Haematological cancer Flashcards
Leukaemia : Definition
Leukaemia is cancer of a particular line of stem cells in the bone marrow, causing unregulated production of a specific type of blood cell.
Leukaemia : Clinical features
Systemic sx
1 . Fatigue
2 . Fever
Interference with normal blood cell production;
1 . Anaemia
2 . Thrombocytopenia
* Non blanching lesions - Petechaei
Abnormal WBC
* Lymphadenopathy
* Weakened immune system
Leukaemia : Myeloid stem cells
Two main types of Haematopietic stem cells;
1. Myeloid stem cells
2. Lymphoid stem cells
Myeloid stem cells gives rise to a series of specialised cells;
1. Erythrocytes
2. Granulocytes: neutrophils, eosinophils, and basophils
3. Monocytes : Macrophages
4. Megakaryocytes : Platelets, Erythrocytes
Myeloid Leukaemia : Types
Two main types of Myeloid Leukaemia
1. Acute Myeloid Leukaemia - aggressive, develops and progresses rapidly
2. Chronic Myeloid Leukaemia - chronic, develops slowly
Acute Myeloid Leukaemia : Definition
Neoplastic monoclonal proliferation of myeloblast stem cells which are precursors of myeloid blood cells, in the bone marrow
Acute Myeloid Leukaemia : Pathophysiology
1 . Genetic and Molecular Abnormalities:
2 . Proliferation of Blast Cells:
* rapid proliferation of myeloblasts
* myeloblasts accumulate in the bone marrow, crowding out normal blood-forming cells
3 . Bone Marrow Infiltration:
excessive accumulation of myeloblasts in the bone marrow disrupts the normal hematopoietic process.
4 . Suppression of Normal Hematopoiesis:
5 . Circulation of Leukemic Cells:
Acute Myeloid Leukaemia : Risk factors
- Age: Peak at 60
- Previous Chemotherapy or Radiation:
- Down’s syndrome
- Environmental Exposures:- to Benzene
- Myelodysplastic Syndromes (MDS):* transformation from a myeloproliferative disorder, such as polycythaemia ruby vera or myelofibrosis.
Acute Myeloid Leukaemia :Clinical features
- Neutropenia - increased infections
- Anaemia
- Thrombocytopenia - low platelet, increased risk of bleeding
- Splenomegaly
- Bone pain
Acute Myeloid Leukaemia : Diagnosis
- Blood smear : Myeloblasts - normally large cells, fine chromatin and prominent nucleoli
- Bone marrow biopsy -: increase in blast cells
- Histology : Auer rods
Chronic myeloid leukaemia : Definition
CML is characterized by
* overproduction of partially mature myeloid cells
and
* presence of a specific genetic abnormality known as the Philadelphia chromosome
Chronic myeloid leukaemia : Pathophysiology
1 . Chromosomal translocation which affects granulocytes
- Translocation of chromosome 9 (ADL gene) and chromosome 22 (BCR gene)
- results in Philidelphia chromosome 22.
2 . Fusion gene - BCR-ABL
* Translocation leads to a fusion gene called BCR-ABL which produced the BRC-ABL protein
3 . BCR-ABL protein acts to switch on tyrosine kinase activity
- Leading to cell division of myeloid cells to be permanently switched on
- Forcing myeloid cell proliferation
CML : Clinical presentation
- Marked splenomegaly - abdominal discomfort
- Weightloss, sweating
- Anaemia - lethargy
Chronic myeloid leukaemia : Ocurrence
Risk factors
- Occurrence : 50-60 years
- Risk factors : Benzene, radiation exposure
Chronic myeloid leukaemia : Diagnosis
- Lab results : ***increased number of granulocytes - in different stages of maturation
- Bone marrow biopsy : hypercellularity of myeloid cells e.g. megakaryocytes
- Genetic testing : identify philidelphia chromosome
Chronic myeloid leukaemia : Management
- Tyrosine kinase inhibitor - Imantinib - aiming to stop cell division caused by the BCR-ABL protein
Lymphoid stem cells : Definition
Two main types of Haematopietic stem cells;
1. Myeloid stem cells
2. Lymphoid stem cells
Lymphoid stem cells can mature into;
1. T cells
2. B cells
3. Natural Killer cells
Lymphoid Leukaemia : Definition
Neoplastic proliferation of a lymphoid stem cells (lymphoblasts) - precursor cell to T/B/Natural killer cells within the bone marrow
- Usually effects one of the lymphocyte precursor cells, causing acute proliferation of a single type of lymphocyte
- B cells most commonly affected
Lymphoid Leukaemia : Types
- Acute Lymphoid Leukaemia
- Chronic Lymphoid Leukaemia
Acute Lymphoid Leukaeimia : Types
- T- cell ALL : proliferation of T cell precursors
Migrate to thymus or lymph nodes like normal T cells and cause these structures to enlarge. - B-cell ALL : proliferation of B cell precursors
Acute Lymphoid Leukaeimia : Clinical features
- Fever
- Lymphadenopathy + hepatosplenomegaly
* Thymus enlargement in T cell ALL - may present as mediastinal growth - Anaemia/Neutropenia/Thrombocytopenia
- Neoplastic infiltration - bone pain, lymphadenopathy, palpable mass over the thymus
Acute Lymphoid Leukaeimia : Occurence and Risk factors
- Children < 5 years
- Down’s syndrome - associated with Philidelphia chromosome (like Chronic Myeloid Leukaemia)
Acute Lymphoid Leukaeimia : Diagnosis
- Blood smear : lymphoblasts- smaller cells, coarse chromatin and small nucleoli
Chronic lymphocytic leukaemia : Definition
Chronic lymphocytic leukaemia is where there is slow proliferation of a single type of well-differentiated lymphocyte, usually B-lymphocytes
Chronic lymphocytic leukaemia : Pathophysiology
- Mutation in B cell pathway maturation
* B cells to interfere with pathways of B cell receptor which activates tyrosine kinases this in turn;
i) Prevents CLL cells maturing fully
ii) Apoptosis is significantly delayed
2 . Leads to a build up of partially mature B cells in bone marrow
- > enter the bloodstream
->deposit mainly in lymphatic system—>lymphadenopathy (occasionallypainful)
CLL - Clinical features
- Lymphocytosis
- Anorexia, weightloss
- Bleeding, infections
- Lymphadenopathy
Chronic lymphocytic leukaemia : Diagnosis
Blood smear : ‘smudge’ cells -
immature B cells broken down during smear
Bloods : Lymphocytosis - low lymphocytes
Chronic Leukaemia : Pathophysiology
- Partial maturation of cells
* key distinction from acute leukaemia
Abnormal premature leukocytes don’t work as effectively which weakens the immune system.
Leukaemia : Investigations
< 48 hours
Bloods;
1. FBC
2. Blood film
3. LDH - non specific marker of tissue damage
Investigations
4. Bone marrow Biopsy
5. CT and PET scan
6. Lymph node biopsy
Leukaemia : Management
- Chemotherapy
- Targetted therapy
* Tyrosine kinase inhibitors (e.g., ibrutinib)
* Monoclonal antibodies (e.g., rituximab, which targets B-cells)
Leukaemia : Complications of Chemotherapy
Infections due to immunosuppression
* Neurotoxicity
* Infertility
* Secondary malignancy
* Cardiotoxicity (heart damage)
* Tumour lysis syndrome
Leukaemia : Tumor lysis syndrome
Tumour lysis syndrome results from chemicals released when cells are destroyed by chemotherapy, resulting in:
* High uric acid
* High potassium (hyperkalaemia)
* High phosphate
* Low calcium (as a result of high phosphate)
- Hyperuricaemia - AKI and uric acid stone } May require Allopurinol
- Hyperkalaemia : Cardiac Arrythmia
Lymphoma : Definition
Lymphoma : a type of cancer affecting the lymphocytes inside the lymphatic system*.
Cancerous cells proliferate inside the lymph nodes, causing the lymph nodes to become abnormally large - lymphadenopathy
Lymphoma : Types
two categories:
* Hodgkin’s lymphoma (a specific disease)
* Non-Hodgkin’s lymphoma (which includes all other types)
Lymphoma : Clinical features
Lymphadenopathy is the key presenting symptom.
neck, axilla or inguinal region. T
non-tender and feel firm or rubbery.
Patients with Hodgkin’s lymphomamay experience lymph node pain after drinking alcohol.
B symptoms refer to systemic symptoms of lymphoma:
* Fever
* Weight loss
* Night sweats
Lymphoma : Management
2 week cancer referral or within 48 hours for children if presenting with
Unexplained Lymphadenopathy or Splenomegaly
Typical criteria for urgent referral:
* Persistent (>6 weeks) lymphadenopathy
* One or more lymph nodes >2 cm in diameter
* Rapidly increasing lymphadenopathy
* Generalised lymphadenopathy
* Persistent and unexplained splenomegaly
Hodgkin’s lymphoma
, is a type of lymphoma characterized by the abnormal proliferation of Reed-Sternberg cells which are large abnormal B cell lymphocytes found in the affected lymph nodes
- Reed-Sternberg cells release excessive cytoskines causing inflammation and systemic symptoms such as fever and weight loss
Hodgkin’s lymphoma : Occurrence
bimodal age distribution with peaks around 20-25 and 80 years.
Hodgkin’s lymphoma : Risk factors
Risk factors for Hodgkin’s lymphoma include:
* HIV
* Epstein-Barr virus - can infect reed-sternberg cells and contribute to disease development
* Autoimmune conditions, such as rheumatoid arthritis and sarcoidosis
* Family history
Hodgkin’s lymphoma : Clinical features
- Non disseminated disease and systemic symptoms
1 . Lymphadenopathy which is:
* Painless
* Asymmetrical
Cervical nodes or mediastinal involvement in 60%
mediastinal lymphadenopathy : compress the airway and lead to dyspnoea, chest pain, and dry cough. It may also cause superior vena cava obstruction.
2 . Alcohol-induced pain at lymph node regions is a non-specific symptom
3 .B symptoms;
Fever >38ºC
Night sweats
Unintentional weight loss of >10% over 6 months
Hodgkin’s Lymphoma : Diagnosis
Gold standard : Lymph node biopsy
- Reed-Sternberg cells - large cancerous B lymphocytes with two nuclei and prominent nucleol
Hodgkin’s Lymphoma : Management
First line : Chemotherapy and radiotherapy.
Chemotherapy may result in infections, cognitive impairment, secondary cancers (e.g., leukaemia) and infertility.
Radiotherapy creates a risk of tissue fibrosis, secondary cancers and infertility.
Non-Hodgkin’s lymphoma : Types
1 . Diffuse large B cell lymphom } Most common form of aggressive NHL
typically presents as a** rapidly growing painless mass in older patients**
2 .Burkitt lymphoma is
particularly associated with Epstein-Barr virus and HIV
3 . MALT lymphoma
affects the mucosa-associated lymphoid tissue, usually around the stomach
Non-Hodgkin’s lymphoma : Risk factors
- HIV
- Epstein-Barr virus
- Helicobacter pylori (H. pylori) infection is associated with MALT lymphoma
- Hepatitis B or C infection
- Exposure to pesticides
Non-Hodgkin’s lymphoma : Clinical presentation
Disseminated disease at presentation
1. Painless lymphadenopathy : cervical, axillary, inguinal, and femoral lymph nodes most commonly involvement
* SVC obstruction : SOB and facial oedema
* External biliary tree : Jaundice
* Ureters : Hydronephrosis
* Lymph system : Lymphoedema
2. Extranodal involvement
* Bone marrow : Pancytopenia
* Burkitt’s lymphoma : large abdominal mass and symptoms of bowel obstruction
Non-Hodgkin’s lymphoma : Investigations
- Blood test : pancytopenia, U+Es (AKI), LDH elevated
- Screening : hepatitis B/C, HIV, HTLV-1
- CXR : mediastinal lymphadenopathy, pleural or pericardial effusions
Gold standard : Lymph node biosy
Non-Hodgkin’s lymphoma : Management
Management of non-Hodgkin’s lymphoma depends on the type and stage. It may involve:
- Watchful waiting if assymptomatic
- Localised disease : Local radiotherapy
- Monoclonal antibodies (e.g., rituximab, which targets B cells)
Hodgkin’s vs Non Hodgkin’s : Clinical features
Hodgkin’s
1. Mature B cells - Reed Sternberg cells
2. Bimodal age distribution
3. Contiguous spread
4. Extranodal disease uncommon
5. Systemic symptoms common
Non Hodgkin’s
1. B or T cells affected, at various stages of maturation
1. More common with increasing age
1. Non-contiguous spread
1. Extranodal disease common
1. Systemic symptoms not common
Plasma cells : Definition
Plasma cells are specialised B Lymphocyte cells which produce antibodies
* Formed following B cell activation after encounter an antigen
* Each type of plasma cell produces a specific antibody against a specific antigen
Myeloma : Pathophysiology
1 . Abnormal Plasma Cell Proliferation
* Arises from a single abnormal plasma cell that undergoes uncontrolled proliferation
* Clonal expansion leads to the accumulation of malignant plasma cells in the bone marrow
2 . Abnormal excess antibody production
* Cloned Plasma cells produce identical monocloal antibodies - ‘Paraproteins’
3 .Renal Dysfunction: - Abnormal proteins produced by myeloma cells can accumulate in the kidneys
4 . Bone Marrow Infiltration:
myeloma cells in the bone marrow disrupts the normal hematopoietic function
anemia, leukopenia, and thrombocytopenia
5 . Bone Destruction:
Abnormal cells activate osteoclasts - bone destruction and the formation of lytic lesions
6 . Hypercalcemia:
* Bone destruction releases calcium into the bloodstream, leading to hypercalcemia.
Myeloma : Blood findings
1 . full blood count: anaemia
Low WCC - high risk of infection
Low platelets : Bleeding
2 . Peripheral blood film: rouleaux formation
* Stacking of RBC due interaction with excess protein in the blood
3 . Urea and electrolytes: renal failure
4 . Bone profile: hypercalcaemia
Myeloma : Diagnosis
1 . Protein electrophoresis
Serum : Raised concentrations of monoclonal IgA/IgG proteins
Urine : they are known as Bence Jones proteins
2 . Bone marrow aspiration
confirms the diagnosis if the number of plasma cells is significantly raised
3 . whole-body MRI - for lytic lesions
X-rays: ‘rain-drop skull’ (likened to the pattern rain forms after hitting a surface and splashing, where it leaves a random pattern of dark spots).
