Haematological malignancy Flashcards
1
Q
Brief epidemiology of haematological malignancies?
A
- Relatively rare: about 1/10 of human cancers
- Acute lymphoblastic leukeamia is most common in kids (ALL)
2
Q
What is the pathogenesis of haematological malignancies?
A
- Multi step process: transformed cell accumulates genetic mutations over period of time – some will initiate disease process, some develop, some are carrier mutations
- Acquired genetic alterations to a long lived cell (such as haemopoitic stem cells)
- Proliferative/survival advantage to that mutated cell, so malignant clone can dominate the tissue
- This produces the malignant clone
- The malignant clone grows to dominate the tissue
3
Q
What are stem cells and what is their role?
A
Multipotential haematopoietic stem cells
- Ability to self renew (one daughter cell will be retained as a stem cell and once daughter given to become RBC),
- Multipoential (able to produce all of the blood cells of the body)
4
Q
What are the origins of bone marrow malignancies?
A
- Gives rise to cells on left side of graph (red, plat, gran, mono) – the myeloid lineage
- Right side b cells and t cells – lymphoid malignancies
5
Q
What causes acute leukaemia?
A
- If affecting myeloid differentiation, ongoing, increased proliferation, but no differentiation – get accumulation of myeloid progenator cells = acute leukaemia = AML
6
Q
What causes chronic leukaemia?
A
- More proliferation but higher rate, and ongoing differentiation = get accumulation of more end cells that needed, more red cells or neutrophils etc, best known is philadelphia mutation = causing chronic myeloid leukaemia
- Key difference between chronic and acute is the differences in mutation
7
Q
What cause acute/chronic lymphoma?
A
- Proliferation without differentiation: acute lymphoblastic leukaemia, but if proliferation and differentiation – occur due to mutations in later place (for CLL/lymphoma/MM) = mature lymphoid leukaemia = Many of these events occur in germinal node of lymph
8
Q
What is the difference between lymphoma and leukaemia?
A
- Describe distribution of the disease
- In lymph glands = lymphoma
- In blood or marrow = leukaemia
- CLL – normally is leukaemia, but every now and then it appears in the lymph glands (so can have varying appearances) – in that situation it is small cell lymphocytic lymphoma
- Burkitt lymphoma (normally presents in lungs) – every now and then will present with ALL, so it is acute Burkitt leukaemia
9
Q
What are the Major Groups of Haematological Malignancies?
A
Acute Leukaemias
- Acute lymphoblastic leukaemia (ALL)
- Acute myeloblastic leukaemia (AML)
Chronic Leukaemias
- Chronic myeloid leukaemia (CML)
- Chronic lymphocytic leukaemia (CLL)
Malginant lymphomas
- Non-Hodgkin lymphoma
- Hodgkin Lymphoma
Multiple Myeloma
Myelodysplastic syndromes
Myeloprolifertive neoplasms
10
Q
Explain the role of lymph nodes and lymphocytes:
A
- Lymph node: sophisticated organ: dotted throughout are follicles – lymphomas commonly occur due to mutations that occur in lymph nodes
- Lymphocytes are created in the bone marrow
- B cells go to lymph nodes, mature there, then are tested to be able to carry out immune function – so will mutate to have immunoglobulins – but because of this genetic pressure that can go wrong, immunoglobulin gene can go with a cancer gene (translocation between 14 and 18)
- Because it’s a b lymphocyte (long lived) – produces antibody production that is switched on all the time, so cancer gene is also switched on all the time – follicular lymphoma
11
Q
In what ways can lymphoma present?
A
- Nodal disease – Lymphadenopathy
- > 90% HL present with nodal disease
- ~ 60% NHL present with purely nodal disease
- Extranodal disease:
- ~ 40% NHL present with an extranodal component, with or without nodal involvement
- Systemic symptoms
- Fever, drenching sweats, loss of weight, pruritis, fatigue
12
Q
Lymphadenopathy
Localised and painful?
A
- Bacterial infection in draining site
13
Q
Lymphadenopathy
Localised and painless differentials?
A
- Rare infections, catch scratch fever, TB
- Metastatic carcinoma from draining site- hard
- Lymphoma-rubbery
- Reactive, no cause identified
14
Q
Lymphadenopathy
Generalised and painful?
A
- Viral infections, EBV, CMV, hepatitis, HIV
15
Q
Generalised and painless?
A
- Lymphoma
- Leukaemia
- Connective tissue diseases, sarcoidosis
- Reactive, no cause identified
- Drugs
