Lymphoma 1 Flashcards
What is the definition of lymphoma?
A malignant neoplasm of lymphoid cells
Where can lymphoma occur?
Lymphatic system: Lymph nodes, bone marrow, blood
Lymphoid organs: spleen, gut-associated lymphoid tissue
Skin
Anywhere else (CNS, ocular, testes, breast)
What is incidence of Hodgkins vs Non Hodgkins?
Hodgkins = 80% NHL = 20%
How are lymphomas classified?
Based on CELL OF ORIGIN
How does lymphoma generally develop?
- Rapid proliferation/division of cells in the germinal centre - means that there is a higher risk of replication errors
- highly dependent on apoptosis (most lymphocytes die in the GC) - means that apoptosis can be switched off, causing damage
- Deliberate gene recombination (somatic hypermutation) - means potential for recombination errors
What is the gene recombination that occurs in bone marrow also called?
VDJ recombination
What is the downside of VDJ recombination?
Could lead to recombination errors and new point mutations
This means the formation of either OVEREXPRESSION OF PROLIFERATIVE ONCOGENE
or
SUPPRESSION OF APOPTOTIC GENE
What kind of lymphoma is a prime example of an error in recombination?
BURKITT’S
What types of malignant genes may be accidentally over expressed in VDJ recombination?
Myc (burkitt’s)
Bcl2
Bcl6
cyclin D
What are 3 MAIN causes for lymphoma?
- CONSTANT ANTIGENIC STIMULATION
- VIRAL INFECTION
- LOSS OF T cell FUNCTION
Give examples of how constant antigenic stimulation can cause lymphoma.
Helicobacter pylori: causes gastric MALT Marginal Zone NHL of stomach
Sjogrens: Marginal zone NHL of parotid
Hashimoto’s: Marginal zone NHL of thyroid
Coeliac: Small Bowel T cell lymphoma
Give examples of how viral infection causes lymphoma
HTLV1
EBV
Explain how HTLV1 works
HTLV1 infects T cells > develop Adult T cell Leukaemia Lymphoma (ATLL)
Explain how EBV works
EBV > infects B lymphocytes > usually quiescent (infected B cells killed by cytotoxic T cells)
If HIV / immunosuppression present, T cells cannot act > EBV causes B cell lymphoma
Give examples of how T cell function can belopst
HIV
Iatrogenic (immunosuppression)
What are the three key tissues of lymphoreticular system?
Generative LR tissue
Reactive LR tissue
Acquired LR tissue
What is function of Generative LR tissue
Generate / maturate B and T lymphoid cells
What are examples of generative LR tissue?
Bone marrow
Thymus
What is function of Reactive LR tissue
Develop immune reaction
What are examples of reactive LR tissue?
lymph node
spleen
What is the function of acquired LR tissue?
Develop LOCAL immune reaction
What are examples of acquired LR tissue?
Extra nodal lymphoid tissue e.g. skin, stomach, lung
Where are T cells found in the lymph node?
In the PARACORTEX
Where are B cells found in the lymph node?
In the LYMPHOID FOLLICLE
In the CORTEX
What are the components of the lymphoid follicle?
Mantle zone - in the periphery, contains naive unstimulated B cells
Germinal centre - in the centre, where B cells which bind to antigen epitopes are selected and activated
What are the main immunomarkers that we use in immunohistochemistry to detect whether cells are B or T cells?
B cells = CD20
T cells = CD5, CD30
How is lymphoma classified?
Hodgkin (20%) Non Hodgkin (80%)
What are the types of Hodgkin Lymphoma?
Classical
Lymphocyte predominant
What are the types of NHL?
B cell
T cell
What is the most common type of Lymphoma?
B cell. NHL
What are histological features related to architecture that occur in lymphoma?
Nodular
Diffuse
What abnormalities are visible in immunophenotyping for lymphoma?
Cell distribution
Loss of normal surface proteins
Abnormal expression of proteins
What molecular tools are used for lymphoma?
FISH
PCR
What can these molecular tools identify?
Chromosome TRANSLOCATIOn
What are common types of B cell NH LOW GRADE lymphoma?
Follicular
Small lymphocytic / chronic lymphocytic
Marginal zone
Mantle cell
What are common types B cell NH HIGH grade lymphoma?
Diffuse large B cell lymphoma
Burkitt’s
Who does follicular lymphoma occur in?
middle aged/elderly
What is the histopathology of follicular lymphoma?
Follicular pattern (Follicles are NEOPLASTIC) Germinal centre cell origin
What translocation occurs in follicular lymphoma?
t(14,18)
Involves Bcl2 gene (There is over expression of Bcl2 in the GERMINAL CENTRE (Bcl2 is usually only found in the mantle zone))
What is follicular lymphoma usually classified as in terms of aggression, and what can it become?
Indolent
Can become high grade lymphoma
What is the difference between Small and Chronic Lymphocytic Leukaemia?
Small = peripheral blood involved Chronic = bone marrow involved
Who does S/CLL present in?
middle aged/elderly
What is the histopathology of S/CLL?
Small lymphocytes
Arises from naive B cells or port germinal centre memory B cells
These replace the entire lymph node so you can no longer see follicles/T cells > become entire rounded sheets
What is Richter transformation?
The transformation of S/CLL from low grade to high gene
What proteins are B cells in S/CLL positive for?
CD5
CD23
What is another name for MALT Lymphoma?
Marginal zone lymphoma
Where does MALT lymphoma arise?
It arises mainly at extranodal sites (gut, lung, spleen)
What does MALT lymphoma arise in response to?^
In response to chronic antigenic stimulation e.g. H pylori
What cells does MALT lymphoma arise from?
Post-geminal centre memory B cells
How can MALT lymphoma be treated?
With NON CHEMOTHERAPEUTIC modalities
By REMOVING THE ANTIGEN (eradicate H pylori)
How does Mantle cell lymphoma present?
In middle aged males,
Affects lymph nodes, GI tract
Presents as disseminated disease
What is the histopathology of Mantle Cell Lymphoma?
In Mantle zone of Lymph nodes
What cells does mantle cell L arise from?
From Pre-germinal centre cells
What proteins are abnormally expressed in Mantle Cell Lymphoma?
Cyclin D1
What translocation is responsible for Mantle cell lymphoma=?
11,14
What is the presentation for Burkitts lymphoma?
Jaw/abdo mass in children/adults respectively
What virus is burkitt’s associated with?
EBV
Explain Burkitt histopathology?
Arises from germinal centre cells
Starry sky appearance
What is the molecular translocation and gene mutation with Burkitt’s?
8,14
2,8
8,22
Resulting in c-Myc TRANSLOCATIon
What is the aggressiveness of Burkitt’s?
HIGHLY AGGRESSIVE
What area does Diffuse Large B cell lymphoma arise from?
From germinal centre OR post-germinal centre B cells
What are 4 types of T cell lymphoma?
Adult T cell leukaemia lymphoma (ATLL)
Enteropathy associated T cell lymphoma (EATL)
Cutaneous T cell lymphoma
Anaplastic large cell lymphoma
What virus is ATLL associated with?
HTLV-1
What comorbidity does EATL occur with=
COELIAC disease
How is Hodgkin presentation different to NHL?
Hodgkin: localised (usually just one node site), spreads contiguously to adjacent lymphocytes
NHL: involves multiple sites, spreads discontinuously
Describe 3 features of classic HL
Nodular sclerosino
Mixed cellularity with REED STERNBERG CELLS
Lymphocyte rich/depleted
What are diagnostic markers for HL?
CD30+, CD15+
CD20-
Whats the presentation of lymphocyte predominant HL=
Isolated lumphadenopathy
What virus is lymphocyte predominant HL associated with?
NONE
What are diagnostic markers for lymphocyte predominant HL?
CD30-, CD15-
CD20+
What do you need to know for diagnosis and staging of HL?
Histological Hx Anatomical stage (CT/MRI/PET) Prognostic factors (LBH; beta2 microglob, albumin, Hep B serology, BM function)
What is the age distribution for Hodgkins?
BIMODAL
1st peak 20-29
2nd peak >60
What is the gender distribution for Hodgkins?
1st peak - females more likely
2nd peak- males more likely
overall - males slightly more likely
What is the general presentation of Hodgkins?
Painless lymphdenopathy
B symptoms
Alcohol induced lymph node pain
What are the 3 B symptoms?
Fever
night sweats
WL
What staging system is used for HL?
Ann Arbour staging
Explain stage 1-4 of Ann Arbour staging for HL
1: one group f nodes
2: >1 group of nodes on the same side of diaphragm (above/below)
3: nodes above AND below diaphragm
4: extra nodal spread
A If no B symptoms
B if min 1 B symptom
What is treatment for Hodgkins?
CHEMOTHERAPY for ALL PTSD
Radiotherapy depending on circumstances
What is the chemotherapy combination used for HL?
ABVD
Adriamycin
Bleomycin
Vincristine
DTIC (dacarbazine)
What is a benefit of this type of chemotherapy?
It preserves fertility
What are long term disadvantages of ABVD?
Pulmonary fibrosis
Cardiomyopathy
What are negative consequences for radiotherapy?
DAMAGE TO NORMAL TISSUE ENCOUNTERED
High risk of breast cancer
leukaemia /myelodysplastic syndrome
lung/skin cancer
What is a risk of combination radio-chemotherapy?
Increases rate pf relapse
