Introduction to Lymphoid Malignancies

Question 1

Describe the epidemiology of Hodgkin’s lymphoma.

Answer 1

• Peak incidence in young adults.
• Possible association with EBV - aka Human Herpes Virus 4 (HHV4).

Question 2

Outline the histopathology, treatment and prognosis of Hodgkin’s lymphoma.

Answer 2

• Presence of Reed-Sternberg cells - malignant B cells.
• Typically 99% of cells are reactive non-malignant cells.
• Treatment - chemotherapy +/- radiotherapy.
• Prognosis - 5 year survival = 50-90%, depending on age, stage and histology.
• Good prognosis in young adults.

Question 3

Outline the classification of Non-Hodgkin’s lymphomas.

Answer 3

Grade:

• Low grade - indolent
• High grade - aggressive

Type:

• T-cell lymphomas
• EBV (HHV4) driven lymphomas in immunosuppressed patients

Question 4

What chromosomal translocation is responsible for most cases of follicular lymphoma, and how does this translocation result in disease?

Answer 4

• t(14;18) - IgH locus on Chr14 translocated to BCL-2 gene on Chr18.
• IgH acts as an enhancer - activates BCL-2 promoter.
• Overexpression of BCL-2 protein.
• BCL-2 is an apoptosis inhibitor.

Question 5

What is the consequence of the t(;8:14) chromosomal translocation?

Answer 5

• MYC gene on Chr8 translocated to IgH locus on Chr14.
• MYC is a powerful proto-oncogene.
• Overactivation of MYC by IgH enhancer leads to uncontrolled B cell proliferation.
• Results in high grade non-Hodgkin lymphoma - “Burkitt’s lymphoma”.

Question 6

Outline the presentation and diagnosis of low grade NHL.

Answer 6

• Enlarged lymph node(s).
• Histology - normal tissue architecture partially preserved.
• Normal cell of origin recognisable - used to name lymphoma - e.g. follicular.
• Diagnosis - histology, immunocytochemistry, light-chain restriction, PCR.
• PCR - analyse clonal Ig gene rearrangement, chromosomal translocations.

Question 7

Outline the treatment and prognosis of low grade NHL.

Answer 7

Treatment:

• Chemotherapy
• Glucocorticoids - e.g. prednisolone
• Radiotherapy
• Monoclonal Ab therpay - e.g. rituximab

Prognosis:

• Relatively indolent - slow growth
• Responds well to therapy
• Hard to cure

Question 8

Outline the presentation and diagnosis of high grade NHL.

Answer 8

• Enlarged lymph nodes.
• Loss of normal tissue architecture.
• Normal cell of origin hard to determine.
• Diagnosis - histology, immunocytochemistry, light-chain restriction, PCR.

Question 9

Describe the prognosis of high grade NHL.

Answer 9

• Prognosis variable depending on type, stage and other factors.
• Long term survival ~ 65%.
• Easier to cure than low grade NHL.

Question 10

Outline the pathophysiology and presentation of multiple myeloma.

Answer 10

• Suppression of normal bone marrow, blood cell and immune cell function - anaemia, recurrent infections, bleeding.
• Bone resoprtion and calcium release - myeloma cells produce cytokines e.g. IL-6 > bone marrow cells produce RANKL > osteoclast activation - bone pain, fractures, hypercalcaemia - mental disturbance.
• Pathological effects of paraprotein - monoclonal Ig in serum - causes renal failure, deposited as amyloid in many tissues - 2% of cases lead to hyperviscosity syndrome - increased viscosity of blood leading to heart failure/stroke.

Question 11

How is multiple myeloma diagnosed?

Answer 11

• Serum electrophoresis for paraprotein.
• Urine electrophoresis - Bence-Jones protein represents free monoclonal light chains.
• Increased plasma cells in bone marrow.
• High erythrocyte sedimentation rate (ESR) - caused by rouleaux formation.
• Radiological investigation of skeleton for lytic lesions.