Haem: Lymphoma MDT (Laz) Flashcards
(66 cards)
1
Q
Outline the difference in prevalence of Hodgkin’s lymphoma and Non-Hodgkin lymphoma.
A
- NHL = 80%
- Hodgkin = 20%
2
Q
Outline the processes by which immunoglobulins and T cell receptors become capable of identifying a wide variety of antigens.
A
- 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.
3
Q
Which proteins carry out VDJ recombination and somatic hypermutation
A
VDJ recombination: RAG1 and RAG2 combine to form RAG complex
SHM: activation induced cytidine deaminase
4
Q
What is the main downside of the processes that generate variety in immunoglobulins and TCR during the adaptive immune response?
A
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
Rapid proliferation within germinal centres - increased risk of DNA replication errors
5
Q
Outline how chromosomal translocations in B cells can lead to malignancy.
A
- 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
6
Q
List some oncogenes that are implicated in lymphoma/leukaemia.
A
- Bcl2
- Bcl6
- Cyclin D1
- c-Myc
7
Q
List some risk factors that contribute to the aetiology of NHL.
A
- Constant antigenic stimulation
- Viral infection
- Loss of T cell function (immunosuppression)
8
Q
List some examples of how constant antigenic stimulation can lead to lymphoma.
A
- 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
9
Q
Give an example of how viral infections that can lead to lymphoma.
A
Direct viral integration: HTLV1
- HTLV1 infects T cells by vertical transmission
- Viral genome integrates into T cell genome and drives proliferation
- May cause adult T cell leukaemia/lymphoma (very aggressive)
10
Q
Give an example of how loss of T cell function can lead to lymphoma
A
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
11
Q
List some different types of tissues of the lymphoreticular system.
A
- 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)
12
Q
List the different cell types of the lymphoreticular system.
A
Lymphocytes
- B cells
- T cells
Accessory cells
- Antigen-presenting cells
- Macrophages
- Connective tissue cells
13
Q
Describe the normal histological appearance of a lymph node.
A
Round areas full of B cells (B cell follicles)
- Mantle zone - a crescent-shaped region where naïve unstimulated B cells are found
- Germinal centre - where naïve B cells will eventually migrate, and mature B cells will end up in the medulla.
- Antigen presenting cells present antigens to B cells in germinal centre to activate them
Paracortical T cell zone - surrounds the B cell follicles
14
Q
Describe the composition of T cell areas in lymph nodes.
A
- 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
15
Q
What is the main technique used to identify different types of lymphocyte within a lymph node biopsy?
A
Immunohistochemistry
16
Q
What are the main markers used for B and T cells?
A
T cell = CD3, CD5
B cell = CD20
17
Q
Define lymphoma.
A
- Neoplastic proliferation of lymphoid cells forming discrete tissue masses
- They arise in and involve lymphoid tissues
18
Q
Which factors are taken into account when classifying a lymphoma?
A
- Clinical
- Histological
- Immunohistochemical
- Molecular
19
Q
Outline the WHO classification of lymphoma.
A
Hodgkin lymphoma
- Classical
- Lymphocyte predominant
- Abnormal B cells
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
20
Q
Why is non-Hodgkin lymphoma often disseminated at presentation?
A
Neoplastic lymphoid cells circulate in the blood leading to disseminated disease at presentation
NOTE: lymphoid neoplasms can disrupt normal immune functioning leading to immunodeficiencies
21
Q
What are the diagnostic tools used by pathologists when investigating lymphoma?
A
- 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
22
Q
Which molecular tools are used when investigating lymphoma?
A
- FISH - identify chromosomal translocations
- PCR - identify chromosomal translocations transcripts (e.g. bcr-abl transcript in CML)
23
Q
Give an example of a chromosomal translocation that is diagnostic of lymphoma.
A
11;14 = Mantle Cell Lymphoma
24
Q
Give an example of a chromosomal translocation that is prognostic in lymphoma.
A
2;5 = anaplastic large cell lymphoma
25
List some types of low grade lymphoma.
* Follicular lymphoma
* Small lymphocytic lymphoma (CLL)
* Marginal zone lymphoma
26
Name 3 types of high grade lymphoma.
* Diffuse large B cell lymphoma
* Burkitt's lymphoma
* Mantle cell lymphoma
27
How does follicular lymphoma typically present?
Lymphadenopathy in middle-aged or elderly patients
NOTE: it is usually indolent but can transform into a high-grade lymphoma
28
Describe the histological features of follilcular 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 **Bcl2**)
29
Which molecular feature is associated with follicular lymphoma?
14;18 translocation involving Bcl2 gene
30
Describe the typical presentation of small lymphocytic lymphoma.
Lymphadenopathy or high blood lymphocyte count in middle-aged or elderly patients
31
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
* They replace the entire lymph node so that you can no longer identify follicles or T cell areas
32
What is the term used to describe the transformation of small lymphocytic lymphoma into a higher grade lymphoma/leukaemia?
Richter transformation
33
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)
34
Outline the typical presentation of mantle cell lymphoma.
* Typically affects middle-aged males
* Affects lymph nodes and the GI tract (diarrhoea, abdominal pain)
* Often present with disseminated disease
NOTE: median survival = 3-5 years
35
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**
* **'anglular / clefted nuclei'**
36
Which molecular features are characteristic of mantle cell lymphoma?
* 11;14 translocation
* Cyclin D1 overexpression
37
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**
38
Outline the histological features of Burkitt's lymphoma.
* Arises from germinal centre cells
* **Starry sky appearance**
39
Which molecular feature is associated with Burkitt's lymphoma.
* c-Myc translocation (8;14, 2;8 or 8;22)
40
Outline the typical presentation of diffuse large B cell lymphoma.
Middle-aged and elderly patients with lymphadenopathy
41
Outline the histological features of diffuse large B cell lymphoma.
* Arise from germinal centre or pre-germinal centre B cells
* Large lymphoid cells
* Lymph node is effaced so follicles and germinal centres cannot be identified
42
List some prognostic association of diffuse large B cell lymphoma.
Good prognosis - germinal centre phenotype
Poor prognosis - p53-positive and high proliferation fraction
43
Outline the typical presentation of T cell lymphomas.
Middle-aged and elderly patients with lymphadenopathy
NOTE: these are aggressive
44
Outline some key histological features of T cell lymphomas.
* Large T lymphocytes
* Associated reactive cell population (especially eosinophils)
45
List some types of T cell lymphoma and their associations.
* Adult T cell leukaemia/lymphoma - HTLV1
* Enteropathy-associated T cell lymphoma - Coeliac disease
* Cutaneous T cell lymphoma (mycosis fungoides)
* Anaplastic large cell lymphoma
46
Outline the typical presentation of anaplastic large cell lymphoma.
Children and young adults with lymphadenopathy
NOTE: this is aggressive
47
Outline the key histological features of anaplastic large cell lymphoma.
* Large epithelioid lymphocytes
* T cell or null phenotype (anaplastic)
48
Which molecular features are associated with anaplastic large cell lymphoma?
* 2;5 translocation
* Alk-1 protein expression - BETTER prognosis
49
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
NOTE: NHL tends to involve multiple lymph node sites and spread discontinuously
50
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
51
Name 3 subtypes of classical Hodgkin's lymphoma
* Nodular sclerosing
* Mixed cellularity
* Lymphocyte rich and lymphocyte depleted
52
Which type of Hodgkin's lymphoma is related to NHL
Lymphocyte predominant Hodgkins
53
What is the difference between a Hodgkin cell and a Reed-Sternberg cells
Hodgkin cell: mononucleated abnormal lymphocyte
Reed-Sternberg cell: bi- or multinucleated abnormal lymphocyte
54
Outline some histological features of classical Hodgkin lymphoma.
* Nodular sclerosis
* Mixed cell population of **Reed-Sternberg cells** and Hodgkin cells
* Lymphoma cells are few in number and are scattered around
* Eosinophils present
* Arise from germinal centre or post-germinal centre cells
55
What are the diagnostic markers for classic Hodgkin lymphoma?
* CD15
* CD30
(CD20 negative)
56
Describe the typical presentation of nodular lymphocyte predominant Hodgkin lymphoma.
* Isolated lymphadenopathy
* NO association with EBV
57
Outline the key histological features of lymphocyte predominant Hodgkin lymphoma.
* B cell rich nodules with scattered around L&H cells
* Arise from germinal centres
* Reactive population in the background consisting of small lymphocytes
* NO eosinophils and macrophages
58
Which markers are key in the diagnosis of lymphocyte predominant Hodgkin lymphoma?
* Positive = CD20
* Negative = CD15, CD30 (unlike classical Hodgkin lymphoma)
59
What constitutional symptoms may be present in a patient with lymphoma?
B symptoms - fever, night sweats, weight loss
Pruritis
60
What are the stages of lymphoma?
1 = 1 group of nodes
2 = \> 1 group of nodes on the same side of the diaphragm
3 = \> 1 group of nodes above and below the diaphragm
4 = extranodal spread
Suffic 'B' if B symptoms are present
61
Which type of scan is often used to stage lymphoma?
FDG-PET/CT
62
Which treatment modalities are used in Hodgkin lymphoma?
* All patients receive chemotherapy
* Radiotherapy is often used because Hodgkin lymphoma is very responsive
* Referred to as 'combined modality' if both are used
63
Which chemotherapy regimen is usually used for Hodgkin lymphoma?
**ABVD**: Adriamycin, Bleomycin, Vinblastine, Dacarbazine
NOTE: this is usually given at 4-weekly intervals for 2-6 cycles
64
What are some possible long-term consequences of chemotherapy for Hodgkin lymphoma?
Pulmonary fibrosis
Cardiomyopathy
65
How might a relapse of Hodgkin lymphoma be treated?
High-dose chemotherapy with autologous stem cell transplant
NOTE: intensifying chemotherapy will lead to an increased cure rate but it will also lead to an increase in secondary cancers
66
Describe the curability of Hodgkin lymphoma.
Stage I and II: \>80%
Stage IV: 50%
