intro to Lymphomas and Myeloma

Question 1

What do lymphoid malignancies include?

Answer 1

• lymphomas
• lymphoid
• leukaemias
• myeloma

Question 2

Define Lymphoma

Answer 2

• a cancer of WBC
• affects mature cells, mostly B lymphocytes
• Heterogeneous group
• many known to be due to specific genetic mutations and chromosomal translocation

Question 3

What is the main function of lymphatic system?

Answer 3

• blood filtration/purification
• removal of excess fluids from tissues
• absorption and transport of lipids
• immune system activation

Question 4

What are primary lymph organs?

Answer 4

• sites where stem cells can divide and become immunocompetent
• eg: Thymus and bone marrow

Question 5

What are secondary lymph organs?

Answer 5

• sites where most of the immune response occurs

- eg: tonsils and adenoids, lymph nodes , appendix, peyer’s patches

Question 6

How do lymphomas develop?

Answer 6

• affect lymphocytes in different maturation stages
• uncontrolled division
• organ size increase: lymph node (adenopathy), other lymph organs (splenomegaly)
• spread to toher tissues through lymphatic system
• might infiltrate in bone marrow (detectable in blood) and/or other organs

Question 7

What is the traditional classification

Answer 7

• Non -Hodkin’s : diffuse and follicular.

- Hodkins

Question 8

Compare Hodgkin and non Hodkin lymphomas.

Answer 8

1. Hodkin
   - less common (<1%)
   - age: 75 -79 y/o
   - trend over time: 36%
2. Non - Hodkin
   - more common (4%)
   - age: 80-84 y/o
   - trend over time : 39%

Question 9

What are signs and symptoms of lymphomas?

Answer 9

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

Question 10

How do you diagnose lymph node?

Answer 10

• lymph node biopsy

- study and identify using FISH, flow cytometry

Question 11

What are stages of PET?

Answer 11

• stage 1 : localised disease, single lymph node region or single organ
• stage 2: 2 or more lymph node regions on the same side of diaphragm
• stage 3: two or more lymph node regions above and below the diaphragm
• stage 4: widespread disease, multiple organs with or without lymph node.

Question 12

What is aetiology of lymphoma?

Answer 12

• 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 13

Hodkin Lymphoma

Answer 13

• 1832 - Thomas Hodkin
• clonal B-cell malignancy
• presentation : non-painful enlarged lymph nodes
• Risk factors: 50% cases due to Epstein -Barr virus (EBV) classic form

Question 14

Diagnosis of Hodkin lymphoma

Answer 14

Excisional lymph node biopsy and :

• normal B lymphocytes
• Reed-sternberg cell

Question 15

What is the treatment for Hodgkin lymphoma?

Answer 15

• chemotherapy +/- radiotherapy

- stem cell transplant

Question 16

What is the prognosis of Hodgkin lympoma?

Answer 16

• 5 year survival ~ 50-90% depending on age, stage and histology.
• Especially good results in young adults (97%)

Question 17

What are 3 grades of non -Hodgkin lymphoma?

Answer 17

1. high grade
   - Diffuse large B cell Lymphoma
   - Burkitt Lymphoma
2. Low grade
   - Marginal Zone Lymphoma
   - Follicular Lymphoma
   - Mantle cell Lymphoma
3. High and low grade
   - T cell Lymphoma (all subtypes)

Question 18

Non- Hodgkin

Answer 18

1. Presentation:
   - enlarged lymph nodes. some form are slow and others grow faster. Symptoms.
2. Causes: chromosome translocations
3. Risk Factors: virus infections (eg; EBV (HHV4) in Brkitt’s lymphoma; human T cell leukaemia virus in adult T cell lymphoma)

Question 19

What causes Non-Hodgkin lymphoma?

Answer 19

• chromosome translocations
• many lymphoma carry chromosome translocations involving the Ig heavy chain or light chain loci (chr14)
• Ig genes are highly expressed in B-cells
• Each Ig gene has a powerful tissue specific enhancer (high expression levels)

Question 20

How does translocation observed in follicular lymphoma lead to decreased apoptosis and increased proliferation leading to cancer?

Answer 20

• due to translocation enhancer starts regulating and enhancing the transcription of genes that are located in other chromosomes.
• Example: in follicular lymphoma translocation between chr14 and chr18.
• the promoter of new adjacent gene becomes regulated by immunoglobulin enhancer.
• in chr18 there is an important gene called BCL-2 gene which is an apoptosis inhibitor so when there is translocation to chr18 the apoptosis inhibitor causes inhibition in apoptosis thus more proliferation.

Question 21

How does translocation observed in Burkitt’s lymphoma lead to cancer?

Answer 21

• translocation between chr8 and chr14
• chr8 has a myc gene
• c-myc is a potent proto-oncogene

Question 22

What are risk factors of Npn-Hodgkin lymphoma?

Answer 22

• virus infections (eg: EBV (HHV4) 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 infections. They do not develop lymphomas due to effective immune surveillance by cytotoxic T- cells

Question 23

How is Non - Hodgkin Lymphoma classified?

Answer 23

1. Low grade
   - normal tissue architecture partially perserved normal cell of origin recognisable
   - divide slowly
   - may be present for many months before diagnosis
   - behave in indolent fashion
2. High grade
   - loss of normal tissue architecture- normal cell origin hard to determine
   - divide rapidly
   - present for a matter of weeks before diagnosis
   - maybe life threatening

Question 24

How do you diagnose Non-Hodgkin lymphoma?

Answer 24

• immunophenotyping
• cytogentics - FISH : for chromosome translocations (eg. t(14, 18) Ig: Bcl -2)
• Light Chain restriction

Question 25

What are treatments for Non-Hodgkin lymphoma?

Answer 25

• chemotherapy
• radiotherapy
• stem cell transplant
• monoclonal Ab therapy - Rituximab(anti-CD20)

Question 26

What is prognosis for non- hodgkin lymphoma?

Answer 26

• overall 5 year survival rate `70%

Question 27

What is multiple myeloma?

Answer 27

• tumour of the bone marrow that involves plasma cells (antibodies production)
  => Presentation:
  -absence of initial symptoms . Later: bone pain, bleeding, frequent infection, and anaemia.
  => Unknown cause (genetics)
  => Risk factors: obesity, radiation exposure, family history, and certain chemicals

Question 28

What are 3 aspects of multiple myeloma?

Answer 28

1. suppression of normal bone marrow, blood cell and immune cell function :
   - anemia
   - bleeding tendency
   - recurrent infections
2. Bone resorption and release of calcium:
   (a) myeloma cells produce cytokines (esp. IL-6) -> bone marrow stromal cells to release the cytokine RANKL -> osteoclasts activation (lytic lesions of bone, bone pain, fractures)
   (b) Calcium released from bone causes hypercalcaemia (multiple symptoms including mental disturbance)
3. Pathological effects of paraprotein - (single monoclonal Ig in the serum - high levels - malignancy)

Question 29

What are treatments for multiple myeloma?

Answer 29

• radiotherapy
• chemotherapy combinations (thalidomide, lenalidomide and Bortzezomib) , targeted therapies, immunotherapy (CAR- T), and allogeneic hematopoietic stem cell transplantation (ASCT)

Question 30

What is prognosis for multiple myeloma?

Answer 30

• chemo + ASCT - overall 5 year survival rate ~ 35%