Haematology 10 - Lymphoma 1: multidisciplinary Flashcards
What is multiple myeloma a malignancy of?
Plasma cells
Why do bacterial infections and autoimmune disorders increase lymphoma risk?
Constant antigenic stimulation
Why do viral infections increase lymphoma risk?
Direct viral integration of lymphocytes
Which lymphoma does Sjorgen’s syndrome increase risk of?
Marginal zone lymphoma of the parotid
Which lymphoma does Hashimoto’s syndrome increase risk of?
Marginal zone lymphoma of the thyroid
How is HTLV1 transmitted, and which cancer does it increase risk of?
A retrovirus that is transmitted at birth, and increases risk of adult T cell leukaemia lymphoma (an aggressive subtype of T cell NHL)
Which type of cells are infected by EBV?
B cells
How are EBV-expressing B cells usually eliminated? What lymphoma does EBV predispose to and how?
Cytotoxic T cell function
B cell NHL
Mechanism:
- if you’re previously infected with EBV and then it becomes latent
- then when you’re immunosuppressed eg on chemo or during old age, and you get reactivation of the virus, T cells are suppressed so normal cytotoxic T cell killing doesn’t occur –> lymphoma
____
can also precipitate classical Hodkin’s lymphoma….
What type of lymphoma does h pylori infection predispose to?
Gastric MALT
Which oncoportein is overexpressed in Burkitt’s lymphoma?
c-myc
Because of t(8.14)
What are the 2 broad subtypes of Non-Hodgkins lymphoma?
B and T cell type
What are the subtypes of B cell NHL?
Low grade: follicular, small lymphocytic, marginal zone
High grade: diffuse large cell, Burkitt’s
Aggressive: mantle cell
What test can prove germinal centre origin of a lymphoma?
For diffuse large b cell lymphoma, which subtype has better prognosis: germinal centre or post germinal centre?
Positive staining for CD10 and bcl6
GERMINAL CENTRE origin has better prognosis
What is the classification of Burkitt’s lymphoma
High grade peripheral B cell lymphoma
What gene mutation is associated with follicular lymphoma?
t(14;18) - it causes overexpression of the bcl-2 gene
Which lymphoma typically has a ‘starry sky appearance’ on histology?
Burkitt’s lymohoma
Where does TCR gene recombination occur?
Bone marrow
What are the key enzymes involved in VDJ (TCR gene) recombination?
RAG1 and RAG2
What are the 2 methods of gene recombination in B cells?
Class switching
Somatic hypermutation
What is the key enzyme involved in B cell class switching?
Adenosine-induced deaminase
Which lymphoma are coeliac’s predisposed to?
EATL (enteropathy-associated t cell lymphoma)
What can PCR be used for in lymphoma diagnosis?
Identifying:
- Translocations
- TCR rearrangement
- IG gene rearrangement
What is the translocation t(11;14) diagnostic of?
Mantle cell lymphoma
What is the translocation of t(2;5) associated with?
A better prognosis for aplastic large cell lymphoma (T cell)
**t for T cell; t for two**
Which lymphoma shows aberrant CD5 and cyclin D1 expression?
Mantle cell lymphoma
Which type of lymphoma can cause either a jaw or abdominal mass?
Burkitt’s lymphoma
Recall one good and one bad prognostic indicator in diffuse large b cell lymphoma?
Good: germinal centre phenotype
Bad: p53 mutation
What is the grade of peripheral T cell lymphomas?
V aggressive
Which lymphoma is particularly common in Japan and the Caribbean?
Adult T cell leukaemia lymphoma
**caused by HTLV-1 which is becoming more common in these areas
What is cutaneous T cell lymphoma known as?
Mycosis fungoides
Which age group tends to be affected by anaplastic large cell lymphoma?
Young adults
What is the t(2;5) translocation associated with?
Anaplastic large cell lymphoma- T cell lymphoma
if you have this translocation it is good prognosis
Which type of lymphoma is associated with ALK-1 expression?
Anaplastic large cell lymphoma
this is associated with good prognosis
Which type of lymphoma is most likely to involve just one lymph node group?
Hodgkin’s
Which type of granulocyte will be present within a classical Hodgkin’s lymphoma?
Eosinophil
other reactive cells: marophages and plasma cells
**in nodular - no reactive cells
Which type of lymphoma is associated with an isolated lymphadenopathy?
Nodular Lymphocyte predominant Hodgkin’s lymphoma
Recall the subtypes of classical Hodgkin’s lymphoma
Nodular sclerosing - most common, more common in females
Mixed cellularity
Lymphocyte rich/ depleted - worst prognosis
Which type of Hodgkin’s lymphoma would show B cell rich nodules?
Nodular lymphocyte-predominant lymphoma (i.e. not classical hodgkin’s lymphoma)
Which type of lymphoma stains positively for CD15 and CD30?
CLASSICAL HODGKIN’S LYMPHOMA
What is the biggest risk of radiotherapy in hodgkin’s lymphoma for women?
Breast Ca
** chemotherapy is mainstay; radiotherapy is in case of relapse but it carries risk of secondary malignancies
What is the translocation t(8;14) associated with?
Burkitt’s lymphoma
What is the best chemotherapy for Burkitt’s lymphoma?
Rituximab
What is the histological finding of “angular nuclei” pathognemonic for?
Mantle cell lymphoma
The Durie-Salmon staging system is used for which type of malignancy?
Multiple myeloma
Where are lymphomas found?
Can arise in any lymphoid tissue
a) generative
b) reactive
c) acquired
Are lymphomas usually disseminated or localised in disease?
Usually disseminated as lymphomas circulate in the blood
Except Hodkin’s lymphoma- tends to affect specific lymph node groups
And also early NHL tends to be localised in presentation
CLassification of lymphoid malignancies
What is the difference between lymphoma and lymphoid leukaeimia?
Lymphoma: predominantly affects lymph nodes with possible LATER involvement of blood/bone marrow
Lymphoid leukaemia: predominantly affects bone marrow and blood with moderate involvement of lymph nodes
What are the precursor lymphoid neoplasms?
B cell: precursor B cell lymphoblastic leukaemia
T cell: precursor T cell lymphoblastic leukaemia
What malignancy do naive B cells give rise to?
Chronic lymphocytic leukaemia
What malignancy do plasma cells give rise to/
Multiple myeloma
What malignancy do mantle cells give rise to?
Mantle cell lymphoma
What malignancy do follicular lymphocytes give rise to?
Follicular lymphoma
Follicular lymphocytes- found in germinal centre
Which mutations give rise to lymphoma? Inherited or somatic?
Mostly somatic!!
Altho there may be genetic predisposition to mutations, the actual mutation that causes cancer arises from a somatic mutatoin
What lymphoma is prediposed to by HIV?
B cell NHL
eg diffuse large b cell and burkitts
**Bc HIV also leads to loss of T cell function - less cytotoxic killing
Broad risk factors for lymphoma development
- most cases are sporadic
- some specific risk factors- constant antigenic stimulation, viral integration into lymphocytes, loss of T cell function
- inherited disorders- genomic instability
- iatrogenic- chemo and radio
- immunosuppression
In certain NHL subtypes you get chromosomal trnaslocations involving the promoter region: what is it? And what is the proto-oncogene?
IgH: immunoglobulin H
proto-oncogenes e.g. c-myc, BCL-2, BCL-6, cyclin-D1
Which type of hodkin’s lymphoma is associated with EBV?
Classical- nodular sclerosing
**nb: nodular lymphocyte predominant is NOT associated with EBV
How does HL spread?
contiguously, often involves a single lymph node group
What type of fever do you get with HL?
Pel ebstein fever- cyclical fever
Markers of classical vs non classical HL
Hodgkin cells vs reed sternberg cells
hodgkin’s cells: mononuclear versions of reed sternberg cells
reed strnberg cells: multinucleate giant cells with reactive cells like eosinophils
Treatment of hodkin’s lymphoma
Allogenic vs autologous stem cell transplant
basc: allogeniec only preferred in leukaemia because of graft vs tumour effect which can be taken advantage of
3 types of burkitt’s lymphoma
Tx of burkitt’s
rituximab
mantle cell lymphoma treatment
R-CHOP
Auto-sct for relapse
Tx of follicular lymphoa
watch and wait
rituximab
or obintuxumab+cvp
what tx can be used for t cell NHL?
alemtuzumab- anti CD52
CD52 is the T cell receptor
what is bcl2 inhibitor?
used in cll - it promotes apoptosis of cells
