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Gwen - Haematology > Multiple Myeloma and Bone Pain > Flashcards

Multiple Myeloma and Bone Pain Flashcards

1
Q

What is multiple myeloma?

A

https://www.youtube.com/watch?v=ghvoKhpAc64

Myeloma is a malignant disease of bone marrow plasma cells. There is a clonal expansion of abnormal, proliferating plasma cells producing a monoclonal paraprotein, mainly IgG or IgA, and rarely IgM and IgD.

The paraproteinaemia may be associated with excretion of light chains in the urine (Bence Jones protein), which are either kappa or lambda.

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2
Q

What age group does multiple myeloma normally affect?

A

Elderly

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3
Q

What is the peak age at which MM presents?

A

70 years

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4
Q

Who is it more common in; Africans or Caucasians?

A

Africans - 2:1

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5
Q

What is an immunoglobulin?

A

Produced by B cells, msotyl plasma cells. Primay role is to recognise and bind to pathogens.

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6
Q

What is the basic structure of an immunoglobulin?

A
  • 2 heavy chains eg IgG, IgA, IgM, IgD, IgG
  • 2 light chains - kappa or lambda
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7
Q

What’s a paraprotein?

A

A monoclonal immunoglobulin that tells us there is monoclonal proliferation of a B lymphocyte/plasma cell somewhere. Note that paraproteins are common - monolonal gammopathy of uncertain significance (MGUS) is when there is nothing wrong

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8
Q

Whats the most common paraproteins to cause myeloma?

A

IgG, IgA

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9
Q

Why can IgM paraproteins notcause myeloma?

A

Because IgM paraproteins = lymphoma

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10
Q

What cells are affected by neoplastic changes in multiple myeloma?

A

Plasma cells

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11
Q

What do neoplastic myeloma cells produce?

A

Monoclonal paraproteins

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12
Q

What proportion of multiple myeloma cases have IgG paraproteins?

A

60%

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13
Q

What proportion of multiple myeloma cases have IgA paraproteins?

A

20%

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14
Q

Why does osteolysis occur in multiple myeloma?

A

The osteolytic destruction of the axial skeleton (sites of haemopoiesis in adults) results from malignant plasma cells stimulating osteoclasts to erode bone.

For some time it has been recognised that chemical messengers (cytokines) produced from the interaction of malignant plasma cells with their microenvironment stimulate the osteoclast activity. Such cytokines were known as osteoclast activating factors (OAFs) and are now known to include interleukin-1 and -6.

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15
Q

What may bee seen on blood film in multiple myeloma?

A

Rouleaux formation - as a consequence of the paraprotein and circulating plasma cells in the aggressive plasma cell leukaemia variant of myeloma.

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16
Q

What type of anaemia occurs in multiple myeloma?

A

Normocytic normochromic

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17
Q

What can be found in the urine in someone with multiple myeloma?

A

Bence-Jones Proteins

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18
Q

What are the following?

A

Roleaux formations

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19
Q

Why are bence jones proteins found in the urine?

A

Found in urine as a result of decreased kidney filtration capabilities due to renal failure, sometimes induced by hypercalcemia from the calcium released as the bones are destroyed or from the light chains themselves

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20
Q

What are the most commonly affected bones in multiple myeloma?

A
  • Spine
  • Skull
  • Long bones
  • Ribs
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21
Q

What does adhesion of bone marrow stromal cells to myeloma cells result in?

A

Produces cytokines, which:

  • Stimulates the production of RANKL, IL-6 and also VEGF -> angiogenesis
    • RANKL -> stimulates osteoclastic osteolysis.
  • OPG levels reduced -> reduced inhibition of osteoclastic activity
  • Paracrine secretion of endothelin 1 and PTH-rp -> increases osteoclastic activity.
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22
Q

What are symptoms of multiple myeloma?

A
  • Bone pain
  • Symptoms of anaemia
  • Recurrent infections
  • Symptoms of renal failure
  • Symptoms of hypercalcaemia
  • Symptoms of hyperviscosity and bleeding - rare
  • Weight loss
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23
Q

What is the most common type of bone pain?

A

Backache

So do serum protein electroporesis and ESR on all over 50 with back pain

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24
Q

What are symptoms of hypercalcaemia?

A

Bones, stones, groans, thrones (plenty pish but nae shite) and psychiatric overtones:

  • Abdominal pain
  • Vomiting
  • Constipation
  • Polyuria
  • Polydipsia
  • Depression
  • Anorexia
  • Weight loss
  • Tiredness
  • Weakness
  • Hypertension
  • Confusion
  • Pyrexia
  • Renal stones
  • Renal failure
  • Cardiac arrest
25
Q

Why does bone pain occur in MM?

A

Malignancy, whether primary or metastatic, changes the osteoblastic/osteoclastic balance. This results in either lytic lesions or abnormally weakened bone that is subject to microfractures.

Increased bone turnover can also produce pain, similar to the ‘growing pains’ of rapid growth in adolescence.

26
Q

If someone presented with bone pain/tenderness, what would consider as part of your differential diagnosis?

A
  • Trauma/fracture
  • Myeloma/Primary malignancy
  • Metastases
  • Osteonecrosis
  • Osteomyelitis/periostitis
  • Hydatid cyst
  • Ostesclerosis
  • Paget’s disease
  • Sickle cell disease
  • Renal osteodystrophy
  • CREST syndrome/Sjogren’s
  • Hyperparathyroidism
27
Q

If someone presented with bone pain, what initial investigations would you do?

A
  • FBC, U+E’s, LFTs
  • PSA
  • ESR
  • Ca2+
  • LFTs
  • Electrophoresis
28
Q

Why can someone with MM get recurrent infections?

A

Due to immunoparesis and neutropenia, plus chemotherapy

29
Q

Why does renal impairment occur in MM?

A

Due to paraprotein deposition, which bind with Tamm-Horsfall proteins in distal loop of henle. Monoclonal antibodies also cause changes in glomeruli.

Metastatic calcification, changes of pyelonephritis and AL amyloid may also be present in the kidneys. Systemic amyloidosis is present in 10% of cases, particularly in the tongue, heart and peripheral nerves, as well as the kidneys

30
Q

When does hyperviscosity and bleeding occur in multiple myeloma?

A

When there is bone infiltration by plasma cells

31
Q

What investigations would you do in someone who you suspected had multiple myeloma?

A
  • Bloods - FBC, ESR, U+E’s, LFTs, Ca2+, Alk phos, PSA, LDH, Blood film
  • Imaging - Skeletal survey - X-rays
  • Specific - Myeloma screen -
    Serum and urine electrophoresis (separates protein based on size and discharge, identifying paraprotein,
    Immunoglobulins (measures subclasses by heavy chain)
    Immunofixation (identifies class of paraprotein eg IgG, IgM
32
Q

What might you see on FBC in someone with MM?

A
  • Hb - normal, or normochromic, normocytic anaemia
  • WCC - normal or neutropenic
  • Platelets - normal or low
33
Q

What might you see on U+E’s in someone with MM?

A

Signs of Renal Failure

34
Q

What might you see on serum Ca2+ investigation in MM?

A

Hypercalcaemia

35
Q

What might you see on investigation of Alk phosphate in MM?

A

Ususally normal - unless there is a healing fracture

36
Q

What might you see on X-ray in someone with MM?

A

Lytic ‘punched out’ lesions

  • Pepper pot skull
  • Vertebral collapse
  • Fractures
37
Q

What might you see on serum protein electrophoresis?

A

Monoclonal bands and immune paresis

38
Q

What might you find on 24-hr urine collection electrophoresis?

A

Bence-Jones proteins

39
Q

What might you see on bone marrow aspirate in someone with MM?

A

Hypercellularity - many plasma cells with abnormal forms

40
Q

What diagnostic criteria are used to diagnose myeloma?

A
  1. Monoclonal protein band in serum or urine electrophoresis
  2. Plasma cells increased in BM biopsy (>10%)
  3. Evidence of end organ damage from myeloma - Hypercalcaemia, Renal failure, anaemia
  4. Bone lesions - skeletal survey
41
Q

What areas would you check as part of a skeletal survey?

A
  • Chest
  • All spine
  • Skull
  • Pelvis
42
Q

What are complications of myeloma?

A
  • Hypercalcaemia
  • Spinal cord compression
  • Hyperviscosity
    • ​Can cause bleeding, cardiac failure, pulmonary congestion, confusion and renal failure
  • Infection
    • ​Hypogammagobulinaemia
  • AKI
    • ​Cast nephropathy, amyloidosis
43
Q

What are features of hyperviscosity in MM?

A
  • Reduced cognition
  • Distrurbed vision
  • Bleeding
44
Q

How would you manage hyperviscosity in MM?

A

Plasmapheresis

45
Q

How would you manage an AKI in someone with MM?

A
  • Rehydration - 3L/day fluid intake
  • Consider urgent dialysis
46
Q

How would you manage someone with spinal cord compression in MM?

A
  • Consider decompression
  • Dexamethasone 8mg BD
  • Ranitidine/PPI
  • Emergency radiotherapy to mass
47
Q

How would you manage someone with MM?

A
  • Analgesia - for bone pain
  • Bisphosphonates
  • Local radiotherapy
  • Chemotherapy
  • Surgery
  • Autologous stem cell transplant - consolidation
48
Q

How would you manage infections in someone with MM?

A
  • Blood cultures
  • Broad spectrum antibiotics
  • IVIG if needed
49
Q

What chemotherapeutic treatments could you use in MM?

A
  • Cyclophosphamide
  • Thalidomide
  • Dexamethasone
  • Proteasome ihibitors
  • IMiDs
  • Monoclonal antibodies
50
Q

What are bisphosphonates used for in MM?

A
  • Bone pain
  • Reduce fracture rate
51
Q

Why can boney pain present in metastatic cancers?

A

Cause alterations in the pain pathway, which lower pain threshold and increase the likelihood a pain impulse will be triggered. Alterations include:

  • Reorganisation of dorsal horn and sensitisation of pain afferents to substance P (which stimulates pain pathways)
  • Astrocyte hypertrophy and decreased glutamate reuptake transporters, causing increased glutamate and excitotoxicity
  • Increased glial proteins in the spinal cord -> increase pain transmission
  • Acidic environment produced by osteoclasts can stimulate pain receptors
  • Increase in the receptive field for neurons and a change in ratio of types of neurons present in dorsal horn -> increased neuronal response to low-level stimuli

It is believed that these changes, among others, contribute to pain directly as well as to hyperexcitability of neurons to stimuli

52
Q

What is Monoclonal gammaglobulin of unknown significance?

A

Pre-malignant clonal disorder of plasma cells, which has low level paraprotein or Bence Jones protein. It is very common in older populations.

This has a small risk of progressing to myeloma (1% per year)

53
Q

Why would you do a PSA in someone with lower back pain?

A

Rule out prostatic cancer as the cause

54
Q

Why does myeloma cause renal damage?

A
  • Light chain deposition (cast nephropathy)
  • NSAID use
  • Infection
  • Hypercalcaemia
  • Amyloid
  • Tubular damage - —renal Fanconi syndrome
55
Q

What mnemonic can you use to help remember the main features of myeloma?

A
  • Calcium - due to bone damage
  • Renal damage
  • Anaemia
  • Bone lesions
  • Infection
56
Q

What is MGUS?

A
  • Premalignant clonal disorder of plasma cells
  • Low level paraprotein/BJP
  • V common in older people
  • Small risk of progression to myeloma or lymphoma
    • IgA>IgM>IgG
57
Q

If someone had MGUS, what conditions would you want to exclude?

A
  • Myeloma
  • Low grade lymphoma
  • AL Amyloidosis
  • POEMS syndrome
  • Light/heavy chain deposition disease
58
Q

Overall survival

A

Approx 7 years

59
Q

What bone disease occurs in myeloma

A
  • Vertebrae
  • Long bones
  • Skull
  • Pathological fracures

Gwen - Haematology (33 decks)

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