Haematology 12 - Lymphoma 2 Flashcards
What are the investigations you would do for suspected lymphoma?
**remember about HIV and HTLV tests which can be contributing factors to certain subtypes of lymphoma
**also HBV as treatment for lymphoma (immunosuppression) can lead to reactivation of the virus
What are the clinical presentations of lymphoma?
- painless lymphadenopathy, enlarging
—> palpable mass OR
–> extrinsic compression of tubes - bile duct, ureter, bowels etc.
- infiltration of organs eg CNS, skin, liver failure
- recurrent infections- tumour of immune cells
- constitutional symptoms if rapidly enlarging and spreading
How do Reed Sternberg cells appear on the blood film?
Giant cell surrounded by reactive eosinophils
**look like owl’s eyes
Classification of lymphoid malignancies
What is the age distribution of Hodgkin’s lymphoma?
20-29: mostly affects females. mostly of the nodular sclerosing type
Elderly: M=F
Classification of HL
Key one is “nodular sclerosing” classical HL- this is the one that affects young people more
What are the symptoms of Hodgkin’s lymphoma?
Painless lymphadenopathy, that becomes painful on drinking alcohol
Constitutional B symptoms- fever, night sweats, weight loss
If advanced lymphadenopathy, may –> obstructive symptoms
What is the cause of constitutional B symptoms in lymphoma?
Hyper-catabolic state
Which investigation is used to diagnose hodgkin’s lymphoma, and which diagnosis is used for staging?
Diagnosis: LN biopsy
Staging: FDG-PET
Recall the different stages of lymphoma (Ann arbor staging)
I: one group of nodes
II: >1 group of nodes, on one side of the diaphragm
III: Nodes on both sides of the diaphragm
IV: extranodal spread
Then:
A: no B symptoms
B: one/ any of fever/ weight loss/ night sweats
**initially developed for Hodkin’s lymphoma but also now used in NHL
Which subtype of lymphoma is most likely to affect young women?
Nodular sclerosing classical Hodgkin’s
*usually presents with a mediastinal mass
What is the mainstay of tretament for HL?
Chemotherapy.
aka ABVD chemotherapy
A- adriamycin
B- bleomycin
C- vincristine
D- dacarbazine
can give radiotherapy as an adjunct but it is not sufficient on its own.
What type of chemotherapy is used in Hodgkin’s lymphoma?
ABVD
**Hodkin’s lymphoma is the first cancer that was treated with chemotherapy
After how many cycles of chemotherapy for Hodgkin’s lymphoma should the FDG-PET be repeated to check response?
2
What is the risk of giving radiotherapy for Hodgkin’s lymphoma?
It produces a lot of collateral damage (eg risk of breast cancer, leukaemia/MDS, lung or skin cancer), and when given alongside chemotherapy increases the risk of secondary malignany significantly
What is the prognosis of hodkin’s lymphoma?
- in the first 10 years the greatest risk is posed by recurrence of lymphoma
- in the next few years the greatest risk is posed by:
a) secondary malignancy
b) cardiovascular events
i. e. the consequences of giving high dose chemotherapy and radiotherapy
What are the most common forms of NHL?
- Follicular NHL - low grade
- Diffuse large B cell - high grade
Recall the clinical severity of 3 different NHL subtypes
- Burkitt’s lymphoma: very aggressive
- Follicular lymphoma- indolent
- Gastric MALT- responsive to antibiotic therapy
Recall 4 prognostic markers in NHL
Performance status
- LDH and B2 microglobulin
- HIV serology
- Hep B serology
How aggressive is diffuse large B cell non-Hodgkin’s lymphoma?
High grade
**this is diff from Burkitt’s lymphoma lol
How is diffuse large B cell non-Hodgkin’s lymphoma treated?
R-CHOP and immunotherapy
R- rituximab
C- cyclophosphamide
O -
P
How aggressive is follicular non-Hodgkin’s lymphoma?
Indolent
How does the median survival and response to chemotherapy vary between the different grades of NHL
As the tumour becomes more aggressive, the median survival decreases (without treatment), but response to treatment (i.e. “curability”) increases
with the indolent tumours you tend to have more relapses and longer clinical course
What mutation is commonly associated with follicular non-Hodgkin’s lymphoma?
t(14;18)
Translocation of Bcl2 –> oncogene
Which subtype of non-Hodgkin’s lymphoma is associated with chronic H. pylori?
Extra-nodal marginal zone lymphoma
Gastric Marginal zone lymphoma
What are the symptoms of extra-nodal marginal zone lymphoma?
Epigastric pain, ulceration and bleeding
How aggressive is enteropathy-associated non-hodgkin’s lymphoma?
Very aggressive
What is the main association of enteropathy-associated non-hodgkin’s lymphoma?
Coeliac
What finding on a blood film is typial of CLL?
Smear/ smudge cells
Recall the surface markers of intermediate B cells vs mature B cells vs CLL mature B cells
Intermediate B cell: CD5 positive
Mature B cell: CD19 positive
Mature CLL B cell: CD5 positive and CD19 positive i.e. they aberrantly express CD5 which should not be seen in mature B cells
What are the 2 staging methods that can be used in CLL?
Rai staging
Binet staging
Is CLL a pre- or post-germinal centre malignancy?
50% pre, 50% post
**rmb it’s a malignancy of naive B cells - i.e. they can still be pre or post germinal centre
How can pre- and post-germinal centre CLL be differentiated?
Look for VH mutation status - unmutated has worse prognosis than mutated
Which one has worse prognosis: pre or post germinal centre CLL?
Pre (unmutated) is worse prognosis
Which mutation is associated with a particularly poor prognosis in CLL?
17p deletion (TP53)
What is Richter’s syndrome?
Rare transformation of CLL to high grade lymphoma
Often presents with New-onset B symptoms on a background of CLL
- fever
- elevated serum levels of LDH
- rapidly enlarging lymph nodes
High grade lymphoma - diffuse large b cell lymphoma. treat it as you would for DLBL (R-CHOP)
How is CLL managed initially?
Like follicular NHL it is an indolent disease so initial approach is watch and wait.
What are the indications to move on from watch and wait approach for CLL and treat it?
If treatment is indicated for CLL what is it?
1) Good prognosis - TP53 intact
- regular immuno-chemo-therapy (systemic)
2) Bad prognosis - TP53 mutation (17q deletion)
- TARGETED THERAPY REQUIRED
eg IBRUTINIB,
Which markers are expressed by CLL?
CD19 (normal)
CD5 (abnormal)
CD23 (abnormal)
What is hairy cell leukaemia?
a subtype of CLL
occurs in middle aged men
fine hair like projections seen on tumour cells
Prognostic markers of CLL
- Clinical
- based on burden of malugannt cells- determined via staging (Rai or Binet) - Molecular
- cd38: poor prognosis
- TP53 deletion - most important prognostic factor
- VH mutation status (immunoglobulin variable heavy chain): UNMUTATED HAS WORSE PROGNOSIS (i..e pre germinal centre has worse prognosis)
How can young patients be cured of CLL?
allogeneic stem cell transplant
chimeric antigen receptor t cell therapy (CAR-T)
What is a significant cause of death in CLL?
infections (rmb they have low serum immunoglobulin levels)
- this is why you need aggressive prophylaxis of infections
what is a long term side effect of rituximab?
can cause reactivation of hepatitis C virus
which is the most common lymphoma in the UK?
diffuse large b cell lymphoma
CLL not NHL
**because CLL is more common in this age group compared to lymphoma**
This is due to underlying EBV
underlying EBV can lead to recurrent tonsillitis
EBV also causes increased proliferation of lymphocytes - lymphocytosis
EBV also causes neutropaenia (mechanism unknown)
