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Path - Haematology > Lymphoma 1 > Flashcards

Lymphoma 1 Flashcards

1
Q

What is the definition of lymphoma?

A

A malignant neoplasm of lymphoid cells

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2
Q

Where can lymphoma occur?

A

Lymphatic system: Lymph nodes, bone marrow, blood
Lymphoid organs: spleen, gut-associated lymphoid tissue
Skin
Anywhere else (CNS, ocular, testes, breast)

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3
Q

What is incidence of Hodgkins vs Non Hodgkins?

A 
Hodgkins = 80%
NHL = 20%
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4
Q

How are lymphomas classified?

A

Based on CELL OF ORIGIN

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5
Q

How does lymphoma generally develop?

A
  • Rapid proliferation/division of cells in the germinal centre - means that there is a higher risk of replication errors
  • highly dependent on apoptosis (most lymphocytes die in the GC) - means that apoptosis can be switched off, causing damage
  • Deliberate gene recombination (somatic hypermutation) - means potential for recombination errors
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6
Q

What is the gene recombination that occurs in bone marrow also called?

A

VDJ recombination

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7
Q

What is the downside of VDJ recombination?

A

Could lead to recombination errors and new point mutations
This means the formation of either OVEREXPRESSION OF PROLIFERATIVE ONCOGENE
or
SUPPRESSION OF APOPTOTIC GENE

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8
Q

What kind of lymphoma is a prime example of an error in recombination?

A

BURKITT’S

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9
Q

What types of malignant genes may be accidentally over expressed in VDJ recombination?

A

Myc (burkitt’s)
Bcl2
Bcl6
cyclin D

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10
Q

What are 3 MAIN causes for lymphoma?

A
  1. CONSTANT ANTIGENIC STIMULATION
  2. VIRAL INFECTION
  3. LOSS OF T cell FUNCTION
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11
Q

Give examples of how constant antigenic stimulation can cause lymphoma.

A

Helicobacter pylori: causes gastric MALT Marginal Zone NHL of stomach

Sjogrens: Marginal zone NHL of parotid

Hashimoto’s: Marginal zone NHL of thyroid

Coeliac: Small Bowel T cell lymphoma

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12
Q

Give examples of how viral infection causes lymphoma

A

HTLV1

EBV

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13
Q

Explain how HTLV1 works

A

HTLV1 infects T cells > develop Adult T cell Leukaemia Lymphoma (ATLL)

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14
Q

Explain how EBV works

A

EBV > infects B lymphocytes > usually quiescent (infected B cells killed by cytotoxic T cells)

If HIV / immunosuppression present, T cells cannot act > EBV causes B cell lymphoma

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15
Q

Give examples of how T cell function can belopst

A

HIV

Iatrogenic (immunosuppression)

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16
Q

What are the three key tissues of lymphoreticular system?

A

Generative LR tissue
Reactive LR tissue
Acquired LR tissue

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17
Q

What is function of Generative LR tissue

A

Generate / maturate B and T lymphoid cells

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18
Q

What are examples of generative LR tissue?

A

Bone marrow

Thymus

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19
Q

What is function of Reactive LR tissue

A

Develop immune reaction

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20
Q

What are examples of reactive LR tissue?

A

lymph node

spleen

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21
Q

What is the function of acquired LR tissue?

A

Develop LOCAL immune reaction

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22
Q

What are examples of acquired LR tissue?

A

Extra nodal lymphoid tissue e.g. skin, stomach, lung

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23
Q

Where are T cells found in the lymph node?

A

In the PARACORTEX

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24
Q

Where are B cells found in the lymph node?

A

In the LYMPHOID FOLLICLE

In the CORTEX

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25
Q

What are the components of the lymphoid follicle?

A

Mantle zone - in the periphery, contains naive unstimulated B cells

Germinal centre - in the centre, where B cells which bind to antigen epitopes are selected and activated

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26
Q

What are the main immunomarkers that we use in immunohistochemistry to detect whether cells are B or T cells?

A

B cells = CD20

T cells = CD5, CD30

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27
Q

How is lymphoma classified?

A 
Hodgkin (20%) 
Non Hodgkin (80%)
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28
Q

What are the types of Hodgkin Lymphoma?

A

Classical

Lymphocyte predominant

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29
Q

What are the types of NHL?

A

B cell

T cell

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30
Q

What is the most common type of Lymphoma?

A

B cell. NHL

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31
Q

What are histological features related to architecture that occur in lymphoma?

A

Nodular

Diffuse

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32
Q

What abnormalities are visible in immunophenotyping for lymphoma?

A

Cell distribution
Loss of normal surface proteins
Abnormal expression of proteins

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33
Q

What molecular tools are used for lymphoma?

A

FISH

PCR

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34
Q

What can these molecular tools identify?

A

Chromosome TRANSLOCATIOn

35
Q

What are common types of B cell NH LOW GRADE lymphoma?

A

Follicular
Small lymphocytic / chronic lymphocytic
Marginal zone
Mantle cell

36
Q

What are common types B cell NH HIGH grade lymphoma?

A

Diffuse large B cell lymphoma

Burkitt’s

37
Q

Who does follicular lymphoma occur in?

A

middle aged/elderly

38
Q

What is the histopathology of follicular lymphoma?

A 
Follicular pattern (Follicles are NEOPLASTIC)
Germinal centre cell origin
39
Q

What translocation occurs in follicular lymphoma?

A

t(14,18)
Involves Bcl2 gene (There is over expression of Bcl2 in the GERMINAL CENTRE (Bcl2 is usually only found in the mantle zone))

40
Q

What is follicular lymphoma usually classified as in terms of aggression, and what can it become?

A

Indolent

Can become high grade lymphoma

41
Q

What is the difference between Small and Chronic Lymphocytic Leukaemia?

A 
Small = peripheral blood involved
Chronic = bone marrow involved
42
Q

Who does S/CLL present in?

A

middle aged/elderly

43
Q

What is the histopathology of S/CLL?

A

Small lymphocytes
Arises from naive B cells or port germinal centre memory B cells
These replace the entire lymph node so you can no longer see follicles/T cells > become entire rounded sheets

44
Q

What is Richter transformation?

A

The transformation of S/CLL from low grade to high gene

45
Q

What proteins are B cells in S/CLL positive for?

A

CD5

CD23

46
Q

What is another name for MALT Lymphoma?

A

Marginal zone lymphoma

47
Q

Where does MALT lymphoma arise?

A

It arises mainly at extranodal sites (gut, lung, spleen)

48
Q

What does MALT lymphoma arise in response to?^

A

In response to chronic antigenic stimulation e.g. H pylori

49
Q

What cells does MALT lymphoma arise from?

A

Post-geminal centre memory B cells

50
Q

How can MALT lymphoma be treated?

A

With NON CHEMOTHERAPEUTIC modalities

By REMOVING THE ANTIGEN (eradicate H pylori)

51
Q

How does Mantle cell lymphoma present?

A

In middle aged males,
Affects lymph nodes, GI tract
Presents as disseminated disease

52
Q

What is the histopathology of Mantle Cell Lymphoma?

A

In Mantle zone of Lymph nodes

53
Q

What cells does mantle cell L arise from?

A

From Pre-germinal centre cells

54
Q

What proteins are abnormally expressed in Mantle Cell Lymphoma?

A

Cyclin D1

55
Q

What translocation is responsible for Mantle cell lymphoma=?

A

11,14

56
Q

What is the presentation for Burkitts lymphoma?

A

Jaw/abdo mass in children/adults respectively

57
Q

What virus is burkitt’s associated with?

A

EBV

58
Q

Explain Burkitt histopathology?

A

Arises from germinal centre cells

Starry sky appearance

59
Q

What is the molecular translocation and gene mutation with Burkitt’s?

A

8,14
2,8
8,22
Resulting in c-Myc TRANSLOCATIon

60
Q

What is the aggressiveness of Burkitt’s?

A

HIGHLY AGGRESSIVE

61
Q

What area does Diffuse Large B cell lymphoma arise from?

A

From germinal centre OR post-germinal centre B cells

62
Q

What are 4 types of T cell lymphoma?

A

Adult T cell leukaemia lymphoma (ATLL)
Enteropathy associated T cell lymphoma (EATL)
Cutaneous T cell lymphoma
Anaplastic large cell lymphoma

63
Q

What virus is ATLL associated with?

A

HTLV-1

64
Q

What comorbidity does EATL occur with=

A

COELIAC disease

65
Q

How is Hodgkin presentation different to NHL?

A

Hodgkin: localised (usually just one node site), spreads contiguously to adjacent lymphocytes

NHL: involves multiple sites, spreads discontinuously

66
Q

Describe 3 features of classic HL

A

Nodular sclerosino
Mixed cellularity with REED STERNBERG CELLS
Lymphocyte rich/depleted

67
Q

What are diagnostic markers for HL?

A

CD30+, CD15+

CD20-

68
Q

Whats the presentation of lymphocyte predominant HL=

A

Isolated lumphadenopathy

69
Q

What virus is lymphocyte predominant HL associated with?

A

NONE

70
Q

What are diagnostic markers for lymphocyte predominant HL?

A

CD30-, CD15-

CD20+

71
Q

What do you need to know for diagnosis and staging of HL?

A 
Histological Hx 
Anatomical stage (CT/MRI/PET)
Prognostic factors (LBH; beta2 microglob, albumin, Hep B serology, BM function)
72
Q

What is the age distribution for Hodgkins?

A

BIMODAL
1st peak 20-29
2nd peak >60

73
Q

What is the gender distribution for Hodgkins?

A

1st peak - females more likely
2nd peak- males more likely
overall - males slightly more likely

74
Q

What is the general presentation of Hodgkins?

A

Painless lymphdenopathy
B symptoms
Alcohol induced lymph node pain

75
Q

What are the 3 B symptoms?

A

Fever
night sweats
WL

76
Q

What staging system is used for HL?

A

Ann Arbour staging

77
Q

Explain stage 1-4 of Ann Arbour staging for HL

A

1: one group f nodes
2: >1 group of nodes on the same side of diaphragm (above/below)
3: nodes above AND below diaphragm
4: extra nodal spread

A If no B symptoms
B if min 1 B symptom

78
Q

What is treatment for Hodgkins?

A

CHEMOTHERAPY for ALL PTSD

Radiotherapy depending on circumstances

79
Q

What is the chemotherapy combination used for HL?

A

ABVD

Adriamycin
Bleomycin
Vincristine
DTIC (dacarbazine)

80
Q

What is a benefit of this type of chemotherapy?

A

It preserves fertility

81
Q

What are long term disadvantages of ABVD?

A

Pulmonary fibrosis

Cardiomyopathy

82
Q

What are negative consequences for radiotherapy?

A

DAMAGE TO NORMAL TISSUE ENCOUNTERED
High risk of breast cancer
leukaemia /myelodysplastic syndrome
lung/skin cancer

83
Q

What is a risk of combination radio-chemotherapy?

A

Increases rate pf relapse

Path - Haematology (17 decks)

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