Haematology: Malignancy Flashcards
What is CML?
- Clonal myeloproliferative disorder
- Increase in neutrophils and neutrophil precursor
- Most patients have the BCR ABL translocation (philapdelphia chromsome)
what is the philadelphia chromosome?
the ABL region of chromosome 9 attaches onto the BCR segment of chromosome 22. This causes an abnormal chromosome 22 which causes synthesis of an abnormal protein with increased tyrosine kinase activity.
What are the symptoms of CML?
patients usually present in the chronic phase
- Weight loss, night sweats, itching, left hypochndrial pain, gout
- Splenomegaly
- May be discovered on a routine blood test
Which genetic tests do you do to look for the BCR ABLe gene?
FISH
PCR for RNA product
What is the FBC like in CML?
Raised WCC - mainly neutrophils and myelocytes
What is the blood film like in CML (chronic and acute phases)
Chronic
1. Immature granulocytes (myelocytes)
Acute
1. Blast cells
What is the treatment of CML?
Imatinib (This is a specific inhibitor of the tyrosine kinase encoded for by BCR ABL
Hydroxyurea lowers WCC
Alpha interferon
Allopurinol (prevents gout)
Allogenic stem cell transplant
In the acute phase the treatment is the samer as AML with the addition of imatinib but the prognosis is poor for this.
What is myelodysplasia?
A clonal haemopoetic stem cell disorder where there is peripheral bloood cytopenias affecting more than one lineage and a cellular marrow (indicates ineffective haemopoesis)
What is the difference between primary and secondary myelodysplasia?
Primary: arises de novo
Secondary: Consequence of previous chemotherapy or radiotherapy
How does myelodysplasia present?
Usually elderly people
- Bone marrow failure
- Enlarged spleen
What does the FBC show in myelodysplasia?
Macrocytic anaemia
What does the blood film show in myelodysplasia?
Hypogranular neutrophils with bilobed nuclei
What genetic abnormalitis are associated with myelodysplasia?
chromosome 5 and 7 deletions or point mutations,
What is the treatment for myelodysplasia?
- Red cell, platelt and antibiotic therapies to reduce symptoms of pancytopenia
Chemotherapy
What do you see on the blood film of AML?
Auer rods in myeloblasts
Vucuolated monoblasts
What is chronic lymphocytic leukemia?
A B cell clonal lympho proliferative disease where lymphocytes accumulate in the bone marrow, lymph nodes and spleen. Tends to occur in older people
How does CLL present?
Lymphadeonpathy Night sweats, weight loss Bone marrow failure Enlarged spleen May also be picked up on a routine blood test
What does the blood film of CLL show?
Large numbers of mature lymphoid cells and some smear cells.
What is the treatment for CLL?
- Observation for asymptomaticpatients with early disease
- Chlorambucil lowers lymphocyes count
- Steroids
Chemotherapy
What is myeloma?
A malignant disorder of plasma cell characterised by
- A monoclonal paraprotein in serum/urine
- Bone changes (can lead to pain and pathological fractures)
- Excess plasma cells in the bone marrow - leads to features of bone marrow failure such as infection
Why does renal failure occur in multiple myeloma?
Occurs in up to 1/3rd of patients and is due to hypercalcaemia, infection, deposition of paraprotein or light chains, uric acid or amyloid
What does the blood film in multiple myeloma show?
Roleoux formation
What are bence jones proteins?
A paraprotein found in the urine and serum of patients with multiple myeloma. Most often this is an IgG paraprotein
What kind of bone lesions are seen in multiple myeloma?
Lytic lesions (break doen bone)
What is the treatment of multiple myeloma?
Chemotherapy
Radiotherapy - localised boen lesions
Allogenic stem cell transplants
What is MGUS?
Low and stationary level of paraprotein with no reduction in other immunoglobulins, no skeletal abnormalities and less than 10% plasma cells in the marrow
What is primary amyloidosis?
Less than 10% marrow Bence jones proteins, low level serum paraproteins and plasma cells but no skeletal lesions
What is walderstroms magroglubulinaemia?
A chronic lymphoproliferative disorder associated with an IgM paraprotein. Hyperviscosity commonly occurs and rthis can cause visual disturbance, CNS chanegs and headache
What imaging is used in multiple myeloma?
Whole body MRI
Describe the diagnostic criteria for myeloma?
One major and one minor criteria or three minor criteria + symtpoms:
Major
1. Plasmacytoma
2. More than 30% plasma cells on boen amrrow biopsy
3. Bence jones proteins in blood or urine
Minor criteria
1. 10 - 30% plasma proteins in bone marrow
2. Minor levels of bence jones proteins
3. Osteolytic lesions
4. Low levels of other blood antibodies
Why do you get hypercalcaemia in myeloma?
- Increased osteoclastic bone resorption caused by local cytokines released by myeloma cells
2. Imapired renal function and calcium reabsorption
What do you see on a lymoh node biopsy of apatient with hodgekins lymphoma?
Reed Sternberg cells
Describe the staging of hodgekins lymphoma?
1: Single lymph node region
2. Two or more regions on the same side of the diaphragm
3. Lymph nodes on both sides of the diaphragm,
4. Extra nodal sites
What is the most common type of hodgekins lymohoma?
Nodular sclerosing
What type of hodgekins lymphoma has the best prognosis?
Lymphocyte predominent
What type of hodgekins lymphoma has the worst prognosi?
Lymphocyte depleted
What cancers are associated with EBV infection?
Burkitts
Hodgekins
HIV associated central nervous system lymmphomas
Nasopharyngeal carcinoma
What is the treatment for hodgekins lymphoma?
Radiotherapy
Chemotherapy
What are myeloproliferative disorders?
Chronic diseases causes by clonal proliferation of bone marrow cells leading to excess production of one or more haemopoietic lineage. The different clinial syndrome include
- Polycythaemia rubra vera (red cells)
- Essential thrombocythaemia
- CML (white cells)
- Myelofibrosis (reactive fibrosis of the bone marrow and extramedulalry haemopoiessis in the liver and spleen
What is myelofibrosis?
a myeloproliferative disorder caused by hyperplasia of abnormal magakaryocytes. The release of platelet derived greith factor is thought to stimulate fibroblasts. Haematopoieiss develops in the liver and spleen.
How does myelofibrosis present?
Anaemia
Massive splemomegaly
Hypermetabolic syndrome (weight loss, night sweats)
What do you see on blood film of myelofibrosis?
Tear drop poikilocytes
What kidn of bone marrow biopsy do you need in myelofibrosis?
trephine biopsy as normal bon marrow biopsy in unobtainable
Whata re you at risk of developing if you have PRV or ET?
Myelofibrosis
AML
What are you at risk of developing if you have myelofibrosis?
AML
What mutation do you see in polycythaemia rubra vera?
JAK2 mutation
What is the main risk of having PRV?
Thrombosis
Whay does the blood film show in essential thrombocythaemia?
Platelt anisocytosis with circulating megakarocytes
How do you treate PRV?
Aspirin
Venesection
Hydroxyurea
