Lymphoma 1 Flashcards

1
Q
  1. Outline the difference in prevalence of Hodgkin’s lymphoma and Non-Hodgkin lymphoma.
A
NHL = 80% 
Hodgkin = 20%
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2
Q
  1. 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

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3
Q
  1. What is the main downside of the processes that generate variety in immunoglobulins and TCR?
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

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4
Q
  1. 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

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5
Q
  1. List some oncogenes that are implicated in lymphoma/leukaemia.
A

Bcl2
Bcl6
Cyclin D1
c-Myc

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6
Q
  1. List some risk factors that contribute to the aetiology of lymphoma.
A

Constant antigenic stimulation (bacterial infection/autoimmune)
Viral infection
Loss of T cell function (HIV)

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7
Q
  1. 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 (autoimmune)
Coeliac disease - small bowel T cell lymphoma, enteropathy-associated T cell NHL

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8
Q
  1. List two examples of viral infections that can lead to lymphoma.
A

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)

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9
Q
  1. 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)

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10
Q
  1. Describe the normal histological appearance of a lymph node.
A

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

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11
Q
  1. 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

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12
Q
  1. What are the main immunohistochemical markers used for B and T cells?
A

T cell = CD3, CD5

B cell = CD20

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13
Q
  1. Define lymphoma.
A

Neoplastic proliferation of lymphoid cells forming discrete tissue masses
They arise in and involve lymphoid tissues

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14
Q
  1. Outline the WHO classification of lymphoma.
A
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
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15
Q
  1. 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

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16
Q
  1. 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 and Mantle cell lymphoma)
Light chain restriction
Molecular tools

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17
Q
  1. Which molecular tools are used when investigating lymphoma?
A

FISH – identify chromosomal translocations

PCR – identify chromosomal translocations, clonal T cell receptor or Ig gene rearrangement

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18
Q
  1. Give an example of a chromosomal translocation that is diagnostic of lymphoma.
A

11;14 = Mantle Cell Lymphoma

19
Q
  1. Give an example of a chromosomal translocation that is prognostic in lymphoma.
A

2;5 = anaplastic large cell lymphoma

20
Q
  1. List some types of low grade lymphoma.
A

Follicular lymphoma
Small lymphocytic lymphoma (CLL)
Marginal zone lymphoma

21
Q
  1. Name types of high grade lymphoma.
A

Diffuse large B cell lymphoma

Burkitt’s lymphoma

22
Q
  1. Name a type of aggressive lymphoma
A

Burkitts lymphoma

23
Q
  1. Describe the histological features of follicular lymphoma.
A

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)

24
Q
  1. Which molecular feature is associated with follicular lymphoma?
A

14;18 translocation involving Bcl2 gene

25
Q
  1. Outline the histological features of small lymphocytic lymphoma.
A

Small lymphocytes
Arise form naïve B cells or post-germinal centre memory B cells
Cells are CD5 and CD23 positive
They replace the entire lymph node so that you can no longer identify follicles or T cell areas

26
Q
  1. What is the term used to describe the transformation of small lymphocytic lymphoma into a higher grade lymphoma/leukaemia?
A

Richter transformation

27
Q
  1. What is marginal zone lymphoma?
A

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)

28
Q
  1. Outline the typical presentation of mantle cell lymphoma.
A

Typically affects middle-aged males
Affects lymph nodes and the GI tract
Often present with disseminated disease
NOTE: median survival = 3-5 years

29
Q
  1. Outline the key histological features of mantle cell lymphoma.
A

Located in the mantle zone of the lymph node
Arise from pre-germinal centre cells
Show aberrant expression of cyclin D1 and CD5

30
Q
  1. Which molecular features are characteristic of mantle cell lymphoma?
A

11;14 translocation

Cyclin D1 overexpression

31
Q
  1. Outline the histological features of Burkitt’s lymphoma.
A

Arises from germinal centre cells

Starry sky appearance

32
Q
  1. Which molecular feature is associated with Burkitt’s lymphoma.
A

c-Myc tranlocation (8;14, 2;8 or 8;22)

33
Q
  1. Outline the histological features of diffuse large B cell lymphoma.
A

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

34
Q
  1. List some prognostic association of diffuse large B cell lymphoma.
A

Good prognosis – germinal centre phenotype

Poor prognosis – p53-positive and high proliferation fraction

35
Q
  1. Outline some key histological features of T cell lymphomas.
A

Large T lymphocytes

Associated reactive cell population (especially eosinophils)

36
Q
  1. List some types of T cell lymphoma and their associations.
A

Adult T cell leukaemia/lymphoma – HTLV1
Enteropathy-associated T cell lymphoma – Coeliac disease
Cutaneous T cell lymphoma (mycosis fungoides)
Anaplastic large cell lymphoma

37
Q
  1. Outline the typical presentation of anaplastic large cell lymphoma.
A

Children and young adults with lymphadenopathy

NOTE: this is aggressive

38
Q
  1. List some key differences between Hodgkin and Non-Hodgkin Lymphoma.
A

Hodgkin is more localised (usually one nodal site)
Hodgkin spreads contiguously to adjacent lymph nodes
NOTE: NHL tends to involve multiple lymph node sites and spread discontinuously

39
Q
  1. Outline some histological features of classical Hodgkin lymphoma.
A

Nodular sclerosis
Mixed cell population of Reed-Sternberg cells
Lymphoma cells are few in number and are scattered around
Eosinophils
Arise from germinal centre or post-germinal centre cells

40
Q
  1. What are the diagnostic markers for Hodgkin lymphoma?
A

CD15

CD30

41
Q
  1. Describe the typical presentation of nodular lymphocyte predominant Hodgkin lymphoma.
A

Isolated lymphadenopathy

NO association with EBV

42
Q
  1. Outline the key histological features of lymphocyte predominant Hodgkin lymphoma.
A

B cell rich nodules
Scattered around L&H cells
Reactive population in the background consisting of small lymphocytes
NO eosinophils and macrophages

43
Q
  1. Which markers are key in the diagnosis of lymphocyte predominant Hodgkin lymphoma?
A
Positive = CD20
Negative = CD15, CD30 (unlike classical Hodgkin lymphoma)