intro to lymphomas and myelomas

Question 1

define lymphoma

Answer 1

cancer of white blood cells

affects to mature blood cells, mostly b lymphocytes but also T lymphocytes

heterogenous group

many known to be due to specific genetic mutations and chromosomal translocations

Question 2

functions of lymph nodes

Answer 2

blood filtration/purification

removal of excess fluid from tissues

absorption and transport of lipids

immune system activation

Question 3

describe primary and secondary lymph organs

Answer 3

primary lymph organs = sites where stem cells can divide and become immunocompetent

secondary lymph organs = sites where most of the immune responses occur

Question 4

stages of lymphoma

Answer 4

1. affect lymphocytes in different maturation stages
2. uncontrolled division
3. organ size increase:
   lymph node and other lymph organs
4. spread to other tissues through lymphatic system
5. might infiltrate in bone marrow and or other organs

Question 5

presentation of lymphoma

Answer 5

fever
swelling of face and neck 
lump in neck, armpits and groin 
excessive sweating at night 
unexpected weight loss 
itchiness
breathlessness
loss of appetite 
feeling of weakness

Question 6

diagnosis methods

Answer 6

lymph node biopsy

flow cytometry

FISH
NGS
immunophenotyping

Question 7

aetiology

Answer 7

multifactorial disorder = malfunctioning of the body’s immune system
exposure to certain infections

triggers are unknown but most of lymphomas occur when a B cell develops/acquires a mutation in its DNA

Question 8

describe Hodgkin lymphoma

Answer 8

• clonal B cell malignancy
• presentation = non painful enlarged lymph nodes

risk factor = 50% cases due to Epstein-barr virus

other risk factors: family history and HIV/AIDS

Question 9

diagnosis for Hodgkin lymphoma

Answer 9

excisional lymph node biopsy

Question 10

treatment and prognosis for Hodgkin lymphoma

Answer 10

chemotherapy or radiation. stem cell transplant

prognosis = 5year survival around 50-90% depending on age, stage and histology. especially good results in young adults

Question 11

non-hodgkin lymphoma

Answer 11

presentation = enlarged lymph nodes. some forms are slow and others grow faster. general lymphoma symptoms

causes = chromosome translocations

risk factors = virus infections, in Burkitts lymphoma, human T cell leukaemia virus in adult T cell lymphoma

Question 12

non-hodgkin lymphoma

Answer 12

many lymphomas carry chromosome translocations involving the Ig heavy chain or light chain loci

ig genes highly expressed in B cells

each Ig gene has a powerful tissue specific enhancer

Question 13

causes of non Hodgkin lymphoma

Answer 13

chromosome translocations

most cases of follicular lymphoma carry t(14;18)(q32;q21)
t(8;14)(q24;q32) is frequently observed in Burkitt’s lymphoma.

Question 14

non Hodgkin lymphoma 2

Answer 14

presentation = enlarged lymph node. some forms are slow and others grow faster. general lymphoma symptoms

causes = chromosome translocations

risk factors = virus infections, driven lymphomas in immunosuppressed patients

Question 15

risk factors of non-hodgkin lymphoma

Answer 15

virus infections driven lymphomas in immunosuppressed patients

• It directly transforms B-lymphocytes in culture. Due to viral oncogene LMP-1.
• Over half of all normal individuals carry latent EBV infection. They do not develop lymphomas due to effective immune surveillance by cytotoxic T-cells.
• In highly immunosuppressed individuals the endogenous latent EBV may transform B-cells.
• No longer eliminated by cytotoxic T-cells.
• Develop high grade lymphoma.

Question 16

classification of non-hodgkin lymphoma

Answer 16

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 fashion

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

Question 17

diagnosis of non-hodgkin lymphoma

Answer 17

immunophenotyping
cytogenetics - FISH

light chain restriction
PCR = for clonal Ig gene rearrangement

Question 18

treatment for non-hodgkin lymphoma and prognosis

Answer 18

chemotherapy
radiotherapy
stem cell transplant
monoclonal Ab therapy - rituximab

prognosis
- overall five year survival rate around 70%

Question 19

what is a multiple myeloma

Answer 19

tumour of the bone marrow that involves plasma cells (antibodies production)
- Presentation: Absence of initial symptoms. Later: bone pain, bleeding, frequent infections, and anaemia.

• Unknown cause. Risk factors: obesity, radiation exposure, family history, and certain chemicals.

Question 20

multiple myeloma - 3 aspects of myeloma give rise to diff clinical features

Answer 20

1. suppression of normal bone marrow, blood cell and immune cell function
2. bone resorption and release of calcium
   - myeloma cell produce cytokines > bone marrow stromal cells to release cytokine RANKL > osteoclasts activation

• calcium released from bone causes hypercalcemia
  3. pathological effects of the paraprotein (single monoclonal Ig in the serum- high levels- malignancy
• ppt in kidney tubules cause renal failure
• deposited as amyloid in many tissues
• 2% cases develop hyper viscosity syndrome

Question 21

what can increased viscosity of blood lead to

Answer 21

stroke

heart failure

Question 22

diagnosis for multiple myeloma

Answer 22

• serum electrophoresis for paraprotein
• urine electrophoresis
• bone marrow biopsy for increased levels of plasma cells
• erythrocyte sedimentation rate - high due to stacking of the RBC
• flow cytometry and cytogenetics to detect cause
• radiological investigation of skeleton for lytic lesions

Question 23

treatment and prognosis for multiple myeloma

Answer 23

treatment = radiotherapy, chemotherapy combinations, targeted therapies, immunotherapy and allogeneic hematopoietic stem cell transplantation in young patients

prognosis = chemo+ASCT = overall 5- year survival rate around 35%