Lymphoma 1 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 lymphoma.
Constant antigenic stimulation (bacterial infection/autoimmune)
Viral infection
Loss of T cell function (HIV)
- 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 (autoimmune)
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)
- 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)
- Describe the normal histological appearance of a lymph node.
There 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 are the main immunohistochemical 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
- Outline the WHO classification of lymphoma.
Hodgkin lymphoma • Classical • Lymphocyte predominant Non-Hodgkin lymphoma • B cell (MOST COMMON) o Precursor B cell neoplasm o Peripheral B cell neoplasm (low and high grade) • T cell o Precursor T cell neoplasm o 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 and 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 or 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
- Name types of high grade lymphoma.
Diffuse large B cell lymphoma
Burkitt’s lymphoma
- Name a type of aggressive lymphoma
Burkitts lymphoma
- Describe the histological features of follicular lymphoma.
Follicular pattern – the follicles are neoplastic and spread from the node into adjacent tissues
Cells have a germinal centre cell origin (positive staining for CD10 and Bcl6)
- Which molecular feature is associated with follicular lymphoma?
14;18 translocation involving Bcl2 gene
