • Spinal cord compression
  • Hyperviscosity
30
Q

How many patients with MGUS develop myeloma?

A
  • Around 10% of pts eventually develop myeloma at 10 years
  • 50% at 15 years
31
Q

Features of MGUS?

A
  • Usually asymptomatic
  • No bone pain or increased risk of infections
  • around 10-30% patients have demyelinating neuropathy
32
Q

MGUS differentiating features from Myeloma

A
  • Normal immune function
  • normal beta-2 microglobulin levels
  • lower level of paraproteinaemia than myeloma
  • stable level of paraproteinaemia
  • no clinical features of myeloma
32
Q

MGUS differentiating features from Myeloma

A
  • Normal immune function
  • normal beta-2 microglobulin levels
  • lower level of paraproteinaemia than myeloma
  • stable level of paraproteinaemia
  • no clinical features of myeloma
33
Q

What is amyloidosis?

what is it, what is its precusor etc.

A
  • amyloidosis is a term which describes the extracellular deposition of an insoluble fibrillar protein termed amyloid
  • amyloid is derived from many different precursor proteins
    • in addition to the fibrillar component, amyloid also contains a non-fibrillary protein called amyloid-P component, derived from the acute phase protein serum amyloid
      other non-fibrillary components include apolipoprotein E and heparan sulphate proteoglycans
  • the accumulation of amyloid fibrils leads to tissue/organ dysfuncti
34
Q

How is amyloidosis classified?

A
  • Systemic or localized
  • further characterised by precursor protein (e.g. AL in myeloma - A for Amyloid, L for immunoglobulin Light chain fragments)
35
Q

Diagnosis of Amyloidosis?

A
  • Congo red staining: apple-green birefringence
    serum amyloid precursor (SAP) scan
  • biopsy of skin, rectal mucosa, or abdominal fat
36
Q

What is ‘smouldering myeloma”?

A

Differentiated from symptomatic myeloma by the absence of end-organ damage.

Often these patients do not receive treatment initially.

Instead, a watch and wait approach is adopted, with regular reviews in a haematology clinic.

Patients are monitored for signs of early end-organ damage developing (progression).

If patients begin to develop end-organ damage, treatment is considered.

37
Q

Criteria for smouldering myeloma?

A

The below criteria must be met for a diagnosis of asymptomatic (smouldering) myeloma:

Serum paraprotein >30 g/L
+/- Clonal plasma cells >10% on bone marrow biopsy
NO myeloma-related organ or tissue impairment

38
Q

Prognosis of myeloma?

A

With high dose chemotherapy followed by autologous stem cell transplantation, the median survival has been estimated to be 4.5 years.
The overall 5-year survival rate is around 35%.

YEAR 4 CANCER CARE (22 decks)

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