This case took us on a romp through the symptoms, signs and diagnosis of myeloma with a glance in the direction of some of the more serious complications. Let’s summarise:
Symptoms and signs:
- Often non-specific, but back pain (due to vertebral collapse with osteoporotic change or lytic lesions) is an exam classic. Similarly pathological fractures or unexplained osteoporosis are one route to diagnosis.
- Hypercalcaemia may develop and is an unusual but important presentation – remember those ‘bones, stones and psychic groans’. And more importantly polyuria and polydipsia. Medical students should be aware of hypercalcaemia as one of the key oncology emergencies to come up in exams. Tweet us about this if you want to know more.
- Anaemia is the problem with which our patient presented and this is may be experienced by the patient as: fatigue, somnolence, ‘rushing in my ears’, dyspnoea on exertion, possible angina in those with ischaemic heart disease, pallor…
- Recurrent infection due to hypogammaglobulinaemia is a feature in some patients.
Making the diagnosis
We debated this in length on twitter, but the main points are as follows:
ANAEMIA – this is normocytic anaemia, with normal haematinics and a normal platelet and white cell count. The blood film will be normal in nearly all cases.
SERUM ELECTROPHORESIS WITH IMMUNOFIXATION – this is a test in which a serum sample is placed on gel plate and an electrical charge is applied. The proteins travel a set distance depending on their size and thus several peaks are seen in healthy patients – representing albumin, immunoglobulins of different sizes, carrier proteins and so on. In patients with myeloma there is a clone of lymphocytes (plasma cells) which are producing just one immunoglobulin, resulting in a large ‘spike’ in the gamma zone. This paraprotein or M-protein (i.e. malignant or abnormal) can then be sub-classfied in the lab as being an IgA, IgG, IgM, IgD or IgE (IgG and IgA being far more common in Myeloma). The details of why this matters is beyond the scope of non-haematologists but it is important in prognostication.
A lot of confusion seems to arise in interpreting the results issued by the labs. A paraprotein will be quantified by the lab and reported as such – e.g. ‘IgG 25g/dl, paraprotein 19g/dl, paraprotein is an IgG kappa’. If the Ig levels are elevated but there is no monoclonal spike the lab will usually make a comment along the lines of ‘polyclonal increase in the gamma zone’ – which is non specific and reflects inflammation, infection and so on.
SERUM FREE LIGHT CHAINS – these are a sub-unit of the abnormal immunoglobulin being produced by the plasma cells – remember those little Ys from your med school lectures? Just as myeloma cells will produce ju
st one type of Ig – e.g. IgG, so they will also commit to one type of light chain – only two choices here, of lambda or kappa. There should be a mixture of the two at low levels in healthy people: when there is myeloma (or other, rarer conditions which we won’t elaborate on today) the level of one light chain will be much higher – demonstrating light chain restriction by the cancerous cells. In some ca
ses the plasma cells only produce light chains, with no paraprotein. This is the reason that patients with suspected myeloma should have their urine tested for bence jones proteins – BJPs are just light chains that pass into the urine. Our ability to test for serum free light chains has really only developed in the last few years and it is still expensive, so most people will test urine for BJPs where suspicion is low; where suspicion of myeloma is high SFLCs will be tested for.
An important footnote with SFLCS is that in renal failure the levels and ratio of SFLCs will be abnormal and the results should be carefully interpreted in this context. More on renal failure later.
IMAGING – skeletal surveys are still the best means of imaging myeloma patients. As discussed during the case ‘bone scans’ are useless, though frequently requested. Bone scans involve remodelling bone taking up isotopes and showing up as ‘hot spots’. Unlike most tumours within bone myeloma activates breakdown (osteoclastic) but not remodelling (osteoblastic) activity and thus no hot spots are created. Plain films of all the long bones, axial skeleton and skull are sufficient a will show lucency where lytic lesions have developed. Medical students should remember the pepperpot skull – another exam classic (myeloma is fab for exams!)
Patients who present with severe progressive back pain should be carefully assessed for neurological signs and symptoms as spinal cord compression is a dreaded complication and is another oncology emergency. MRI is the imaging of choice in this context and must be done urgently – even if this entails transfer to another hospital in the middle of the night. Please see references for further reading on spinal cord compression.
Collapse of vertebrae can lead to severe intractable pain and the orthopaedic team might consider kyphoplasty or vertebroplasty (injecting cement into a vertebrae) to improve the anatomy and relieve pain symptoms. Imaging of the spine (MRI or CT) is useful in deciding whether this is likely to help a patient.
To clinch the diagnosis a bone marrow aspirate (to look at the cell shape- cytology) and trephine (to look at the tissue structure – histology) is required. This will demonstrate an infiltrate of plasma cells. For MRCP you should be able to identify these – they are large, dark blue and have an eccentric nucleus (i.e. off to one side). New guidance suggests that flow cytometry should be used to demonstrate clonality – that is that all the plasma cells are identical and express proteins that shouldn’t normally be there. This is done by mixing the aspirate (liquid) marrow with fluorescent labelled antibodies and passing it through a machine to see which antibodies have bound to the proteins expressed by the plasma cells.
Renal Failure in Myeloma
We asked you to list the causes of renal failure in myeloma. The list is long and includes:
- Light chain deposition
- Dehydration due to hypercalcaemia
- The use of NSAIDs for back pain
- The use of gentamicin for sepsis (and sepsis itself)
- The use of bisphosphonates for hypercalcaemia (or as treatment after diagnosis is made)
- Urate stones
- Cast nephropathy
During the case our renal colleagues gave us a few tips – disproportionate renal failure in elderly septic patients should ring myeloma warning bells, as should hypercalcaemia in renal failure (renal failure is normally associated with hyPOcalcaemia or at least a normal calcium.)
This summary is not an exhaustive document on myeloma diagnosis, but a summary of the discussion that occurred during the teamhaem case. You may find the following documents/sites useful:
BCSH GUIDELINES : MYELOMA 2014: http://www.bcshguidelines.com/documents/MYELOMA_GUIDELINE_Feb_2014_for_BCSH.pdf
NICE guidance on Spinal Cord Compression: http://guidance.nice.org.uk/CG75/QuickRefGuide/pdf/English