Lymphoid Malignancy Flashcards
What is leukaemia cancers of?
Lymphoid origin
Presentation of leukaemia
Enlarged lymph nodes (lymphadenopathy) OR with extranodal involvement OR with bone marrow involvement Systemic symptoms - weight loss (>10% in 6 months) - fever - night sweats - pruritis - fatigue
What test tells us the type of leukaemia?
Biopsy (lymph node, bone marrow etc)
What test tells us where the leukaemia is?
Clinical exam
imaging (e.g. CT)
What is a broad difference of Hodgkin Lymphoma vs Non-Hodgkin Lymphoma?
Hodgkin = specific disease
Non - Hodgkin = everything else (approx. 50 subtypes)
Lymphoproliferative disorders
Acute lymphoblastic leukaemia (ALL)
Chronic lymphocytic leukaemia (CLL)
Hodgkin Lymphoma
Non-Hodgkin Lymphoma (NHL)
Types of Non-Hodgkin Lymphoma (NHL)
High grade
- diffuse large B cell lymphoma
Low grade
- follicular, marginal zone
What is acute lymphoblastic leukaemia (ALL)?
Neoplastic disorder of lymphoblasts
How is ALL diagnosed?
By > 20% lymphoblasts present in bone marrow
Who does 75% of cases of ALL occur in?
Children < 6 y/o
How much of ALL is B cell lineage?
75-90%
Presentation of ALL
2-3 week history of bone marrow failure +/- raised white cell count or bone/joint pain
Infection
Sweats
Treatment of ALL
Induction chemo to obtain remission Consolidation therapy CNS directed treatment Maintenance therapy for 18 months Allogenic stem cell transplantation (if HIGH RISK) newer therapies - Bispecific T cell engagers - CAR
S/Es of T cell immunotherapy
Cytokine release syndrome
Neurotoxicity
Presentation of cytokine release syndrome
Fever
Hypotension
Dyspnoea
Presentation of neurotoxicity
Confusion with normal conscious level seizure headache focal neurology coma
Poor risk factors for ALL
Increasing age increased WCC immunophenotyped (more primitive forms) Cytogenetics/molecular genetics (t(9;22), t(4;11)) Slow/poor response to treatment
Prognosis of ALL
Adults - complete remission 78-91% - leukaemia free survival a 5 y - 30-35% Children - 5 yr overall survival 90% - Poor risk patients (slow response to induction or Philadelphia positive) 5 yr overall survival 45%
What is the commonest leukaemia worldwide?
Chronic Lymphocytic Leukaemia (CLL)
Which gender gets CLL?
M > F 2:1
Where is CLL rare?
Far east
Presentation of CLL
Often asymptomatic at presentation Bone marrow failure - anaemia - thrombocytopenia Lymphadenopathy Splenomegaly (30%) Fever and sweats (<25%) Hepatomegaly
Diagnosis of CLL
Blood > 5 x10 9/L lymphocytes Bone marrow > 30% lymphocytes Characteristic immunophenotyping - B cell markers (CD 19, 20, 23) - CD5 positive
Associated findings of CLL
Immune Paresis (loss of normal immunoglobulin production) Haemolytic anaemia
Binet staging of CLL
Stage A - < 3 lymph node areas - same survival as matched controls Stage B - 3 or more lymph node areas - survival approx. 8 years Stage C - stage B and anaemia or thrombocytopenia - survival approx. 6 years
Indications for treatment of CLL
Progressive bone marrow failure Massive lymphadenopathy Progressive splenomegaly Lymphocyte doubling time < 6 months or > 50% increase over 2 months Systemic symptoms Autoimmune cytopenias
Treatment of CLL
Often nothing - watch and wait Cytotoxic chemotherapy e.g. fludarabine Monoclonal antibodies e.g. rituximab Novel agents - bruton tyrokinase inhibitor - PI3K inhibitor - BCL-2 inhibitor
Poor prognostic markers of CLL
Advanced disease (Binet Stage B or C)
Atypical lymphocytes morphology
Rapid lymphocyte doubling time < 12 months
CD38 + expression
Loss / mutation p53; dell 11q23 (ATM gene)
Unmutated IgVH gene status
Presentation of lymphoma
Lymphadenopathy / Hepatosplenomegaly
Extranodal disease
B symptoms
Bone marrow involvement
Assessment of staging of lymphoma
Lymph node biopsy
CT scan
Bone marrow aspirate
Trephine
Non-Hodgkin Lymphoma is classified according to what?
Lineage - B or T cell Grade of disease - high grade - low grade Histological features of disease
What is the majority of lineage of Non-Hodgkin’s lymphoma?
B cell in origin
Features of high grade Non-Hodgkin Lymphoma
Aggressive
fast growing
requires combination chemotherapy
Can be cured, but again varies widely
Features of low grade Non-Hodgkin lymphoma
Indolent, often asymptomatic
Responds to chemo but incurable
Medial survival varies by subtype
Specific disease entities of Non-Hodgkin Lymphoma
Diffuse large B cell lymphoma
Follicular lymphoma
What is the commonest subtype of lymphoma?
Diffuse large B cell lymphoma
Is diffuse large B cell non-hodgkins lymphoma high grade or low grade?
High grade
Is follicular lymphoma a high grade or low grade lymphoma?
Low grade
Who gets Hodgkin Lymphoma?
1st peak 15 - 35 y/o
2nd peak later in life
M > F 1.9:1
Associations of Hodgkin lymphoma
Epstein Barr virus
Familial
Geographical clustering
Treatment of Hodgkin Lymphoma
Combination chemotherapy (ABVD) \+ / - radiotherapy Monoclonal antibodies (anti-CD30) Immunotherapy (checkpoint inhibitors)
What is used in Hodgkin Lymphoma to assess response to treatment and limit use of radiotherapy?
PET scan
What does the bone marrow produce?
Granulocytes
Red cells
Platelets
Precursor lymphocytes
The granulocytes, red cells and platelets are released into where? Are they precursor cells or ready to work?
Blood
Ready to work
What kind of immune system are the precursor lymphocytes involved in?
Adaptive immune system
What do B precursor lymphocytes become?
Plasma cells that produce specific antibodies
Where are B precursor lymphocytes found when they are maturing?
The pale bit of a lymph node
What cells are over proliferating in AML?
Myeloid progenitor cells / myeloblast
What do myeloproliferative disorders involve?
Mutations after differentiation but still uncontrolled proliferation
What cells are over proliferating in ALL?
Lymphoid progenitor cells / lymphoblasts
What are the lymph organs?
Lymph nodes Spleen Tonsils Adenoids MALT
What structures are involved in MALT?
Gut
Bronchus
Salivary glands
Where does the mutation occur to give lymphoma?
Post bone marrow
When does leukaemia occur?
When bone marrow spills into the blood
What blood changes are likely to occur in bacterial meningitis?
Increase in neutrophils
What blood changes are likely to be seen in leukaemia?
Blasts
Pancytopenia
What is the bleeding time?
Formation of a platelet clot
What is the clotting time?
Formation of a thrombin clot
What is the normal lymphoblast count?
0
What test would differentiate between AML and ALL?
Flow cytometry
What would be found in the differences between AML and ALL?
Different antigens on the lymphoblasts
Why do blood cells flow well on flow cytometry?
They are single cells
What does cytogenetics tell us?
If there are poor prognostic markers
What results in cytogenetics indicate high risk groups for ALL?
t (9;22)
t (4;11)
What is the classification of weight loss as a B symptom?
> 10% weight loss in 6 months
Lymphoblasts vs lymphocytes on blood film?
Lymphoblasts much bigger on blood film
What type of cells are classic on a blood film of CLL?
Smudge cells
What type of cells are involved in CLL?
Naïve mature lymphocytes
What can CLL present as? Why?
Lymphoma or Leukaemia
Can have lymphocytosis in blood and in bone marrow OR can be just in lymph nodes
As soon as there is lymphocytosis in the blood, what is the condition?
Leukaemia
Lymphocytosis just in the lymph node is known as what?
Small lymphocytic lymphoma
When to treat CLL?
Uncontrolled cytopenias Autoimmune haemolytic complications B symptoms Bulky lymph nodes Splenomegaly
What is another name for DAT?
Coombs test
What is a cyst on the side of the neck called?
Brachial cyst
What is a cyst on the midline of the neck called?
Thyroglossal cyst
Which lymphomas are common in the young?
Hodgkins
Burkitts
What is Hodgkins lymphoma defined by?
A cell in the lymph node
Why can Hodgkins lymphoma have a bacterial look about it?
As cytokines are produced - making you think it may be bacterial
What do lymphomas often have (to do with blood)?
Anaemia
If miss the cell in a hodgkins node, what is the next test?
An excision biopsy
Key diagnostic test for HL
Nodal biopsy
When would a PET scan light up, not related to malignancy?
Site of surgery
Complication of burkitts lymphoma which has been treated with chemotherapy
Tumour lysis syndrome
Hodgkins lymphoma can cause severe pain when doing what? How many people does this occur in?
Drinking alcohol
In 10% of patients
What type of cells are present in HL?
Reed-Sternberg cells
What can CLL turn into, what is this called and what is the presentation?
High grade lymphoma (fast growing diffuse large B cell non hodgkins lymphoma) Called Richters transformation Presentation - patient becomes unwell VERY suddenly - lymph node swelling - fever without infection - weight loss - night sweats - nausea - abdominal pain
Type of HL with worst prognosis
Lymphocyte depleted
Type of HL with best prognosis
Lymphocyte predominant
What may myelodysplasia progress to?
AML
Most common histological type of HL
Nodular sclerosing
Poor prognosis factors for HL
Age > 45 Male Stage IV disease Haemoglobin < 10.5g/L Lymphocyte count < 600/ul or < 8% Albumin < 40 WBC > 15,000
What does Burkitts lymphoma look like on lymph node biopsy?
‘Starry sky’ appearance
What is Burkitts lymphoma associated with?
EBV
What malignancy may present with asymmetrical spreading lymphadenopathy?
HL
What gene translocation is related to Burkitts lymphoma?
C-myc translocation
Complication of CLL
Recurrent infection (due to hypogammaglobulinaemia)
