Concepts in Malignant Haematology Flashcards
What is the likely diagnosis?
Acute leukemia
Multiple myeloma
Lymphoma
Localised breast carcinoma
severe sepsis and disseminated intravascular coagulation
Acute leukemia
An excess of blasts in blood, originating from blast excess in the marrow is likely to be acute leukemia
Additional support for this diagnosis comes from the reduction in normal cells (Hb/RBC, platelets, neutrophils) suggesting absence of maturation. Immunophenotyping will clarify if it is acute myeloid leukemia or acute lymphoblastic leukaemia
What is the diagnosis?
Glandular fever
Acute leukemia
Aplastic anaemia
Chronic lymphocytic leukemia
Diabetic ulcer
Chronic lymphocytic leukaemia
A persistent small to medium sized lymphocytosis for years, that is asymptomatic.
What further action should be taken?
None as the blood count is normal
Bone marrow biopsy
Repeat blood count in 4 weeks
Serology for EBV (IgM)
Urgent lymph node biopsy
Urgent lymph node biopsy as diagnosis is extensive
What are kinetics of normal haemopoeisis?
Self renewal
Proliferation
Differentiation or lineage commitment
Maturation
Apoptosis
How can we identify normal, more mature non-lymphoid cells?
Morphology
- Cell surface antigens (Glycophorin A = red cells)
- Enzyme expression (myeloperoxidase = neutrophils)
Blood count + blood film
How can we identify normal progenitor / stem cells?
Cell surface antigens (immunophenotyping) - e.g. CD34
Cell culture assays
What happens in haematological malignancies?
Increased numbers of abnormal and dysfunctional cells
Loss of normal activity
Haemopoeisis - e.g. acute leukemias / marrow based malignancies
Immune function - e.g. certain lymphomas
Due to one or more of the following
- Increased proliferation (in absence of a stimulus)
Lack of differentiation / maturation
Lack of apoptosis
What happens in acute leukemia?
Proliferation of abnormal progenitors with block in differentiation / maturation e.g. acute myeloid leukemia
What happens in chronic myeloproliferative disorders /neoplasms?
Proliferation of abnormal progenitors but NO differentiation / maturation block
e.g. Chronic myeloid leukemia
What are causes of haematological malignancies?
Genetic, epigenetic, environmental interaction
Acquired somatic mutations in regulatory genes (driver mutations vs passenger mutations)
What is a clone?
Population of cells derived from a single parent cell
This parent cell has a genetic marker (driver mutation or chromosomal change) that is shared by the daughter cells
Clones can diversity but contain a similar genetic backbone
Describe the difference in normal haemopoeisis vs malignant haemopoeisis in terms of clonality
Normal haemopoeisis - polyclonal
Malignant haemopoeisis - monoclonal
Describe difference between driver mutations vs passenger mutations
Driver mutations confer growth advantage on the cells and are selected during evolution of cancer
Passenger mutations do not confer growth advantage, but happened to be present in an ancestor of the cancer cell when it acquired one of its drivers
What are the reasons for different haematological malignancy subtypes?
Cells at different developmental stages can undergo neoplastic transformation
Involvement of different anatomical regions unique to cell type, either at point of origin or after migration
Different clinicopathological characteristics (clinical and biological behaviour)
Patterns of antigen expression / signature (suggestive of developmental stage) - immunophenoptying / immunohistochemistry have a critical role in diagnosis
How can we classify cancers of the haemopoeitic and lymphoid systems?
Site
Lineage
Stage of developmental / histology
Preservation of differentiation / maturation
How can we classify cancers based on lineage?
How can we classify cancers based on stage of development and histology?
