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Case History

Image not available. A 62-year-old female attends a General Practitioner's surgery with a 4-week history of lower back pain, tiredness and lethargy. Initial investigations reveal a normochromic, normocytic anaemia with haemoglobin 10.4 g/dl and a raised plasma viscosity at 2.1.

What further investigations would be indicated for the diagnosis of multiple myeloma?

Which parameters should be assessed to appropriately stage this myeloma?

Background

Image not available. Plasma cell myeloma (PCM; multiple myeloma) is a plasma cell tumour with an incidence of 3–4 new cases per 100 000 population per year and accounts for approximately 10% of haematological malignancies. Patients usually present with a monoclonal band on protein electrophoresis. Most (60%) are immunoglobulin G (IgG) subclass and approximately 15% are IgA, with IgM, IgD and IgE accounting for less than 2% of patients. Occasionally there is a monoclonal excess of light chains only (approximately 20% of patients have κ or λ light chains) and in approximately 1% the myeloma is non-secretory without any serum or urinary evidence of excess antibody or light chain production.

Owing to increased awareness of the disease and availability of rapid biochemical analysis, less than 40% of patients now present with symptomatic bone disease and at least 20% of patients are now diagnosed whilst totally asymptomatic. Patients may present with hyperCalcaemia, Renal dysfunction, Anaemia, Bone fractures or lytic lesions (CRAB) but also with recurrent bacterial infections, signs and symptoms of spinal cord compression, features suggestive of amyloidosis or a persistently raised erythrocyte sedimentation rate, plasma viscosity or serum paraprotein detectable on routine investigations. Less than 10% of patients present with symptoms of hyperviscosity syndrome, which is most likely to occur in patients with IgA subclass variant. Bleeding defects also occur in approximately 15% of patients with IgG subclass and 30% of patients with IgA subclass.1

Initial investigations of a patient suspected of suffering from PCM should include serum and concentrated urine electrophoresis followed by immunofixation to confirm and type the monoclonal protein (paraprotein, M-protein). Quantification should be performed by electrophoretic densitometry of the monoclonal peak. Urinary light chain quantification can be performed either on a 24-hour urinary collection or on a random urinary sample calibrated in relation to the urinary creatinine level (protein creatinine index [PCI]). More recently, serum free light chain excess production (FLC assay) has been used as an alternative methodology in patients with light chain disease or those who have non-secretory disease.2

Bone marrow aspiration for the examination of the marrow morphology can confirm the diagnosis of myeloma (plasma cell infiltrate >10%) and a trephine biopsy should be performed at diagnosis as it provides a suitable baseline measurement to determine response to therapy (Figure 33.1). Malignant plasma cells can be differentiated from normal plasma cells by flow cytometry by the surface phenotype CD19– CD45– CD56[plus] CD138[plus]. The role of conventional metaphase ...

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