Intro To Lymphoma And Myeloma Flashcards
What is lymphoma and state the 2 key risk factors?
- Cancer of mature WBCs (lymphocytes) -> B (mostly) + T LP -> heterogenous group
- Risk factors: Specific genetic mutations + Chromosomal translocations
State the 4 main functions of the lymphatic system and what it is aided by? VD
- Blood filtration
- Removal of excess fluids from tissues
- Absorption, Transport of lipids
- Immune system activation
- Occurs within lymph nodes throughout body
Describe the difference in function between primary + secondary lymph organs and state organ examples
- Primary: SC divide + become immunocompetent -> thymus + bone marrow
- Secondary: Where most of the immune responses occur -> tonsils, lymph nodes, appendix, spleen
Describe how chromosomal translocation leads to lymphoma?
- Affects lymphocytes in different maturation stages - uncontrolled division
- Organ size increases (adenopathy = LN) (splenomegaly = other L organs)
- Lymphoma spread to other tissues through lympathic system
- May infiltrate in bone marrow (detectable in blood) and/or organs
State key symptoms of lymphoma?
- Fever
- Itchiness
- breathlessness
- Swelling of the face and neck
- Lump in your neck, armpits or grain
- Excessive sweating at night
- Unexpected weight loss
- Feeling of weakness
- Loss of appetite
Describe the full diagnostic process behind lymphoma? VD
- Symptoms -> lymph node biopsy (presence of informer) -> analyse via microscope (detect LP) - identify genetic alteration + subtype of lymphoma (via FISH, flow cytometry, NGS OR immunophenotyping) - Identify stage (I-IV) of LP via PET
Describe the aetiology of lymphoma and the main trigger?
- Aetiology: multifactorial disorder -> malfunctioning of immunity + exposure to certain infections
- Main trigger: Unknown -> Mostly due to B cell mutation
State the traditional + updated (WHO) classification?
- Traditional: Non Hodgkin’s (<) + Hodgkin lymphoma
- WHO: Mature B-cell neoplasms, mature T-cell & NK neoplasms + Hodgkin lymphoma
Describe hodgkin lymphoma, its presentation + risk factors?
- Hodgkin lymphoma: Clonal B-cell malignancy
- Presentation: Non-painful enlarged lymph node(s)
- Risk factors: Epstein-barr virus (50%), family history + HIV/AIDs
Describe the diagnosis and treatment of hodgkin lymphoma?
- Diagnosis: Excisional lymph node biopsy -> Reed-Sternberg cells present
Treatment: Chemotherapy, radiotherapy, SC transplant
Briefly describe Reed sternberg cells
- Hodgkin lymphoma is diagnosed by the detection of Reed Sternberg cells
- They’re derived from B lymphocyte mutations
- Key marker of Hedgkin lymphoma
Non-hodgkin lymphoma
State the presentation, cause + risk factors of non-hodgkin lymphoma?
- Presentation: Enlarged lymph node + general lymphoma symptoms
- Cause: Chromosome translocations
- Risk factors: Virus infections -> EBV (Burkitt’s lym.). Human T-cell leukaemia virus (adult T-cel lym)
Describe how virus infections become a risk factor of non-hodgkin lymphoma?
- Directly transforms B-lymp. via viral oncogene LMP-1 -> over half of all normal individuals carry latent EBV infection -> no lymphoma development -> effective immunity via Tc cells
- Highly immunosuppressed individuals -> latent EB may transform B-cells -> no longer be eliminated via Tc cells -> development of high grade lymphoma
Describe the low grade classification and features of them for non-hodgkin lymphoma?
- Low grade
- Normal tissue architecture partially preserved (normal cell of origin recognisable)
- Divide slowly
- May be present for many months before diagnosis, Behave in an indolent (lazy) fashion
Describe the high grade classification and features of them for non-hodgkin lymphoma?
- High grade:
- Loss of normal tissue architecture -(normal cell of origin hard to determine)
- Divide rapidly
- Present for a matter of weeks before diagnosis
- May be life-threatening
State the diagnostic methods for non-hodgkin lymphoma?
- Diagnosis:
- Immunophenotyping
- Cytogenetics - FISH (For chromosome translocations (e.g. t(14;18) Ig : Bcl-2))
- Light chain restriction (k>^)
- PCR (clonal Ig gene rearrangement)
State the treatments for non-hodgkin lymphoma?
- Treatment:
- Chemotherapy
- Radiotherapy
- SC transplant
- Monoclonal Ab therapy - Rituximab (anti-CD20)
Describe the main cause of non-hodgkin lymphoma?
- Chromosomal translocation - involve lg heavy or light chain loci (Cr 14) - Ig genes highly expressed in B-cells - Ig gene has tissue specific enhancer (increase expression)
- Enhancer role - promotor activation of rearranged V segment of lg
- However, in lymphoma, this enhancer translocates to a different chromosome and begins enhancing the expression of a different unwanted gene through its promoter.
Describe how follicular lymphoma arises?
- Chromosomal translocation -> enhancer (cr14) + BCL-2 (apoptosis inhibitor) (cr18) brought together -> Enhancer causes increased BCL-2 -> Increased inhibition of apoptosis
Describe how Burkitt’s lymphoma arises?
- Chromosomal translocation -> c-myc (potent proto-oncogene) (cr8) + enhancer (cr-14) brought together -> E causes increased c-myc expression -> oncogene -> Increased cell proliferation
What is multiple myeloma?
- Tumour of the bone marrow
- Involving plasma cells (AB production).
Describe the presentation + risk factors of multiple myeloma?
- Presentation: Absence of initial symptoms -> Later: bone pain, bleeding, frequent infections + anaemia -> unknown cause
- Risk factor: Obesity, radiation exposure, family history, + certain chemicals.
Describe methods of diagnosis of multiple myeloma (6)
- Serum electrophoresis for paraprotein
- Urine electrophoresis
- Bone marrow biopsy for increased levels of plasma cells
- Erythrocyte sedimentation rate (ESR) - increased due to stacking of the RBC Myeloma
- Flow cytometry + cytogenetics to detect causes
- Radiological investigation of skeleton for lytic lesions
Describe the treatments for multiple myeloma?
- Radiotherapy, chemotherapy combinations (thalidomide, lenalidomide and bortezomib)
- targeted therapies
- immunotherapy (CAR-T)
- allogeneic hematopoietic SC transplantation (ASCT) in young patients
State the 3 major clinical features of multiple myeloma?
- Suppression of normal bone marrow, blood cell + immune cell function-> anaemia, recurrent infections + bleeding tendency
- Bone resorption + release of calcium
- Pathological effects of the paraprotein
Describe the bone resorption effect from multiple myeloma?
- Myeloma cells produce cytokines (esp. IL-6)
- BM stromal cells release RANKL
- Osteoclasts activation
- Calcium released from bone causes hypercalcaemia
- Multiple symptoms (including mental disturbance)
Describe the pathological effects of the paraprotein?
- Abnormal WBC (myeloma cell) -> contains paraprotein -> single monoclonal Ig in serum -> Increased levels = malignancy
- Precipitates in kidney tubules - renal failures
- Deposited as amyloid
- Can develop into hyperviscosity syndrome -> stroke + heart failure
