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Non-Hodgkin’s Lymphoma Flashcards

1
Q

What is non-Hodgkin’s lymphoma?

A

A (very!) heterogenous group of lymphomas which have several things in common:

  • They are derived from lymphocytes.
  • Are not Hodgkin’s lymphoma!
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2
Q

What % of lymphomas are non-Hodgkin’s

A

85%

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3
Q

What is Burkitt’s lymphoma?

A

B-cell germinal centre lymphoma.

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4
Q

What are the 3 variants?

A

Endemic
Sporadic
Immunodeficient

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5
Q

Do they have something in common?

A

Endemic and ID variants often associated with EBV.

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6
Q

What viral infection is associated with endemic varient?

A

endemic variant is geographically associated with malaria endemic regions.

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7
Q

How is Malaria is believed to increase patient susceptibility to EBV?

A

Sporozoites downregulate TNF-a, IL-6 and MCP-1
Sporozoites upregulate IL-10
Blood stage parasite can induce expression of sFGL2.

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8
Q

c-myc is associated with strongly with Burkitt’s.

What is the common cytogenetic abnormality?

A

Common cytogenetic abnormality is t(8;14)(q24;q32)
Found in 85% of cases.
Places c-Myc under the regulatory control of IGH enhancer/promoter.

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9
Q

What about the other 15%?

A

T(2;8)(p12;q24)

T(8;22)(q24;q11)

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10
Q

The overall Morphological appearance of Burkitt’s in histology

A

“Starry skied” appearance under H&E.

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11
Q

Appearance of cytoplasm

A

Scant basophilic cytoplasm characterised by numerous lipid vacuoles

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12
Q

Appearance of nuclei

A

Round nuclei with stippled chromatin and multiple small nucleoli.

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13
Q

What other IHC stains give positive result?

A

Ki67.

Bcl-2 and Bcl-6

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14
Q

What is the Treatment for BL?

A

Similar to other lymphoma, treatment is via combination therapy.

Treatment for most NHL are very similar.

R-EPOCH has been shown to have 100% remission induction.

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15
Q

How many cycles of treatment?

A

21 day cycle.

6-8 cycles.

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16
Q

Which of the following lymphoma would rituximab work against?

A Lymphoma negatively stained with anti-CD20
B Lymphoma positively stained with anti-CD20

A

B

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17
Q

Follicular Lymphoma

A

An extremely heterogenous (and poorly understood) disease.

At least 8 sub-types

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18
Q

FL accounts for what % of non-hodgkins?

A

Accounts for ~20% of NHL cases.

~2600 cases per annum in UK.

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19
Q

Where is in situ FL found?

A

Lymph nodes (hence in situ!)

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20
Q

What is in situ FL?

A

Presents as a monoclonal expansion of malignant (?) B-cells in germinal centres.

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21
Q

Is In situ FL significant?

A

Studies suggest that ISFL can be seen as a pre-cancerous condition.
Patients have a 3% chance of transforming into FL.

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22
Q

Smoking is believed to significantly increase the risk of ISFL. By what %?

A

45% more likely to develop ISFL than non-smokers.

Interestingly this finding may not apply to other FL.

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23
Q

H&E Lymph node with ISFL (low mag)

A
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24
Q

Same lymph node but with anti-Bcl-2

A
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25
Initial cytogenetic abnormality of FL
seems to be t(14;18)(q32;q21). | Found in majority (~90%) of ISFL cases.
26
Accumulation of other abnormalities will then cause a transformation of ISFL into FL proper. What are Examples of common FL mutations?
``` Examples of common FL mutations include: Chromosome 1p36 deletion (70% of cases). KMT2D mutations (90% of cases). CREBBP mutations (~70% of cases) ```
27
Aggressive transformations are associated with which mutations?
CD58 CDKN2B CD79B Transformation of FL into more aggressive forms is quite common (50%)
28
Are transformations common in malignancy?
``` Transformations occur in many haematological malignancies and are associated with poor prognosis: Richter transformation CML -> ALL transformation MDS -> AML HL into NHL ```
29
What is the underlying cause of haematological malignancies and are associated with poor prognosis?
(almost) always genetic.
30
Classification of FL
is via a variant of the Mann-Berard criteria (WHO modified).
31
FL can be divided into 3 classifications. Describe Grade 1
small, cleaved centrocyte proliferation.
32
Describe Grade II
mixed proliferation of small-cleaved centrocytes and large centroblast cells.
33
Describe Grade III
proliferation of large centroblast cells
34
Prognosis of FL
Prognosis for patients with FL can be variable. Most patients diagnosed in later stages of the disease Based on Follicular Lymphoma International Prognostic Index (FLIPI1/2)
35
Follicular Lymphoma International Prognostic Index (FLIPI1/2)
The FILIPI scheme utilises a points based system to offer a prognosis: >60 years olf. >4 lymph node groups implicated. Stage 3 or 4 disease (Ann Arbor classification). Low Hb (<120g/L) Increased LDH.
36
Most common treatment of FL
``` Many forms of FL are indolent and do not require active treatment (watchful waiting) Masterly inactivity (my preferred, but slightly frowned upon wording!) ```
37
Which type of FL can be treat with radiotherapy?
Localised FL
38
Survival rate of FL?
~90% 10 year survival.
39
Why is relapse common after radiotherapy?
Only eradiates particular parts of body, if a single cell else were will come back
40
Which FL requires chemotherapeutic intervention?
Systemic FL | R-CHOP
41
what is MALT lymphoma?
B-cell lymphoma originating in mucosa associated lymphoid tissue.
42
What % of lymphoma are associated with MALT lymphoma?
<10% of all lymphoma
43
What is MALT lymphoma associated with?
~100% of cases are associated with chronic inflammation.
44
What causes MALT lymphoma?
~100% of MALT Lymphoma is caused by persistent H.pylori infection.
45
How to diagnose H.pylori?
Breath test.
46
Can biopsies diagnose H.pylori?
At least 5 biopsies taken and can be cultured and/or histologically examined. 95% sensitive for H.pylori
47
What Serology tests can be used to diagnose H.pylori?
Anti-H.pylori antibodies. | Can be a bit like a broken pencil.
48
How to culture of helicobacter?
H.pylori is a microaerophilic organism. ~5% atmospheric O2 Non-selective media is recommended, Horse blood agar.
49
Histology of MALT lymphoma Healthy tissue
MALT
50
What is the incidence of T-cell lymphoma?
T-cell lymphoma are much rarer than B-cell lymphoma (<15% of NHL cases). Incidence seems to be raising. Celtic genome increases risk
51
What is the classical finding of T-cell lymphoma?
Haemophagocytic syndrome.
52
Aetiology of T-cell Lymphoma
is varied but can include: EBV HTLV1
53
Human T-cell Leukaemia Virus-1 (HTLV1)
Retrovirus which is believed to contribute to cancer development in 5% of infected individuals.
54
Is HTLV more common in animals or humans?
Such viruses are common in animals, not so much in humans!
55
Mechanism of HTLV
Positive strand RNA genome and virus makes use of reverse transcriptase.
56
How many specific serotypes of HTLV have geographical variation?
7
57
Where is serotype A found?
A found globally.
58
C?
C found in Asia (particularly Japan)
59
The rest?
Rest found mainly in Africa
60
Most common Cutaneous T-cell lymphoma?
mycoides fungoides
61
Prognosis in MF
is generally positive (70% 10 year) Sezary syndrome can complicate this. Generally die with it rather than because of it (old patients)
62
There is three stages of MF | Describe stage 1
Patchy MF
63
Stage 2
Plaque
64
Stage 3
tumour
65
Histological appearance, what is the one key aspect?
Pautrier's microabcesses are the lipid rich t cells washed away by prep of slide
66
Sezary syndrome
Often considered as an evolution/transformation of MF. | Haematological manifestations are present.
67
What kind of manifestations does SS present with?
Haematological manifestations are present.
68
Kind of cells present?
Buttock cells (cerebriform cells)
69
cytogenetic abnormalities are common, which three?
6q23-27 MYB IL22RA2
70
Treatment involves use of which monoclonal antibodies?
Mogamulizumab Brentuximab vedotin Prognosis is poor.

Molecular Pathology (10 decks)

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