HAEM: Lymphoma and CLL Flashcards
Where is the BCR-ABL translocation seen?
Myeloid neoplasms
What is the MOA of Ibrutinib and Idelasilib?
BCR kinase inhibitors
What is the MOA of venetoclax?
BCL2 inhibitor = causes apoptosis of CLL cells
What are smear cells characteristic of?
CLL
What is the complication that results from extra mutations gained in CLL?
Richter transformation –>high grade lymphoma
What CD may be present on immature B cells? What about mature B cells?
CD5 - immature
CD19 - mature
Which mutation causes BCL2 overexpression in follicular NHL?
t(14;18) –> anti-apoptosis
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
Name a T cell lymphoma of the skin.
Mycosis fungoides
Is NHL or HL more common?
80% NHL
Which process allows immune system to have diversity in Ig?
(1) VDJ recombination,
(2) somatic hypermutation and class switching
What enzyme is involved in somatic hypermutation of Ig?
Adenosine induced deaminase (AID)
Give 3 locations for MZL (B cell).
Stomach - H.pylori
Salivary glands - Sjogren’s
Thyroid -3 causes
Give a location for T cell MZL.
EATL - coeliac
What are 3 causes of thyroid MZL.
Riedel’s - IgG4
Hashimoto’s
de Quervain’s - viral
Which type of T cell NHL is caused by a virus?
HTLV1 –> adult T-cell leukaemia lymphoma (ATLL)
*usually Caribbean/Japanese
Which type of B cell lymphoma is caused by a virus?
EBV –> PTLD (post-transplant lymphoproliferative disorder)
Does HIV cause lymphoma?
Increases risk of B cell lymphoma x60
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
What does each layer of the lymphoid follicles contain?
GC = B cells and APCs Mantle = naive B cells Paracortical = T cell zone
Which lymphoid neoplasm is associated with small round cells? What about large cells?
CLL = small round
High grade lymphoma = large
Cyclin D1 expression = ?
Mantle cell lymphoma
t(11;14) = ?
Mantle cell lymphoma
t(2;5) = ?
Anaplastic large cell lymphoma (prognostic factor)
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
