Lymphoma Flashcards
Where do different types of lymphomas occur?
Depends on stage of B cell maturation :
- germinal centre proliferation = follicular lymphoma
- differentiation = classical Hodgkin lymphoma
- mature cells = ABC-DLBCL
What cell types undergo lymphomas?
90% B cells
10% T and NK cells
How are lymphomas classified?
- non-Hodgkin are vast majority
- also get Hodgkin
- low grade vs. high grade/aggressive
- B cell vs T cell/NK
Features of non-Hodgkin lymphomas
- follicular
- diffuse large B cell (germinal centre type and activated B cell type)
Types and examples of Hodgkin lymphomas
CLASSICAL = - nodular sclerosing - mixed cellularity - lymphocyte rich - lymphocyte deplete vs rarer = - nodular lymphocyte predominant
Associations with lymphoma
- viral infections = EBV, HIV, Hep C, TLV, HHV 8
- Bacterial infections = H. pylori, chlamydia psittaci
- inflammatory conditions = coeliac disease, Sjogren’s syndrome
- medical exposure = ionising radiation, benzene, immunosuppression
What is the patient pathway?
- referral from GP/hospital
- look for signs and symptoms
- investigations (blood tests, biopsy, CT imaging, specific tests so diagnosis is made)
- treatment (depends on late effects, fertility, psychosocial, prognosis)
What are some disease specific treatments?
- curative = transplantation, novel agents
- clinical trial
What are some non-disease specific treatments?
- symptoms relief
- palliative
(steroids, immunotherapy, chemo, radio, supportive)
Symptoms of lymphoma
- fever >38
- night sweats
- > 10% weight loss
- may be asymptomatic
- fatigue
- pain/swelling from lymphadenopathy
- pruritus (itching)
Signs on exam of lymphoma
Hepatomegaly
Lymphadenopathy (neck, axillae, abdo, groin)
- skin (pallor, jaundice)
- organ specific (enlargement)
Investigations of lymphoma
FBC blood film high WBC = lymphoma - immunophenotyping - LDH, uric acid = raised as high cell turnover and breakdown of cells (tumorlysis) - serum electrophoresis B2 macroglobulin serology = hep B, C, HIV - biopsy - imaging = CT for where there are masses or CT PET (radioactive in whole body to see where) - MRI if CNS involvement or lumbar puncture - USS abdominal?
Types of biopsy for lymphoma
- fine needle aspirate (often don’t get enough cells and info on architecture)
- core biopsy taking more of material out
- excision lymph node biopsy is gold standard
- may do biopsy of bone marrow instead of lymph node
Classification of Lymphomas
- stage 1 to 4
- 1) 1 localised lymph node above or below diaphragm
2) more than 1 on one side of diaphragm
3) on both sides of diaphragm
4) bone marrow and extra nodal involvement
A or B
A - no associated symptoms
B - unexplained fever, night sweats, weight loss >10% in last 6 months
Genetic hallmark of follicular lymphoma
translocation 14:18
use CD20 B cell for staining
use CD3 T cell for staining
CD10 positive!
Diagnostic characteristics of stage 4 A follicular lymphoma
Blood film - cleaved lymphocytes Biopsy - darker smaller centrocytes - larger paler centroblasts with nucleolus (centroblasts = follicular) - effaced with tumour cells Bone Marrow - paratrabecular infiltration of small lymphocytes (bone marrow involvement = sage 4)
- A as no B symptoms
Treatment for follicular lymphoma
variable depending on severity/burden = asymptomatic/mild symp/high tumor burden
- watch and wait
- non chemo or chemo?
- rituximab
- radioimmunotherapy
Pathophysiology of follicular lymphoma
- pre B cells in bone marrow
- translocation of 14:18 but also secondary genetic alterations
- migration into germinal centre with accumulation of these 2ry events
Features of follicular lymphoma
- 65 years
- low grade, hard to cure
- B symptoms uncommon
- most stage 3 or 4
- high risk survival is 50% and low risk is 90%
Diagnostic features of diffuse large B cell lymphoma
- normal blood film with normal segmented neutrophils and red cells
Biopsy - centroblasts normal large and non cleaved
- lack of other cells or inflamm infiltrate
Treatment of diffuse large B cell lymphoma
Scoring system dependent
- 4 categories of system which are age, LDH, stage, performance status, extra-nodal sites
- standard treatment regime = 6 cycle intense regime RCHOP (rituximab, cyclophosphoramide, doxorubicin, vincristine and prednisolone)
- CNS prophylaxis in high risk disease
Pathophysiology of diffuse large B cell lymphoma
heterogeneous differential gene expression =
- germinal centre type (better prognosis via BCL2 pathway)
- activated B cell type (worse prognosis via NF-Kappa B pathway)
Features of diffuse large B cell lymphoma
- 64 years
- common B symptoms
- aggressive high grade
- potentially curable
- commonly stage 1-2
- low risk 90% survival, high 50%
Diagnostic features of Classical Hodgkin Lymphoma (nodular sclerosing type)
- normal blood film Biopsy - reed Sternberg cell with hourglass appearance - inflammatory infiltrate/fibrosis - eosinophil - lacunar cell CT PET disease just above diaphragm - CT very sensitive for bone marrow involvement
Treatment of Hodgkin lymphoma
stratify again
- limitied, intermediate and advanced stage
- based on RF and stage of disease
- 2 cycles ABVD treatment = doxorubicin, bleomycin, vinblastine, dacarbazine
- then PET scan, if positive still then escalate chemo but negative continue chemo as it is
- involved node radiotherapy on top
Pathophys of Hodgkin lymphoma
- germinal centre cell
- mutation/transforming event
- RS cell and loss of apoptosis and cytokines = inflammatory/fibrosis/eosinophillia/macrophage activation
Hodgkin Lymphoma Features
Bimodal age distribution Aggressive/curable 40% presence of B symptoms Stage 1 and 2 most common 80-90% cured
How do you assess response to treatment?
at 6-8 weeks clinical assessment and PETCT scan
- 3 monthly for first 1-2 years, then 6 monthly, yearly from 5 years
Example of classes of different target therapies
- anti CD20 mAB
- HDAC inhibitors
- alkylators
- BCL-2 inhibitors
- checkpoint inhibitors
- proteasome inhibitors
- Kinase inhibitors
