HAEM: Lymphoma: MDT, CLL, NHL, lymphoproliferative disorder Flashcards
Define lymphoma. Where are they usually found?
- Lymphoma = neoplastic (malignant) tumour of lymphoid cells; usually found in:
- Lymph nodes, bone marrow and/or blood (the lymphatic system)
- Lymphoid organs; spleen or the gut-associated lymphoid tissue
- Skin (often T cell disease; e.g. Mycoses Fungoides)
- Rarely “anywhere” (CNS, ocular, testes, breast, etc.)
How common is lymphoma? What are the types?
- Incidence = 200 per 1,000,000 per year (i.e. 10,000/year in UK)
- NHL = 80%
- HL = 20%
- Types of lymphoid malignancies:
- Acute Lymphoblastic Leukaemia (ALL)
- Non-Hodgkin Lymphomas (B-cell lineage)
- Non-Hodgkin Lymphomas (T and NK cell lineage)
- Hodgkin Lymphoma
What are the consequences of having an adaptive immune system in increasing risk of lymphoma?
- The process of lymphoma – immune modulation and the costs of having modulation:
-
Recombination – DNA molecules cut and recombined (deliberate point mutations; somatic hypermutation)
- +ve = diversity in Ig (and Ig class switching) and TCR
- -ve = unwanted point mutations
-
Rapid cell proliferation in germinal centres
- +ve = rapid response to infection
- -ve = replication errors
-
Apoptosis dependency (90% lymphocytes die in germinal centres)
- +ve = antibody specificity, elimination of self-reactive clones
- -ve = apoptosis switched off in germinal centre, acquired DNA mutation in apoptosis-regulating genes
-
Recombination – DNA molecules cut and recombined (deliberate point mutations; somatic hypermutation)
What is the molecular basis of adaptive immunity and what mutations can arise in each of the two stages?
Immunoglobulin & TCR gene recombination – 2 STAGES: the molecular basis of an adaptive immune response:
(1) VDJ recombination – creates a molecule that recognises an epitope:
- Occurs in bone marrow
- Involves enzymes: RAG1 and RAG2
(2) Class switch recombination –> more important for lymphoma genesis:
- Somatic hypermutation in germinal centre (heavy chain of Ig changed – i.e. IgM to IgG)
-
Involves enzyme: Adenosine induced Deaminase (AID)
- Ig promotor highly active in B-cells to drive AB production
- Recombination errors occur
- Oncogenes brought close to the promotor
- Oncogenes = anti-apoptotic or proliferative:
- Bcl2
- Bcl6
- (C-)MYC
- CyclinD1
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/745/a_image_thumb.png?1634113095)
What are the risk factors for different NHL subtypes?
Can be split into two main types:
- Immune system diseases
- Loss of T cell function
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/747/a_image_thumb.png?1634113525)
Give examples of how chornic bacterial infection/AI disorders can cause lymphoma.
Chronic bacterial infection** or **auto-immune disorders:
- B-cell NHL Marginal Zone Lymphoma sub-type (B-cell NHL, MZL)
- H. pylori à gastric MALT = MZL of stomach
- Sjogren’s syndrome = causes MZL of salivary glands
- Hashimoto’s thyroiditis (lymphocytic destruction) = MZL of thyroid
- Thyroiditis = de Quervain’s (viral), Reiter’s (IgG4-related), Hashimoto’s
- Enteropathy associated T-cell NHL (EATL)
- Coeliac disease = small intestine EATL (enteropathy-associated T cell lymphoma)
Give examples of how viral infection can cause NHL development.
Viral infection (direct viral integration into genome of lymphocytes stimulates lymphoma genesis)
- HTLV1 retrovirus –> Adult T-cell Leukaemia Lymphoma (ATLL) = sub-type of T-cell NHL
- Caribbean, Japan endemic infection
- Risk of ATLL = 2.5% at 70 years
Describe how EBV can cause NHL development.
- EBV infects B-cells –> stimulates proliferation –> B-cells expresses EBV-associated antigens on cell surface –> CTL attack EBV-expressing B-cells –> carrier state for years…
- EBV switches on at later life and drives proliferation (normally CTL will control this but if you have a low CTL due to (1) HIV or (2) immunosuppression, the EBV can drive a lymphoma)
Describe how iatrogenic immunosuppression can increase risk of NHL.
- (1) Viral killing of T-cells (HIV) –> low CTL
- HIV –> B-cell NHL (60x increased incidence)
- (2) Iatrogenic immunosuppression / after HSCT –> low CTL
- Transplant immunosuppression –> Post-Transplant Lymphoproliferative Disorder (PTLD)
What are the 3 parts of the lymphoreticular system?
- Generative LR tissue –> generation/maturation of lymphoid cells
- Bone marrow and thymus
- Reactive LR tissue –> development of immune reaction
- Lymph nodes and spleen
- Acquired LR tissue –> development of local immune reaction
- Extra-nodal lymphoid tissue (e.g. skin, stomach, lung)
What are the cells of the lymphoreticular system?
- Lymphocytes
- B lymphocytes
- Express surface Ig
- Antibody production
- T lymphocytes
- Surface TCR
- Regulation of B cells and macrophage function
- Cytotoxic function
- B lymphocytes
- Accessory Cells:
- Antigen-presenting cells
- Macrophages
- Connective tissue cells
Describe the lymph node histology.
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/754/q_image_thumb.png?1634113875)
- Rounded areas = B cell follicles
- Between B cell follicles = T cell areas
- Central medulla = where mature B cells eventually end up
Describe each of these parts of the lymph node (B and T cell areas).
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/756/q_image_thumb.png?1634113925)
- B-cell area:
- Crescent shaped region is the mantle zone where naïve unstimulated B cells are located
- B-cells migrate into germinal centre where they encounter APCs and undergo activation and selection
- There is a lot of cell turnover in this area, which is a predisposing factor for lymphoma
- T-cell area – comprises:
- T-cells
- APCs
- High endothelial vessels
What is the WHO classification of lymphoma?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/757/a_image_thumb.png?1634114070)
Describe the basic principles of lymphoma.
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/762/q_image_thumb.png?1634114129)
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/762/a_image_thumb.png?1634114194)
Which investigations are used in lymphoma?
- Cytology
- Histology
- Architecture (nodular like in folllicular or HL, diffuse)
- Cells (small round [CLL], small cleaved [nuceli show irregularity grooving in follicular lymphomal, large (centroblastic, immunoblastic, plasmoblastic) – large cells are suggestive of a high-grade lymphoma)
- Immunophenotyping
- Cell types identified by CD markers
- Cell distribution e.g. in sheaths
- Abnormal expression of proteins
- Clonality of B cells (light chain expression – normal clonal proliferation –> even kappa and lambda)
-
Cytogenetics / molecular tools –> identify genetics:
- FISH – identify chromosome translocations
- PCR – identify chromosome translocations, clonal T cell receptor or Ig gene rearrangement
Which lymphoma is cyclin D1 expression associated with?
Mantle cell lymphoma
How can cytogenetic investigations provide prognostic information in lymphoma?
- DIAGNOSTIC – i.e. t (11; 14) = Mantle Cell Lymphoma
- PROGNOSTIC – i.e. t (2; 5) = Anaplastic Large Cell Lymphoma
What are the common types of NHL B cell type?
- Common B-cell NHL include:
-
Low-grade:
- Follicular lymphoma
- Small lymphocytic lymphoma/chronic lymphocytic leukaemia (CLL)
- Marginal zone lymphoma (MALT)
-
High-grade:
- Diffuse large B cell lymphoma
- Mantle zone lymphoma
-
Aggressive:
- Burkitt’s lymphoma
-
Low-grade:
Summarise the histopathological features of follicular lymphoma.
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/768/a_image_thumb.png?1634114701)
Describe the histopathological features of small lymphocytic lymphoma.
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/769/a_image_thumb.png?1634114777)
What are the histopathological features of margincal cell lymphoma?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/770/a_image_thumb.png?1634114828)
What are the histopathological features of mantle cell lymphoma?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/772/a_image_thumb.png?1634114882)
What are the histopathological features of Burkitt;s lymphoma?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/774/a_image_thumb.png?1634114915)
What are the histopathological features of diffuse large B cell lymphoma?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/775/a_image_thumb.png?1634114952)
What are the general features of T cell lymphomas?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/776/a_image_thumb.png?1634115000)
List 4 types of T cell lymphoma? Name a risk factor for each.
- Anaplastic large cell lymphoma
- Adult T cell leukaemia lymphoma / ATLL (Caribbean and Japan; HTLV-1 infection)
- Enteropathy-associated T cell lymphoma / EATL (long-standing Coeliac disease)
- Cutaneous T cell lymphoma (i.e. mycosis fungoides)
What are the features of anaplastic large cell lymphoma?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/778/a_image_thumb.png?1634115099)
What are the types of Hodgkin’s lymphoma?
- Types of HL:
-
Classical Hodgkin Lymphoma: subtypes are…
- Nodular sclerosing
- Mixed cellularity
- Lymphocyte rich/depleted
-
Lymphocyte Predominant
- Some relationship to NHL
-
Classical Hodgkin Lymphoma: subtypes are…
What are key differences between HL and NHL?
Hodgkin is more localised (usually only one nodal site)
Hodgkin spreads contiguously to adjacent lymph nodes (NHL involves multiple sites and spreads sporadically)
What are the features of classical HL?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/782/a_image_thumb.png?1634115234)
What are the features of nodular LP Hodgkin’s lymphoma?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/783/a_image_thumb.png?1634115271)
What are the features of nodular lymphocyte predominant lymphoma?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/831/784/a_image_thumb.png?1634115402)
Part 2