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YEAR 5: Haematology AS > Haem: Lymphoma MDT (Laz) > Flashcards

Haem: Lymphoma MDT (Laz) Flashcards

(70 cards)

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1
Q

What are some sites lymphoma may be found?

A
  • lymph nodes, bone marrow, blood
  • lymphoid tissue: GALT, spleen
  • other: kidney or sanctuary sites: CNS, eye, testes
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2
Q

Outline the difference in prevalence of Hodgkin’s lymphoma and Non-Hodgkin lymphoma.

A
  • NHL = 80%
  • Hodgkin = 20%
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3
Q

How can lymphoma be divided?

A
  • HL
    • classical
    • lymphocyte predominant
  • NHL
    • B cell
      • precursor
      • mature/peripheral
        • low grade
        • high grade
    • T cell
      • precursor
      • mature/peripheral
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4
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.
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5
Q

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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6
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
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7
Q

List some oncogenes that are implicated in lymphoma/leukaemia.

A
  • Bcl2
  • Bcl6
  • Cyclin D1
  • c-Myc
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8
Q

List some risk factors that contribute to the aetiology of NHL lyphoma.

A
  • Constant antigenic stimulation
    • chronic bacterial infection or chronic AI condition
  • Infection
    • HTLV1 passed in breastfeeding
  • EBV in loss of T cell function
    • HIV or immunosuppression
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9
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
  • Hashimoto’s thyroiditis: MZL thyroid
  • Coeliac disease → small bowel T cell lymphoma, enteropathy-associated T cell NHL
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10
Q

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
  • Also present with tropical spastic paraparesis

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
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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)
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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
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13
Q

Describe the normal histological appearance of a lymph node.

A
  • These 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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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
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15
Q

What is the main technique used to identify different types of lymphocyte within a lymph node biopsy?

A

Immunohistochemistry: stain with antibody with specific cell-surface receptor

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16
Q

What are the main markers used for B and T cells?

A

T cell = CD3, CD5

B cell = CD20

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17
Q

Define lymphoma.

A
  • Neoplastic proliferation of lymphoid cells forming discrete tissue masses
  • They arise in and involve lymphoid tissues
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18
Q

Which factors are taken into account when classifying a lymphoma?

A
  • Clinical
  • Histological
  • Immunohistochemical
  • Molecular
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19
Q

Outline the WHO classification of lymphoma.

A

Hodgkin lymphoma

  • Classical
  • Lymphocyte predominant

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
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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

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21
Q

Which lymphomas are often not disseminated?

A

HL

some very early NHL

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22
Q

Lymphoma types

A
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23
Q

What are the diagnostic tools used by pathologists when investigating lymphoma?

A
  • Cytology (from aspiration)
  • Histology (architecture: nodular (follic), diffuse (CLL); cells: small round (CLL, MCL), small cleaved (follic), large (high grade))
  • Immunohistochemistry
  • Loss of normal surface proteins: T cell
  • Expression of abnormal proteins (e.g. cyclin D1 an Mantle cell lymphoma + hairy cell leuk)
  • Light chain restriction
  • Molecular tools
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24
Q

Which molecular tools are used when investigating lymphoma?

A
  • FISH - identify chromosomal translocations
  • PCR - identify chromosomal translocations, clonal T cell receptor of Ig gene rearrangement
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25
Give an example of a chromosomal translocation that is diagnostic of lymphoma.
11;14 = Mantle Cell Lymphoma
26
Give an example of a chromosomal translocation that is prognostic in lymphoma.
2;5 = anaplastic large cell lymphoma
27
List some types of low grade lymphoma.
* Follicular lymphoma * Small lymphocytic lymphoma (CLL) * Marginal zone lymphoma * Mantle cell lymphoma (aggressive)
28
Name a type of high grade lymphoma.
Diffuse large B cell lymphoma
29
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
30
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 Bcl6)
31
Which molecular feature is associated with follicular lymphoma?
14;18 translocation involving Bcl2 gene
32
Describe the typical presentation of small lymphocytic lymphoma.
Lymphadenopathy or high blood lymphocyte count in middle-aged or elderly patients
33
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
34
Immunohistochemistry in follicular cell lymphoma
detection of Bcl-2 expression by B cells in follicle
35
What is the term used to describe the transformation of small lymphocytic lymphoma into a higher grade lymphoma/leukaemia?
Richter transformation
36
Small lymphocytic lymphoma/ CLL histopathology
small lymphocytes small nuclei naive or post germinal centre B cells abnormal expression of CD5 and CD23+
37
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) * indolent but can transform
38
Outline the typical presentation of mantle cell lymphoma.
* Typically affects middle-aged males * Affects lymph nodes and the GI tract * Often present with disseminated disease NOTE: median survival = 3-5 years
39
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 * infiltrates normal epithelial tissue in the area
40
Which molecular features are characteristic of mantle cell lymphoma?
* 11;14 translocation * Cyclin D1 overexpression 3-5 year median survival
41
Outline the typical presentation of Burkitt's lymphoma.
* Jaw or abdominal mass in children and young adults * Associated with EBV * endemic or sporadic NOTE: this is very agressive
42
Outline the histological features of Burkitt's lymphoma.
* Arises from germinal centre cells * Starry sky appearance (macrophages mopping up apoptotic cells)
43
Which molecular feature is associated with Burkitt's lymphoma.
* c-Myc translocation (8;14, 2;8 or 8;22)
44
Outline the typical presentation of diffuse large B cell lymphoma.
Middle-aged and elderly patients with lymphadenopathy
45
Outline the histological features of diffuse large B cell lymphoma.
* Arise from germinal centre (CD10+) or non/post-germinal centre B cells (CD10-) * Sheets of large lymphoid cells * Lymph node is effaced so follicles and germinal centres cannot be identified
46
List some prognostic association of diffuse large B cell lymphoma.
Good prognosis - germinal centre phenotype Poor prognosis - p53-positive and high proliferation fraction
47
Outline the typical presentation of T cell lymphomas.
Middle-aged and elderly patients with lymphadenopathy NOTE: these are aggressive but rarer
48
Outline some key histological features of T cell lymphomas.
* Large T lymphocytes * Associated reactive cell population (especially eosinophils) * larger nuclei
49
List some types of T cell lymphoma and their associations.
* Adult T cell leukaemia/lymphoma - HTLV1 * Carribean and Japan but now everywhere! * arises from CD4+ * Enteropathy-associated T cell lymphoma - Coeliac disease * CD8+ intraepithelial * ulcerated small bowel lesions: poor prognosis * Cutaneous T cell lymphoma (mycosis fungoides) * CD4+ infiltrates epidermis and forms abscess * Anaplastic large cell lymphoma
50
Outline the typical presentation of anaplastic large cell lymphoma.
Children and young adults with lymphadenopathy NOTE: this is aggressive
51
Outline the key histological features of anaplastic large cell lymphoma.
* Large epithelioid lymphocytes * T cell or null phenotype (anaplastic) * weird shape nuclei
52
Which molecular features are associated with anaplastic large cell lymphoma?
* 2;5 translocation * Alk-1 protein expression - BETTER prognosis
53
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
54
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
55
How can classical HL be divided?
1. nodular sclerosing 2. mixed cellularity 3. lymphocyte rich and lymphocyte depleted
56
Outline some histological features of classical Hodgkin lymphoma.
* Nodular sclerosis * Mixed cell population of Reed-Sternberg cells * owl's eye * Lymphoma cells are few in number and are scattered around- mainly reactive cells instead * Eosinophils * Arise from germinal centre or post-germinal centre cells
57
What are the diagnostic markers for Hodgkin lymphoma?
* CD15 + * CD30 + * CD20 -
58
Describe the typical presentation of nodular lymphocyte predominant Hodgkin lymphoma.
* Isolated lymphadenopathy * NO association with EBV
59
Outline the key histological features of lymphocyte predominant Hodgkin lymphoma.
* B cell rich nodules * Singularly scattered L&H cells * Reactive population in the background consisting of small lymphocytes * NO eosinophils and macrophages
60
Which markers are key in the diagnosis of lymphocyte predominant Hodgkin lymphoma?
* Positive = CD20 * Negative = CD15, CD30 (unlike classical Hodgkin lymphoma) * germinal centre B cell
61
What constitutional symptoms may be present in a patient with lymphoma?
B symptoms - fever, night sweats, weight loss Pruritis
62
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
63
Which type of scan is often used to stage lymphoma?
FDG-PET/CT
64
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
65
Which chemotherapy regimen is usually used for Hodgkin lymphoma?
ABVD: Adriamycin, Bleomycin, Vincristine, Dacarbazine NOTE: this is usually given at 4-weekly intervals for 2-6 cycles
66
What are some possible long-term consequences of chemotherapy for Hodgkin lymphoma?
Pulmonary fibrosis Cardiomyopathy
67
What is a risk of radiotherapy for Hodgkin lymphoma?
Collateral damage to surrounding tissues
68
How might a relapse of Hodgkin lymphoma be treated?
* High-dose chemotherapy * 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
69
Describe the curability of Hodgkin lymphoma.
Stage I and II: \>80% Stage IV: 50%
70
Difference between small lymphocytic lymphoma and CLL?
if patient presents with enlarged nodes vs blood symptoms

YEAR 5: Haematology AS (20 decks)

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