Lymphoma 1: MDT Flashcards
What is Lymphoma?
The term ‘lymphoma’ means a neoplastic (malignant) tumour of lymphoid cells.
Where are lymphomas usually found?
Lymphomas usually found in lymph nodes, bone marrow and/or blood (the lymphatic system) lymphoid organs; spleen or the gut-associated lymphoid tissue Skin (often T cell disease)
Rarely “anywhere” (breast kidney){*Immune privilege sites CNS, occular, testes}
What is the incidence of Lymphoma (Incl. HL and NHL)?
There are approximately 200 new cases per year for every million of the population (around 10,000 new cases a year in the UK).
Non-Hodgkin’s Lymphomas 80%
Hodgkin Lymphoma 20%
What are precursor malignancies?
Precursor cell neoplasia of B or T cell lineage:
Precursor B cell lymphoblastic leukaemia
Precursor T cell lymphoblastic leukaemia
What are mature B cell malignancies?
NHL
HL
What are mature T cell malignancies?
T cell or NK cell NHL
What are lymphoma RFs?
Most lymphoma subtypes/cases are sporadic with no known risk factors
Some lymphoma subtypes have specific risk factors immune diseases acquired or iatrogenic
Associated specific infections or inflammation
How does the limited instability of DNA become problematic in lymphoma?
- Lymphocytes undergo DNA changes in development:
Potential for recombination errors and new point mutations - Rapid cell proliferation in the germinal centre
Allows rapid response to infection
Rapid cell division = increased risk of DNA replication errors - Dependent on apoptosis
Exquisite antibody specificity & eliminates self reactive clones
Apoptosis is “switched off” in germinal centre
Consequences of mutation ins in apoptosis regulating genes
What is VDJ recombination?
Occurs in BM
Key enzymes: RAG1+2
TdT
What do B cells undergo?
Class switch recombination
Somatic hypermutation
Key enzyme: Adenosine induced Deaminase
What are immune gene recombination errors and lymphoma linked translocations?
Lymphoma/recombination associated translocations
Involves the Ig Locus (IgH, K or l loci)
Ig promoter highly active in B cells
Bring intact oncogenes close to the Ig promoter
Oncogenes may be anti apoptotic, proliferative.
bcl2
bcl6
Myc
cyclinD1
What are the 3 main groups of rare NHL subtypes?
- Constant antigenic stimulation- bacteria/ AI
- Viral infection (direct viral integration of lymphocytes)
- Loss of T cell function and EBV infection (B cell) - Loss of T cells (HIV), iatrogenic immunosuppression
What are the bacterial or AI driven causes of rare NHL (chronic inflammation)?
B cell Non Hodgkin Lymphoma Marginal zone sub type (MZL)
H.Pylori : Gastric MALT (mucosa associated lymphoid tissue) (MZL of stomach)
Sjogren syndrome : MZL of salivary glands
Hashimoto’s : MZL of thyroid
Enteropathy associated T-Cell
Non Hodgkin lymphoma (EATL)
Coeliac disease/Gluten: small intestine EATL
How does direct viral integration and lymphomagenesis occur?
HTLV1 retrovirus infects T cells by vertical transmission
Caribbean, Japan (and world wide) endemic infection
Risk of Adult T cell leukaemia lymphoma is 2.5% at 70 years
ATLL is a subtype of T cell Non Hodgkin Lymphoma
How does loss of T cell function occur?
HIV (in uncontrolled infection there is x60 increased incidence of B NHL )
Iatrogenic (transplant immunosuppression)
PTLD (post transplant lymphoproliferative disorder)
How does EBV infection result in lymphoma?
EBV infects B lymphocytes, healthy carrier state post glandular fever.
EBV driven proliferation of B cells is associated with surface expression of EBV antigens.
Proliferating B cells targeted and killed by EBV specific cytotoxic T cell response
How do CTLs cause EBV to cause havoc?
Loss of cytotoxic T cell function can cause failure to eliminate EBV driven proliferation of B cells
How do you make a haemato-oncology diagnosis?
Morphology (Cytology/ cytochemistry/ histo) Immunophenotye (Flow cytometry, immunohistochemistry) Cytogenetics (Conventional karyotyping, FISH) Molecular genetics (Sequencing, PCR, gene profiling, whole genome sequencing)
How many types of lymphoma are there?
> 60
How do we do diagnosis and staging?
Histological diagnosis
Anatomical stage (CT/ MRI/ PET/ BM biopsy)
Prognostic factors (LDH, beta2 mic, albumin, kidney or BM function)
What cells are specific to HL/ NLPHL?
Reed Sternberg cells
How many Lymphomas are HL?
15% (NHL = 85%)
What are the mature B and T cell lymphomas?
Mature B cell neoplasm
DLBCL, Follicular NHL, CLL etc
Mature T and NK neoplasm
PTCL, Anaplastic, Cutaneous
What is the epidemiology of HL?
1% of all cancer, 3:100,000 population
HL is more common in males than females.
Bimodal age incidence
Most common age 20-29, young women NS subtype
Second smaller peak affecting elderly >60 years old
What are the S/S of HL?
Painless enlargement of lymph node/nodes.
May cause obstructive symptoms/signs
Constitutional symptoms; fever, night sweats weight loss (the B symptoms) and pruritis may be present. Rarely alcohol induced pain
What is the classification of HLs?
Classical HL
Nodular sclerosing 80% Good prognosis (causes the peak incidence in young women)
Mixed cellularity 17% Good prognosis
Lymphocyte rich (rare) Good prognosis
Lymphocyte depleted (rare) Poor Prognosis
How common is NLPHL?
Nodular Lymphocyte predominant HL 5% (disorder of the elderly multiple recurrences)
How do you stage HL?
Following pathological diagnosis of a lymph node biopsy patients are ‘staged’ this has prognostic significance and also may determine the best approach for therapy.
FDG-PET/CT scan
Consider biopsy of other site if possibly infiltrated e.g. liver
