Multiple Myeloma

Question 1

What is MM?

Answer 1

haematological malignancy characterised by plasma cell proliferation. It arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells.

Question 2

The median age at presentation?

Answer 2

70 years old

Question 3

Clinical presentation of MM?

Answer 3

Use the mnemonic CRABBI:

Calcium
- hypercalcaemia
- 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
- 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

Renal
- 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

Anaemia
- bone marrow crowding suppresses erythropoiesis leading to anaemia
- this causes fatigue and pallor

Bleeding
- bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising

Bones
- 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

Infection
- a reduction in the production of normal immunoglobulins results in increased susceptibility to infection

Question 4

Other features apart from CRABBI?

Answer 4

amyloidosis e.g. macroglossia
carpal tunnel syndrome
neuropathy
hyperviscosity

Question 5

Investigations for MM?

Answer 5

Bloods
full blood count: anaemia
peripheral blood film: rouleaux formation
urea and electrolytes: renal failure
bone profile: hypercalcaemia

Protein electrophoresis
raised concentrations of monoclonal IgA/IgG proteins will be present in the serum
in the urine, they are known as Bence Jones proteins

Bone marrow aspiration
confirms the diagnosis if the number of plasma cells is significantly raised

Imaging
historically a skeletal survey has been done to look for bone lesions
however, whole-body MRI is increasingly used and is now recommended in the 2016 NICE guidelines
X-rays: ‘rain-drop skull’ (likened to the pattern rain forms after hitting a surface and splashing, where it leaves a random pattern of dark spots). Note that a very similar, but subtly different finding is found in primary hyperparathyroidism - ‘pepperpot skull’

Question 6

Diagnostic criteria for MM

Answer 6

The 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.