A 61-year-old male under investigation for a 6 month history of fatigue returns to his GP for follow up results of his blood tests.  On examination, he is wearing a back brace as he has sustained a recent vertebral fracture. His blood test results show: 


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|--------------|:-------:|---------------|
|Haemoglobin|97 g/L|(M) 130 - 170, (F) 115 - 155|
|White Cell Count|2.1 x10<sup>9</sup>/L|3.0 - 10.0|
|Sodium|140 mmol/L|135 - 145|
|Potassium|4.1 mmol/L|3.5 - 5.3|
|Urea|7.9 mmol/L|2.5 - 7.8|
|Calcium|3.1 mmol/L|2.2 - 2.6|
|eGFR|49 mL/min/1.73m<sup>2</sup>|> 60|

Liver function tests are normal.


Which of the following is the most likely underlying diagnosis?

Options:
explanation: Osteoarthritis presents with chronic joint pain made worse on activity. There are no associated blood abnormalities or increased risk of fractures, and so this diagnosis does not, therefore, explain the clinical presentation.
name: Osteoarthritis
label: d
answer: no
explanation: This patient has renal impairment, anaemia, hypercalcaemia, and evidence of fractures. These characteristics make myeloma the most likely diagnosis. Myeloma is a haematological malignancy caused by the clonal proliferation of plasma cells which secrete monoclonal antibodies. Myeloma investigation requires a combination of serum immunoglobulins, serum protein electrophoresis, and serum free light chains, to identify a monoclonal gammopathy with isotype suppression. Serum free light chains function in lieu of urinary Bence Jones proteins, which are liable to false negative results if not processed rapidly. The ALP is normal in multiple myeloma.
name: Multiple myeloma
label: a
answer: yes
explanation: Light chain amyloidosis is a potential complication of multiple myeloma. Amyloidosis can cause dysfunction in virtually any organ due to widespread deposition of the proteins. This patient may well have amyloidosis secondary to his multiple myeloma, but this does not represent the underlying diagnosis, and so the better answer is multiple myeloma. Histology of fat biopsies (taken from samples of the rectum or abdomen) typically shows apple green birefringence with congo red stain under polarised light.
name: Amyloid light chain amyloidosis
label: e
answer: no
explanation: Waldenstrom's macroglobulinaemia is a lymphoplasmacytic lymphoma (non-Hodgkin) where there is excess production of IgM paraprotein. The clinical features of myeloma are absent, such as hypercalcaemia, bone lesions (which are characteristically lytic), anaemia, and kidney disease, and the patient presents with hyperviscosity syndrome instead (such as bleeding gums, blurred vision, headache, confusion.) Since this is a lymphoma, lymphadenopathy and hepatosplenomegaly may be present. These features are not present in this case.
name: Waldenstrom's macroglobulinemia
label: b
answer: no
explanation: Paget's disease is usually found incidentally on a blood test with an isolated raised ALP. It clinically presents with bone pain and pathological fractures. This question stem eludes to the use of a back brace secondary to a recent compression fracture. Although this is expected for myeloma and Paget's, you would expect to see bony deformities in Paget's disease (such as frontal bossing), as well as a raised ALP.
name: Paget's disease
label: c
answer: no

Correct answer: a


Learning point: Multiple myeloma is characterised by renal impairment, anaemia, hypercalcaemia, and bone fractures due to clonal plasma cell proliferation.