Multiple Myeloma Flashcards
Myeloma
Overview
neoplastic proliferation of bone marrow plasma cells
peak age = 70 years
equal sex ratio
Monoclonal products produced
IgG (50-60%)
IgA (20-30%)
light chain disease (20%)
Multiple Myeloma and Renal Failure - Example question
A 60-year-old man is seen in the ambulatory care clinic with a two week history of reduced urine output. This has been associated with a general malaise and fatigue. He denies any fever, abdominal pain, dysuria or change in flow He has a past history of multiple myeloma, hypertension and benign prostatic hypertrophy. He has been on lenalidomide and dexamethasone chemotherapy for the last four months and was told at a clinic appointment one month ago that there were no problems with his blood results. His other medications are ramipril, finasteride and tamsulosin, and these have not been altered in many years.
On examination he appears fatigued and pale. His abdomen is soft with no palpable masses.
His investigation results are as follows:
Urine dip:
Blood - Protein ++ Ketones - Leucocytes + Nitrites -
Blood tests:
Hb 110 g/l
Platelets 130 * 109/l
WBC 9 * 109/l
Na+ 139 mmol/l K+ 4.7 mmol/l Urea 10 mmol/l Creatinine 184 µmol/l Ca2+ 2.3 mmol/l
Which investigation is most likely to reveal the cause of his renal failure?
Blood film Mid-stream urine > Serum free light chains Serum protein electrophoresis Ultrasound renal tract
In the absence of any symptoms of obstruction or infection, this gentleman’s renal failure likely results from progression of his multiple myeloma. Importantly, calcium is normal. Although blood film, serum protein electrophoresis and serum free light chains are all likely to be abnormal, it is the serum free light chains that are the direct cause of damage to the nephrons in myeloma and are likely to have increased since this gentleman’s last follow-up.
In practice, ultrasound renal tract and mid-stream urine would still be performed to exclude obstruction and infection respectively.
Multiple Myeloma - TETRAD of Sx: CRAB
The affects of myeloma can easily be remembered by the tetrad of high calcium (c), renal disease (r), anaemia (a) and bone pain (b) (crab).
Myeloma - Prognosis
B2-microglobulin is a useful marker of prognosis - raised levels imply poor prognosis. Low levels of albumin are also associated with a poor prognosis
Stage I:
Criteria = B2 microglobulin < 3.5 mg/l
Albumin > 35 g/l
Median Survival (months) = 62 - 5 years
Stage II: Criteria = Not I or III Median Survival (months) = 45 - 3 years
Stage III: Criteria = B2 microglobulin > 5.5 mg/l Median Survival (months) = 29 - 2 years
Multiple Myeloma - Diagnosis and Prognosis: Example Question
A previously healthy 68-year-old male patient is referred by his GP to the general medical clinic. He has mixed symptoms of pain in multiple areas, including his upper arm, neck and legs. This has worsened over a period of months and seems not to have been helped with multiple analgesics, including paracetamol, codeine phosphate and ibuprofen. In this time the patient has also become increasingly short of breath.
A full work up is undertaken and the results are shown -
Hb 9.4 g/dl
Platelets 174 * 109/l
WBC 8.4 * 109/l
Na+ 136 mmol/l K+ 4.7 mmol/l Urea 8.4 mmol/l Creatinine 125 µmol/l Corrected calcium 2.9mmol/l Albumin 34g/L
Kappa light chains detected
Lambda light chains absent
IgG elevated
IgA normal
IgM normal
Urine Bence Jones proteins detected
Skeletal survey multiple osteolytic lesions seen throughtout axial skeleton including on the right humerus, thoracic spine and both femurs.
Given the presumed diagnosis, what tests are most relevant for staging of the condition?
Calcium, x-rays and creatinine Free light chain level Renal function > B2-microglobulin and albumin Haemaglobin and albumin
The diagnosis here is multiple myeloma. Myeloma is a plasma cell dyscrasia that is more common in men than women. It is most common in elderly populations. The affects of myeloma can easily be remembered by the tetrad of high calcium (c), renal disease (r), anaemia (a) and bone pain (b) (crab). The original staging system was known as the Durie-Salmon Staging system which was developed in 1975. It is still commonly used as a supplementary measure but it’s role in staging has been replaced by the International Staging System (ISS) that was implemented by the International Myeloma Working Group in 2005.
Multiple Myeloma - Features
Multiple myeloma is a neoplasm of the bone marrow plasma cells. The peak incidence is patients aged 60-70 years.
Clinical features
bone disease: bone pain, osteoporosis + pathological fractures (typically vertebral), osteolytic lesions
lethargy
infection
hypercalcaemia (see below)
renal failure
other features: amyloidosis e.g. Macroglossia, carpal tunnel syndrome; neuropathy; hyperviscosity
Multiple Myeloma - Ix
Investigations
monoclonal proteins (usually IgG or IgA) in the serum and urine (Bence Jones proteins)
increased plasma cells in the bone marrow
bone lesions on the skeletal survey
Multiple Myeloma - Diagnostic Criteria
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.
Hypercalcaemia in Myeloma
Hypercalcaemia in myeloma
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
Multiple Myeloma - Diagnosis: Example Question
A 70 year-old woman presents with severe back pain which has been worsening over the last month. Prior to this she has never suffered from back pain. She has been lethargic, and her husband notes some intermittent confusion. A systemic enquiry reveals long standing exertional breathlessness, and constipation. She has no other bowel or bladder disturbance.
Her background includes chronic obstructive pulmonary disease, which is managed by her GP. She gave up smoking two years ago. Her well woman check up 12 months ago was entirely normal, aside from a slightly raised cholesterol which is being management with diet.
On examination, she has a normal gait. There is some mild tenderness over L3/L4 vertebra with no lower limb neurological deficit. Cardiorespiratory examination reveals an ejection systolic murmur, with a normal second heart sound.
Hb 90 g/l Na+ 135 mmol/l Bilirubin 5 µmol/l
Platelets 200* 109/l K+ 5.5 mmol/l ALP 101 u/l
WBC 10 * 109/l Urea 15 mmol/l ALT 40 u/l
Neuts 8 * 109/l Creatinine 230 µmol/l corrected calcium 2.7 u/l
ESR 40 mm/hr
What is the most likely diagnosis?
> Multiple myeloma Monoclonal gammopathy of undetermined significance Non-Hodgkin's, lymphoma Paget's disease Renal cell carcinoma with spinal metastases
Multiple myeloma is malignant proliferation of plasma cells, producing a monoclonal protein detected in blood and/or urine; this causes organ or tissue damage. The median age of presentation is 70 years old.
Presenting clinical features include symptoms of:
Impaired renal function- from light chain deposition from plasma cells, other causes include amyloid deposition, dehydration, hypercalcaemia, hyperviscosity, and nephrotoxic drugs
Anaemia
Hypercalcaemia- myeloma cells cause an increased production of osteoclast activating factors and cytokines that inhibit osteoblast differentiation
Recurrent infections- decreased humoral immunity
Hyperviscosity symptoms (headaches, epistaxis, blurred vision, and confusion)- high paraprotein levels
Bone pain
Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic condition thought to precede multiple myeloma.
Multiple Myeloma Prognosis: Example Question
A 67-year-old gentleman presents to the emergency department following a fall. He tripped on the carpet and landed on his back. Following this he has been complaining of lower back pain, but this pain was present prior to his fall and only slightly worsened with the accident. He undergoes a CT scan which unfortunately demonstrates lytic lesions in his lumbar vertebrae. He is suspected of having multiple myeloma. He undergoes blood and urine tests which unfortunately raises further suspicion of the diagnosis. He is due to undergo a bone marrow biopsy. What investigation prior to the biopsy can give prognostic information?
Serum immunofixation > B2 microglobulin Serum corrected calcium Protein electrophoresis Urine electrophoresis
The correct answer is B2 microglobulin. This is a patient who has unfortunately found to have multiple myeloma and is awaiting further investigation to obtain histology. B2 microglobulin elevation and fall in albumin are associated with a poor prognosis. Serum immunofixation and electrophoresis studies are useful diagnostic tools but are not as useful in terms of prognosis.
Asymptomatic vs Symptomatic Myeloma
In terms of myeloma this can be classified as below, taking note of both asymptomatic and symptomatic myeloma:
Symptomatic myeloma:
Clonal plasma cells >10% on bone marrow biopsy or (in any quantity) in a biopsy from other tissues (plasmacytoma)
A monoclonal protein (paraprotein) in either serum or urine (except in cases of true non-secretory myeloma)
Evidence of end-organ damage felt related to the plasma cell disorder (related organ or tissue impairment, ROTI, commonly referred to by the acronym “CRAB”):
hyperCalcemia (corrected calcium >2.75mmol/L)
Renal insufficiency attributable to myeloma
Anemia (hemoglobin <10 g/dL)
Bone lesions (lytic lesions or osteoporosis with compression fractures)
Asymptomatic (smoldering) myeloma:
Serum paraprotein >30 g/L AND/OR
Clonal plasma cells >10% on bone marrow biopsy AND
NO myeloma-related organ or tissue impairment
Multiple Myeloma - Ix: Example Question
A 62-year-old woman presents to the haematology clinic. She has had lower back pain, which has been progressive in nature. She has also been noted to develop unexplained anaemia. Her initial protein electrophoresis and serum-free light chain assays raised suspicion of multiple myeloma. She has a past medical history of transient ischaemic attacks and hypertension. She takes clopidogrel, amlodipine and ramipril. What imaging should be offered to further assess her?
Lumbosacral X-rays Skeletal survey Whole body CT > Whole body MRI PET scan
The correct answer is whole body MRI. NICE advises that all patients suspected to have a diagnosis of myeloma should be offered whole body MRI as first-line imaging, and only consider whole body CT if the patient declines MRI or is unable to have it. Skeletal survey should only be considered if CT and MRI are both not possible. Fluorodeoxyglucose positron emission tomography CT (FDG PET CT) can be considered once a diagnosis is confirmed.
Multiple Myeloma Screen
The following tests are needed to complete a myeloma screen:
FBC, ESR, U+E, calcium, albumin, uric acid
Serum protein electrophoresis
Urine protein electrophoresis
Immunoglobulin levels
Plain X-ray of symptomatic areas
If initial investigations are suggestive of myeloma then bone marrow aspirate and trephine biopsies are indicated, as well as immunofixation of the serum and urine to demonstrate the nature of the paraprotein.
Ix of Lytic Lesions:
NICE advises that all patients suspected to have a diagnosis of myeloma should be offered whole body MRI as first-line imaging, and only consider whole body CT if the patient declines MRI or is unable to have it. Skeletal survey should only be considered if CT and MRI are both not possible.
Excluding Myeloma with a Pathological Fracture - Example Question
A 72-year-old woman presents to the emergency department following a fall. On examination, her right leg is shortened and externally rotated and she is unable to weight bear. A hip X-ray demonstrates a fractured neck of femur which appears pathological. She has no history of cancer. Following a dynamic hip screw insertion, she recovers well. She has blood tests sent for FBC, U&E, LDH, calcium, albumin, uric acid, serum electrophoresis, immunoglobulins and ESR. She has had a chest X-ray which was normal.
What additional tests should be requested to complete the initial investigations of the pathological nature of the fracture?
MRI whole spine MRI hip > Urinary electrophoresis Trephine biopsy Bone marrow biopsy
The correct answer answer is urinary eletrophoresis. This is a patient with a pathological fracture and at high risk of myeloma and needs to be fully investigated.
The following tests are needed to complete a myeloma screen:
FBC, ESR, U&E, calcium, albumin, uric acid
Serum protein electrophoresis
Urine protein electrophoresis
Immunoglobulin levels
Plain X-ray of symptomatic areas
If initial investigations are suggestive of myeloma then bone marrow aspirate and trephine biopsies are indicated, as well as immunofixation of the serum and urine to demonstrate the nature of the paraprotein.
MRI would be contra-indicated due to the recent operation.
