Lymphoma 1 Flashcards by Ellie Smyth

What is lymphoma?

Neoplastic (malignant) tumour of lymphoid cells

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Where are lymphomas usually found?

Lymph nodes, bone marrow and/or blood (lymphatic system)
Lymphoid organs; spleen or the gut-associated lymphoid tissue
Skin (often T cell disease)

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What is the proportion of Hodgkin vs Non-Hodgkin lymphoma?

Non-Hodgkin Lymphoma - 80%

Hodgkin Lymphoma - 20%

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What is the relationship between lymphomas and risk factors?

Most lymphoma subtypes/cases are sporadic with no known risk factors
Some lymphoma subtypes have specific risk factors - immune diseases acquired or iatrogenic, associated specific infections or inflammation

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What is the reason for existing ‘limited’ DNA instability of lymphocytes?

For an adaptive immune response
Generates immunoglobulin and T cell receptor diversity and Ig class switching

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What happens to lymphocytes to generate antibody diversity?

Cut and recombined

Subjected to deliberate DNA mutagenesis (somatic hypermutation)

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What is the benefit of rapid cell proliferation in the germinal centre?

Allows rapid response to infection

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What is the downside to rapid cell proliferation in the germinal centre?

Rapid multiple cell divisions = increased chance of DNA replication errors

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What is the benefit for lymphocytes being dependent on apoptosis?

Exquisite antibody specificity & eliminates self reactive clones

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What is the downside to lymphocytes dependent on apoptosis?

Apoptosis is ‘switched off’ in germinal centre

Consequences of mutations in apoptosis regulating genes

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What happens in the t(8;14) gene recombination error?

C-MYC oncogenes are located downstream of the IgH promoter (instead of the Ig Heavy chain gene) and are over expressed

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What are the main groups/mechanisms of the risk factors for certain NHL subtypes?

Constant antigenic stimulation
Viral infection (direct viral integration of lymphocytes)
Loss of T cell function and EBV infection plus EBV infections of B cells

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What can cause constant antigenic stimulation?

Bacterial infection (chronic)
Auto immune disorders

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What can cause loss of T cell function and EBV infection plus EBV infections of B cells?

Loss of T cells (untreated HIV infection)

Iatrogenic immunosuppression

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What lymphoma can arise as a result of bacterial or auto immune antigenic drive?

B cell Non Hodgkin Lymphoma Marginal zone subtype (MZL)

Enteropathy associated T-Cell Non Hodgkin lymphoma (EATL)

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What bacterial infections can cause MZL?

H. pylori - Gastric MALT (mucosa associated lymphoid tissue, MZL of stomach)
Sjogren syndrome (MZL of salivary glands
Hashimoto’s (MZL of thyroid)

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What can cause EATL?

Coeliac disease/Gluten: small intestine EATL

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What is an example of direct viral integration and lymphomagenesis?

HTLV1 retrovirus infects T cells by vertical transmission

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What infection is associated with loss of T cell function lymphoma?

EBV infection

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What are the elements of the lymphoreticular system?

Generative LR tissue
Reactive LR tissue
Acquired LR tissue

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Give examples of generative lymphoreticular tissue and their function

Bone marrow and thymus

Generation/maturation of lymphoid cells

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Give examples and function of reactive lymphoreticular tissue

Lymph nodes and spleen

Development of immune reaction

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Give examples and function of acquired lymphoreticular tissue

Extranodal lymphoid tissue e.g. skin, stomach, lungs

Development of local immune reaction

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Summarise the role of B cells

Express surface immunoglobulin

Antibody production

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Summarise the role of T lymphocytes

Express surface T cell receptor Regulation of B cells and macrophage function Cytotoxic function

What can be found in the mantle zone of the lymphoid follicle?

Naïve unstimulated B cells

What can be found in the germinal centre of the lymphoid follicle?

B cells | Antigen presenting cells

What comprises the T cell area?

T cells Antigen presenting cells High endothelial vessels

How are types of lymphocytes detected?

Detected in tissue samples using immunohistochemistry Identify subtypes and different stages of development by the different types of cell surface receptors expressed by the cells

Define lymphoma

Neoplastic proliferation of lymphoid cells forming discrete tissue masses

What is the site of lymphoma?

Arise in and involve lymphoid tissues (including acquired lymphoid tissue - extranodal lymphomas)

What are the various pathogenic causes of lymphoma?

Inherent instability of lymphoid cells Inherited disorders increasing instability Viral agents (EBV, HTLV-1) Environmental agents (mutagens, chronic immune stimulation) Iatrogenic causes (chemotherapy, radiotherapy)

What are the types of Hodgkin lymphoma?

Classical | Lymphocyte predominant

Which cell type stains CD20?

B cell

Give examples of low grade B cell Non-Hodgkin lymphomas

Follicular lymphoma Small lymphocytic lymphoma / chronic lymphocytic leukaemia Marginal zone lymphoma

Give examples of high grade B cell non-Hodgkin lymphoma

Diffuse large B cell lymphoma | Burkitt's lymphoma

Give an example of an aggressive B cell Non-Hodgkin lymphoma

Mantle cell lymphoma

Which cell type stains CD3 and CD5?

T cell

How does follicular lymphoma present?

Disease of middle age/elderly | Lymphadenopathy

What is the histopathology of follicular lymphoma?

Follicular pattern | Germinal centre cell origin CD10, bcl-6+

What are the molecular features of follicular lymphoma?

14;18 translocation involving bcl-2 gene

How do you make an immunohistochemical diagnosis of follicular lymphoma?

Detection of bcl-2

What are the clinical features of small lymphocytic lymphoma / CLL?

Middle age / elderly | Nodes - lymphadenopathy, or blood - high white count

What is the histopathology of small lymphocytic lymphoma / CLL?

Small lymphocytes, naïve or post-germinal centre memory B cell CD5, CD23+

What do you call the transformation of small lymphocytic lymphoma / CLL to high grade lymphoma?

Richter transformation

Where and why does marginal zone lymphoma arise?

Extranodal sites (gut, lung spleen) in response to chronic antigen stimulation

What are the clinical features of mantle cell lymphoma?

Middle age, male predominance Lymph nodes, GI tract Disseminated disease at presentation

What is the histopathology of mantle cell lymphoma?

Located in mantle zone Pre-germinal centre cell Aberrant CD5, cyclin D1 expression

What are the molecular features of mantle cell lymphoma?

11;14 translocation | Cyclin D1 over expression

What are the clinical features of Burkitt's lymphoma?

Jaw or abdominal mass children/young adults Endemic, sporadic, immunodeficiency EBV associated

What is the histopathology of Burkitt's lymphoma?

Germinal cell centre origin | Starry sky appearance

What are the molecular features of Burkitt's lymphoma?

C-myc translocation (8:14, 2:8, 8;22)

What are the clinical features of diffuse large B cell lymphoma?

Middle age / elderly | Lymphadenopathy

What is the histopathology of diffuse large B cell lymphoma?

Germinal centre or post-germinal centre B cell Sheets of large lymphoid cells Germinal centre phenotype = good prognosis P53 positive, high proliferation fraction = poor prognosis

What are the features of peripheral T cell lymphoma?

``` MA / elderly Lymphadenopathy and extranodal sites Large T lymphocytes Often with associated reactive cell population, esp eosinophils Aggressive ```

What are the clinical features of anaplastic large cell lymphoma?

Children / young adults | Lymphadenopathy

What are the histopathology features of anaplastic large cell lymphoma?

Large epithelioid lymphocytes | T cell or null phenotype

What are the molecular features of anaplastic large cell lymphoma?

2;5 translocation | Alk-1 protein expression

What are the subtypes of classical Hodgkin's lymphoma?

Nodular sclerosing Mixed cellularity Lymphocyte rich and lymphocyte depleted

What are the clinical features of classical HL?

Young and MA Often involves just single lymph node group

What are some key features of classical HL?

Thought to be germinal centre/post-germinal centre B cell origin EBV associated CD30+, CD15+, CD20-

What is the histopathology of classical HL?

Sclerosis, mixed cell population in which Reed-Sternberg and Hodgkin cells with eosinophils

What is the key clinical feature of nodular LP Hodgkins Lymphoma?

Isolated lymphadenopathy

What are some other features of nodular LP Hodgkins Lymphoma?

Germinal centre B cell (positive for some germinal centre B cell markers) No association with EBV CD20+, CD30-, CD15- Indolent, can transform to high grade B cell lymphoma

What is the histopathology of nodular LP Hodgkins lymphoma?

B cell rich nodules with scattered L&H cells

Lymphoma 1 Flashcards

(65 cards)