Haem: Lymphoma MDT (Laz) Flashcards
Outline the difference in prevalence of Hodgkin’s lymphoma and Non-Hodgkin lymphoma.
- NHL = 80%
- Hodgkin = 20%
Outline the processes by which immunoglobulins and T cell receptors become capable of identifying a wide variety of antigens.
- The germline VDJ genes undergo recombination in the bone marrow to generate a wide repertoire of specificities.
- In germinal centres, a second stage of DNA alteration involving isotype switching and somatic hypermutation (point mutations) generates even more diversity.
What is the main downside of the processes that generate variety in immunoglobulins and TCR?
- Recombination errors and new point mutations can occur
- Lymphocytes are reliant on apoptosis to keep their massive proliferation under control (90% of lymphocytes die in the germinal centre)
- If a mutation turns off apoptosis, it can lead to malignancy or autoimmunity
Outline how chromosomal translocations in B cells can lead to malignancy.
- Immunoglobulin gene promoters in B cells are highly active because they are designed to produce loads of immunoglobulin
- If an error occurs and an oncogene is translocated downstream of the promoter, malignant genes can be expressed
List some oncogenes that are implicated in lymphoma/leukaemia.
- Bcl2
- Bcl6
- Cyclin D1
- c-Myc
List some risk factors that contribute to the aetiology of lyphoma.
- Constant antigenic stimulation
- Infection
- Loss of T cell function
List some examples of how constant antigenic stimulation can lead to lymphoma.
- H. pylori → gastric MALT marginal zone NHL of the stomach
- Sjogren syndrome → marginal zone NHL of the parotid
- Coeliac disease → small bowel T cell lymphoma, enteropathy-associated T cell NHL
List two examples of viral infections that can lead to lymphoma.
Direct viral integration: HTLV1
- HTLV1 infects T cells by vertical transmission
- May cause adult T cell leukaemia/lymphoma (very aggressive)
- Caused by viral genome integrating into T cell genome and driving proliferation
EBV infection and immunosuppression
- EBV established latent infection in B cells which is kept in check by cytotoxic T cell (kill EBV antigen-expressing B cells)
- Loss of T cell function (e.g. HIV, post-transplant immunosuppression) can lead to EBV-driven lymphoma
List some different types of tissues of the lymphoreticular system.
- Generative tissue: bone marrow and thymus (generates or matures lymphoid cells)
- Reactive tissue: lymph nodes and spleen (development of immune reaction)
- Acquired tissue: extra-nodal lymphoid tissue (e.g. skin, stomach, lung - responsible for developing a local immune response)
List the different cell types of the lymphoreticular system.
- B cells
- T cells
- Antigen-presenting cells
- Macrophages
- Connective tissue cells
Describe the normal histological appearance of a lymph node.
- These are rounded areas full of B cells (B cell follicles)
- The mantle zone is a crescent-shaped region where naïve unstimulated B cells are found
- These naïve B cells will eventually migrate into the germinal centre, and mature B cells will end up in the medulla
- T cells are found in T cell areas surrounding the B cell follicles
Describe the composition of T cell areas in lymph nodes.
- Consists of lots of T cells, antigen-presenting cells and high-endothelial venules
- This is the site where T cells bind to antigens and are selected/activated
What is the main technique used to identify different types of lymphocyte within a lymph node biopsy?
Immunohistochemistry
What are the main markers used for B and T cells?
T cell = CD3, CD5
B cell = CD20
Define lymphoma.
- Neoplastic proliferation of lymphoid cells forming discrete tissue masses
- They arise in and involve lymphoid tissues
Which factors are taken into account when classifying a lymphoma?
- Clinical
- Histological
- Immunohistochemical
- Molecular
Outline the WHO classification of lymphoma.
Hodgkin lymphoma
- Classical
- Lymphocyte predominant
Non-Hodgkin lymphoma
- B cell (MOST COMMON)
- Precursor B cell neoplasm
- Peripheral B cell neoplasm (low and high grade)
- T cell
- Precursor T cell neoplasm
- Peripheral T cell neoplasm
Why is non-Hodgkin lymphoma often disseminated at presentation?
Neoplastic lymphoid cells circulate in the blood leading to disseminated disease at presentation
NOTE: lymphoid neoplasms can disrupt normal immune functioning leading to immunodeficiencies
What are the diagnostic tools used by pathologists when investigating lymphoma?
- Cytology (from aspiration)
- Histology (architecture: nodular, diffuse; cells: small round, small cleaved, large)
- Immunohistochemistry
- Loss of normal surface proteins
- Expression of abnormal proteins (e.g. cyclin D1 an Mantle cell lymphoma)
- Light chain restriction
- Molecular tools
Which molecular tools are used when investigating lymphoma?
- FISH - identify chromosomal translocations
- PCR - identify chromosomal translocations, clonal T cell receptor of Ig gene rearrangement
Give an example of a chromosomal translocation that is diagnostic of lymphoma.
11;14 = Mantle Cell Lymphoma
Give an example of a chromosomal translocation that is prognostic in lymphoma.
2;5 = anaplastic large cell lymphoma
List some types of low grade lymphoma.
- Follicular lymphoma
- Small lymphocytic lymphoma (CLL)
- Marginal zone lymphoma
- Mantle cell lymphoma
Name a type of intermediate grade lymphoma
Burkitt’s lymphoma
Name a type of high grade lymphoma.
Diffuse large B cell lymphoma