Lymphoma Flashcards

1
Q
  • Describe the lymphoreticular system and the function of each component
A

The lymphoreticular system:

  • Generative LR tissue - bone marrow and thymus. Fuction = generation/maturation of lymphoid cells
  • Reactive LR tissue - lymph nodes and spleen. Function = development of immune reaction
  • Acquired LR tissue - extranodal lymphoid tissue e.g. skin, stomach, lung. Function = development of local immune reaction
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2
Q

What are the cells of the lymphoreticular system and their individual functions?

A
  • Lymphocytes - classified according to function:
  • B lymphocytes - xpress surface immunoglobulin and production of antibodies
  • T lymphocytes - Express surface T cell receptor, regulation of B cell and macrophage function and cytotoxic function
  • Accessory cells
  • Antigen presenting cells
  • Macrophages
  • Connective tissue cells
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3
Q

What does this image show?

A

Normal lymph node

B cell follicles (right) and inbetween are T cell follicles

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4
Q

Describe the different parts of the B cell area as seen in th picture

A
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5
Q

What is the T cell area of a lymph node composed of?

A

T cell area is comprised of:

  • T cells
  • Antigen Presenting cells
  • High endothelial vessels

This is where T cells which bind antigen epitopes are selected and activated

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6
Q

How are different types of lymphocytes identified in the lab?

A

Lymphocyte subtypes and cells at different stages of development ae identified by the different types of cell surface receptors expressed by the cells

These are called CD markers, and they can be detected in tissue samples using immunohistochemistry

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7
Q
  1. Define lymphoma
  2. Define where lymphoma arises
  3. Describe the classification of lymphoma
A
  1. Lymphoma is the neoplastic proliferation of lymphpid cells forming discrete tissue masses
  2. Lymphoma arises in and involves lymphoid tissues - including acquired lymphoid tissue causing extranodal lymphomas
  3. Classification: Two clinically distinct groups:
  • Hodgkin lymphoma
  • Non-Hodgkin lymphoma - B cell type, low and high grade (most common), T cell type and other
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8
Q

Describe the pathogenesis of lymphoma

A
  • Neoplastic - proliferation of lymphoid cells - clonal
  • Mutation in genes to allow uncontrolled growth
    • Normal lymphocytes undergo controlled genomic “instability” of lymphoid cells- mistakes in this process produce neoplastic mutations
    • Inherited disorders - leading to increased/abnormal genomic instability
    • Viral agents - EBV, HTLV-1
    • Environmental agents - mutagens, chronic immune stimulation e.g. H.Pylori
    • Iatrogenic causes - radiotherapy, chemotherapy
  • Immunosuppression predisposes to development of lymphoma e.g. infection or loss of surveillance
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9
Q

Describe the WHO classification of the following:

  1. Hodgkin lymphoma
  2. Non-Hodgkin lymphoma
A
  1. Hodgkin lymphoma - classic type and is lymphocyte predominant. Presence of Reed-Sternberg cells
  2. Non-Hodgkin lymphoma
  • B cell
    • Precursor B cell neoplasms
    • Peripheral B cell neoplasms (low grade and high grade)
  • T cell
    • Precursor T cell neoplasms
    • Peripheral T cell neoplasms
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10
Q
  1. What is the most common type of lymphoma?
  2. What can lymphoid neoplasms do to the normal immune system?
  3. Do cells of lymphoma spread?
A
  1. B cell Non-hodgkin lymphoma is the most common type (80-85%)
  2. Lymphoid neoplasms may disrupt normal immune system function - therefore patients may develop immunodeficiencies
  3. Neoplastic lymphoid cells circulate in the blood - hence often disseminated at presentation. The exception to this rule is Hodgkin lymphoma
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11
Q

Describe the following diagnostic tools:

  1. Cytology
  2. Histology
  3. Immunophenotyping
A
  1. Cytology lookes at a single cells from a lump - look at cell morphology
  2. Histology looks at tissue sections looking at:
  • Architecture - nodular or diffuse
  • Cells - small round, small cleaved or large
  1. Immunophenotyping like immunohistochemistry is used to identify proteins in/on cells in tissue sections
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12
Q

Describe what immunohistochemistry can show about a lymphoma and what markers are used

A

Immunohistochemistry can show:

  • Cell type
    • T cell - CD3 and CD5
    • B cell = CD20
  • Cell distribution
  • Loss of normal surface proteins e.g neoplastic T cells
  • Abnormal expression of proteins e.g. Cyclin D1
  • Clonality of B cells - light chain expression
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13
Q

What molecular tools can be used to identify mutations that occur and can lead to lymphoma?

A
  • FISH - identify chromosome translocations
  • PCR - identify chromososme translocations and clonal T cell receptor or immunoglobulin gene rearrangement.

Can be a diagnostic or prognostic depending on the type of lymphoma

Diagnostic - 11;14 = Mantle cell lymphoma

Prognostic = 2;5 Anaplastic large cell lymphoma

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14
Q

What are the commn B cell Non-Hodgkin lymphomas?

  1. Low grade
  2. High grade
  3. Intermediate
A
  1. Low grade
  • Follicular lymphoma
  • Small lymphocytic lymphoma/chronic lymphocytic leukemia
  • Marginal zone lymphoma
  • Mantle zone lymphoma
  1. High grade
    * Diffuse large B cell lymphoma
  2. Intermediate
    * Burkitt’s lymphoma
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15
Q

Describe the following about follicular lymphoma

  1. Clinical features/epidemiology
  2. Histopathology
  3. Molecular- using FISH
A

Follicular lymphoma:

  1. Clinical - lymphadenopathy is the main sign. Seen in the elderly
  2. Histopathology -Follicular pattern, germinal centre cell origin CD10, bcl-6+
  3. Molecular - 14;18 translocation involving bcl-2 gene

indolent (causing little to no effect) but can transform to high grade lymphoma

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16
Q

Describe the following about small lymphocytic lymphoma/CLL

  1. Clinical features/epidemiology
  2. Histopathology
  3. Molecular- using FISH
A

CLL:

  1. Clinical - nodes or blood. Seen in the elderly/MA
  2. Histopathology - Small lymphocytes, naive or post-germinal center memory B cell. CD5, CD23+
  3. Molecular - multiple genetic abnormalities

Indolent but can transform to high grade lymphoma is what is known as Richter transformation

17
Q

Describe the following for marginal zone lymphoma/MALT lymphoma

  1. Where do they arise?
  2. What is the suscpected cause?
  3. Histopathology
  4. How do they develop?
A
  1. MALT lymphomas arise mainly at extranodal sites e.g. gut, lung and spleen
  2. Thought to arise in response to chronic antigen stimulation e.g. Helicobacter in stomach
  3. Post-germinal centre memory B cell
  4. Indolent but can transform to high grade lymphoma. Low grade disease can be treated by non-chemotheraputic modalities e.g. H pylori eradication
18
Q

Describe the following about Mantle cell lymphoma:

  1. Clinical features/epidemiology
  2. Histopathology
  3. Molecular
A

Mantle cell lymphoma: HIGH GRADE

  1. Clinical
  • MA male predominance
  • Lymph nodes and GI tract affected
  • Disseminated disease at presentation
  1. Histopathology:
  • Located in the mantle zone around B cell follicles
  • Pre-germinal centre cell
  • Aberrant CD5, cyclin D1 expression
  1. Molecular
  • 11;14 translocation
  • Cyclin D1 overexpression

Median survival rate is 3-5 years

19
Q

Describe the following about Burkitt’s lymphoma

  1. Clinical features/epidemiology
  2. Histopathology
  3. Molecular
A

Burkitt’s lymphoma

  1. Clinical:
  • Jaw or abdominal mass in children/young adults
  • Endemic - regularly found in the same area/groups of people
  • Sporadic
  • Immunodeficiency
  • Associated with EBV
  1. Histopathology:
  • Germinal center cell origun
  • ‘starry sky appearance’
  1. Molecular
    * C-myc translocation (8;14, 2:8, 8;22)

Aggressive disease

20
Q

Describe the following about Diffuse large B cell lymphoma

  1. Clinical features/epidemiology
  2. Histopathology
A

Diffuse large B cell lymphoma

  1. Clinical
  • MA/elderly
  • Lymphadenopathy

Histopathology:

  • Germinal center or post-germinal center B cell
  • Sheets of large lymphoid cells
  • Germinal center = good prognosis
  • p52 positive, high proliferation fraction = poor prognosis

Aggressive, high grade

21
Q

Describe Peripheral T cell lymphoma NOS (not otherwise specified)

A
  • Seen more commonly in MA/elderly
  • Causes lymphadenopathy and can occur at extranodal sites
  • Large T lymphocytes in histopathology
  • Often associated with reactive cell population, especially eosinophils
  • Aggressive
22
Q

What infections are associated with each of these special forms of T cell lymphoma?

  1. Adult T cell leukemia/lymphoma
  2. Enteropathy associated T cell lymphoma
  3. Cutaneous T cell lymphomas
A
  1. Adult T cell leukemia/lymphoma - seen mainly in the Caribbean and Japan. Associated with HTLV-1 infection
  2. Enteropathy associated T cell lymphoma - associated with chronic coeliac disease
  3. Cutaneous T cell lymphomas - helper T cells e.g. mycosis fungoides
23
Q

Describe the followig about Anaplastic large cell lymphoma

  1. Clinical features/epidemiology
  2. Histopathology
  3. Molecular
  4. What gives a better prognosis?
A

Anaplastic large cell lymphoma

  1. Clinical
  • Children/young adults
  • Lymphadenopathy is the main sign
  1. Histopathology:
  • Large “epithelioid” lymphocytes
  • T cell or null phenotype
  • Presence of anaplastic cells - vary in shape/size and nucleus shape
  1. Molecular
  • 2;5 translocation
  • Alk-1 protein expression
  1. Aggressive, but Alk-1 positive provides a better prognosis
24
Q

Describe the following for both Hodgkin lymphoma and non-hodgkin lymphoma

  1. Site
  2. Spread
A
  1. Hodgkin lymphoma is often localised to a single nodal site. Non-HL is often involves multiple lymph node sites
  2. HL spreads continuously to adjacent lymph nodes. Non-HL spreads discontinuously
25
Q

What are the different subtypes of classical Hodgkin’s lymphoma?

A
  • Nodular sclerosing
  • Mixed cellularity
  • Lymphocyte rich and lymphocyte depeleted
26
Q

Describe the following about classical Hodgkin’s lymphoma

  1. Clinical features/epidemiology
  2. Histopathology
  3. Associations
  4. What does the image show? What markers are being expressed?
A

Classical HL:

  1. Clinical
  • Young and MA
  • Often involvs just a single lymph node group
  1. Histopathology
  • Thought to be germinal center/post germinal center B cell origin
  • Sclerosis
  • Mixed cell population in which scattered Reed-Sternberg and Hodgkin cells with eosinophils are seen
  • Moderately aggressive
  1. Associated with EBV
  2. Owl’s eyes appearnace of a lymphoma cell/Reed sternberg cells. Expressing CD30 and CD15
27
Q

Describe the following for Nodular lymphoycte predominant Hodgkins lymphoma

  1. Clinical features/epidemiology
  2. Histopathology
  3. Transformation
A

Nodular LP HL

  1. Clinical
    * Isolated lymphadenopathy
  2. Histopathology
  • Germinal center B cell (positive for some germinal center B cell markers
  • B cell rich nodulrs with scattered L&H cells
  1. Indolent but can transform to high grade B cell lymphoma