Introduction to Lymphomas and Myeloma

Question 1

Define lymphoma and what cells does it affect

Is it heterogenous and why?

Answer 1

cancer of the white blood cells (lymphocytes)

Affects to mature blood cells, mostly B lymphocytes but also T lymphocytes.

Heterogeneous group.

Many known to be due to specific genetic mutations and chromosomal translocations.

Question 2

What are the 4 main functions of lymph nodes?

Answer 2

a) blood filtration/purification
b) removal of excess fluids from tissues
c) absorption and transport of lipids
d) Immune system activation

Question 3

Define 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

What are the 5 stages of lymphoma?

Answer 4

Affect lymphocytes in different maturation stages

Uncontrolled division

Organ size increase:
Lymph node (adenopathy)
Other lymph organs (splenomegaly)

Spread to other tissues through lymphatic system

Might infiltrate in bone marrow (detectable in blood)
and/or other organs

Question 5

How do we classify lymphoma?

Answer 5

Non-Hodgkins (diffuse and follicular) and hodgkins

Question 6

What are the warning signs of lymphoma?

Answer 6

fever

swelling of face and neck

sweating

lump in armpit or groin

weight loss

appetite loss

itchness

Question 7

How do we diagnose lymphoma?

Answer 7

On image

Question 8

What are the stages of THE diagnosis lymphoma?

Answer 8

On image

Question 9

Describe the aetiology of lymphoma

Answer 9

o Multifactorial disorder:
- Malfunctioning of the body’s immune system
- Exposure to certain infections
o The triggers are unknown but… most of lymphomas occur when a B cell develops/acquires a mutation in its DNA.

o Different Lymphoid malignancies correspond to normal stages of lymphoid development

Question 10

What causes Hodgkin’s lymphoma?

How does it present?

How do we diagnose it?

What is the treatment?

Answer 10

Clonal B-cell malignancy.

Presentation- non-painful enlarged lymph node(s).

Excisional lymph node biopsy and…

Treatment: Chemotherapy +/- radiotherapy. Stem cell transplant.

Question 11

What causes non-Hodgkin lymphoma?

How does it present itself?

What are the risk factors?

How do we diagnose and treat it?

Answer 11

Chromosome translocations

• Presentation: enlarged lymph node(s). Some forms are slow and others grow faster. General lymphoma symptoms.

Risk factors: virus infections (e.g. EBV (HHV4) in Burkitt’s lymphoma; Human T-cell leukaemia virus in adult T-cell lymphoma)

• Many lymphomas 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).

o Chemotherapy
o Radiotherapy
o Stem cell transplant
o Monoclonal Ab therapy -Rituximab (anti-CD20)

Question 12

Describe Chromosome translocations and lymphoma

Answer 12

o Many lymphomas carry chromosome translocations involving the Ig heavy chain or light chain loci (chr14).
o Ig genes are highly expressed in B-cells
o Each Ig gene has a powerful tissue specific enhancer (high expression levels) near to the constant (C) segment

o Normal role: activating the promoter of the rearranged V segment
o Most cases of follicular lymphoma carry t(14;18)(q32;q21)

• t(8;14)(q24;q32) is frequently observed in Burkitt’s lymphoma.
• c-myc is a potent oncogene

Question 13

What are the types of Non-Hodgkin’s Lymphomas

Answer 13

o Low grade

o High grade

Question 14

How do we diagnose Non-Hodgkin’s Lymphomas

Answer 14

o	Immunophenotyping
o	Cytogenetics –FISH
o	For chromosome translocations (e.g. t(14;18) Ig : Bcl-2)
o	Light chain restriction
o	PCR
o	For clonal Ig gene rearrangement

Question 15

How do we treat Non-Hodgkin’s Lymphomas

Answer 15

o Chemotherapy
o Radiotherapy
o Stem cell transplant
o Monoclonal Ab therapy -Rituximab (anti-CD20)

Question 16

Compare low and high grade

Answer 16

 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

 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

What is Multiple Myeloma?

How does it present itself?

What are the risk factors?

Answer 17

Tumour of the bone marrow that involves plasma cells (antibodies production).

Absence of initial symptoms. Later: bone pain, bleeding, frequent infections, and anaemia.

Obesity, radiation exposure, family history, and certain chemicals.

Question 18

How do we diagnose Multiple Myeloma?

How do we treat it?

Answer 18

Serum electrophoresis for paraprotein

Urine electrophoresis

Bone marrow biopsy for increased levels of plasma cells

Erythrocyte sedimentation rate (ESR)-high due to stacking of the RBC

Flow cytometry and cytogenetics to detect cause

Radiological investigation of skeleton for lytic lesions

Radiotherapy, chemotherapy, allogeneic hematopoietic stem cell transplantation (ASCT) in young patients.

Question 19

What are the Three aspects of myeloma give rise to different clinical features?

Answer 19

1. Suppression of normal bone marrow, blood cell and immune cell function
   - Anaemia
   - Recurrent infections
   - Bleeding tendency
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 the paraprotein –(single monoclonal Igɣ in the serum- high levels – malignancy)
   - Precipitates in kidney tubules cause renal failure
   - Deposited as amyloid in many tissues
   - 2% of cases develop hyperviscosity syndrome
    Increased viscosity of blood leading to
    Stroke
    Heart failure