Lecture 10 - Lymphoma Flashcards
1
Q
What is lymphoma?
A
- malignant disease in which lymphocytes proliferate in an uncontrolled manner leading to lymphocyte accumulation in lymph nodes and or in BM
- results in lymph node enlargement and marrow failure
2
Q
Epidemiology of lymphoma
A
- 5th and 6th most common cancers among males and females
- one of few cancers with rising incidence
- incidence of NHL in particulat increeases with age
3
Q
Types of lymphoma
A
B cell lymphomas are much more common than T cell lymphomas
4
Q
Some important facts
A
- each lymphocyte has one receptor for antigen on its surface and responds to only one antigen
- this receptor remains unchanged for the whole of the lymphocytes life
- thus in a lymphoma: all cells share the same receptor
- if its a B cell, all lymphoma cells express a single type of light chain, or express the same differentiation proteins on their surface
- if the parent B cell produces antibody, all lymphoma cells produce that same antibody: paraprotein
5
Q
Two types of lymphoma
A
- NHL
- HL
Based on standard morphology
6
Q
Identifyhing lymphocute population
A
- histology: small cells, little cytoplasm, dense chromatin
- flow cytometry: B cell markers, one type of light chain. CD34 marker is for HSC, CD19 for pro-B cell on , CD20 for pre-B cell on
- karyotype
- FISH
- PCR
7
Q
Gene translocations in lymphoma
A
- t (14,18): IgH/bcl2 -> apoptosis through bcl2 -> indolent lymphoma
- t (11:14): IgH/Bcl1 -> cell cycle via cyclin D -> mantle cell lymphoma
- t(8:14): IgH/c-myc -> cell cycle via cmyc -> Burkitts lymphoma
8
Q
Major classes of NHL
A
- indolent (low grade, slow growing) -> folllicular, marginal zone, other
- aggressive (intermediate and high grade, fast growing -> DLBCL, Burkitts, other
9
Q
Indolent NHL
A
- slow growing but often widespread
- typically asymptomatic
- watch and wait strategy
- respond to treatment but relapse
- not considerable curable
- can transform to higher grade lymphoma
10
Q
Aggressive NHL
A
- most often symptomatic at diagnosis
- quite often localised at diagnosis
- progress relatively rapidly without treatment
- death within months to 1-2 years if not treated effectively
- always aggressively treated in fit patients
11
Q
DLBCL
A
- diffuse infiltate of large B cells in node
- patients of all ages
- 50% curable with chemotherapy, those that relapse progress and die of lymphoma
- some relapsong patients can be salvaged with a stem cell transplant usually using the patients own stem cells
12
Q
Burkitt’s lymphoma
A
- aggressive lymphoma with a particular genetic alteration involving a translocation between chromosomes 8 and 14 that justaposes the cmyc oncogene and the iGH gene
- cells have a high mutation rate
- starry sky morphology
- affects all ages and has a predilection to involve the ileum and the NS
- requires aggressive multiagent chemotherapy that can be curative
13
Q
Waldenstroms macroglobulinaemia
A
- indolent lymphoma of lymphoplasmacytoid cells in the BM
- characterised by the morphology and the presence of an IgM paraprotein
- frequently associated with a mutation in the Myd88 signalling pathway protein
- often associated with anemia and splenomegaly
- not treated aggressively as many cases slow to progress
14
Q
Surgical biopsy
A
- cell detail, architecture, flow cytometry, immunohistochemistry and genetics
- required for accurate diagnosis and classification
- gold standard
15
Q
Core biopsy
A
- using ultasound or CT scan is used if excision is difficult
- give limited material and architecture
16
Q
Fine needle biopsy
A
- gives only cytology and flow cytometry but never architecture and is inadequate for initial diagnosis
- can be used as an initial screen to exclude other cancers or to confirm relapse in a case of known lymphoma
17
Q
Immunophenotyping
A
- important for lymphoma diagnosis and classification
- detects antigen expression and monoclonality using kappa and lambda
- can be done on tissue by flow cytometry and immunohistochemistry or on blood and BM using flow cytometry
18
Q
Ann arbor staging system
A
Takes into account
- number of disease stes
- presence of disease above or below diaphragm
- presence of extranodal disease
- systemic disease
- used to distnguish local from extensive disease
- the higher the stage, the worse the outcome
19
Q
CLBCL international prognostic index (IPI)
A
One point per risk factor
- age >60 yo
- stages III or IV
- 2 extranodal sites
- ECOG performance status >22
- LDH elevated
- if score is 0,1 -> 73% 5 year survival rate
- if score is 4,5 -> 26% 5 year survival rate
20
Q
Treatment
A
- watch and wait
- chemotherapy (CHOP)
- immunotherapy: rituximab
21
Q
CD20
A
- transmembrane phosphoprotein
- single extracellular loop
- natural ligand not identified
- physiologic function uncertain
- expressed on most B cell malignancies
- resistant to internalisation or shedding after ligation by antibody
22
Q
Rituximab: anti-cd20
A
- binds CD20 molecule present on normal and malignant B cells
- improves response rate in B cell lymphomas when given in chemotherapy
- used routinely as maintenance therapy in low grade lymphoma after completion of chemo-immunotherapy where it prolongs survival
- used routinely in diffuse laarge B cell lymphoma where it improves response rate and overall survival
- newer anti-cd20 antibodies have been angineered to improve various aspects of target binding and immune cell recruitment
- also used in many non-lymphoma situations especially where pathological autoantibodies are formed
23
Q
3 potential effects of anti-cd20 on tumour cells
A
- complement fixation
- antibody dependent cellular cytotoxicity
- active signalling
24
Q
Rituximab evidence
A
- improved the outcome of patients with advanced stage follicular NHL
- improves overall survival of patients with DLBCL
25
Q
New drug classes emerging in lymphoma
A
- immunomodulating drugs - lenalidomide
- proteasome inhibitors - bortezomib
- B cell receptor signaling inhibitors - ibrutinib, idelalisib
- BH3 mimetics that induce apoptosis - ABT-199
