HAEM: Lymphoma and CLL Flashcards by Zuzanna Łoboda

Where is the BCR-ABL translocation seen?

Myeloid neoplasms

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What is the MOA of Ibrutinib and Idelasilib?

BCR kinase inhibitors

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What is the MOA of venetoclax?

BCL2 inhibitor = causes apoptosis of CLL cells

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What are smear cells characteristic of?

CLL

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What is the complication that results from extra mutations gained in CLL?

Richter transformation –>high grade lymphoma

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What CD may be present on immature B cells? What about mature B cells?

CD5 - immature

CD19 - mature

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Which mutation causes BCL2 overexpression in follicular NHL?

t(14;18) –> anti-apoptosis

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Does IGHV mutated CLL indicate good prognosis? Why/why not?

IgHV mutated indicates good prognosis because it means that the cell has undergone development in the germinal centre

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Name a T cell lymphoma of the skin.

Mycosis fungoides

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Is NHL or HL more common?

80% NHL

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Which process allows immune system to have diversity in Ig?

(1) VDJ recombination,

(2) somatic hypermutation and class switching

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What enzyme is involved in somatic hypermutation of Ig?

Adenosine induced deaminase (AID)

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Give 3 locations for MZL (B cell).

Stomach - H.pylori
Salivary glands - Sjogren’s
Thyroid -3 causes

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Give a location for T cell MZL.

EATL - coeliac

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What are 3 causes of thyroid MZL.

Riedel’s - IgG4
Hashimoto’s
de Quervain’s - viral

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Which type of T cell NHL is caused by a virus?

HTLV1 –> adult T-cell leukaemia lymphoma (ATLL)

*usually Caribbean/Japanese

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Which type of B cell lymphoma is caused by a virus?

EBV –> PTLD (post-transplant lymphoproliferative disorder)

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Does HIV cause lymphoma?

Increases risk of B cell lymphoma x60

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What are the areas of a lymphoid follicle from the centre outwards?

GC –> mantle zone –> marginal zone –> paracortical

Between the B cell follicles are T cell areas

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What does each layer of the lymphoid follicles contain?

GC = B cells and APCs
Mantle = naive B cells
Paracortical = T cell zone

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Which lymphoid neoplasm is associated with small round cells? What about large cells?

CLL = small round

High grade lymphoma = large

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Cyclin D1 expression = ?

Mantle cell lymphoma

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t(11;14) = ?

Mantle cell lymphoma

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t(2;5) = ?

Anaplastic large cell lymphoma (prognostic factor)

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Name 3 low grade/indolent B cell NHLs.

Follicular CLL a.k.a. small lymphocytic lymphoma Mantle zone lymphoma (MALT)

Name 2 high grade B cell NHLs.

DLBCL | Mantle zone lymphoma

Name an aggressive B cell NHL.

Burkitt's

t(14;18) = ?

Follicular lymphoma --> BCL2

Where does follicular lymphoma originate? What CD is it associated with?

Germinal centre CD10 BCL-6+ve

Where does CLL originate? What CD is it associated with?

Naive or post-germinal centre CD5+ve CD23+ve CD19-ve May be SmIg and CD79 +ve/-ve

Where does marginal zone lymphoma originate?

Extra-nodal sites by chronic antigen stimulation

Where does mantle cell lymphoma originate? What CD is it associated with?

Mantle zone origin i.e. pre-GC CD5 aberrant Cyclin D1 overexpression

Where does Burkitt's lymphoma originate? What mutations is it associated with?

Germinal centre origin | C-myc translocation (4:14, 2:8, 8:22)

Which 3 mutations is C-myc in Burkitt's associated with?

4: 14, 2: 8, 8: 22

What is the origin of DLBCL?

GC or post-GC NB: GC phenotype = good prognosis

What is seen on histopathology in DLBCL?

Sheets of large lymphoid cells

What mutation confers poor prognosis in DLBLC?

p53 +ve | and high proliferation

Which cell type is T cell lymphoma commonly associated with?

eosinophils

Name 4 T cell lymphomas.

Anaplastic large cell ATLL EATL Cutaneous

What is seen on histology in anaplastic large cell lymphoma?

Large "epithelioid" lymphocytes | Might not recognise the T cells

What mutation is associated with anaplastic large cell lymphoma?

t(2:5)

What protein is expressed in anaplastic large cell lymphoma? What does this indicate?

Alk-1 = better prognosis

What are the types of HL?

``` Classical... -sclerosing -mixed cellularity -lymphocyte rich -lymphocyte depleted Nodular lymphocyte predominant (NLPHL) ```

What is the localisation of HL vs NHL?

HL spreads locally, NHL is found at multiple distant sites

What CD are found in classical HL? What is the origin of classical HL?

CD30+ve CD15+ve CD20-ve GC/post-GC origin

What is seen on histopathology in classical HL?

Reed-Sternberg | Hodgkin cells with eosinophils

What is seen on histopathology in nodular HL?

B cell rich nodules | Scattered L&H cells

What CD are found in nodular HL?

CD20+ve (!) - unlike classical HL CD30-ve CD15-ve

What weight loss is a significant B symptom in Hodgkin's lymphoma staging?

10% in 6 months

Which HL has the best prognosis?

Nodular sclerosing - best | Lymphocyte depleted - poor prognosis

Which HL subtype is most common in young women?

Nodular sclerosing cHL - usually affects neck and mediastinum

What is ABVD therapy? What are its advantages over R-CHOP in follicular NHL?

A - adriamycin B - bleomycin V - vinblastine D- DTIC Very effective and maintains fertility. Better than R-CHOP in this way. But causes cardiomyopathy and pulm fibrosis.

Which NHL is antibiotic responsive ?

Gastric MALT

What is the most common NHL?

DLBCL (30%) | Follicular (22%)

Can you cure aggressive or indolent lymphomas?

Aggressive curable | Indolent not curable

How are aggressive lymphomas treated?

Like acute leukaemia

What prognostic index is used in DLBCL?

IPI - international prognostic index

What blood investigation is part of the IPI?

LDH IPI = Age, Stage, LDH, Extra-nodal sites. ECOG status

What is the treatment regimen for DLBCL?

R-CHOP (rituximab-cyclophosphamide-adriamycin-vincristine-prednsolone) with curative aim

What prognostic index is used for follicular NHL?

FLIPI

What is the survival in follicular lymphoma?

12-15yrs

Is watch and wait acceptable in lymphoma?

Yes - if indicated in follicular and CLL only. But not if causing symptoms of compression or pain

What is the prognosis with EATL?

Generally responds poorly to treatment and is fatal

What type of anaemia is seen in CLL?

Normocytic normochromic.

What are the platelets in CLL?

Low

What is the immunophenotype of a normal B cell in relation to Cd3/5/19?

CD3 -ve CD5 -ve CD19 +ve

Name 2 prognostic factors in CLL.

IgHV mutation status - mutated means better prognosis as cells are mature Tp53 (17p del or TP53 point mutation) - bad prognosis

What staging is used in CLL?

Binet(A,B,C) or Rai(0-IV)

What prognostic index is used in CLL?

IPI for CLL

What is the progression with CLL?

1/3 don't progress 1/3 progress but respond 1/3/ progress and don't respond/die

How do you decide when to stop watch and wait and to instead treat CLL?

IwCLL criteria

Young women with swollen nodes and pain in neck when she drinks. Diagnosis?

nodular sclerosing cHL