Haematological Malignancy Flashcards
What percentage of human cancers are accounted for by haematological malignancies?
Approx 10%
In adults, what sex is more commonly affected by haematological malignancy?
Males > females
How can you identify the population of stem cells in bone marrow?
Immune phenotyping
What percentage of bone marrow cells are accounted for by stem cells?
< 0.1%
What are the origins of bone marrow malignancies?
Myeloid compartment - erythrocytes, platelets, monocytes, granulocytes
Lymphoid compartment - B cell and T cell
Mutations may arise in haematopoietic stem cell or in progenitor cells
What does the phenotype of disease depend on?
Features of mutation
What does a mutation resulting in proliferation without differentiation cause?
Accumulation of useless progenitor cells which causes acute leukaemia
If this process is in myeloid line then acute myeloid leukaemia
If in lymphoid line then acute lymphoblastic leukaemia
What does a mutation resulting in proliferation and differentiation cause?
Overproduction of end cells leading to myeloproliferative disease e.g. chronic lymphocytic leukaemia
What kind of malignancies are CLL, lymphomas and MM?
Mature lymphoid malignancies
Mutational events here do not occur in stem cell compartment, they occur as cells pass through germinal centre of secondary lymphoid organs
In what cell does a mutation occur that results in acute lymphoblastic leukaemia?
Lymphoid progenitor
In what cell does a mutation occur that results in acute myeloid leukaemia?
Myeloid progenitor
What is the difference between leukaemia and lymphoma in terms of where they occur?
If disease predominantly occurs in blood and bone marrow then leukaemia
If disease predominantly occurs in lymph nodes and solid organs then lymphoma
What is the commonest type of leukaemia?
Chronic lymphocytic leukaemia
If a patient presents with widespread lymphadenopathy, normal FBC, with blood films and genetic testing showing CLL, what is the diagnosis?
Small cell lymphocytic lymphoma
What are the major groups of haematological malignancies?
Acute leukaemias
- acute lymphoblastic leukaemia
- acute myeloid leukaemia
Chronic leukaemias
- chronic myeloid leukaemia
- chronic lymphocytic leukaemia
Malignant lymphomas
- non-Hodgkin lymphoma
- Hodgkin lymphoma
Multiple myeloma
Myelodysplastic syndromes
What are the features of acute leukaemia?
Leukaemic cells do not differentiate - proliferation without differentiation so bone marrow fills up with useless immature cells and bone marrow fails
Rapidly fatal if untreated
Potentially curable
What are the features of chronic leukaemia?
Leukaemic cells retain ability to differentiate
Proliferation without bone marrow failure
Not presently curable but slow progression with generally good survival
What are the clinical features of acute leukaemia?
Bone marrow failure
Anaemia
Thrombocytopenic bleeding
Infection due to neutropenia
In lymphoma, where do mutational events tend to occur?
In more mature cells
In B cell lymphoma mutational events occur during transit through germinal centre
Somatic hypermutation of immunoglobulin genes occurs to create a good match for antigen, this requires a lot of
cell division - huge pressure on immunoglobulin gene so potential source for mutation
What are the presentations of lymphoma?
Nodal disease
- lymphadenopathy
Extra-nodal disease
Systemic symptoms
- fever (B symptom)
- drenching night sweats (B symptom)
- loss of weight (10% body weight loss = B symptom)
- pruritus
- fatigue
What percentage of Hodgkin lymphoma presents with nodal disease?
> 90%
What percentage of non-Hodgkin lymphoma presents with purely nodal disease?
Around 60%
What percentage of non-Hodgkin lymphoma presents with extra-nodal component?
40%
