Myeloma Flashcards
What tests are used to assess immunoglobulin (Ab) - do these if suspect myeloma
Serum immunoglobulin total level Electrophoresis - urine and plasma Immunofixation Serum light chain Urinary bence jones protein - light chain part of Ab present in urine
What does electrophoresis do
Identify paraprotein - appears as spike
Separates Ig based on size and charge
What does immunofixation do
Identify class of paraprotein
What is a paraprotein and how do you identify type
Monoclonal immunoglobulin present in blood or urine
Should all be different
Do electrophoresis
What does presence of paraprotein tell you
Monoclonal proliferation of a B lymphocyte or matured plasma cell
What disease is associated with IgM paraprotein
Low grade Lymphoma
Can’ t get myeloma as IgM produced by B cell NOT plasma cell
What does IgA or IgG paraproteins suggest
Myeloma
Produced by plasma cells after isotope switching in secondary response
Will then have either light chain affected as well
Can have a situation whee only light chain affected
Do most cancers arise in B or T cell
B cells as germinal centre of LN where B cells proliferate and rearrange and Ab production starts
What is myeloma
Neoplastic disorder of plasma cells (mature B lymphocytes)
Due to single clone of plasma cell undergoing abnormal proliferation so secrete excessive amount of Ab / Ig (paraprotein or monoclonal Ab)
Results as B-lymphocytes differentiate into mature plasma cells in LN etc.
Step 1 = MGUS develops
- Clone of plasma producing same monoclonal Ab
- Usually inciting event during normal immune response
- Asymptomatic
Step 2 = MM develop
- Cytogenetic and bone marrow changes
- 1% of MGUS will develop each year
Subtype
- Classic
- Light chain only
- Non-secretoy = rare
What is myeloma common in
Elderly Black population Male FH Obesity
What are the features of myeloma / direct effect of plasma cells
CRAB High calcium Renal impairment Anaemia - Due to Bone marrow failure / infiltration - May have relative EPO deficiency Bone disease
Will also have increased infections - lack of normal Ig
What bone disease occurs
Due to proliferation of plasma cells in bone marrow
Lytic bone lesion = pain due to increased osteoclast and reduced osteoblast (due to cytokines)
Pathological fracture
Cord compression
Hypercalcaemia
Osteoporosis
How does hypercalcaemia occur
Increased osteoclast activity
Also could be due to impaired renal function / elevated PTH
Can present as oncologication emergency
Phosphate and ALP normal
What are main features of bone marrow failure
Anaemia = common - lethargy Thrombocytopenia = bruising / bleeding Neutropenia = infection
What effects does paraprotein have on body
Hyperviscosity -> stroke Hypogammaglobulinaemia Amyloidosis Neuropathy Paraesthesia - Due to hypo or hyperCa Spinal cord compression due to fracture / bone disease Carpal tunnel Night sweats/ cramping = Ix
Rarely HSM / LN / fever
- If present with this consider other malignancies
What causes renal failure (can be new AKI or CKD)
Cast nephropathy - light chain deposition which damages loop of Henle
Ig deposition - blockage of renal tubules = main
Multiple ways Hyperviscosity Hypercalcaemia Hyperuricaemia Dehydration Medication used to treat can be harmful e.g. biphosphoantes Amyloidosis NSAID Infection
What is hyper viscosity and how do you Rx
Syndrome caused by increased viscosity in blood
Leads to impaired microcirculation and hypo perfusion
Plasmapharesis to remove
What does it lead too
Bleeding as capillaries burst - retinal, oral, nasal, cutaneous Cardiac failure Pulmonary congestion Renal failure Confusion Stroke
What does hypogammaglobulinaemia suggest
Paraprotein is switching of production of other Ig
Leads to infection
What is Amyloidosis
Group of diseases characterised by deposition of fibrillary protein
What is AL amyloid
Amyloidosis caused by protein or light chain
Common cause
How does it present
Nephrotic syndrome Cardiac failure Carpal tunnel Autonomic neuropathy Cutaneous infiltration
How do you treat AL amyloid
Get rid of paraprotein by chemotherapy
High mortality as patient very ill
How do you investigate suspected myeloma
FBC+ film, U+E, LFT, ESR, LDH bone profile, PSA and urinanaylsis
Detect monoclonal AB - product of malignant plasma cells
- Myeloma screen
- Serum or urine protein electrophoresis + serum light chain to look for light chains = typical screen
- Can do other Ig tests
Assess bone marrow to look for malignant clone
- Bone marrow aspirate and trephine = diagnostic
Look for organ damage e.g. CRAB
- Bloods
- Whole body MRI = 1st line for bone
- CT if CI
- Skeletal survey 2nd line if no CT or MRI to look for lytic lesions
What will FBC show and film
Anaemia - normocytic
Rouleux cells in film
Film is useful to show if there is a problem in BM e.g.blasts etc
Thrombocytopenia
Raised ESR - KEY to Dx
Shouldn’t have raised WCC as problem but can be low if BM is taken over by plasma cells
Issue in BM not peripheral blood
Raised urea, creatinine and calcium and potassium if renal failure
Anaemia + raised ESR = suspect myeloma
What will electrophoresis show
Raised IgA or IgG
Bence Jones if in urine
What confirms Dx
Bone marrow aspiration >10% plasma cells
What do you do MRI for
Survey skeleton
Can do CT or Xr-ay if CI
What is evidence of end organ damage
Hypercalcaemia
Hyper creatinine
Anaemia
Lytic lesions
What does Dx require
One major + on minor Sx
3 minor + S+S
What are major criteria
Plasmacytoma on biopsy
30% plasma cell
Elevated IgM in blood or urine
What are minor criteria
10-30% plasma cell
Minor elevation IgM
Osteolytic lesion
Low levels of Ab
What types of paraprotein do you get
IgG = 55%
IgA = 21%
Light chain = 22%
Other
How do you Dx light chain
Light chain assay
What is staging of myeloma dependent on
Albumin - decreases as para-protein goes up
Beta 2 microglobulin - how fast its growing
Can you cure myeloma
Atm incurable
Aim to increase period of remission
Rx depends on co-morbid condition and witness
How do you Rx
Chemotherapy followed by transplant - Usually three drug combination Biphosphonates RT Steroids as reduce inflammation Surgery Autologous stem cell transplant - own cells (only haem malignancy that uses this) - Best option for long term remission - High dose chemo first to obliterate bone marrow
How do you monitor
Blood test
Electrophoresis
How do you manage complications
Analgesia for pain Biphosphonates for osteoporosis and fractures and hypercalcaemia IV fluid for hypercalcaemia Influenza vaccine Ig replacement to reduce infection Transfusion for anaemia VTE prophylaxis Fluid / dialysis for renal failure
What are surgical options
Pinning of long bone
Decompression of spinal cord
How does IgM paraprotein present
Known as WAlderston’s Microglobuilnaemia
Form of NHL
Feature of plasmas ell and lymphoid cells
Bone marrow failure as mostly where cells grow
Lymphadenopathy
HSM if lymphoma cells growing there
B symptoms
Paraprotein symptoms can occur
IgM = massive molecule so lots of problems with hyperviscosity
What is rare
Bone disease
Pathological fracure
Cord compression
What is MGUS
Monoclonal gammopathy of uncertain significance
Presence of paraprotein / monoclonal Ab but not myeloma
Increased risk of developing
What are features
Usually asymptomatic
No bone pain or infection risk or organ damage
May have neuropathy
How do you differentiate from myeloma
Normal immune
Normal beta-2
Lower paraprotein level + stable in blood
Bone marrow shows less plasma cells than myeloma <10%
No clinical features e.g. lytic lesion on skeletal survey
How do you remember features
CRAB Calcium Renal failure Anaemia Bone disease
If someone presents with back pain not responding what should you do
MRI spine
If shows soft tissue mass immediate management
Dexamethasone + PPI
RT
Refer surgery or oncology
What are differentials
Metastasis - prostate / lung / renal / breast / thyroid
Lymphoma
Myeloma
What investigations
FBC, U+E, LFT, Ca, PSA, LDH Myeloma screen CXR MRI whole spine CT CAP
What is further management
Chemo - CTD
IV biphoshponates
Autologous SCT after max chemo
Patients require VTE prohypalxis
What are Ddx of fracture
Malignant bone disease
Osteoporosis
Osteomalacia
How do you investigate
FBC, U+E, LFT, Ca, phosphate, ESR, CRP
Myeloma screen
Further imaging if suspect malignancy
Osteoporosis + raised ESR
MM till proven otherwise
What has worse prognosis
> 2 osteolysis lesion
B2 microglobulin high
Low Hb
Low albumin
Expected blood results for myeloma in the early stages
Hypercalcaemia
Normal phosphate
Normal ALP - only raised in mets
What bones tend to be affected
Area where lots of haumatopoeisis
- Pelvis
- Femur
- Skull
DDX lytic bone lesion
MM = lytic
Other malignancy
- Prostate or bony mets tend to be more sclerotic
Infection can mimic
Patient presents with N+V / confusion / lower back pain
What tests
FBC U+E Bone - Ca + phos PTH Urinanalysis Myeloma screen X-ray - CXR + lumbar
Why PTH
Most common reason for hypercalcaemia
What is worrying level of Hypercalcaemia
Anything >2.75
What do you do if you identify monoclonal protein
Refer haematology
