Intro. to Haematological Malignancy Flashcards
Describe the pathogenesis of haematological malignancies
Multi-step process
Acquired genetic alteration in a long lived cell
Proliferative/ survival advantage to that mutated cell - produces malignant clone which grows to dominate the tissue
What are some important features of stem cells?
Ability to self-renew
Has to be able to give rise to every cellular blood products - multipotential
Describe the growth of malignant clone of cells in development of leukaemia
With time clone of cells gain mutations and grow
After growth advantage it dominates other cells
Pre-leukemic HSC then leukaemia
What are the cells involved in myeloid malignancies?
Red cells, platelets, granular cells (neutrophils) and monocytes
What cells are involved in lymphoid malignancies?
B-cells and T-cells
How does acute myeloid leukaemia arise?
When there has been mutation in stem cells - lead to growth advantage but can’t differentiate as it is blocked
Affects myeloid cells
Stay as immature blast cells which replace the bone marrow
How does myeloproliferative disorders arise?
Undergone mutations in stem cell - growth advantage and differentiate
Accumulate more end cells like neutrophils, basophils, eosinophils, platelets…
Mature cells
How does ALL arise?
Stem cells grow and cant mature as differentiation is blocked
Immature blast cells
Proliferation but no differentiation
Describe the structure of the lymph node
Medulla and cortex
Embedded in cortex is the germinal centres with marginal and mantle zone - B cells grow up in germinal centre
Describe B cell maturation
B cells go to germinal centre - exposed to antigen presenting cells
B cell now knows how to recognise and fight the infection - antibody molecule on surface to bind to antigen and attack it
Needs genetic rearrangement
What is more likely to cause the lymphadenopathy if it is localised and painful?
Bacterial infection in draining site
What is the cause if the lymphadenopathy is localised and painless?
Rare infections, catch severe fever and TB
Hard - metastatic carcinoma
Rubbery - lymphoma
Reactive and no cause identified
What is the most likely cause if the lymphadenopathy is generalised and painful/ tender?
Viral infection, EBV, CMV, hepatitis and HIV
What is the most likely cause if the lymphadenopathy is generalised and painless?
Lymphoma, leukaemia, connective tissue disorders, sarcoidosis, reactive, no cause identified and drugs
What are the lymphoma presentations?
Nodal disease - lymphadenopathy
Extra-nodal disease
Systemic symptoms - fever, drenching sweats, loss of weight, pruritic and fatigue
What are the major groups of haematological malignancies?
Acute leukaemia - acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (ACL)
Chronic - CML and CLL
Malignant lymphoma - NHL and Hodgkin lymphoma
Multiple myeloma, myelodysplastic syndromes and chronic myeloproliferative disease
