Myeloma Flashcards
What is the link between amyloidosis and myeloma?
Link between myeloma and AL amyloidosis
AL amyloidosis and multiple myeloma share several clinical features such as clonal plasma cells and the production of monoclonal immunoglobulins
Diagnosis of AL amyloidosis requires histological confirmation with a biopsy specimen staining positive with Congo red and demonstrating apple green birefringence under polarissed light
Diagnosis of AL amyloidosis is made at presentation or some time during the course of the myeloma in 10–15% of patients
Is amyloidosis common?
No, it is rare, affects 500-600 people each year in the UK
What is AL amyloidosis?
Amyloidosis Light chain - it is this form of amyloidosis that is associated with myeloma
What are the common symptoms of myeloma?
Calcemia
Renal failure
Anaemia
Bone lesions
What is multiple myeloma/ myeloma?
Malignant disease of plasma cells
2nd most common blood cancer
Characterised by the production of abnormal antibody/ immunoglobulin
What are plasma cells?
Terminally differentiated B-cells which produce immunoglobulins
What are the signs and symptoms of myeloma?
- Back pain
- Anaemia
- Renal failure
- Proteinuria
- Fractures
- Dehydration
- Resp. tract infections
What are haemopoietic stem cells?
Stem cells that give rise to blood cells
Give rise to common lymphoid progenitors which give rise to B lymphocytes which produce plasma cells
In the bone marrow of a normal person, what % of the bone marrow is plasma cells?
5%
What % of the bone marrow is made up of plasma cells in patients with myeloma?
>10%
What are paraproteins?
An abnormal immunoglobulin found in the blood as a result of myeloma
AKA M-proteins
The antibodies made by malignant plasma cells in myeloma are abnormal and light chains are produced by themselves
What is the most common type of heavy chain produced in myeloma?
IgG, followed by IgA and then IgD
Elevated IgM in the blood would be most likely caused by what?
Waldenstrom’s macroglobulinemia
What is Bence Jones myeloma?
20% of people with myeloma only produce the light chains of immunoglobulins (either kappa or lambda)
The light chains show up in the urine and are known as Bence Jones proteins
How does myeloma cause hypercalcemia and bone fractures?
Myeloma cells secrete cytokines
- IL-3: reduces osteoblastic activity
- DKK1: increases osteoclast activity
- M1P1 alpha: increases osteoclast activity
How does myeloma cause renal failure?
Paraproteins in the blood get stuck in he neprhons and cause renal damage
Hypercalcemia also causes calcification of the nephrons
How does myeloma cause anaemia?
There is a shift from myeloid progenitor cell production to lymphoid progenitor cell production - over production of plasma cells clogs the bone marrow and there is no room for RBC production
Kidney failure potentiates this as there is no EPO for RBC production
Outline investigations for myeloma
Discuss the clinical features of myeloma
- Disease of the elderly
- Mean age of presentation is 60+
- More common in men and black Africans
- Bone destruction
- Kidney injury
- Recurrent infections
- Lytic bone lesions
- Increased osteoclast function without increase in osteoblast function
Where are lytic bone lesions seen in myeloma?
Skull - pepper pot skull
Spine
Long bones
Ribs
80% of patients have lytic lesions at time of presentation
Other than myeloma, where can a pepper pot skull be seen?
Hyperparathyroidism
Discuss immunoglobulin levels in myeloma
- 60% IgG
- 20% IgA
- 20% light chain only
Discuss laboratory features of myeloma
Routine biochemistry: raised calcium, raised urea and creatinine, raised total protein
Bone marrow: increased plasma cells that are abnormal, >10% plasma cells is diagnositc of myeloma
Plasma cells often show an enlarged golgi apparatus
Binucleated plasma cells can also be seen
What is beta-2 microglobulin?
Low molecular weight proteins found on the surface of all nucleated cells
Increased levels in patients with myeloma has been associated with poor prognosis
Which mutations are associated with worse outcomes in myeloma?
Anything involving chromosomes 14 or 17
What is smouldering myeloma?
Type of plasma cell dyscrasia
Precancerous condition
50% will develop mutliple myeloma within 5yrs
Discuss staging of myeloma
Prognosis determined by International Staging System (ISS) and cytogenetics.
Stage 1 Beta-2 microglobulin <3.5mg/l, Albumin >35g/l. OS 62 months.
Stage 2 Beta-2 microglobulin 3.5-5.5mg/l and/or Albumin <35g/l. OS 44 months.
Stage 3 Beta-2 microglobulin >5.5mg/l. OS 29 months.
Discuss management of myeloma
5-10% have no symptoms and do not require immediate therapy
Patients <70yrs: thalidomide/ lenalidomine/ bortezomib combination therapy (induction therapy)
/ stem cell transplantation with high dose melphalan if not successful
Bisphosphonates for myeloma bone disease
What is diagnostic of myeloma?
