Blood cancers Flashcards
Define ALL
• Malignancy of the bone marrow and blood characterised by the proliferation of lymphoblasts (primitive lymphoid cells)
Pathophysiology of ALL
- Lymphoblasts undergo malignancy transformation and proliferation
- This leads to the replacement of normal marrow elements, leading to bone marrow failure and infiltration into other tissues
RF of ALL (9)
- Environmental (Radiation, Smoking, Viral Infection)
- Genetic (Down’s syndrome, Neurofibromatosis type 1, Fanconi’s anaemia, Xeroderma Pigmentosum)
- Age < 6 or mid-late 30s/mid 80s
- Family history
- History of malignancy
Epidemiology of ALL
- MOST COMMON malignancy of CHILDHOOD
- Peak incidence: 2-5 yrs old
- There is a second peak in incidence in the elderly
- Annual UK incidence: 1/70,000
In which 2 ways does ALL manifest
Bone marrow failure and organ infiltration
S/s of ALL (8 for 1 manifestation, 14 in the other)
• Symptoms of Bone Marrow Failure: o Anaemia (fatigue, dyspnoea) o Bleeding (spontaneous bruising, bleeding gums, menorrhagia) o Opportunistic infections o Pallor o Bruising o Bleeding o Infection
• Symptoms of Organ Infiltration: o Tender bones o Enlarged lymph nodes o Mediastinal compression o Meningeal involvement (headache, visual disturbances, nausea) o Lymphadenopathy o Hepatosplenomegaly o Cranial nerve palsies o Retinal haemorrhage o Papilloedema on fundoscopy o Leukaemic infiltration of the anterior chamber of the eye o Testicular swelling
Ix for ALL (11)
• Bloods o FBC - normochromic normocytic anaemia, low platelets, variable WCC o High uric acid o High LDH o Clotting screen • Blood Film o Abundant lymphoblasts
• Bone Marrow Aspirate or Trephine Biopsy
o Hypercellular with > 20% lymphoblasts
• Immunophenotyping - using antibodies to recognise cell surface antigens
• Cytogenetic - karyotyping to look for chromosomal abnormalities or translocations
• Cytochemistry
• Lumbar Puncture - check for CNS involvement
• CXR - may show mediastinal lymphadenopathy, lytic bone lesions
• Bone Radiographs - mottled appearance with punched out lesions due to leukaemic infiltration
Define AML and how is it classified
AML describes malignancy of primitive myeloid lineage white blood cells (myeloblasts) with proliferation in the bone marrow and blood (clonal expansion of myeloid blasts in bone marrow, peripheral blood or extramedullary tissues).
Classified using the FAB (French-American-British) System into 8 morphological variants (M0-M7).
Pathophysiology of AML
- Myeloblasts undergo malignant transformation and proliferation
- This leads to replacement of normal marrow and bone marrow failure
- Usually due to mutations of transcription factors
RF of AML (5)
- Age > 65
- Family history
- Radiation Exposure
- Benzene Exposure
- History of chemotherapy
Epidemiology of AML
- MOST COMMON acute leukaemia in ADULTS
- Incidence INCREASES with age
S/s of AML (9 for 1 manifestation, 8 in the other)
• Symptoms of Bone Marrow Failure: o Anaemia (lethargy, dyspnoea) o Bleeding (due to thrombocytopaenia or DIC) o Opportunistic or recurrent infections o Pallor o Cardiac flow murmur o Ecchymosis o Bleeding o Opportunistic or recurrent infections (e.g. fever, mouth ulcers, skin infections)
• Symptoms of Tissue Infiltration:
o Gum swelling or bleeding
o CNS involvement (headaches, nausea, diplopia)
o Hepatosplenomegaly
o Skin rashes
o Gum hypertrophy
o Deposit of leukaemic blasts in the eye, tongue and bone (RARE)
Ix for AML (8)
• Bloods o FBC - low Hb, low platelets, variable WCC o High uric acid o High LDH o Clotting studies, fibrinogen and D-dimers (to check for DIC) • Blood Film o Myeloblasts o Auer Rods o Bilobed nucleus/indented nucleus • Bone Marrow Aspirate or Biopsy o Hypercellular with > 20% blasts o Biopsy is diagnostic • Immunophenotyping o Antibodies against surface antigens used to classify the lineage of the abnormal clones – this is to differentiate from ALL • Cytogenetics – helps decide treatment and guide prognosis • Immunocytochemistry
Define CLL
• Characterised by progressive accumulation of functionally incompetent mature B cells, which are monoclonal in origin, which have escaped programmed cell death. There is an overlap between CLL and non-Hodgkin’s lymphoma
Chromosomal changes leading to CLL
o Trisomy 12
o 11q and 13q deletions
RF of CLL (3)
- Age > 60 (median age at diagnosis is 70)
- Male, white ethnicity
- Family history of CLL
Epidemiology of CLL
- 90% are > 50 yrs
- Commonest leukaemia – incidence 4/100,000/yr
- More common in MALES
- Rare in Asians
S/s of CLL (12)
• Asymptomatic - 40-50% of cases are diagnosed following routine blood tests • May be anaemic or infection-prone • Systemic Symptoms: o Lethargy o Malaise o Night sweats • Symptoms of Bone Marrow Failure: o Recurrent infections o Herpes zoster infection o Easy bruising or bleeding • If severe: weight loss, sweats, anorexia
• Non-tender lymphadenopathy – enlarged, rubbery, non-tender
• Hepatomegaly
• Splenomegaly
• LATE STAGE signs of bone marrow failure:
o Pallor
o Cardiac flow murmur
o Purpura/ecchymosis
Ix for CLL (FBC 6, 3 others)
• Bloods
o FBC
• Lymphocytosis – marked raised lymphocytes
• Low Hb
Could be due to bone marrow infiltration, hypersplenism or autoimmune haemolysis
• Low platelets – marrow infiltration
• Low serum Ig – marrow infiltration
• Low neutrophils – marrow infiltration
• Later: autoimmune haemolysis
• Blood Film
o Small lymphocytes with thin rims of cytoplasm
o Smudge cells
• Bone Marrow Aspirate or Biopsy
o Lymphocytic replacement of normal marrow
• Cytogenetics
What can CLL be associated with
CLL may be associated with autoimmune phenomena such as haemolytic anaemia (warm agglutinins) or thrombocytopaenia/
Define CML
- Chronic myeloblastic leukaemia is a malignant clonal disease characterised by uncontrolled proliferation of myeloid cells in the bone marrow and blood, distinguished from AML by its slower progression
- Myeloproliferative disorder
Which blood cancer involves the Philadelphia chromosome and which chromosomes and gene is that
CML
9 and 22
Fusion gene BCR/ABL
Pathophysiology of CML
• Pathogenesis
o The Philadelphia chromosome results in the formation of the BCR-ABL fusion gene
o The product of this gene enhances tyrosine kinas e activity and drives cell replication
What are the three phases of CML and their durations
o Relatively stable chronic phase (4-6 yr duration)
o Accelerated phase (3-9 months)
o Acute leukaemia phase - blast transformation
RF of CML
- Age 65-74 years
- Ionising Radiation Exposure
- Male
Epidemiology of CML
- Incidence increases with age
- Mean age of diagnosis: 40-60 yrs
- 4 x more common in MALES
S/s of CML (12)
• ASYMPTOMATIC in 40-50% of cases - diagnosed on routine blood count
• Hypermetabolic Symptoms:
o Weight loss
o Malaise
o Sweating
• Bone Marrow Failure Symptoms:
o Lethargy
o Dyspnoea
o Easy bruising
o Epistaxis
o Abdominal discomfort and early satiety – due to splenic enlargement
o Rare symptoms:
• Gout
• Hyperviscosity symptoms (visual disturbance, headaches, priapism)
o May present during a blast crisis with symptoms of AML and ALL
• SPLENOMEGALY - most common physical finding (90% of cases) • Hepatomegaly • Signs of bone marrow failure: o Pallor o Bleeding o Ecchymosis
Ix for CML (6 in FBC, then 3)
• Bloods o FBC • High WCC with whole spectrum of myeloid cells – high neutrophils, myelocytes, basophils, eosinophils • Low Hb • High/normal/low platelets • High uric acid • High B12 and transcobalamin I • Low neutrophil ALP score • Blood Film o Immature granulocytes • Bone Marrow Aspirate or Biopsy o Hypercellular with raised myeloid-erythroid ratio • Cytogenetics o Show the Philadelphia chromosome
Define Hodgkin’s lymphoma
Lymphomas are neoplasms of lymphocytes cells, originating in the lymph nodes or other lymphoid tissues. Hodgkin’s lymphoma (15% of all lymphomas) is diagnosed histopathologically by the presence of Reed-Sternberg Cells (binucleate lymphocytes).
What has been detected in 50% of Hodgkin’s lymphomas
EBV genome
RF of Hodgkin’s lymphoma
- History of EBV Infection
- Family history of Hodgkin’s lymphoma
- HLA Subtypes
Epidemiology of Hodgkin’s lymphoma
- Bimodal age distribution with peaks at 20-30 yrs and > 50 yrs
- More common in MALES (2:1)
S/s of Hodgkin’s lymphoma (14)
• Painless enlarging mass – enlarged, painless, non-tender, rubbery, superficial
o Most commonly in the neck
o Can also be in the axilla or inguinal
• The mass may become painful after alcohol ingestion
• Mediastinal lymph node involvement can cause mass effect e.g. bronchial/SVC obstruction
• B symptoms of Lymphoma (systemic)
o Fever > 38 degrees
• If this is cyclical it is referred to as Pel-Ebstein fever
o Night sweats
o Weight loss > 10% body weight in the past 6 months
• Other symptoms
o Pruritis
o Cough
o Dyspnoea
- Splenomegaly (or sometimes, hepatosplenomegaly)
- Cachexia
- Anaemia – pallor
- Skin excoriations
- Signs of intrathoracic disease (e.g. pleural effusion, superior vena cava obstruction)
Ix for Hodgkin’s lymphoma and what system is used to stage it (FBC 4, 5 others)
• Bloods
o FBC: high WCC
• Anaemia of chronic disease
• Leucocytosis
• High neutrophils
• High eosinophils
• Lymphopaenia in advanced disease
o High ESR and CRP
o High LDH (released during cell turnover)
• Lymph Node Biopsy – will show REED-STERNBERG cells
• Bone Marrow Aspirate and Trephine Biopsy – can spread to bone marrow in late stage
• Imaging - CXR, CT, PET
• Ann Arbor Staging
o I = single lymph node region
o II = 2+ lymph node regions on one side of the diaphragm
o III = lymph node regions on both sides of the diaphragm
o IV = extranodal involvement e.g. liver/bone marrow
o Each stage is either A/B +/- subscript A/E
o A = absence of B symptoms except pruritis
o B = presence of B symptoms – worse prognosis
o E = localised extranodal extension
o S = involvement of spleen
What system is used to stage lymphomas
Ann Arbor
What is the main thing found in Hodgkin’s lymphoma vs non
REED-STERNBERG cells
What rash is found in non-Hodgkins lymphoma
o Mycosis fungoides
o T cell lymphoma of the skin
What is the Ann Arbor staging and what is it used for
Lymphoma
• Ann Arbor Staging
o I = single lymph node region
o II = 2+ lymph node regions on one side of the diaphragm
o III = lymph node regions on both sides of the diaphragm
o IV = extranodal involvement e.g. liver/bone marrow
o Each stage is either A/B +/- subscript A/E
o A = absence of B symptoms except pruritis
o B = presence of B symptoms – wors
Which non-Hodgkin lymphomas have associations with which oncogenic viruses
• Diffuse Large B Cell Lymphoma
o Most common
o Aggressive
o Associated with hepatitis C
• Burkitt’s lymphoma
o Very aggressive
o Associated with EBV infection
• Lymphoplasmacytic lymphoma (Waldenstrom’s macroglobulinaemia)
o Affects bone marrow, lymph nodes and spleen
o Causes thick and viscous blood
o Associated with hepatitis C virus
Which blood cancer is coeliac disease associated with
• Enteropathy associated T Cell lymphoma
o Associated with coeliac disease
RF of non-Hodgkin’s lymphoma (12)
- Age >50 years
- Male
- Radiotherapy
- Immunosuppressive agents
- Chemotherapy
- Infection: HIV, HBV, HCV, EBV
- Connective tissue disease (e.g. SLE), Auto-Immune diseases (Sjogren’s)
Malabsorptive disease (Coeliac)
Epidemiology of non-Hodgkin’s lymphoma
- Incidence increases with age
- More common in MALES
- More common in the WESTERN WORLD
S/s of non-Hodgkin lymphoma (16)
Painless enlarging mass (in neck, axilla or groin) – superficial lymphadenopathy • Systemic Symptoms (occurs less frequently than in Hodgkin's): o Fever o Night sweats o Weight loss > 10% body weight o Symptoms of hypercalcaemia • Symptoms related to organ involvement o Extranodal disease is MORE COMMON in NHL than in Hodgkin's lymphoma o Skin rashes o Headache o Sore throat o Abdominal discomfort o Testicular swelling
• Skin rashes o Mycosis fungoides - looks like a fungal infection but is in fact a cutaneous T-cell lymphoma) • Abdominal mass • Hepatosplenomegaly • Signs of bone marrow involvement: o Anaemia o Infections o Purpura
Ix for non-Hodgkin’s lymphoma (FBC 3, 11 other)
• Bloods o FBC • Anaemia • Neutropaenia • Thrombocytopaenia o High ESR and CRP o Raised LDH o Calcium may be raised o HIV, HBV and HCV serology • Blood Film o Lymphoma cells may be visible in some patients • Bone Marrow Aspiration and Biopsy • Imaging - CXR, CT, PET • Lymph Node Biopsy - allows histopathological evaluation, immunophenotyping and cytogenetics • Staging - Ann-Arbor
Define multiple myeloma
- Haematological malignancy characterised by proliferation of plasma cells resulting in bone lesions and the production of a monoclonal immunoglobulin (paraprotein, usually IgG or IgA)
- Classification based on immunoglobulin product
RF of multiple myeloma (3)
- Family history
- Exposure to petroleum products and radiation
Epidemiology of multiple myeloma
- Peak incidence: 70 yrs
* Afro-Caribbean > White People > Asians
S/s of multiple myeloma (20+)
• May be an INCIDENTAL finding on routine blood tests • Bone Pain o Usually in the back and ribs o Sudden and severe bone pain may be caused by a pathological fracture o May get symptoms of hypercalcaemia • Infections - often recurrent bacterial • General o Tiredness o Thirst o Polyuria – renal impairment due to light chain deposition o Nausea o Constipation o Mental change (due to hypercalcaemia) • Hyperviscosity o Bleeding o Headaches o Visual disturbance
- Pallor
- Tachycardia
- Flow murmur
- Signs of heart failure
- Dehydration
- Purpura
- Hepatosplenomegaly
- Macroglossia
- Carpal tunnel syndrome
- Peripheral neuropathies
Mnemonic to help remember things in multiple myeloma.
MULTIPLE MYELOMA = CRAB Calcium is high Renal impairement Anaemia Bone pain and lesions
Dx criteria for multiple myeloma
- High suspicion if bone/back pain that is not improving
- Diagnostic criteria:
1. Monoclonal protein band in serum/urine electrophoresis
2. High plasma cells on marrow biopsy
3. Evidence of end-organ damage from myeloma e.g. hypercalcaemia/renal insufficiency/anaemia
4. Bone lesions – x-rays
Ix for multiple myeloma
• Bloods
o FBC - low Hb, normochromic normocytic anaemia
o High ESR (and possible high CRP)
o U&Es - high creatinine, high Ca2+
o Normal ALP
• Blood Film
o Rouleaux formation with bluish background (suggests high protein)
• Serum or Urine Electrophoresis o Serum paraprotein o Bence-Jones protein (monoclonal immunoglobulin light chain that's found in the urine and suggests multiple myeloma) • Bone Marrow Aspirate and Trephine o High plasma cells (usually > 20%) • Chest, Pelvic or Vertebral X-Ray o Osteolytic lesions without surrounding sclerosis e.g. pepper pot skull o Pathological fractures
