Haem: Lymphoma Flashcards
Define lymphoma
Neoplastic tumour of lymphoid tissue
Often involving:
Lymph nodes +/- bone marrow
- at times other lymphoid tissues (spleen, MALT)
Outline the aetiology for lymphomas
Acquired somatic mutations
- sporadic in nature (most cases - and this occurs due to adaptive immune system’s DNA instability in order to achieve its diversity)
- arising from immune disease
- associated with specific infections
Outline how the processes by which immunoglobulins and T cell receptors become capable of identifying a wide variety of antigens increases the risk of lymphoma.
- DNA recombination (VDJ gene and somatic hypermutation) - increase risk of point mutations and fusion genes (may place intact oncogenes next to the Ig gene promoter which is extremely active - hence increasing expression of oncogene)
- Rapid cell turnover - increases risk of DNA repitition errors. If a mutation turns off apoptosis (lymphocytes are heavily reliant on apoptosis to control auto-reactive cells) increases risk of malignancy and/or autoimmunity.
What are the specific risk factors that predispose someone to develop certain types of lymphoma
- Constant antigenic stimulation (chronic bacterial or autoimmune disease)
- Viral infection (direct viral integration in lymphocyte)
- Loss of T cell function in those co-infected with EBV
Explain which types of lymphoma can arise from 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
- Hashimoto → marginal zone NHL of thyroid
- Coeliac disease → small bowel T cell lymphoma: enteropathy-associated T cell NHL
List an example of a viral infection that can lead to a 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
Explain how the loss of T cell function in those co-infected with EBV can result in a lymphoma
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) causes the cytotoxic T cells from being unable to keep proliferative EBV-infected B cells in check and tehrefore result in a EBV-driven B cell 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.
Lymphocytes:
* B cells
* T cells
Accessory cells:
* Antigen-presenting cells
* Macrophages
* Connective tissue cells
Describe the normal histological appearance of a lymph node.
Composed of 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 (lighter circle),
* In the germinal centre, B cells will be exposed to APC which can result in them being maturing and becoming antibody producing plasma cell OR becoming marginal zone B cells and leaving germinal centre.
T cells are found in T cell areas surrounding the B cell follicles. Filled with APCs and high-endothelial venules.
What is the main technique used to identify different types of lymphocytes within a lymph node biopsy?
Immunohistochemistry
What are the main markers used for B and T cells?
T cell = CD3, CD4, CD5, CD8
B cell = CD19, CD20, CD22
Define lymphoma.
- Neoplastic proliferation of lymphoid cells forming discrete tissue masses
- They arise in and involve lymphoid tissues
Which pathology tools can be performed to classify a lymphoma?
-
Cytology (looking at single cell shape and size, nuclei)
- larger cells = high grade B cell lymphoma
-
Histology (assessing architecture and cellular arrangement)
- diffuse arrangement = CLL/small lymphocytic lymphoma
- small cleaved cells = mantle lymphoma, follicular lymphoma
- large cells with large nuclei = high grade diffuse lymphoma
-
Immunohistochemistry (allows CD markers to differentiate between T and B cell)
* allows further differentiation of germinal centre vs post-germinal centre B cell lymphomas -
Molecular tools
- FISH/PCR for chromosomal translocations
Outline the WHO classification of lymphoma.
Hodgkin lymphoma (20%)
- Classical
- Non-Classic Lymphocyte predominant
Non-Hodgkin lymphoma (80%)
- 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 NHL lymphoid cells circulate in the blood rathertahn lymph leading to disseminated disease at presentation
NOTE: lymphoid neoplasms can disrupt normal immune functioning leading to immunodeficiencies
Histology grading system for B cell Lymphomas
Lower grade (small lymphocytes)
* Follicular lymphoma
* Small lymphocytic lymphoma (CLL)
* Marginal zone lymphoma
High Grade (large lymphocytes)
* Aggressive = Diffuse Large B-cell + Mantle cell lymphoma (histologically looks similiar to lower grade)
* Very Aggressive = Burkitt’s (fastest developing cancer in humans)
Describe the histological features of follilcular lymphoma.
- Follicular pattern in the lymph nodes - the follicles are neoplastic (there are loads of them in the lymph node) and spread from the node into adjacent tissues
- “Nodular appearance”
- Cells have a germinal centre cell origin (hence positive staining for CD10)
- Also Bcl6 +ve due to translocation (14;18)
Which molecular feature (translocation) is associated with follicular lymphoma? and what protoncogene is overexpressed
14;18 translocation = Bcl2 gene
Outline the histological features of small lymphocyte lymphoma.
- Small lymphocytes
- Arise from naïve B cells or post-germinal centre memory B cells
- Cells are CD5 and CD23 positivie (these +ve results are only seen in B cells if they are neoplastic!)
- They replace the entire lymph node so that you can no longer identify follicles or T cell areas
What is the term used to describe the transformation of small lymphocytic lymphoma into a higher grade lymphoma/leukaemia?
Richter transformation
What is marginal zone lymphoma?
- Arise mainly in extra-nodal sites (e.g. gut, spleen)
- Thought to arise due to chronic antigenic stimulation
- Arise from post-germinal centre memory B cells
- Low-grade disease can be treated by non-chemotherapeutic methods (e.g. H. pylori eradication)
Outline the typical demographic of patients with mantle cell lymphoma.
- Typically affects middle-aged males
NOTE: median survival = 3-5 years
Outline the key histological features of mantle cell lymphoma.
- Located in the mantle zone of the lymph node
- Arise from pre-germinal centre cells
- Show aberrant expression of cyclin D1 and CD5
cyclin D1 +ve = confirms diagnosis
Which molecular features are characteristic of mantle cell lymphoma?
- 11;14 translocation
- Cyclin D1 overexpression
Outline the typical presentation of Burkitt’s lymphoma.
- Jaw or abdominal mass in children and young adults
- Associated with EBV
NOTE: this is very agressive
Outline the histological features of Burkitt’s lymphoma.
- Arises from germinal centre cells
- Starry sky appearance of sheets of medium sized lymphoma with small nuclei with macrophages filled with cellular debris
- c-Myc +ve
Outline the different types of Burkitt’s Lymphoma
Endemic
- most common malignancy in equitoral Africa
- EBV-associated
- Characteristic jaw involvement and abdominal masses
Sporadic
- EBV associated
- Jaw less commonly involved
Immuno-deficiency
- HIV/Post transplant patients
- EBV-associated
Which molecular feature is associated with Burkitt’s lymphoma.
- c-Myc translocation (8;14, 2;8 or 8;22)
Outline the histological features of diffuse large B cell lymphoma.
- Arise from germinal centre (CD10+) or pre-germinal centre B cells
- Large lymphoid cells
- Lymph node is effaced so follicles and germinal centres cannot be identified - described as “sheets of large lymphoid cells with variable shaped nuclei”
List some prognostic association of diffuse large B cell lymphoma.
Good prognosis - germinal centre phenotype
Outline some key histological features of T cell lymphomas.
- Large T lymphocytes
- Associated reactive cell population in histology (especially eosinophils)
List some types of T cell lymphoma and their associations.
- Adult T cell leukaemia/lymphoma - HTLV1 (CD4+ve)
- Enteropathy-associated T cell lymphoma - Coeliac disease
- Cutaneous T cell lymphoma (mycosis fungoides)
- Anaplastic large cell lymphoma - t(2;5)
Outline the typical demographics of anaplastic large cell lymphoma.
Children and young adults with lymphadenopathy
NOTE: this is aggressive
Outline the key histological features of anaplastic large T cell lymphoma.
- Large epithelioid lymphocytes
- T cell (CD3 +ve) or null phenotype (anaplastic - CD3 -ve cells, all other CD markers negative too)
Which molecular features are associated with anaplastic large cell lymphoma?
- 2;5 translocation
- Alk-1 protein expression - (used for diagnosis)
Outline the key histological features of Enteropathy-associated T cell lymphoma
Intraepithelial CD8 +ve T cells mainly in small bowel causing solid tumours.
Outline the key histological features of cutaneous T cell lymphoma
CD4+ve in epidermis and dermis
Causes tumours and nodules in skin.
List some key differences between Hodgkin and Non-Hodgkin Lymphoma.
- Hodgkin is more localised (usually one nodal site)
- Hodgkin spreads contiguously to adjacent to adjacent lymph nodes
Types of Hodgkins Lymphoma
Classic Hodgkins Lymphoma
Non-classic Lymphocyte predominant Hodgkins Lymphoma
Outline the typical presentation of classical Hodgkin lymphoma.
- Young and middle-aged patients with only a single group of lymph nodes involved
- Associated with EBV
Outline some histological features of classical Hodgkin lymphoma.
- Nodular sclerosis
- Lymphoma infiltrate composes of a mixed cellular population (eosinophils, macrophages) with some neoplastic lymphocytes scattered around (Reed-Sternberg cells). - this is unlike NHL lymphomas!
- Reed sternberg cells (lymphocytes with large prominent nuclei surrounding a darker nulei - often binuclear)
- Neoplastic cells are CD20-ve but CD15+ve and CD30+ve
What are the diagnostic CD markers for Hodgkin lymphoma?
- CD15
- CD30
Negative for CD20!
Outline the key histological features of lymphocyte predominant Hodgkin lymphoma.
- Tumor is composed of few neoplastic Reed-Sternberg cell variants, also known as “popcorn” cells, in a background of non-neoplastic small lymphocytes
- But unlike classic = CD20+ve, CD15 -ve, CD30 -ve
- Neoplastic cells are germinal centre B cell (hence CD10+ve and Bcl 6+ve)
Which markers are key in the diagnosis of lymphocyte predominant Hodgkin lymphoma?
- Positive = CD20
- Negative = CD15, CD30 (unlike classical Hodgkin lymphoma)
Translocation associated with Burkitt’s Lymphoma
t(8;14) = c-myc oncogene overexpression
Translocation associated with Mantle cell lymphoma
t(11;14) = cyclinD1 deregulation
Translocation associated with Follicular Lymphoma
t(14;18) = bcl2
Translocation associated with Anaplastic large cell lymphoma
t(2;5) = Alk1 overexpression
