Lymphoma: Multidisciplinary Flashcards
(111 cards)
1
Q
What systems are part of the lymphoreticular system (3)
A
Generative LR tissue
Reactive LR tissue
Acquired LR tissue
2
Q
What forms the generative lymphoreticular system (2)
A
Bone marrow and thymus
3
Q
Function of generative LR tissue
A
Generation/maturation of lymphoid cells
4
Q
Components of reactive LR tissue (2)
A
Lymph node
spleen
5
Q
Function reactive LR tissue
A
Development of immune reaction
6
Q
Components acquired LR tissue
A
Extranodal lymphoid tissue (skin, stomach, lung)
7
Q
Function LR tissue
A
Development of local immune reaction
8
Q
Cells of LR system (2)
A
Lymphocytes
Accessory cells
9
Q
How are lymphocytes classified
A
B lymphocytes
T lymphocytes
10
Q
Characteristics of B lymphocytes (2)
A
Express surface immunoglobulin
Antibody production
11
Q
Characteristics of T lymphocytes (3)
A
Express surface T cell receptor
Regulation of B cell and macrophge function
Cytotoxic function
12
Q
Some accessory cells (3)
A
Antigen presenting cells
Macrophages
Connective tissue cells
13
Q
What comprises the B cell area in the lymph node (2)
A
Paracortical T cell zone Lymphoid follicle (mantle zone, germinal centre)
14
Q
What are the components of the lymphoid follicle (2)
A
Mantle zone - naive unstimulated B cells
Germinal centre - B cells, antigen presenting cells
15
Q
What is significant about the germinal centre
A
This is where B cells which bind antigen epitopes are selected and activated
16
Q
What is significant about the T cell area
A
This is where T cells which bind antigen epitopes are selected and activated
17
Q
Components of the T cell area (3)
A
T cells
Antigen presenting cells
High endothelial vessels
18
Q
How are lymphocyte subtypes identified
A
Identify lymphocyte subtypes and different stages of development by the different types of cell surface receptors expressed by the cells (CD markers)
Detected in tissue sampling by immunohistochemistry
19
Q
Definition of lymphoma
A
Neoplastic proliferation of lymphoid cells forming discrete tissue masses
20
Q
Where do lymphomas arise
A
Arise in and involve lymphoid tissues (including acquired lymphoid tissue - extranodal lymphomas)
21
Q
Classification of lymphomas (2)
A
Hodgkin lymphoma
Non-Hodgkin lymphoma (B cell type most common, T cell type)
22
Q
What predisposes to lymphoma
A
Immunosuppression predisposes to development of lymphoma (infection, loss of surveillance)
23
Q
What is the pathogenesis of lymphoma (2)
A
Neoplastic proliferation of lymphoid cells - clonal
Mutation in genes to allow uncontrolled cell growth
24
Q
Causes of mutations leading to lymphoma (5)
A
Normal lymphocytes undergo controlled genomic “instability” of lymphoid cells - mistakes in this process produce neoplastic mutations
Inherited disorders – inherited disorder resulting in increased/abnormal genomic instability
Viral agents – EBV, HTLV-1
Environmental agents – mutagens, chronic immune stimulation (e.g H pylori)
Iatrogenic causes – radiotherapy, chemotherapy
25
WHO classification of lymphoma
Hodgkin: Classical, lymphocyte predominant
| Non-Hodgkin lymphoma: B cell (precursor B cell, peripheral B cell), T cell (precursor T cell, peripheral T cell)
26
Most common form of lymphoma
B cell Non-Hodgkin lymphomas (80-85%)
27
When do lymphomas arise
Can arise at different stages of lymphocyte development and activation
Therefore in certain lymphomas the neoplastic lymphoid cell resembles a normal counterpoint both in morphology and in the pattern of CD markers expressed
28
Where are the neoplastic lymphoid cells present
Circulate in the blood
Hence often disseminated at presentation - exception is Hodgkin lymphoma and some very early NHL
29
What effect do lymphomas have on the immune system
They may disrupt normal immune system - therefore patients may develop immunodeficiencies
30
Lymphomas arising from germinal centre (4)
Follicular lymphoma
Burkitt lymphoma
Diffuse large B cell lymphoma
Hodgkin lymphoma
31
Lymphomas arising from post germinal centre (4)
Diffuse large B cell lymphoma
marginal zone lymphoma
Small lymphocytic lymphoma
Chronic lymphocytic leukaemia
32
What are the diagnostic tools for lymphoma (2)
Cytology: look at single cells aspirated from a lump
Histology: look at tissue sections
33
What do you look at histologically in lymphoma (2)
Architecture (nodular, diffuse)
| Cells (small round, small cleaved, large (centroblastic, immunoblastic, plasmoblastic))
34
What is immunohistochemistry used for
Used to identify proteins on/in cells in tissue sections
35
How does immunohistochemistry work
Use labelled antibody to cell surface receptor
| Dye label is visible under light microscope in tissue sections
36
What can you determine with immunopheontyping (5)
Cell type (T = CD3, CD5, B = CD20)
Cell distribution
Loss of normal surface proteins (e.g. neoplastic T cells)
Abnormal expression of proteins (often secondary to specific chromosomal/gene abnormalities e.g. cyclin D1)
Clonality of B cells - light chain expression
37
What molecular tools are available for lymphoma analysis (2)
FISH - identify chromosome translocations
| PCR - identify chromosome translocations and clonal T cell receptor or immunoglobulin gene rearrangement
38
How can PCR be used in lymphoma (2)
Diagnostic - e.g. 11;14 mantle cell lymphoma
| Prognostic - e.g. 2;5 Anaplastic large cell lymphoma
39
Low grade Non-Hodgkin lymphomas (4)
Follicular lymphoma
Small lymphocytic lymphoma/chronic lymphocytic leukaemia
Marginal zone lymphoma
Mantle zone lymphoma
40
High grade Non-Hodgkin lymphoma
Diffuse large B cell lymphoma
41
Intermediate grade Non-Hodgkin lymphoma
Burkitt's lymphoma
42
Clinical presentation of follicular lymphoma (2)
Lymphadenopathy
| MA/elderly
43
Histopathology follicular lymphoma (2)
Follicular pattern
| Germinal centre cell origin CD10, bcl-6+
44
Molecular pattern follicular lymphoma
14;18 translocation involving bcl-2 gene
45
Typical grade of follicular lymphoma
Indolent but can transform to high grade lymphoma
46
Immunohistochemistry in follicular lymophoma
Detection of bcl-2 expression by neopalstic B cells in follicles
47
Clinical presentation small lymphocytic lymphoma/CLL (2)
MA/elderly
| Nodes or blood
48
Histopathology small lymphocytic lymphoma/CLL
Small lymphocytes
Naive or post-germinal centre memory B cell
CD5, CD23
49
Molecular pattern small lymphocytic lymphoma/CLL
Multiple genetic abnormalities
50
Typical grade for small lymphocytic lymphoma/CLL
Indolent, but can transform to high grade lymphoma (richter transformation)
51
Cause of marginal zone lymphoma/MALT
Thought to arise in response to chronic antigen stimulation (e.g. by Helicobacter in stomach)
52
Site of origin for marginal zone lymphoma/MALT
Arise mainly at extranodal sites (many sites e.g. gut, lung, spleen)
Post germinal centre memory B cell
53
Typical grade marginal zone lymphoma/MALT
Indolent but can transform to high grade lymphoma
54
Treatment of low grade marginal zone lymphoma/MALT
Can treat low grade disease with non-chemotherapeutic modalities - i.e. remove antigen
55
Clinical features mantle cell lymphoma (3)
MA male predominence
Lymph nodes, GI tract
Disseminated disease at presentation
56
What is the histopathology of mantle cell lymphoma (3)
Located in mantle zone
Pre-germinal centre cell
Aberrant CD5, cyclin D1 expression
57
What are the molecular features of mantle cell lymphoma (2)
11;14 translocation
| Cyclin D1 over expression
58
What is the median survival rate for mantle cell lymphoma
3-5 years
59
Clinical features of Burkitt's lymphoma (3)
Jaw or abdominal mass in children and young adults (endemic, sporadic, immunodeficiency)
EBV associated
Aggressive disease
60
Histopathology of burkitt's lymphoma (2)
Germinal centre cell origin
| Starry sky appearance
61
Molecular features of burkitt's lymphoma
c-myc translocation (8;14, 2;8, 8;22)
62
Clinical features of diffuse large B cell lymphoma (2)
MA/elderly
| Lymphadenopathy
63
Histopathology of diffuse large B cell lymphoma (4)
Germinal center or post-germinal center B cell
Sheets of large lymphoid cells
Germinal center phenotype = good prognosis
p53 positive, high proliferation fraction = poor prognosis
64
Features of T cell lymphoma (5)
```
MA/elderly
Lymphadenopathy and extranodal sites
Large T lymphocytes
Often with associated reactive cell population, esp eosinophils
Aggressive
```
65
Special forms of T cell lymphoma (4)
Adult T cell leukaemia/lymphoma
Enteropathy associated T cell lymphoma
Cutaneous T cell lymphoma
Anaplastic large cell lymphoma
66
What are the associations with adult T cell leukaemia/lymphoma (2)
Caribbean and Japan
| HTLV1 infection
67
What is associated with enteropathy associated T cell lymphoma
Some patients with long standing coeliac disease
68
Clinical features of anaplastic large cell lymphoma (3)
Children/young adults
Lymphadenopathy
Agressive
69
Histopathology anaplastic large cell lymphoma (2)
Large epithelioid lymphocytes
| T cell or null phenotype
70
Molecular features of anaplastic large cell lymphopma (2)
2;5 translocation
| Alk-1 protein expression - better prognosis
71
Features of Hodgkin lymphoma (5)
More often localised to a single nodal site
Spreads contiguously to adjacent lymph nodes
Classical, with several subtypes
Lymphocyte predominent
Moderately agressive
72
Features of Non-Hodgkin lymphoma (2)
More often involves multiple lymph node sites
| Spreads discontinuously
73
Subtypes of classical Hodgkin's lymphoma (3)
Nodular sclerosing
Mixed cellularity
Lymphocyte rich and lymphocyte depleted
74
Clinical features of classical HL (2)
Young and MA
| Often involves just a single lymph node group
75
Origin of classical HL
Germinal centre/post-germinal centre B cell origin
76
Associations of classical HL
EBV
77
Histopathology of classical HL
Sclerosis, mixed cell population in which scattered Reed-Sternberg and Hodgkin cells with eosinophils
78
Clinical features of nodular HL (4)
Isolated LN
Lymphadenopathy
Indolent
Can transform to high grade B cell lymphoma
79
Origin of nodular HL
Germinal centre B cell (positive for some germinal centre B cell markers)
80
Nodular HL associations
No associations, not associated with EBV
81
Histopathology of nodular HL
B cell rich nodules with scattered L&H cells
82
What is involved in haemato-oncological diagnosis (4)
Morphology
Immunophenotyping
Cytogenetics
Molecular genetics
83
What is meant by morphology of a tumour (3)
Architecture of the tumour
Cytology
Cytochemistry
84
What is involved in immunopheonotype (2)
Flow cytometry
| Immunohistochemistry
85
What is involved in cytogenetics (2)
Conventional karyotyping
| FISH
86
What is involved in molecular genetics (4)
Mutation detection
PCR analysis
Gene expression profile
Whole genome sequencing
87
What is lymphoma
It is a neoplasm of lymphoid cells
88
Where do lymphomas occur (4)
Lymph nodes, bone marrow and/or blood (lymphatics)
Lymphoid organs (spleen, GALT)
Skin (often T cell disease)
Rarely, anywhere (CNS, occular, testes, brest, etc...)
89
What is the incidence of lymphoma
10,000 new cases/year in the UK
NHL - 80%
HL - 20%
90
Why are cancers of the immune system so dangerous (3)
Rapid proliferation - increases risk of DNA replication error.
Normal cells are dependent on apoptosis - apoptosis is switched off in the geminal centre, acquired DNA mutation in pro apoptotic genes
Great potential for recombination errors and new point mutations
91
What immunoglobulin gene recombinations are involved in lymphoma (2)
VDJ recombination. Occurs in bone marrow, Key enzymes RAG1+2, TdT
Class switch recombination. Somatic hypermutation. Key enzymes: adenosine induced deaminase.
92
What chromosomal translocations are involved in lymphoma
t(8;14)
Lymphoma/recombination associated translocations involve the Ig locus. Ig promoter is highly active in B cells, bring intact oncogenes close to the Ig promoter. Oncogenes may be anti-apoptotic, proliferative (bcl2, bcl6, Myc, cyclinD1)
93
Risk factors for lymphoma (4)
Majority of cases no identifiable risk factor.
Constant antigenic stimulation
Infection (direct viral infection of lymphocytes)
Loss of T cell function
94
Give examples of antigenic stimulation that may lead to lymphoma (3)
H.Pylori : Gastric MALT (mucosa associated lymphoid tissue) Marginal Zone NHL of stomach
Sjogren syndrome : Marginal Zone NHL of Parotid lymphoma
Coeliac disease: small bowel T cell lymphoma EATL (enteropathy associated T-Cell Non Hodgkin lymphoma)
95
What infections are associated with lymphoma (2)
HTLV1 infection of T cells
Immunosuppression and EBV infection (e.g. HIV, PTLD - post transplant lymphoproliferative disorder)
96
Reed Sternberg cells
Classical Hodgkin Lymphoma
97
B cell lymphomas (2)
Precursor B lymphoblastic leukaemia or lymphoma
| Mature B cell neoplasm: DLBCL, Follicular, NHL, CLL
98
T/NK cell lymphoma (2)
Precursor T lymphoblastic leukaemia or lymphoma
| Mature T and NK neoplasm: PTCL, anaplastic, cutaneous
99
Features of HL
HL is more common in males than females.
Bimodal age incidence: Most common age 20-29, young women NS subtype; Second smaller peak affecting elderly >60 years old
Painless enlargement of lymph node/nodes.
May cause obstructive symptoms/signs
Constitutional symptoms; fever, night sweats weight loss (the B symptoms) and pruritis may be present. Rarely alcohol induced pain present.
100
Classical HL subtypes (4)
Nodular sclerosing 80%- Good prognosis (causes the peak incidence in young women)
Mixed cellularity 17% - Good prognosis
Lymphocyte rich (rare)- Good prognosis
Lymphocyte depleted (rare)- Poor Prognosis
101
How are HL staged
FDG-PET/CT scan
| Consider biopsy of other site if possibly infiltrated e.g. liver
102
Staging in lymphoma
Stage 1 - one group of nodes
Stage 2 - >1 group of nodes on same side f diaphragm
Stage 3 - nodes above and below the diaphragm
Stage 4 - extra nodal spread
Suffix A if none of below, B if any of below:
Fever
Unexplained weight loss >10% in 6 months
Night sweats
103
How does chemotherapy work for lymphoma
Given as a combination of drugs which affect the malignant cells in different way s
104
How does radiotherapy work in lymphoma
HL is highly responsive to radiotherapy, can be given at end of chemo as an Involved field a small area only targeting diseased nodes (less toxicity to normal tissue)
105
Chemotherapy for HL (4)
```
ABVD - given at 4 weekly intervals (2-6 cycles)
Adriamycin
Bleomycin
Vinbalstine
DTIC
```
Effective treatment
Preserves fertility
Can cause pulmonary fibrosis and cardiomyopathy (long term)
106
What are the risks of radiotherapy for lymphoma treatment (3)
Ca breast (risk 1:4 after 25 years)
Leukaemia/mds (3%@10years)
Lung or skin cancer
107
How is radiotherapy given for lymphoma
Modern practice involved field only
108
What is the risk of combined chemotherapy and radiotherapy treatment for lymphoma
Greatest risk of secondary malignancy
109
Treatment of lymphoma
Chemotherapy for all cases (ABVD 2-6 cycles)
+/- Radiotherapy
PET CT scanning
Relapse - high dose salvage chemotherapy, autologous PB stem cell transplant as salvage.
110
HL prognosis
Older patients generally do less well as do those with lymphocyte depleted histology
Prognosis depends on stage
Cure rates range from 50-90% (over 80% of patients with stage 1 or 2 disease are cured, only 50% of stage 4 patients are cured)
111
Arguments for and against reduced therapy
Reduced therapy - chemotherapy only, reduce risk of secondary malignancy, increased HL relapse
Intensify therapy - chemo +/- radiotherapy. Decrease HL relapse, increase secondary malignancy after 10 years.
