Lymphoma 1 Flashcards
Where are Lymphomas usually found?
lymph nodes, bone marrow and/or blood (the lymphatic system)
lymphoid organs; spleen or the gut-associated lymphoid tissue (GALT) & MALT
Skin (often T cell disease - Cutaneous T cell lymphoma )
Non-Hodgkin’s Lymphomas __%
Hodgkin Lymphoma __%
Non-Hodgkin’s Lymphomas 85%
Hodgkin Lymphoma 15%
how is a diverse variety of different antibodies and T cell receptors made?
germ line genes are recombined known as VDJ recombination
where does VDJ recombination happen?
bone marrow
how is even more diversity generated in somatic hypermutation?
Recombination: Ig class switching at the germinal centre,
the insertion of nucleotide point mutations at the sites of VDJ recombination
this is second stage of DNA alteration
how is autoimmunity prevented in the generation of antibody diversity?
apoptosis
Great antibody specificity, eliminate self reactive clones
(90% of normal lymphocytes die in the Germinal centre!)
what increases the risk of DNA replication error in germinal centre?
rapid cell proliferation
what are the key enzymes regulation VDJ recombination?
RAG1+2
key enzymes regulation class switch recombination?
Adenosine induced Deaminase (AID)
which oncogenes can be translocated as an error, at/near the ig H promoter (chromosome 14)?
what does this result in?
bcl2, bcl6 (follicular)
Myc (burkitts)
cyclinD1 (mantle cell l)
oncognes have been translocated near a promoter sequence -> uncontrolled proliferation/cancer will occur!
Note that all these lymphomas involve chromosome 14 as the oncogenes arer moved near this promoter sequence!
oncogenes can be translocated as an error, at the ig H promoter. they come in which 2 forms?
proliferative or anti-apoptotic oncogenes
3 risk factors of LYMPHOMA?
○ Constant antigenic stimulation
○ Infection (direct viral infection of lymphocytes)
○ Loss of T cell function
which 3 conditions cause lymphoma via
Constant antigenic stimulation?
- Helicobacter pylori: gastric MALT. MZL
- Sjogren syndrome: MZL NHL - parotid
- Hashimoto’s : MZl - thyroid
- Coeliac disease: small bowel T cell lymphoma, EATL (enteropathy-associated T cell non-Hodgkin lymphoma)
mzl - Marginal zone sub type (MZL)
which virus infects T cells by vertical transmission ?
consequence?
HTLV1
human T-lymphotropic virus,
-> adult T cell leukaemia lymphoma - ATLL
EBV infects __ lymphocytes?
B lymphocytes
why does HIV cause EBV-driven lymphomas?
EBV infects B lymphocytes
When the EBV is quiescent, the healthy carrier state is maintained by cytotoxic T cells killing B cells expressing EBV antigen.
HIV = loss of T cell function = B cell tumours.
HIV causes EBV-driven lymphomas. What else
transplant immunosuppression:
PTLD (post transplant lymphoproliferative disorder)
where in the lymphoid follicle are naïve unstimulated B cells located ?
mantle zone
○ CD20 = ___ lymphocytes
○ CD3, CD5 = ___ lymphocytes
○ CD20 = B cells
○ CD3, CD5 = T cells
what is the basic WHO Classification of Lymphoma?
○ Hodgkin Lymphoma
§ Classical one
§ B Lymphocyte predominant one
○ Non-Hodgkin Lymphoma § B cell & TCell □ Precursor B cell neoplasms □ Peripheral B cell neoplasms ® Low grade ® High grade
which is the MOST COMMON lymphoma?
B Cell Non-Hodgkin Lymphoma
difference between Hodgkins and other lymphoma?
NHL : lymphoid cells circulate in the blood. involves multiple sites.
Hodgkin’s lymphoma tends to only affect one or two lymph node groups and spreads contiguously - local spread.
Over expression of cyclin D1 (from bcl-1) is suggestive of ?
Mantle cell lymphoma
how do you know there is normal clonal proliferation in a B cell?
will show roughly even amounts of kappa and lambda light chains)
60:40
Bcl 1 overexpression due to t(11;14)
q13;q32
translocation is consistent with which lymphoma?
Mantle cell lymphoma
t(2;5) (p23;q35)
translocation is consistent with which lymphoma?
Anaplastic Large Cell Lymphoma ALCL
Every lymphoma you see is LOW grade apart which 2?
• Burkitt’s lymphoma
○ high grade histology- Very aggressive
• Diffuse large B cell lymphoma & Mantle cell
○ high grade - aggressive
remember - diffuse means disseminated
Histology showed;
Follicular pattern and
positive staining on flow cytometry for CD10 and bcl-6
which lymphoma is this?
Follicular Lymphoma
remeber this is B cell so even though CD10 is most common, it can have CD20, CD19, CD22 too as is common with B cells
Histology showed;
CD5 and CD23 positive
and can undergo Richter transformation
which lymphoma is this?
Chronic Lymphocytic Leukaemia - CLL
histology showed:
○ Arise from pre-germinal centre cells
expression of CD5 and cyclin D1 (from bcl-1)
also 11;14 translocation
which lymphoma is this?
Mantle Cell Lymphoma
Which lymphoma involves 14;18 translocation involving B-cell lymphoma 2 (BCL-2) gene
Follicular Lymphoma
follicular - 4licular
Half of four is 2 -> BCL2 GENE
another name for Chronic Lymphocytic Leukaemia? CLL
Small Lymphocytic Lymphoma - SLL
Follicular lymphoma presents as? (origin?)
Lymph node enlargement
LNs
which lymphoma arises from naïve B cells or post-germinal centre memory B cells ?
Chronic Lymphocytic Leukaemia?
which lymphoma arises from extranodal sites (e.g. gut, lung, spleen) ?
and from post-germinal centre memory B cells?
Marginal Zone Lymphoma/MALT Lymphoma
how to treat Marginal Zone Lymphoma/MALT Lymphoma caused by H.pylori
can be treated by getting rid of h. pylori/ cause
which lymphoma presents as Jaw or abdominal mass in children/young adults
Burkitt’s Lymphoma
which lymphoma arises from germinal centre cells AND
has a Starry-sky appearance on histology
what is the starry sky?
Burkitt’s Lymphoma
note the starry sky appearance can be present in other highly proliferative lymphomas
starry - reactive histiocytes (macrophages)
sky - background of malignant B cells
which tumour has c-Myc translocation (8;14)
(2;8 or 8;22) ?
Burkitt’s Lymphoma
A Diffuse large B cell lymphoma with a germinal centre phenotype is associated with a __ prognosis
GOOD
A Diffuse large B cell lymphoma with p53 positive and high proliferation fraction is associated with a__ prognosis
POOR
which lymphoma is Often found with an associated reactive cell population (especially eosinophils) and are
AGGRESSIVE
T Cell Lymphomas
Cutaneous T cell lymphoma is caused by?
mycosis fungoides
Anaplastic Large Cell Lymphoma - ALCL
occurs in which age group?
Kids and Young people
histology showed: ○ T cell or anaplastic cells also has: ○ 2;5 translocation ○ Alk-1 protein expression
what condition?
Anaplastic Large Cell Lymphoma - ALCL
○ Alk-1 protein expression is associated with a better prognosis
difference between classical and Nodular lymphocyte predominant H lymphoma?
Hodkin L /classical: young people group of nodes EBV Reed-Sternberg sclerosis stain cells with CD30 CD15
NLP - 5%: CD20 1 lymph node only lymphocytes ELDERLY and more
Alcohol-induced pain is a classic but rare symptom in?
Hodgkin Lymphoma
patient comes with painless enlarging lymph nodes
fever, night sweats, weight loss and pruritus.
name the symptoms.
what’s does he have?
B symptoms: Fever, Night sweats, Weight loss >10% in 6 months + unexplained
Hodgkin or NH Lymphoma
How to treat Hodgkin Lymphoma?
Chemotherapy
ABVD ○ Adriamycin - Doxorubicin ○ Bleomycin ○ Vincristine ○ DTIC (Dacarbazine)
ABVD, is given at 4-weekly intervals.
all patients should get this. +/ radiotherapy (increases risk of 2nd cancer elsewhere eg breast if chemo +radio)
Intensive chemo + Autologous Stem cell transplant - relapsed patients
2nd relapse: anti CD30-MAME + PD1 checkpoint inhibitor
what are the features of burkitts lymphoma?
Histologically, Burkitt lymphoma (BL) is characterized by a monoclonal proliferation of medium-sized, noncleaved B-cells that are uniform in appearance and that produce a diffuse pattern of tissue involvement
presence of itching is associated with which lymphoma?
what is the typical distribution?
Hodgkins - 1/3 (more common)
Non Hodgkins - 1/10
distribution: around affected LNs or skin or whole body
why are some people with lymphoma more susceptible to infection?
somee lymphoma can lead to:
Hypergammaglobulinaemia - high IgG ->hyper viscosity syndrome, autoimmune cytopaenia eg haemolytic anaemia
Agammaglobulinaemia - no IgG -> increased infections
what are reed sternberg cells?
giant B cells from germinal centre
– bi-nucleate/multinucleate (‘owl eyed’) cell
on a background of lymphocytes & reactive cells
what is the most common subtype of HL?
nodular sclerosing 80% - young women > men
what is the nodal involvement in HL?
Nodes tend to be mediastinal / cervical but
not always
How is lymphoma staged?
Staging (Ann-Arbor)
Stage 1 – one LN region (LN region can include spleen)
Stage 2 – two or more LN regions on the same side of the diaphragm
Stage 3 – two or more LN regions on opposite sides of the diaphragm
Stage 4 – extranodal sites (liver, BM) spleen not included here
A: No constitutional symptoms B: Constitutional symptoms (1 or more)
E.g. Stage 2a – patient with involvement in 3 LN regions above the diaphragm, pain after alcohol
and SVC syndrome but no weight loss, night sweats etc.
what are the risks of mediastinal lymph node swelling?
SVC syndrome :
- face and neck swelling (worse in morning)
- headache, lightheaded
- upper limb edema
- distended neck veins, cough, SOB
Airway obstruction
name the mature B cell NHL?
DLBCL, Follicular NHL, CLL (Chronic Lymphocytic Leukaemia)
name the mature T cell NHL?
Anaplastic, Cutaneous
PTCL
on biopsy of the lymph node what would you find for a diagnosis of mantle cell lymphoma?
malignant cells in the mantle of the follicle
what is burkitts leukaemia?
when there is bone marrow involvement leading to a ‘leukaemic phase’ of BL
