Lymphoma 1: MDT

Question 1

Define lymphoma

Answer 1

Lymphoma means neoplastic (malignant) tumour of lymphoid cells

Question 2

Where are lymphomas most commonly found?

Answer 2

• Lymph nodes, bone marrow and/or blood (the lymphatic system)
• Lymphoid organs: spleen or the gut-associated lymphoid tissue
• Skin (often T cell disease)
• Rarely “anywhere” (CNS, occular, testes, breasts etc)

Question 3

What is the incidence of lymphoma?

Answer 3

200 new cases per year for every million of the population

• Non-Hodgkin’s lymphoma = 80%
• Hodgkin Lymphoma = 20%

Question 4

How many types of lymphoma are there?

Answer 4

>60 types of lymphoma exist

Question 5

What are the downside of an adaptive immune system that increases lymphoma risk?

Answer 5

• DNA molecules are

1. cut and rejoined plus
2. undergo deliberate point mutation, which allows for the generation of immunoglobulin and T cell receptor diversity

• Dependent on apoptosis (90% of normal lymphocytes die in the germinal center)
  
  • Ensures antibody specificitty - preventing autoimmune disease
  • Apoptosis is switched off in germinal center (cancer)
  • Acquired DNA mutation in pro-apoptotic genes (cancer)
• Rapid cell proliferation in the germinal center
  
  • Cell division = risk of DNA replication error

Question 6

Describe lymphoma recombination associated translocations

Answer 6

• Involve the Ig locus
• Ig promoter highly active in B cells
• Bring intact oncogenese close to the Ig promoter
• Oncogenes may be anti-apototic, proliferative
  
  • bcl2
  • bcl6
  • Myc
  • cyclin D1

Question 7

What are the known risk factors for lymphoma?

Answer 7

• Constant antigenic stimulation
• Infection (direct viral infection of lymphoyctes)
• Loss of T cell function

Question 8

Describe lymphoma and chronic antigenic stimulation, and what conditions could be a risk

Answer 8

• Initially antigen dependent, eventually become autonomous (malignant)

Conditions:

• H.pylori: Gastric MALT area affected
• Sjorgen syndrome: marginal zone NHL of parotid lymphoma
• Coeliac disease: small bowel T cell lymphoma (enteropathy associated T cell Non-Hodgkin Lymphoma (EATL))

Question 9

Describe viral infection and the risk of lymphoma:

1. Direct Viral integration
2. EBC infection and immunosuppression

Answer 9

1. Direct viral integration
   
   • HTLV1 infects T cells by vertical transmission
   • Caribbean and Japan carriers
   • May develop Adult T cell leukemia (2.5% at 70 years)
2. EBV infection and immunosuppression

• EBV infects B lymphocytes
• Healthy carrier state maintained by cytotoxic T cells kill EBV antigen expressing B cells
• Loss of T cells function give risk of EBV driven lymphomas

HIV - 60 fold increase in lymphoma (high grade B-Non-Hodgkin’s lymphoma)

Post transplant lymphoproliferative disorder

Question 10

Describe what is involved in the diagnosis and staging of lymphoma

Answer 10

• Histological diagnosis
• Anatomical stage - using CT PET, BM biopsy etc
• Prognostic factors
  
  • LDH
  • Beta2 microglobulin
  • Albumin
  • Kidney/BM function

Question 11

1. What do Reed Sternberg cells signify?

Answer 11

1. Classical Hodgkin Lymphoma

15% of all lymphoma/leukemia

Question 12

15% of lymphoma is classical hodgkin lymphoma, describe what makes up the other 85%

Answer 12

Other 85% of lymphoma is Non-Hodgkin lymphoma

B cell

• Precursor B lymphoblastic leukemia (B-ALL) or lymphoma
• Mature B cell neoplasm - DLBCL, Follicular NHL, CLL etc

T or NK cell

• Precursor T lymphoblastic leukemia or lymphoma (T-ALL)
• Mature T and NK neoplasm - PTCL, Anaplastic, cutaneous

Question 13

1. Describe the epidemiology of Hodgkin Lymphoma
2. What are the signs and symptoms of Hodgkin lymphoma

Answer 13

1. Hodgkin lymphoma

• 1% of all cancer, 3:100,000 population
• HL is more common in males than females
• Bimodal age incidence
  
  • Most common age 20-29, young women NS subtype
  • Second smaller peak affecting elderly >60 years old

2. Signs and Symptoms:

• Painless enlargement of lymph node/nodes which may cause obstructive symptoms/signs
• Constitutional symptoms:
  
  • Fever
  • Night sweats
  • Weight loss (the B symptoms)
  • Pruritis
  • RARE: Alcohol induced pain

Question 14

Describe the sub-types of Classical Hodgkin Lymphoma

Answer 14

• Nodular sclerosing (80%) - good prognosis
• Mixed cellularity (17%) Good prognosis
• Lymphocyte rich (rare) Good prognosis
• Lymphocyte depleted (rare) Poor prognosis

Nodular lymphocyte predominant HL 5% - More a disorder of the elderly

Question 15

1. How is Hodgkin Lymphoma staged?
2. What is the staging system?

Answer 15

1.

• Pathological diagnosis of a lymph node biopsy
• FDG-PET/CT scan
• Consider biospy of other site if possiblly infiltrated

2. Stages

• I = one group of nodes
• II = >1 group of nodes same side of the body
• III = nodes above and below the diaphragm
• IV = extra-nodal spread
• Suffix A if none of the below, B if any of the below:
  
  • Fever
  • Unexplained weight loss >10% in 6 months
  • Night sweats
    ​

Question 16

What is the outline of therapy for lymphoma?

Answer 16

• Chemotherapy - if often given as a combination of drugs which affect the malignant cells in different ways
• Radiotherapy - HL is highly responsive to radiotherapy, can be given at the end of chemo as an involved field is a small area only targeting diseased nodes (less toxicity to normal tissue)
• Combined modality - uses both chemo and radiotherapy

Question 17

• What is ABVD and the treatment of HL?
• What are the risks and benefits of ABVD?

Answer 17

ABVD are the drugs used for chemotherapy in HL, given at 4 weekly intervals

• Adriamycin
• Bleomycin
• Vinblastine
• DTIC

Benefits:

• Effective treatment
• Preserves fertility (unlike MOPP the original chemo)

Risks:

• Can cause long term
  
  • pulmonary fibrosis
  • cardiomyopathy

Question 18

Describe the pros and cons for the use of radiotherapy for HL

Answer 18

Pros:

• Modern practice and only targets the involved field, so less toxicity to healthy tissue
• Low/negligible risk of relapse within field

Cons:

• Risk of damage to normal tissue
  
  • Breast cancer - 1:4 risk after 25 years
  • Leukaemia/MDS - 3% at 10 years
  • Lung or skin cancer
• Combined modality gives greatest risk of secondary malignancy (as gives two mechanisms of DNA damage)

Question 19

1. Describe the treatment for HL
2. What is the prognosis?

Answer 19

• Chemotherapy required for all cases (ABVD)
  
  • ABVD 2-6 cycles (depending on stage)
  • +/- radiotherapy
  • PET CT
    
    • Interim post 2 cycles, response assessment
    • End of treatment: guides further treatment
• Relapse
  
  • High dose salvage chemotherapy Autologous PB stem cell transplant as salvage

2. Prognosis:

• Depends on stage
• Cure rates range from 50-90% - better prognosis for people who have stage 1 or 2 disease.
• Only 50% of people with stage 4 disease are cured

Question 20

What does cure mean in HL?

• 80% of patients with stage 1 or 2 HL are cured
• only 50% of patients with stage 4 disease get cured

Answer 20

Cure means

• Overall 80% are long term survivors can we improve
• 10% die from relapse of HL (first 10 years)
• 10% die from long term treatment complications (after 10 years)
• Eradicating HL in a 25 year old patient with highly toxic lymphoma therapy does not guarantee long term survival

Question 21

Describe the treatment dilemmas with treating HL

Answer 21

• HL is a curable disease overall approx 80%
• More intense therapy cures more but has a risk of causing more secondary cancers
• Reduce therapy cures less but less secondary cancer

Reduce therapy:

• Chemotherapy only
• Reduce risk of secondary malignancy
• Increased HL relapse
• 10% die of HL

Intensify therapy:

• Chemo/+radiotherapy
• Decrease HL relapse
• Increase secondary malignancy of breast skin, BM
• 10% die of therapy complication