Introduction to Lymphoma and Myeloma Flashcards
What are the lymphoid malignancies?
Lymphoma
Myeloma
Lymphoid leukaemia
What are the primary lymphoid organs?
What are the secondary lymphoid organs?
Primary lymphoid organs:
- Bone marrow
- Thymus
Secondary lymphoid organs:
- Spleen
- Lymph nodes
Define and outline Lymphoma
Lymphoma: A cancer of white blood cells (lymphocytes)
- Affects mature WBCs - mostly B-lymphocytes, but also T-lymphocytes
- Heterogeneous group of diseases
- Many are due to specific genetic mutations, chromosomal translocations
Which cells are affected in Lymphomas?
- (Small lymphocyte ->)B-cells + T-cells
- NK cell (large granular lymphocyte)
What is lymph?
Lymph: Fluid that accumulates in tiny spaces b/w cells. Contains proteins, lipids, lymphocytes.
Functions of Lymphatic System:
- Blood filtration /purification
- Removal of excess fluids from tissues
- Absorption and transport of lipids
- Immune system activation
What are the lymph nodes ?
Lymph nodes: Glands that filter lymph(clear fluid that circulates through the lymphatic system).
Remove microorganisms+foreign matter.
All throughout body, but ↑ in neck, arms, elbows, chest, abdomen
What are lymph organs ?
Primary lymph organs: Sites where stem cells can divide and become immunocompetent
- Bone Marrow
- Thymus
Secondary lymph organs: Sites where most of the immune responses occur
- Spleen
- Lymph nodes
- Appendix
- Peyer’s Patches
- Tonsils + Adenoids
How do Lymphomas develop?
Mutation/Chr translocation affects mature lymphocytes (not stem cells) which leads to uncontrolled division .
Organ size increase due to ↑ lymphocytes:
- Lymph node - Adenopathy = enlarged lymph nodes due to infection/autoimmune disease/Lymphoma
- Other lymph organs - Splenomegaly
Mutated lymphocytes then spread to other tissues through the lymphatic system
Mutated lymphocytes may infiltrate bone marrow(=can detect the altered lymphocytes in blood) and other organs
How is Lymphoma classified ?
- Hodgin’s Lymphoma - adolescence, 75-79yo
- Non Hodgkin’s Lymphoma (more common) - 80-84yo. Incidence of NHL ↑ with age
Presentation of Lymphoma
Large, usually painless lymph nodes Fever Swelling on face Lump in neck,armpit or groin Excessive sweating at night Unexpected weight loss Loss of appetite Weakness Breathlessness Itchiness
How is lymphoma diagnosed ?
Lymph node biopsy using a biopsy needle. Examine partial/total lymph node under microscope. Indicates lymphoma.
Then do further tests to identify lymphoma subtype: Flow cytometry FISH NGS Immunophenotyping
What is the staging of Lymphoma ?
After diagnosis, stage the lymphoma - same system for HL + NHL
A series of tests carried out by PET to identify which body regions affected .
Stage 1: Localised disease , 1 lymph node region/1 single organ
Stage 2: 2 or more lymph node regions on the same side of the diaphragm
Stage 3: 2 or more lymph nodes regions above and below diaphragm
Stage 4 : Widespread disease, Multiple organs with/without lymph node involvement, cancer has disseminated - spread to extralymphatic organs
What is the aetiology of Lymphoma ?
Multifactorial disorder:
- Malfunctioning of the body’s immune system
- Exposure to certain infections
Most lymphomas occur when a B cell develops/acquires a mutation in its DNA
What is the traditional classification of Lymphoma ?
Hodgkin’s and Non Hodgkin’s (larger group)
Non Hodgkin’s -
Diffuse / Follicular
Hodgkin’s
Lymphoma Classification:
HL/NHL
Affected cell: T-cell/B-cell
Site at which the cell arises
- Mature B-cell neoplasms
- Mature T-cell + NK cell neoplasms
- Hodgkin’s lymphoma
slide 18
What is Hodgkin lymphoma?
Outline the disease and its presentation
Hodgkin’s Lymphoma = A Clonal B-Cell malignancy
Presentation: Non-Painful, enlarged lymph node(s)
Risk factors : Epstein Barr virus (EBV,HHV4), Family History of HL, HIV/AIDS
How can we diagnose Hodgkin’s Lymphoma ?
Lymph node biopsy:
-Observe Hodgkin cell (multinucleated Reed-Sternberg cell) in lymph node which are derived from normal B lymphocytes. Using light microscope bc v. big cells w/ a bilobed nucleus .
These cells are only present in Hodgkin’s lymphomas
What is the Treatment of Hodgkin’s Lymphoma ?
- Chemotherapy/Radiotherapy, Stem Cell Transplant
- Prognosis: 5 year survival. Good treatment results in young adults
What are Non-Hodgkin’s Lymphomas?
Non-Hodgkin’s Lymphomas = All lymphomas aprt from Hodgkin’s lymphoma.
Outline Non-Hodgkins Lymphoma - Presentation, Cause, Risk Factors
Presentation : Enlarged lymph nodes. General lymphoma symptoms.
Cause: Chromosome translocations
Risk factors : Virus infections - EBV(HHV4) in Burkitt’s lymphoma , Human T-cell leukaemia virus in adult T-cell lymphoma.
What are the chromosome translocations which occour in Non-Hodgkins Lymphoma ?
Chromosome translocations involving Ig heavy chain/light chain loci (chr14)
- Ig genes are highly expressed in B-cells
- Each Ig gene has a powerful tissue-specific enhancer (high expression levels)
Identify chr translocation using lymph node biopsy, then FISH
What are the consequences of these chromosome translocations in Non-Hodgkin lymphoma ?
Normal role of Ig enhancer: Activates the promoter of the rearranged V segment of the Ig
Due to the translocation b/w chr14 + other chr, the enhancer starts enhancing transcription of other genes of the chr fused to chr14.
= Overexpression of the BCL-2 gene (an apoptosis inhibitor) on chr18
Most Follicular Lymphoma cases carry t(14:18) (q32:q21)
Chr Translocation = Ig enhancer regulates promoter of the new adjacent gene. = overexpress BCL-2 gene = ↓ apoptosis, ↑ cell survival+proliferation
Where does the Ig V segment gene reside?
chr 14
What is Follicular Lymphoma ?
Follicular lymphoma is a type of non-Hodgkin lymphoma
What is the translocation observed in Burkitt’s lymphoma ?
Burkitt’s lymphoma = NHL
t(8;14)(q24;q32)
Balanced translocation; brings together Ig enhancer(chr14) + c-myc gene.
c-myc = a potent proto-oncogene.
translocation fusion = converts c-myc (proto-oncogene) →oncogene. now highly expressed due to highly expressed Ig on chr14
