Malignancy Flashcards
What is leukaemia?
Haematological malignancies where there is malignant monoclonoal expansion of a single cell line
What are risk factors for leukaemia?
Irradiation
Chromosomal abnormalities (Down syndrome)
Drugs (cytotoxic - cyclophosphamide, melphalan)
What are the types of leukaemia?
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Chronic lymphocytic anameia
Chronic myeloid leukaemia
What are features of aggressive disease in leukaemia?
Acute onset, rapid progression of symptoms
Large cells with high nuclear:cytoplasmic ratio
Prominent nucleoli
Rapid proliferation
What is acute leukaemia?
Malignant proliferation of abnormal progenitors (blasts) with arrested maturation
The abnormal cells replace the normal cells resulting in reduction in bone marrow function
In what circumstance can acute myeloid leukaemia arise secondary to something else?
Can arise secondary to treatment with chemotherapy fro other malignancies
What are the common sites of infiltration outside the bone marrow in acute lymphoblastic leukaemia?
CNS
Lymph nodes
Liver/spleen
Testicles
What are the common sites of infiltration outside the bone marrow in acute myeloid leukaemia?
Skin Gums Lymph nodes Liver/spleen (no CNS)
What is the most common childhood cancer?
Acute lymphoblastic leukaemia
What age does acute lymphoblastic leukaemia most commonly occur?
2-8
What age does acute myeloid leukaemia most commonly occur?
Adults
What is the presentation of acute leukaemia?
Symptoms of marrow failure - anaemia (fatigue) - thrombocytopenia (braising, bleeding) - leukopenia (infections) Bone pain Lymphadenopathy Hepatosplenomegaly
Which infections are commonest in acute leukaemia?
Throat and ear
Mostly bacterial
What are the symptoms of extra-marrow infiltration in acute lymphoblastic leukaemia?
CNS - cranial nerve palsies, meningism
Liver/spleen - abdominal pain, swelling
Orchidomegaly
What are the symptoms of extra-marrow infiltration in acute myeloid leukaemia?
Gum hypertrophy
Liver/spleen - abdominal pain, swelling
What do blood tests show in acute leukaemia?
Normocytic, normochromic anaemia
Neutropenia
Thrombocytopenia in AML
Leucocytosis - high WCC (variable in AML)
What does a blood film show in acute lymphoblastic leukaemia?
> 20% blasts
What do blasts cells look like?
High nuclear:cytoplasm ratio
Prominent nucleus
Abnormal granulation
What does a blood film show in acute myeloid leukaemia?
> 20% blasts
Auer rods
What are Auer rods?
Cells seen in acute myeloid leukaemia - diagnostic
What is required for a definitive diagnosis of acute leukaemia?
Immunophenotyping
What investigation is used to look for infiltration in acute leukaemia?
CT CAP (chest, abdomen, pelvis) or CT head
What is the management for acute lymphoblastic leukaemia?
Chemotherapy
Long duration, curative intent
What is the cure rate for acute lymphoblastic leukaemia?
90% in children
How long is chemo given in acute lymphoblastic leukaemia?
Maintenance chemo is given for 2-3 years
What is the treatment for acute myeloid leukaemia?
Intense chemotherapy
What chemotherapy drugs can be given in acute myeloid leukaemia?
Danorubicin
Cytarabine
What is neutropenic fever?
Neutropenia increases severity and duration of infections so in neutropenia gram negative bacteria can cause life-threatening sepsis in neutropenic patients that comes on quickly and with great severity
Bacterial or fungal
What is the management of neutropenic fever?
Quick clinical assessment and culture of fluids
Start on broad spectrum antibiotics before cultures come back
What are the complications of chemotherapy?
Nausea and vomiting Hair loss Liver, renal dysfunction Tumour lysis syndrome Infection Late - loss of fertility, cardiomyopathy
What is tumour lysis syndrome?
Potentially deadly condition presenting in the first round of chemo
hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia
What is given as protection against tumour lysis syndrome?
IV allopurinol prior to and in the first days of chemo
What are the blood test results in chemotherapy?
High potassium
High phosphate
Low calcium
What are the complications of tumour lysis syndrome?
Cardiac arrhythmias
Seizures
Sudden death
When should you suspect a fungal infection in neutropenic fever?
Prolonged neutropenia and persisting fever unresponsive to antibiotics
Which protozoal infection can cause neutropenic fever, and which leukaemia is thus more common in?
Pneumocystis jiroveci pneumonia
Acute lymphoblastic anaemia
What is chronic lymphocytic leukaemia?
Expansion of a B cell population
Proliferation of abnormal progenitors with no maturation block
So too many lymphoid cells
What are the lymphoid cells?
T cells
B cells
Plasma cells
NK cells
What are the myeloid cells?
Erythrocytes
Platelets
Granulocytes (basophils, neutrophils, eosinophils)
Macrophages
What is the most common leukaemia?
Chronic lymphocytic leukaemia
What is the median age of presentation of chronic lymphocytic leukaemia?
70
What condition is chronic lymphocytic leukaemia associated with?
Autoimmune haemolytic anaemia
Idiopathic thrombocytic purpura
What is the presentation of chronic lymphocytic leukaemia?
Can be asymptomatic Symptoms of marrow failure (anaemia, bleeding, infections) B symptoms - night sweats - weight loss Lymphadenopathy
What do blood tests show in chronic lymphocytic leukaemia?
Normochromic normocytic anaemia
Low neutrophils, low platelets
High WCC - high lymphocytes
What does electrophoresis show in chronic lymphocytic leukaemia?
Hypogammaglobinaemia
What does a blood film show in chronic lymphocytic leukaemia?
Smear/smudge cells
No blasts
What is the progression of chronic lymphocytic leukaemia?
Rule of 3rds
- 1/3 don’t progress
- 1/3 will progress with time
- 1/3 actively progressing at presentation
What is the management of chronic lymphocytic leukaemia that is not actively progressing?
Observation
What is the management of chronic lymphocytic leukaemia that IS actively progressing?
Chemotherapy
- cyclophosphamide, fludarabine
+/- stem cell transplant
When is chemotherapy indicated in chronic lymphocytic leukaemia?
Marrow failure
Massive or progressive splenomegaly or lymphadenopathy
Progressive - doubling of lymphocyte count in less than 6 months
Systemic symptoms (fever, night sweats, weight loss)
Haemolysis
What can chronic lymphocytic leukaemia progress to?
Lymphoma
If chronic lymphocytic leukaemia has progressed to another condition, what investigation is done?
Lymph node biopsy
What is chronic myeloid leukaemia?
Considered to be a myeloproliferative disorder where there is clonal expansion of a stem cell population producing myeloid cells
Proliferation of abnormal progenitors but not maturation block - so too many myeloid cells
What is pathognomonic for chronic myeloid leukaemia?
Philadelphia chromosome
9;22
What is the philadelphia chromosome?
Pathognomonic for chronic myeloid leukaemia
Resultant gene is BCR-ABL1
Produces abnormal tyrosine kinase that drives stem cell proliferation
What are the phases of chronic myeloid leukaemia?
Chronic - 3-5 years of myeloproliferation with sparing of maturation
Accelerated - maturation begins to slow an symptoms worsen
Blast crisis - maturation fails and immature blasts accumulate (essentially becomes AML)
Who does chronic myeloid leukaemia most commonly affect?
40-60 year olds
What is the presentation of chronic myeloid leukaemia?
Slow onset Weight loss Fatigue Fever Night sweats Gout Abdominal pain/bloating, early severity (splenomegaly)
Why does gout present in chronic myeloid leukaemia?
Increased rate due to increased cell turnover
What do blood show in chronic myeloid leukaemia?
High urate
Normochromic, normocytic anaemia
High WCC (neutrophils, basophils, eosinophils)
What does a bone marrow biopsy show in chronic myeloid leukaemia?
Hypercellular marrow
What is the management of chronic myeloid leukaemia?
Tyrosine kinase inhibitors - imatinib
What effect do tyrosine kinase inhibitors have on chronic myeloid leukaemia?
Not curative but completely control the disease
What is lymphoma?
Malignant proliferations of lymphocytes that accumulate in lymph nodes causing lymphadenopathy
What are risk factors for lymphoma?
Idiopathic Immunosuppression - HIV, inherited immunodeficiency Autoimmune disorders Infections - EBV, H pylori Genetic predisposition Environment
What is the presentation of lymphoma?
Lymphadenopathy B symptoms - fever - night sweats - weight loss Lethargy Itch without rash Alcohol-induced pain Compression, infiltration and extra-modal disease
What is the character of lymphadenopathy in lymphoma?
Painless, soft, rubbery, persistent
What is the degree of weight loss seen in lymphoma?
10% over a 6 month period
What are the symptoms of compression, infiltration and extra-modal disease in lymphoma?
Renal failure Superior vena cava obstruction - SOB - Dilated neck veins - Facial swelling Effusions Marrow failure
What is the diagnostic investigation for lymphoma?
Lymph node biopsy
What is the staging system for lymphoma?
Ann Arbor staging
Stage 1 - one lymph node or extra-lymph node area
Stage 2 - 2 or more lymph nodes on one side of the diaphragm
Stage 3 - 2 or more lymph nodes on both sides of the diaphragm
Stage 4 - disseminated or multiple extra-nodal area involvement (including bone marrow)
What do blood tests show in lymphoma?
Raised lactate dehydrogenase (prognostic not diagnostic)
Lymphocytosis in CLL
What is Hodgkin’s lymphoma?
Malignant proliferations of B cells
What is Hodgkin’s lymphoma characterised by?
Reed-Steinberg cell
What do reed-steinberg cells look like?
2 nuclei
Owls (salad fingers)
What is the most common subtype of Hodgkin’s lymphoma?
Nodular sclerosing
What is the spread of Hodgkin’s lymphoma?
Orderly lymph node spread
What features of lymphoma presentation are specific to Hodgkin’s lymphoma?
Lymph node pain on drinking alcohol
Who presents most commonly with Hodgkin’s lymphoma?
Young adults (15-30) Or elderly
What is the management of Hodgkin’s lymphoma?
Multi-agent chemotherapy
- Adriamycin, bleomycin, vincristine, dacarbazine
What are complications of Hodgkin’s lymphoma treatment?
Bleomycin can cause pneumonitis
Associated with marrow suppression and risk of AML
What is the second line treatment for Hodgkin’s lymphoma?
Immunotherapy/stem cell transplantation
What is non-Hodgkin’s lymphoma?
Diverse group go lymphomas that are not Reed-Steinberg positive
Which is the more common non-Hodgkin’s lymphoma - B or T cell lymphoma?
B cell
Are B cell lymphomas generally low or high grade?
Low grade
What is a common high grade non-Hodgkin’s lymphoma?
Diffuse large B cell lymphoma
What are risk factors for non-Hodgkin’s lymphoma?
Immunosuppression
Infection - HIV, EBV, malaria, hepatitis C, H pylori
What are some features of Burkitt lymphoma?
Fastest growing
EBV and HIV association
Beware of tumour lysis
What are symptoms that can be caused by extra-nodal involvements in non-Hodgkin’s lymphoma?
CNS Spleen - splenomegaly Marrow - marrow failure Skin - papular rash, usually T cell Waldeyer's ring - difficulty breathing
Who usually presents with non-Hodgkin’s lymphoma?
Usually older patients but can vary
What is the management of non-Hodgkin’s lymphoma?
R-CHOP
(Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Vinicristine, Predisolone)
Steroids
What is the role of steroids in management of non-Hodgkin’s lymphoma?
Can be used in emergency management of suspected lymphoma but starting steroid before biopsy can cause cell necrosis and distort cellular and tissue architecture to confuse the diagnosis - do biopsy before starting steroids
