Lymphoma Flashcards
What are the different tissue types in the lymphoreticular system?
i) Generative LR tissue
-> Bone Marrow
-> Thymus
involved in the generation/maturation of lymphoid cells
ii) Reactive LR tissue
-> Lymph Nodes
-> Spleen
involved in the development of an immune reaction
iii) Acquired LR tissue i.e. Extranodal Lymphoid Tissue
-> Skin/Stomach/Lung
involved in the development of local immune reactions
What are the different cell types found in the lymphoreticular system?
i) Lymphocytes
-> B Lymphocytes
express surface Ig, responsible for antibody production
-> T Lymphocytes
express surface T cell Receptors, responsible for B Cell/Macrophage Regulation and Cytotoxic functions
ii) Accessory Cells
- > Antigen Presenting Cells
- > Macrophages
- > Connective Tissue Cells
Where are B cells found in the lymph nodes?
the Mantle Zone and Germinal Centres
Where are T cells found in the lymph nodes?
Inbetween the follicles in the “interfollicular areas”
What is a lymphoma?
Lymphoma’s are the neoplastic proliferation of lymphoid cells forming discrete tissue masses. They arise in and involve lymphoid tisssues.
Why are lymphocytes physiologically susceptible to oncogenesis? (3)
i) Recombination
DNA molecules are cut and recombined -> undergo deliberate point mutation
ii) Rapid cell proliferation in the germinal centre
- > More cell division means more risk of DNA replication error
iii) Dependent on apoptosis
If you have rapid turnover and you acquire a mutation that blocks apoptosis, it can lead to malignancy
What are 3 broad risk factors for lymphoma?
i) Chronic Antigen Stimulation
- > H. Pylori => Marginal Zone Lymphoma of Stomach
- > Sjogren’s Syndrome => Marginal Zone Lymphoma of Parotid
- > Hashimoto’s => Marginal Zone Lymphoma of Thyroid
ii) Direct Viral Integration
i. e. HTLV1 retrovirus. Human T Cell Lymphotropic Virus Type 1.
iii) Loss of T Cell Function
This is particularly important in EBV
What percentage of lymphomas are hodgkins and Non-hodgkins?
Hodgkin = 15% REED-STERNBERG NHL = 85%
What is the epidemiology of HL?
Bimodal Age Incidence
i) Most common age is 20-29, Young Women
ii) Second peak affecting those >60 years of age.
What is the most common subtype of HL?
Nodular Sclerosing 80% (good prognosis)
What are the clinical features of a patient with HL?
-> Painless enlargement of lymph node/nodes
this may cause secondary effects from obstructing on local areas i.e. bowel, ureter, biliary tract
-> Constitutional Symptoms i.e. B SYMPTOMS - Fever, Night sweats and Weight loss.
What is the staging of HL?
Stage 1 - One Group of Nodes
Stage 2 - >1 group of nodes on the same side of the diaphragm
Stage 3 - Nodes above and below the diaphragm
Stage 4 - Extranodal spread
A/B -> B if the patient has the constitutional B symptoms i.e. Fever, Unexplained Weight Loss over 10%), Night Sweats
*If a Lymphoma has developed extranodal spread it is immediately described as a Stage 4 Lymphoma.
What is the management of HL?
- Chemotherapy (all patients with HL need chemo)
ABVD - number of cycles depends on staging - Radiotherapy
What is the radiotherapy dilemma for HL?
Radiotherapy PRO
-> Reduces the risk of HL recurrence to low/negligible
Radiotherapy CON
-> Higher risk of secondary cancers as there are two mechanisms of DNA damage i.e. Chemo+Radio
Therefore intensifying treatment may reduce the risk of relapsing but will increase the risk of treatment complications.
What is NHL?
Neoplastic proliferation of lymphoid cells
How is NHL staged?
same as HL
What are two of the most common types of HL?
- Diffuse large B-cell lymphoma
2. Follicular lymphoma
What predicts the clinical course of NHL?
Histology:
Different types of NHL are more aggressive than others (Burkitt v aggressive, follicular is indolent)
How aggressive is Diffuse large B cell lymphoma?
Not as aggressive as Burkitt, but more than follicular
What is the prognosis and treatment for diffuse large B-cell lymphoma determined by?
i) Age>60
ii) Serum LDH>Normal
iii) Performance status 2-4
iv) Stage III/IV
v) More than one extranodal site
What is the treatment for diffuse large B-cell lymphoma?
Treated with 6-8 cycles of R-CHOP (chemo and immunotherapy)
What is follicular lymphoma?
It is an indolent type of lymphoma
It is incurable and has a median survival of 12-15 years
How do you treat follicular NHL?
- At presentation = watch and wait unless
- nodal extrinsic compression
- massive painful nodes - Treatment = chemo (not curative)
What is extra nodal marginal zone lymphoma (MZL)?
- It is a NHL involving extra nodal lymphoid tissue (e.g. gastric mucosa or parotids)
- Rare
- Due to chronic antigen stimulation
75% of xtra nodal marginal zone lymphoma (MZL) patients can be cured by…
H.pylori eradication
How do MZL patients present?
- Epigastric pain, ulceration or bleeding (most commonly arise in stomach)
- Usually in stage 1
What is Enteropathy associated T cell lymphoma (EATL)?
- It is aT cell NHL in patients with Coeliac disease (due to chronic antigen stimulation)
- Involves Jejunum and Ileum
- It is aggressive
How do patients with Enteropathy associated T cell lymphoma (EATL) present?
- Abdo pain. obstruction, bleeding
- Malabsorption
- Systemic symptoms
What is Chronic Lymphocytic Leukaemia?
- Proliferation of mature B lymphocytes
- Involves bone marrow, blood and nodes
- Commonest Leukaemia in western world
- Median age 72
What are the laboratory findings of CLL?
- Lymphocytosis (5-300)
- Smear cells
- Anaemia
- Thrombocytopenia
- Immunotyping
What are smear cells?
Found in CLL
Mature fragile B lymphocytes that break during slide presentation
What are the clinical issues of CLL?
- Increased risk of infection (non functional B cells)
- Bone marrow failure
- Lymphadenopathy.splenomegaly
- Richter transformation (acquire further mutations)
- Autoimmune complications
What is Richter’s transformation?
Low Grade CLL converts into Diffuse Large B Cell Lymphoma due to acquired mutations
What is the supportive care for CLL?
- Sino-pulmonary infections
- Prophylaxyis for pneumocystis
- IVIG
- Early Antibiotics - Vaccinations
- seasoal flu
- pneumococcal
- avoid live vaccines
What is the treatment for CLL?
- Watch and wait unless
- Bone marrow failure
- massive lymphadenopathy
- progressive lymphocytosis - CLL therapy
- Combination immuno-chemotherapy
What are targetted therapies for CLL?
- BCR Kinase inhibitors
- BCL2 inhibitors
- Experimental cell based therapies
What is the immunophenotype of:
- a normal peripheral blood B-cell
- A malignant peripheral B-cell
- CD19+ve
2. CD5+ve and CD19+ve
