4 Haematological Malignancies Flashcards
Describe the difference between leukaemia and lymphoma
The main difference between lymphocytic leukemias and lymphomas is that:
- in leukemia, the cancer cells are mainly in the bone marrow and blood
- while in lymphoma they tend to be in lymph nodes and other tissues
Give some examples of myeloid neoplasms
- Acute myeloid leukaemia (AML)
- Chronic myeloid leukaemia (CML)
- Myeloproliferative neoplasms (MPN)
- Myelodysplastic syndromes (MDS)
Give some examples of Lymphoid neoplasms
- Acute lymphoblastic leukaemia (ALL)
- Chronic lymphoblastic leukaemia (CLL)
- Plasma cell disorders (Myeloma)
- Non-Hodgkin’s Lymphoma e.g. Hodgkin’s disease
- T-cell lymphoma
Describe acute leukemia
Leukemia = malignancy of bone marrow
- Results in very rapid cell growth
- May fill marrow before spilling out into the blood
- May present with High WBC (not always - can be low level)
- Presents with bone marrow failure\
May arise from pre-existing conditions e.g. Myelodysplasia
Describe bone marrow failure (it is a clinical presentation of leukemia)
Bone marrow failure
- Anaemia - tiredness, fatigue, pallor
- Thrombocytopenia - bleeding, bruising
- Neutropenia - infections
Describe the origin of acute myeloid leukaemia (AML)
- There is a defect in the common myeloid progenitor cells (they have not differentiated properly, and keep on growing - myeloblast)
- Morphology:
> Cells can be monomorphic, pleomorphic, inclusions, anomalies like inclusion bodies, and atypical granules
Describe acute lymphoblastic leukemia (ALL)
It is the most common malignancy in children
- peak incidence in children from ages 4-5
- May present with cytopenia’s or chest masses
- 90% can be brought into remission with induction chemotherapy
- 85% cured
- High relapse rates in older children and boys (Testes and CNS are ‘sanctuary sites’)
Name the origin of acute lymphoblastic leukemia (ALL)
- Common lymphoid progenitor (defects)
Describe the morphology of acute lymphoblastic leukemia
Different from the myeloid blast - more monoblastic - they resemble lymphocyte
- Differences in chromatin, structures of nucleus, and differences in nucleus:cytoplasm ratio
List common symptoms of acute leukemia
- Systemic (weight loss, fever, frequent infections)
- Lungs (easy SoB)
- Muscular (weakness - low Hb)
- Bones or Joints (pain or tenderness)
- Psychological (fatigue, loss of appetite)
- Lymph nodes (swelling, invasion)
- Spleen and/or liver (enlargement - invasion)
- Skin (night sweats, easy bleeding, and bruising, purplish patched or spots)
List the treatment principles for acute leukemia
- Delay in treatment makes infective complications worse
- Commence chemotherapy immediately on diagnosis
Describe common treatment for acute myeloid leukemia (AML)
strong IV chemotherapy in short, sharp bursts
- younger patients may have a better prognosis as they can tolerate high dose chemotherapy better
- older patients may receive gentler palliative chemotherapy
Describe common treatment for acute lymphoblastic leukemia (ALL)
A mix of strong chemotherapy and persisting milder tablets to prevent relapse
Describe chronic myeloid leukemia (CML)
Chronic leukaemia’s present with high white cells but not usually due to bone marrow failure
- it is due to a gene; t(9:22) = Philadelphia chromosome
- gene fusion produces BCR-ABL fusion protein > leads to tyrosine kinase activity
Describe some clinical presentations of chronic myeloid leukemia (CML)
- High WBC (+/- leukostasis)
- Splenomegaly
- Priapism
Describe the treatment of chronic myeloid leukaemias (CML)
Treatment now involves specific inhibition of the tumour cell-specific enzyme
- by the drug Imatinib
- It blocks the BCR-ABL protein - reverts DNA change > treat patient (blocking of the TK activity)
- Does not need a lot of chemotherapy
Describe myeloproliferative neoplasms (MPNs)
They present with an excess of mature cells in the blood
> Polycythaemia Ruba Vera (PRV)
> Essential thrombocytopenia (ET)
- Both PRV/EV may progress to myelofibrosis or acute leukaemia
Due to mutations affecting the JAK/STAT (JAK2 [tyrosine kinase], CALR, MPL)
It may cause stroke or heart attack due to abnormal clotting
What is Polycythaemia Ruba Vera (PRV), and what is it a clinical presentation of?
excess red cells
- myeloproliferative neoplasms
What is Essential thrombocytopenia (ET), and what is it a clinical presentation of?
excess platelets
- myeloproliferative neoplasms
State the origin of myeloproliferative neoplasms (MPN)
Comes from more mature progenitors (megakaryocyte, myeloblast, common myeloid progenitor - depends on which cell is affected)
Describe myelodysplastic syndromes (MDS)
It is the disordered maturation of blood cells in the bone marrow
- Bone marrow dysplasia can affect any or all cell lines (e.g. isolated thrombocytopenia or pancytopenia)
The pre-leukemic stage can progress to acute leukemia with time
How are myelodysplastic syndromes (MDS) detected and diagnosed?
It is easy to diagnose if a chromosomal abnormality is detected or if disorganization of marrow is severe
- May be hard to distinguish from reactive marrow changes e.g. from rheumatoid arthritis, chronic infection, or other systemic illness
Describe common lymphoblastic leukaemia (CLL)
Relatively common (3000 cases/year in the UK)
- increases with age
- majority of patient die of unrelated conditions
Usually presents accidentally on a routine FBC for other reasons, but may present with Lymphadenopathy
Describe the morphology of common lymphoblastic leukaemia (CLL)
- Lymphocytes look similar to normal cells but there are just too many
- They are also more fragile than normal lymphocytes
Describe the origin of common lymphoblastic leukaemia (CLL)
- Later on in differentiation of lymphoid progenitor (next cell line)
Describe non-Hodkin Lymphoma
Lymphoma is a sold cancer (cancer of lymph glands, not in blood)
- It is usually a grouping of a variety of different disease entities all showing tumour growth of lymphoid cells
- 30% occur outside lymph nodes
- More common in elderly
- Some may be related to viruses e.g. EBV, HTLV, HHV8, HIV
- Some related to chemical exposure
- Some related to sunlight exposure
List some common symptoms of lymphoma (Non-Hodgkins lymphoma)
B symptoms or lymphadenopathy are usual clues to lymphoma
- Asymptomatic
- Systemic symptoms (weight loss, fatigue, night sweats, pleuritis)
Describe Hodgkin’s lymphoma
It is strictly a subtype of Non-Hodgkin’s lymphoma
- Related to EBV infection
- 2 age peaks - teens/the early 20s and elderly
- Age peaks may be related to where EBV has integrated into the lymphocyte DNA - closer or further away from the proto-oncogene
The bulk of tumor in HD is ‘normal’ white cells reacting to the presence of tumor cells
Describe the origin of Hodgkin’s lymphoma
Neoplastic cell is Reed-Sternberg cell
- they are multinucleated,
- with prominent nuclei,
- appear much larger than other cells
There are different types of HD, occurring due to varying amount of Reed-Sternberg cell.
- The more the number of the R-S cell, the worse the prognosis
List clinical signs and symptoms of Hodgkin’s lymphoma
- Presents with B symptoms + continuous nodal spread
- Isolated lymphadenopathy
- Symptoms can depend on where mass is growing, as it can compress different structures
(in the mediastinum, enlarged nodes > compress vessels > mediastinal syndromes in abdomen compresses ureters > affects kidney > renal failure
or, enlarged nodes can compress nerves in the spinal cord) - Generic systemic symptoms > cells produce cytokines (syndromes + symptoms of fever, weight loss, sweats, pleuritis, and fatigue)
Describe how a diagnosis of lymphoma may be carried out
- History of weight loss, fevers, night sweats
- Scan or examination suggesting lymphadenopathy
- Biopsy is vital (no biopsy = no diagnosis) - > can either take the whole lymph node out > or good proportion (e.g. not fine needle aspiration, need better representation for differentials)
PETCT scan used to stage tumour extent and to gauge the response to therapy
Describe what multiple myeloma is
It is an immunosecretory disorder
- A condition of abnormal plasma cells, that proliferate without control
- And as a result, the plasma cells produce the same form of antibody (instead of multiple forms of antibodies that normal plasma cells would)
Due to this, you can detect a disproportionate amount of a single type of immunoglobulin (this is a ‘PARAPROTEIN’)
Different types of myeloma exist:
- IgG and IgA myelomas are the most common
What is a paraprotein, and how can it be used in the detection of myelomas
- Monoclonal antibody (mAb), in myelomas, the same type of immunoglobulin is produced (large proportion are the same)
- These paraproteins can be detected in a urine test
What are the conditions to confirm a myeloma
2 out of 3 of these conditions must be met:
- Plasma cells in marrow > 10%
- Detectable paraprotein in blood or urine
- Lytic lesion on MRI (seen on the bone)
What are the exceptions to the conditions to confirm a myeloma
Exceptions:
- Paraprotein alone = MGUS (monoclonal gammopathy of uncertain significance)
- IgM paraprotein = Waldenstorms or lymphoma, not myeloma
Describe the origin of myelomas
Latest differentiation stage of B cells
List symptoms of myelomas
- Hypercalcaemia - because of bone remodelling without control, releasing Calcium into the blood
- Renal failure - the proteins secreted by myeloma can intoxicate the kidney
- Marrow failure (anaemia, neutropenia and thrombocytopenia); can be due to the expansion of myeloma cells in marrow leading to marrow failure
- Bone pain: constant remodelling + lytic lesions
List some diagnostic tools in Haematological Malignancies
- Blood test (FBC)
- Bone marrow biopsy (morphology, flow cytometry, cytogenetics, molecular)
- CT, PET scans
- MRI scans
- Tissue biopsy
