Myelomas Flashcards
What is myeloma?
Myeloma is a malignant disease of bone marrow plasma cells, accounting for 1% of all malignant disease. There is a clonal expansion of abnormal, proliferating plasma cells pro- ducing a monoclonal paraprotein, mainly IgG (55%) or IgA (20%) and rarely IgM and IgD
Wat immunoglobulins do myelomas mainly produce?
IgG (55%)
IgA (20%)
Barely IgM or IgD
What is the median age of onset for myelomas?
60
What are the clinical features of myelomas?
- Bone destruction, often causing fractures of long bones or vertebral collapse, and hypercalcaemia
- Bone marrow infiltration with plasma cells, resulting in anaemia, neutropenia, thrombocytopenia
- Kidney injury
- Reduction in the normal immunoglobulin levels , contributing to the tendency for patients with myeloma to have recurrent infections
What are risk factors for developing myelomas?
- Monoclonal gammopathy of undetermined significance
- Smoldering multiple myeloma
- Obesity
What is monoclonal gammopathy of undetermined significance (MGUS)?
A is a plasma cell dyscrasia in which plasma cells secrete a myeloma protein, i.e. an abnormal antibody, into the blood
What is the pathophysiology of myelomas?
The immune system keeps the proliferation of B cells and the secretion of antibodies under tight control. When chromosomes and genes are damaged, often through rearrangement, this control is lost
A chromosomal translocation between the immunoglobulin heavy chain gene on chromosome 14 and an oncogene is frequently observed in people with multiple myeloma
This mutation results in dysregulation of the oncogene which is thought to be an important initiating event in the pathogenesis of myeloma
The result is a proliferation of a plasma cell clone and genomic instability that leads to further mutations and translocations
What are common genetic abnormalities in myelomas?
The chromosome 14 abnormality is observed in about 50% of all cases of myeloma.
Deletion of (parts of) chromosome 13 is also observed in about 50% of cases.
What cytokines are mainly produced by myelomas?
Cytokines: IL-6
Causes much of their localised damage, such as osteoporosis, and creates a microenvironment in which the malignant cells thrive
Read the following pathological sign
“increased osteoclastic activity with no increased osteoblast formation of bone”
With what cancer is this associated?
myelomas
What are symptoms of myelomas?
Bone pain – most commonly backache owing to vertebral involvement (60%) Symptoms of anaemia Recurrent infections Symptoms of renal failure (20–30%) Symptoms of hypercalcaemia
Patients can be asymptomatic, the diagnosis being sus-
pected by ‘routine’ abnormal blood tests
What are life-threatening complications of myelomas?
- Renal impairment – often a consequence of hypercalcaemia – requires urgent attention and patients may need to be referred for long-term peritoneal or haemodialysis
- Hypercalcaemia should be treated by rehydration and use of bisphosphonates
- Spinal cord compression due to myeloma is treated with dexamethasone
What do investigations for myeloma show?
- Full blood count → Hb, WCC and platelet count are normal or low.
- ESR → high
- U&E → kidney injury
- Serum calcium → raised
- Serum protein electrophoresis and immunofixation → monoclonal band and immune paresis
- 24-hour urine electrophoresis and immunofixation is used for assessment of light-chain excretion
- Skeletal survey → lytic lesions, mainly in skull
- Bone marrow aspirate shows plasma cell infiltration
What cancer causes lytic lesions (mainly in the skull)?
Myelomas
How do you diagnose myeloma?
Symptomatic myeloma (SMM) can be diagnosed if either of the following are present:
1. Significant paraproteinaemia
2. Increased bone marrow plasma cells (>10%);
with evidence of end organ failure, i.e. hypercalcaemia, renal impairment, anaemia, lytic bone lesions (CRAB).
