Lecture 10: Hodgkin's Lymphoma Flashcards
ToD: Lymphoma = Leukaemia
False
What is lymphoma?
Cancer of WBC. Form solid tumours in lymphatics and reticuloendothelial system. Depending on the spread of the lymphoma, their WBC count may look normal.
Which WBC does lymphoma specifically affect?
B-cell
What cell are Reed-Sternberg cells derived from?
B-lymphocytes that don’t express an antibody
What two CD receptors make it easier to identify Reed-Sternberg cells?
CD30 and C15 receptors
Where do Reed-Sternberg cells originate from?
The germinal centres of lymphatic tissue
Why is it the germinal centres that produce Reed-Sternberg cells? (2 marks)
Germinal centres are where all the proliferation of the cell and VDJ recombination occurs
Because germinal centres are found in the lymph node, lymph nodes are able to suppress apoptosis. This fact is made worse if there is malignancy in a lymph node.
What are the histological features of a Reed-Sternberg cell? (2 points)
Large cells (50 microns)
Bi-lobed/ multinucleated cells
What are the three clinical symptoms of Hodgkin’s Lymphoma?
Lymphadenopathy
Night sweats
Weight loss
What is lymphadenopathy?
Swelling of the lymph nodes
Why does weight loss occur because of HL?
Rapid proliferation causes the tumour to start sapping as many nutrients as possible, starving the rest of the body.
What virus is associated with HL?
Epstein-Barr virus
What percentage of HL patients are found with EBV DNA?
90%
Describe why the EBV increases the chance of HL?
Can transform lymphocytes into a more cancerous version of itself.
If the EBV genes are inserted in the wrong place within the Host’s DNA then it can act as a huge disruptor during transcription and translation.
This can cause the cell to continue proliferating because the stop codon has stopped working.
Which 3 EBV genes are associated with malignancy?
LMP1
LMP2a
EBNA1
What are some non-specific tests for HL?
Full blood count
Serum lactate dehydrogenase
Liver function tests
What are some specific tests for HL?
Lymph node biopsy
Immunohistochemistry
Why can we use lactate dehydrogenase levels as a non-specific test?
The environment in the tumour becomes low in oxygen. To produce energy the lymphoma relies on glycolytic respiration.
Lactate dehydrogenase is released when tumour cells die.
The measurement within the blood can be used as an indicator that something is wrong.
By tiring out the mitochondria the tumour can stay alive longer
How many types of HD are there?
5
Which out of the 5 HD is a variant of classical HD?
Nodular lymphocyte predominant
What cells characterise Nodular lymphocyte predominant HD?
Popcorn cells or lymphocyte predominant cell
Name the 4 Classical Hodgkins lymphoma
Nodular sclerosis Hodgkins lymphoma
Lymphocyte rich classical Hodgkins lymphoma
Mixed cellularity Hodgkins lymphoma
Lymphocyte depletion Hodgkiins lymphoma
What is the name of the common staging methodology for HD?
Ann Arbor system
How many stages are in the Ann Arbor system?
4
What does the B categorisation mean in the AA system?
Fever, night sweats and weight loss
What does the S categorisation mean in the AA system?
Splenic involvement
What does the E categorisation mean in the AA system?
Tissue other than lymphatics are involved
What does the X categorisation mean in the AA system?
Large tumour (>10cm)
What happens in Stage I of the AA system?
Involvement of single lymph node region or single extralymphatic site (Ig)
What happens in Stage II of the AA system?
Involvement of two or more lymph node regions on same side of diaphragm; may include localised extra lymphatic involvement on same side of diaphragm (IIg)
What happens in Stage III of the AA system?
Involvement of lymph node regions on both sides of the diaphragm; may include spleen (IIIs) or localised extranodal disease (IIIg)
What happens in Stage IV of the AA system?
Diffuse extra lymphatic disease (e.g. in liver, bone marrow, lung, skin)
What percentage of HL cases, is the spleen involved?
30%
ToD: Spleen involvement differs based on the type of HL
True
What percentage of HL cases, is the skin involved?
<1% of cases
What percentage of HL cases, is the skin indirectly involved?
30%
What symptoms are seen on skin when the skin is indirectly involved?
Itching, hives, rash.
What is paraneoplastic syndrome?
Caused by chemokine synthesis by tumour or the host immune response directed against the tumour
What causes indirect skin conditions seen in HL patients?
Paraneoplastic syndrome
What atypical symptoms does paraneoplastic syndrome cause?
Endocrine
Haematological
Skin
Neuronal
What is the name of the point system that is used in the prognosis of HL?
International Prognostic Factors Project
How many points are symptoms allocated if we are looking at stage 1 and 2 of the disease?
1
What are the 5 prognostic features used for stage 1 and 2 of the disease?
Bulky tumour
ESR >50mm/hr (Erythrocyte Sedimentation Rate)
>3 sites of involvement
B symptoms
Extranodal disease
What are the 6 prognostic features used for advanced Hodgkins disease?
Serum albumin <4 g/dl
Haemoglobin <105 g/l
Male
Age >45 years old
Leucocytosis > 15 x10^9 cells/l
Lymphopenia <0.6 x 10^6 cells/l
What treatment is given during the early stage of Hodgkins disease?
ABVD therapy
Surgery to remove tumour
What does ABVD stand for in the context of ‘ABVD therapy’?
Adriamycin, bleomycin, vinblastine and dacarbazine
What is used to treat advanced Hodgkin’s disease?
BEACOPP
or
G-CSF
What does BEACOPP stand for in the context of treatment?
Bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine and prednisone
What does Adriamycin do?
Inhibits topoisomerase II (intercalating poison)
What does Bleomycin do?
Induces dsDNA breaks
What does Vinblastine do?
Disrupts microtubule formation
What does Dacarbazine do?
Alkylating agent
What are the remission rates following ABVD?
70-90%
When are drugs during ABVD therapy infused?
Via IV on days 1 and 15
How many cycles of ABVD are usually prescribed?
6
What stage of HL are patients treated with BEACOPP instead of ABVD?
Stage 2 and above
What does Etoposide do?
Topoisomerase II non-intercalating poison
What does Cyclophosphamide do?
Alkylating agent
What does Procarbazine do?
Alkylating agent
What is Prednisone?
Steroid
What is the remission induction rate of BEACOPP?
80%
What are three other supportive therapies?
Prophylactic antimicrobials
Blood products
Antiemetic drugs
What is recommended for refractive lymphoma?
Brentuximab vedotin
Nivolumab and Pembrolizumab
