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Haematology > Haem: Lymphomas 1 - Multidisciplinary > Flashcards

Haem: Lymphomas 1 - Multidisciplinary Flashcards

1
Q

What is lymphoma?

A

tumour of lymphoid cells

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2
Q

What are the 2 types of lymphomas and which is more common?

A 
80%= Non-Hodgkin’s
20%= Hodgkin’s
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3
Q

What are the 2 other ways of classifying lymphoid malignancies?

A

T or B cell (myeloid) lineage

Have precursor haematopoietic malignancies or Have mature lymphoid malignancies

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4
Q

What are the 3 reasons lymphocytes have such a high risk of developing maligancies?

A

1- Go through several point mutations that there is a high potential for recombination errors

2- Hyperproliferation so higher chances of DNA replication error

3- Rely on apoptosis. If mutation turns off apoptosis - DANGER

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5
Q

What happens in somatic hypermutation?

A

VDJ recombination - Class switching (from IgM to IgG/IgA)

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6
Q

How is there an over-expression of oncogenes in lymphomas?

A

A B cell that is tuned to respond to antibody will have a highly active immunoglobulin promoter (which sits upstream of the rearranged immunoglobulin molecule), with the purpose of driving antibody production.
However, if there has been a recombination error (e.g. when switching from IgM to IgG), the DNA being translocated and recombined may have pro-oncogenic potential.
These cell-promoting oncogenes can get translocated (due to error) downstream from the immunoglobulin promoter.

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7
Q

What are 3 risk factors for lymphoma?

A

Constant antigenic stimulation - Due to infections or autoimmune diseases

Viral infections

Loss of T cell fx - HIV killing T cells or Iatrogenic immunosuppresion
(Lose the sureveillance effect of cytotoxic T cells)

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8
Q

What are some examples of chronic antigen stimulation?

A

B cell Non-Hodgkin’s Lymphoma- Marginal Zone Subtype (MZL)

- H pylori Gastric MALT
- Sjogren's - MZL of parotid 
- Hashimoto's - MZL of thyroid

Enteropathy associated T-cell Non-Hodgkin’s lymphoma (EATL)
- Due to coeliac

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9
Q

How does HTLV1 affect T cells and how can it present?

A

Vertical transmission and after a lifetime of carrying it, they can present neurologically as Tropical Spastic Paraparesis

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10
Q

What kind of T cell lymphomas can HTLV1 cause and how does it present?

A

ATLL - lymphadenopathy, hepatosplenomegaly, skin lesions + hypercalcaemia

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11
Q

What are the 2 ways in which viral infections can give rise to post-transplant or immunosuppression-associated B cell lymphomas?

A

EBV- drives B cell proliferation

HIV- leads to loss of T cell function (or loss of function via steroids, immunosuppression etc.)

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12
Q

What happens in Iatrogenic (transplant immunosuppression)- Post-transplant lymphoproliferative disorder?

A

Loss of T cell function

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13
Q

What are the 3 lymphoreticular tissues?

A

Generative lymphoreticular tissue

Reactive lymphoreticular tissue

Acquired lymphoreticular tissue

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14
Q

What are the 2 types of cells in the lymphoreticular system?

A

Lymphocytes - T and B cells

Accessory cells - Antigen presenting cells

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15
Q

Explain where and how B cells mature?

A

They mature in the bone marrow.

Naive B cells enter the lymph nodes and reside in the mantle zone. They then enter the germinal centre where their maturation and proliferation begins. This is where most things can go wrong.

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16
Q

What are the 2 types of cells B cells can grow into?

A

Antibody secreting plasma cells

Memory B cells

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17
Q

Where do T cells develop and what are the 2 types they can develop into?

A

Thymus

CD8+ cytotoxic cells

CD4+ helper cells

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18
Q

What are the main cell markers expressed by B cells?

A

CD20

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19
Q

What are the main cell markers expressed by T cells?

A

CD2, CD3 and CD5

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20
Q

What are the main cell markers expressed by early lymphocytes developing in the bone marrow?

A

CD 34 and TDT

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21
Q

What are the main cell markers expressed by lymphocytes in the germinal / follicular centres of lymph nodes?

A

CD10 and BCL-6

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22
Q

Why does immunosuppression increase the risk of lymphomas?

A

Predisposed to infection

Loss of surveillance of cell replication

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23
Q

What are the 2 ways of classifying lymphomas

A

Hodgkins and non Hodgkin

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24
Q

What are the 2 ways of classifying Hodgkins

A

Classical

Lymphocyte predominant

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25
Q

What are the 2 ways of classifying non - Hodgkins

A

T cell

  • Precursor T cell neoplasm
  • Mature/ Peripheral T cell neoplasm

B Cell

  • Precursor B cell neoplasm
  • Mature/ Peripheral B cell neoplasm - Low or high grade
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26
Q

Why does Non Hodgkins tend to not be disseminated?

A

As it affects only one or two lymph nodes

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27
Q

Which cells give rise to CLL

A

Naive B cells

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28
Q

What is multiple myeloma?

A

Sheets of cells that resemble normal plasma cells and secrete abnormal amounts of antibodies

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29
Q

When looking at tissue architecture, if it is nodular, what type of lymphoma could it be?

A

Follicular

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30
Q

When looking at tissue architecture, if it is diffuse, what type of lymphoma could it be?

A

CLL

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31
Q

When looking at tissue cells, if it is small and round, what grade of lymphoma could it be?

A

Low

If round, small and uniform - CLL

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32
Q

When looking at tissue cells, if it is small and cleaved, what type of lymphoma could it be?

A

Mantle cell or follicular

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33
Q

When looking at tissue cells, if it is large, what grade of lymphoma could it be?

A

High

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34
Q

When looking at tissue cells, if it is large with large nuclei and prominent nucleoli, what type of lymphoma could it be?

A

Burkitt’s

Diffuse B cell

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35
Q

What does CD20 in the mantle zone suggest?

A

Mantle zone lymphoma

36
Q

What markers do neoplastic T cells have?

A

None, they lose normal surface proteins

37
Q

What abnormal proteins do B cells express in mantle cell lymphoma?

A

Cyclin D1

38
Q

What light chains do B cells usually express?

A

A mixture of K and Lamba light chains

39
Q

What light chains do B lymphoma cells usually express?

A

K OR Lamda light chains EXCLUSIVELY

40
Q

What molecular tools are used to diagnose lymphomas?

A

FISH

PCR

41
Q

What are the low grade Non-Hodgkins lymphomas?

A

Follicular
CLL
Mantle zone

42
Q

What are the high grade Non-Hodgkins lymphomas?

A

Burkitt’s

Diffuse large B cell

43
Q

What are the aggressive Non-Hodgkins lymphomas?

A

Mantle cell

44
Q

How does follicular lymphoma present?

A

Lymphadenopathy in middle aged or elderly

45
Q

What does the follicular pattern for follicular lymphoma look lie?

A

Neoplastic nodules

Normal follicular cells appearance but irregularly shaped nuclei

46
Q

What do follicular lymphoma cells stain for?

A

CD10
BCL 6
BCL 2 (Normal follicles DO NOT express this)

47
Q

What is the main difference between CLL and Small Lymphocytic Lymphoma

A

SLL - Lymph nodes and tissue forming masses

CLL - High WCC

48
Q

What do you see on histo for CLL and SLL

A

Sheets of small uniform lymphocytes
There are perfectly round nuclei and chromatin pattern
They replace the entire lymph node so that you no longer see follicles or T cell areas

49
Q

What cells do CLL and SLL arise from?

A

Arises from naïve B cells or post-germinal centre memory B cells

50
Q

What cell markers do CLL and SLL have?

A

These cells are CD5 and CD23 POSITIVE

NOTE: CD5 should never be seen in a normal B cell

51
Q

What is Richter transformation?

A

CLL transforming into higher grade lymphoma

52
Q

Where do marginal zone lymphomas arise at?

A

Extra nodal sites

53
Q

Where do marginal zone lymphomas arise from?

A

Post germinal centre memory B cells

54
Q

Why do marginal zone lymphomas arise and how can they be treated?

A

Chronic antigenic stiumaltion

Removal of such stimulation can treat this lymphoma

55
Q

How does Mantle cell lymphoma present?

A

Lymphadenopathy and large polyps in large bowel and other GIT disturbances

56
Q

What does the histo for Mantle cell lymphoma show?

A

Mantle zone

Arise from pre germinal centre cells

57
Q

What cell markers are aberrantly expressed by Mantle cell lymphoma?

A

CD5 and cyclin D1

58
Q

What translocation is Mantle cell lymphoma associated with?

A

11;14

Cyclin D1 overexpression

59
Q

How does Burkitts lymphoma present?

A

Jaw or abdo mass

60
Q

What diseases are associated with Burkitts lymphoma

A

EBV

HIV

61
Q

What cells do Burkitts lymphoma arise from?

A

Germinal centre cells

62
Q

What is the classic histo appearance for Burkitts lymphoma?

A

Starry sky appearance

63
Q

What translocation is seen in Burkitts lymphoma

A

c-Myc

64
Q

What is the histo for Diffuse Large B cell Lymphoma

A

There are sheets of LARGE lymphoid cells
There are pleiomorphic nuclei, prominent nucleoli
There are many mitotic figures
The lymph node is effaced so it is NOT possible to identify germinal centres and follicles

65
Q

What are the 2 types of cells Diffuse Large B cell Lymphoma can arise from?

A

Germinal centre OR post germinal centre B cells

66
Q

What do Diffuse Large B cell Lymphoma arising from germinal centres express

A

CD10 and Bcl 6

67
Q

What do the poor and good prognosis of Diffuse Large B cell Lymphoma show?

A

Having a germinal centre phenotype is associated with a GOOD prognosis
p53 +ve and high proliferation fraction is associated with a POOR prognosis

68
Q

How do T cell lymphomas present?

A

lymphadenopathy and extranodal sites

Large T lymphocytes

Often found with an associated reactive cell population (especially eosinophils, plasma cells)

69
Q

What is the histo for Adult T cell leukaemia/ lymphoma look like?

A

Associated with HTLV-1 infection

Nuclei of the cells often resemble clover-leaves in the peripheral blood (known as flower cells)

70
Q

Who commonly gets Enteropathy-associated T cell lymphoma and how does it present?

A

Occurs in some patients with long-standing coeliac disease

This arises from intra-epithelial T cells

71
Q

What causes Cutaneous T cell lymphoma and how does it present?

A

E.g. mycosis fungoides
The lymphoma cells will infiltrate the epidermis in the early stages, forming raised plaques
In later stages, the cells form nodules in the dermis

72
Q

How does Anaplastic Large Cell Lymphoma usually present?

A

Children and young adults

Lymphadenopathy

73
Q

What does the histo for anaplastic large cell lymphoma look like

A

Atypical large epithelioid lymphocytes
T cell or null phenotype (e.g. anaplastic)
Very variably sized nuclei and oddly shaped (i.e. kidney, long stretched)

74
Q

What cell markers does anaplastic large cell lymphoma usually express?

A

CD30

75
Q

What is the genetic translocation usually associated with anaplastic large cell lymphoma

A

2;5

Alk-1 protein expression

76
Q

What are the main difference betwenn NHL and HL?

A

HL usually invovles just one node

HL spread contagiously to adjacent lymph nodes

NHL tends to involve multiple lymph node sites and spreads discontinuously

77
Q

How does Classical Hodgkin’s Lymphoma usually present?

A

Young and middle-aged
Often involves just a single group of lymph nodes
Arises from the germinal centre or post-germinal centre cells
Associated with EBV

78
Q

What is the histo for classical HL look like?

A

Mixed cell population with Reed-Sternberg and Hodgkin cells
Lymphoma cells are RELATIVELY FEW in number and tend to be scattered around
The infiltrate have many reactive cells e.g. eosinophils (along with macrophages, plasma cells etc.)
Show large nuclei with prominent nucleoli (often multi-nucleate- ‘Owl’s eye appearance’)

79
Q

What are the cell markers for Classical HL?

A

CD30 and CD15

NEGATIVE FOR CD20!!!

80
Q

How does Nodular Lymphocyte Predominant Hodgkin’s Lymphoma present?

A

Isolated lymphadenopathy
Arise from the germinal centre B cells (which will stain POSITIVE for some germinal cell B ell markers)
NO association with EBV

81
Q

What is the histo for Nodular Lymphocyte Predominant Hodgkin’s Lymphoma
look like?

A

B cell rich nodules
Scattered around L&H cells
The reactive population in the background will be just small lymphocytes
You do NOT see eosinophils or macrophages like you would in classical Hodgkin’s

82
Q

What is to be noted for Nodular Lymphocyte Predominant Hodgkin’s Lymphoma?

A

It can transform into NHL

83
Q

What are the cell markers for Nodular Lymphocyte Predominant Hodgkin’s Lymphoma?

A

POSITIVE FOR CD20

NEGATIVE FOR CD30 AND CD15

84
Q

What disease is Marginal zone lymphoma of parotid linked to?

A

Sjogren’s syndrome due to chronic antigenic stimulation

85
Q

What does ciclosporin therapy usually lead to?

A

EBV driven post transplant lymphoma

Haematology (10 decks)

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