Malignancy Flashcards
What protein is expressed by haematopoetic stem cells on immunohistochemistry?
- CD34
Define acute leukaemia?
- proliferation of abnormal progenitors with block in differentiation/maturation
Define chronic myeloproliferative disorders?
- proliferation of abnormal progenitors but no differentiation/maturation block
What are driver mutations?
- clone cells selected
- normal haemopoeis = polyclonal
- malignant haemopoesis = monoclonal
Describe passenger mutations
- do not confer a growth advantage
- happen to be present
Haematological malignancy types based on lineage
- myeloid
- lymphoid
Haematological malignancy types based on developmental stage
- primitive (acute lymphoblastic, chronic myeloid)
- mature (chronic lymphoblastic, myeloma, acute myeloid)
Leukaemia means?
- malignancy of blood
Lymphoma means
- malignancy of lymph nodes
Myeloma means?
- malignancy of plasma cells
Types of acute leukaemia?
- acute myeloid leukaemia
- acute lymphoblastic leukaemia
What is acute leukaemia?
- rapidly progressive
- malignancy of clonal cells
- defects in marrow / blood maturation
Which is the commonest leukaemia in children
- acute lymphoblastic anaemia
How might ALL present?
- anaemia
- bleeding
- bone pain
- infection
- CNS involvement
How might AML present?
- Older patient
- secondary or de novo
- aneamia
- infection
- gum infiltration
Name a complication of AML?
- Disseminated intravascular coagulation
Auer rods suggest?
- acute myeloid leukaemia
What is a test to confirm between ALL and AML?
- Immunophenotyping
What are immunoglobulins?
- produced by b-cells and plasma cells
What is the structure of immunoglobulins?
- 2 heavy
- 2 light
Where can immunoglobulins be found?
- on the B cell surface
- in blood (released by plasma cells)
Name some monomer immunoglobulins?
- IgD
- IgE
- IgG
Name dimer immunoglobulins?
- IgA
Name a pentamer immunoglobulin?
- IgM
What forms the variable region of an immunoglobulin?
- V D J
What is the name given to the cell when a B cell travels back to the bone marrow
- plasma cell
What are plasma cells
- factory cell
- produce a large amount of antibodies
How are plasma cells recognised under the microscope?
- blue cytoplasm
- pale perinuclear areas (Golgi apparatus)
Polyclonal increase in immunoglobulins may be a result of what?
- infection
- autoimmune
- malignancy
- liver disease
Monoclonal rise in immunoglobulins may be suggestive of?
- marker of underlying disorder
- called paraproteins
How are immunoglobulins detected?
- serum electrophoresis
- quantifies by serum immunofixation
What are bence jones proteins?
- usual light chain immunoglobulin precipitates
- detected in the urine electropheresis
What conditions are paraproteins seen in?
- MGUS
- Myeloma
- Amyloidosis
- Lymphoma
What are paraproteins
Monoclonal immunoglobulins
What is myeloma?
- plasma cell malignancy
How does myeloma affect the body?
- direct tumour cell effect
- bone lesions
- increased calcium
- bone pain
- marrow failure
- paraprotein mediated
- renal failure
- immune suppression
- hyperviscosity
- amyloid
What is the commonest myeloma?
- IgG
How is myeloma classified?
- by immunoglobulin
- IgG is most common
- IgA
- Bence jones
Symptoms of hypercalcaemia?
- stones
- bones
- abdominal groans
- psychiatric moans
- kidney impairmetn
How is cast nephropathy treated?
- hydration
- steroids
- chemo
Treatment of myeloma?
- chemotherapy
- dexamethasone
- cyclophosphamide
- monoclonal antibodies
- opiates
- radiotherapy
- bishopshonates
What does MGUS stand for?
- monoclonal gammopathy of underdetermined significance
How is MGUS diagnosed?
- paraprotein <30g/l
- plasma cells <10%
- no myeloma end organ damage
What causes the symptoms of AL amyloidosis?
- misfold of amyloid protein to form an insoluble beta pleated sheet
- accumulation in multi organ systems
How is AL amyloidosis diagnosed?
- Organ biopsy with Congo red stain
- SAP scan
Waldenstrom’s macroglobulinaemia symptoms?
- IgM paraprotein leads to hyperviscosity symptoms
Treatment of waldenstroms macrotgloblinaemia?
- plasmapheresis
- chemotherapy
Define remission?
- no detectable cancer cells
- may relapse
Cytotoxic drugs can either be ___ or ___
- cell cycle specific
- non-cell cycle specific
Name examples of cell cycle specific drugs?
- antimetabolites (methotrexate)
- mitotic spindle inhibitors
Name non-cell cycle specific drugs?
- alkylating agents
- platinum derivatives
- cytotoxic antibiotics
Immediate cytotoxic drug effects?
- bone marrow suppression
- gut mucosal damage
- alopecia
Vina alkaloids may cause?
- neuropathy
Anthracyclines may cause
- cardiotoxicity
Cis-platinum may cause?
- nephrotoxicity
Long term side effects of chemotherapy
- infertility
- secondary malignancy
- cardiomyopathy (anthracyclines)
What may be a reason why chemotherapy fails to work?
- tumour slow turn over
- drug resistant mechanisms
What limits intensifying chemotherapy?
- limited by myelosuppression
What may be used to overcome myelosuppression in chemotherapy?
- haematopoietic growth factors (G-CSF)
- Monoclonal antibodies
- bone marrow transplantation
Name an example monoclonal antibody that may be used in combination with chemotherapy?
- rituximab
- targets malignant protein
What could be a target treatment in myeloma?
- biological agent
- proteasome inhibitor
What is a good treatment option in CML and how does it work?
- tyrosine kinase inhibitor
- targets specific to cancer cell
- molecularly targeted
3 types of immune therapy
- bone marrow transplant
- T cells from donor
- adoptive immunotherapy (using patients own cells to mark cancer as foreign)
