Checked: 12-01-2018 by
vicky.ryan Next Review: 17-01-2020
Myeloma NS MOM
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investigation and initial management of patients with paraproteinaemias in primary care
indications for specialist referral and management
identification of paraproteinaemias
conditions associated with paraproteinaemias
A paraprotein (monoclonal band, M-protein) is a monoclonal excess of immunoglobulin produced by plasma cells or other mature B cells.
A paraprotein conventionally refers to a monoclonal band identified by serum electrophoresis (intact immunoglobulin made up of heavy and light chains).
This pathway also refers to abnormal light chain bands in the serum (serum free light chains) or urine (Bence Jones protein) which can occur alongside or independent of an intact immunoglobulin paraprotein.
incidence 7.0 per 100,000 males, 5.9 per 100,000 females in UK
neoplastic proliferation of bone marrow plasma cells
most commonly IgG or IgA paraproteins
rarely IgD or IgE
approximately 15% light chain only
approximately 3% non-secretory
Monoclonal gammopathy of undetermined significance (MGUS):
incidence 16 per 100,000 all ages, 100 per 100,00 over age of 70
prevalence 5% over age of 80
see MGUS section for full details
most commonly IgG, IgA or IgM
Solitary extramedullary plasmacytoma (SEM) and solitary plasmacytoma of bone (SBP):
neoplastic proliferation of plasma cells in extramedullary soft tissue e.g. mucosa (SEM) or single bone lesion (SPB) without widespread bone marrow infiltration
paraprotein isotype as myeloma
Light chain (AL) amyloidosis:
associated with abnormal light chain deposition with or without evidence of underlying symptomatic myeloma
most cases do not have intact immunoglobulin paraprotein
most cases have clonal plasma cells in bone marrow
neoplastic proliferation of mature B cells and plasma cells in bone marrow, spleen and/or lymph nodes
associated with IgM paraproteins
occasionally abnormal light chains in serum or urine
not associated with lytic bone disease
Risk factors for paraproteinaemias:
increasing incidence with age
increased incidence in African-Caribbean ethnic groups
weak association with radiation, petrochemicals and agricultural chemicals
almost all cases idiopathic
Bird J, Behrens J, Westin J, Turesson I, Drayson M, Beetham R, D’Sa S, Soutar R, Waage A, Gulbrandsen N, Gregersen H, Low E, Writing group: On behalf of the Haemato-oncology Task Force of the British Committee for Standards in Haematology, UK Myeloma Forum and NordicMyeloma Study GroupUK Myeloma Forum (UKMF) and Nordic Myeloma Study Group (NMSG): guidelines for the investigation of newly detected M-proteins and the management of monoclonal gammopathy of undetermined significance (MGUS) Br J Haematol 2009; 147: 22–42
BCSH and UKMF Guidelines on the Management and Diagnosis of Multiple Myeloma Sept 2010.
National Institute for Health and Clinical Excellence (NICE). Guidance on cancer services: improving outcomes in haemato-oncology cancer - the manual. London: NICE; 2003.
Symptoms which should trigger consideration of myeloma include:
bone disease (common):
bone pain especially non-lumbar back pain (e.g. thoracic)
pathological fracture or low impact fracture
spinal cord compression
recurrent or persistent bacterial infection (common)
hyperviscosity syndrome (very rare in myeloma, more typically associated with Waldenström’s macroglobulinaemia):
neurological symptoms, including vertigo, headache, ataxia, hearing loss, seizures, coma
shortness of breath
fatigue and anorexia
Serum paraproteins may be identified by the incidental finding of raised total protein when a blood test is carried out for a condition other than suspected myeloma.
Other laboratory abnormalities that may suggest myeloma include:
unexplained renal impairment
raised ESR/ viscosity / CRP
Globulins are the main contributor to the total plasma protein that is not accounted for by albumin. An elevated globulin can be inferred when there is a high total protein. When the non albumin fraction of the total protein exceeds the normal range, then it is likely that excess serum globulin (gammopathy) is responsible.
There are many causes of raised serum globulin, including transient increases associated with acute infection and more prolonged increases seen with chronic inflammatory disorders or chronic infections such as HIV or TB.
Differentiating polyclonal gammopathy that occurs in inflammatory conditions from monoclonal gammopathy, which arises from plasma cell dyscrasias, requires serum electrophoresis.
A myeloma screen includes:
Full blood count
serum protein electrophoresis
Serum immunoglobulins and protein electrophoresis should be considered if there is clinical suspicion of a paraprotein-related disorder, such as:
unexplained anaemia or other cytopenia
hypercalcaemia (especially if plasma ALP is normal)
unexplained renal failure
unexplained raised ESR / viscosity / CRP
pathological fracture or low-impact fracture
Initially request serum immunoglobulins.
It is important to remember that myeloma can present without monoclonal gammopathy in blood. Such cases may be identified by light chain secretion in urine (Bence-Jones protein) with the majority of these cases also having low serum immunoglobulins (immune paresis) and/or serum free light chains.
Approximately 3% of myeloma cases will have no detectable paraprotein in the blood or abnormal light chains in blood or urine (non-secretory myeloma). Bone marrow aspiration is the usual route of diagnosis.
Serum free light chains are not currently available in primary care – specialist haematology advice is required.
Results of serum protein electrophoresis AND urinary BJP suggest myeloma
Radiology reported as suggestive of myeloma and myeloma screen confirms myeloma.
When considering referral, take into account other features including:
acute kidney injury
Myeloma is unlikely with a IgG<15g/l or IgA<10g/l in the absence of other symptoms (e.g. renal failure, hypercalcaemia, back pain, bone marrow failure) in which case consider a routine referral.
A polyclonal (diffuse increase in gammaglobulin is not associated with haematological malignancy
2WW Haematology Services are available at Weston (WAHT), Bristol Haematology & Oncology Centre (UHB) and Southmead (NBT)
A combination of symptoms and laboratory results can be used to determine the probability of myeloma being present.
Outpatient referral to haematologist advised if paraproteinaemia and one or more of the following:
IgD or IgE paraproteins irrespective of concentration
IgG paraproteins >15 g/l
IgA or IgM paraproteins >10 g/l
significant Bence Jones proteinuria (>500mg/l)
unexplained immune paresis (low serum immunoglobulins) in absence of paraproteinaemia
unexplained stable renal impairment
mild hypercalcaemia (2.6 to 2.8 mmol/l)
unexpected osteoporosis or fragility fracture (i.e. younger age group)