T7-L11: Myeloma, Lymphoma and CLL

Question 1

What is the epidemiology of Myeloma?

Answer 1

• Median age of presentation is 70 years
• Higher incidence in Afro-Caribbean ethnic groups compared to Caucasians
• All cases of Myeloma are preceded by asymptomatic MGUS

Question 2

What can we use to test for Myeloma?

Answer 2

Electrophoresis - In Myeloma there is one type of gamma-globin dominating. We can then use immunofixation to identify the immunoglobulin being produced.

Question 3

What is MGUS?

Answer 3

Monoclonal gammopathy of undetermined significance (MGUS). In MGUS, abnormal plasma cells in the bone marrow release an abnormal protein, known as paraprotein. MGUS is characterised by the presence of this abnormal protein in the blood and/or urine.

MGUS is a benign disorder. We do find a small number of clonal antibodies in the bone marrow but less than 10% by definition. There are no CRAB features or MDE. It is quite common particularly as you get older. There is a risk of progression to malignancy  (1%) - 27% of which progress to Myeloma but others can progress to Waldenstromn's macroglobulinemia, Primary AL amyloidosis and lymphoproliferative disorders.

Question 4

What do we need to diagnose Myeloma?

Answer 4

CRAB Features or MDE (Myeloma defining events).

Question 5

What CRAB features?

Answer 5

C - Hypercalcaemia
R - Renal insufficiency
A - Anaemia
B - Bone lesions

Question 6

What organ insufficiency do we tend to see in 50% of Myeloma patients at some point during their disease course?

Answer 6

Renal Insufficiency. This may be due to a number of reasons such as:

• HTN
• Risk of renal Vein Thrombosis as Myeloma is a prothrombotic disease
• Drugs used in treatment such as Bisphosphates (Slow down osteoporosis), ACEi, NSAIDs forgone pain etc.
• Hyperviscosity

Question 7

What are complications of Myeloma?

Answer 7

• Sepsis
• AKI with hypercalcaemia
• Hypercalcaemia can lead to cardiac toxicity
• Spinal cord compression due to plasmacytoma or bony lesions
• Hyperviscosity - retinal dilation and haemorrhage

Question 8

How do we investigate Myeloma?

Answer 8

• FBC: Hb (Check for Anaemia), WBC (active infections), Platelets; and blood film
• Degree of bone marrow infiltration?
• Check for the presence of Plasma cells in blood as this is a pathological sign
• U&Es
• Dehydration
• Elavted calcium?
• Inflammatory markers
• Raised immunoglobulin
• Protein electrophoresis
• Light chain analysis

Question 9

In what condition do kappa or lama light chains (usually at the level of MGUS) misfiled and self-aggregate to form beta-pleated fibrils deposited in organs?

Answer 9

Amyloid Light Chain (AL) Amyloidosis

This is found in 1.5% of native kidney biopsies. It often presents with nephrotic range proteinuria - mainly albumin and small monoclonal light chain components. Therefore classic myeloma symptoms (anaemia, hypercalcaemia, bony lesions) are not usually present. This is as the plasma cells are usually in the range of MGUS rather than myeloma. We can get cardiac and liver involvement, peripheral neuropathy and ESRF (40%).

Clinical features are again non-specific. Macroglossia is a cardinal sign.

Question 10

How are B-cell lymphomas classified?

Answer 10

By the presence of Reed-Sternberg cells.

If present = Hodgkin Lymphoma

If not present = Non-Hodgkin Lymphoma. IF these cells are not found the diagnosis could alternatively be T cell lymphoma but these are rare.

Question 11

What is the typical presentation of Hodgkin and Non-Hodgkin Lymphoma?

Answer 11

Hodgkin Lymphoma - B symptoms such as weight loss, night sweats and fatigue. We also see lymphadenopathy. Thus tends to be seen in 20-29 or 60-70 - shows a bimodal distribution. It has excellent cure rates (>90%).

Non-Hodgkin Lymphoma - This can be aggressive or Indolent. That that is aggressive tends also to show B symptoms and lymphadenopathy. It has a rapid onset but is curable. Indolent NHL has an insidious onset of lymphadenopathy. It is usually not curable. But the patient tends to be systematically well for a long time.

Question 12

Give causes of a neck lump.

Answer 12

Malignant causes: Lymphoma, Chronic Lymphocytic Leukaemia, Metastasis of the lung, Breast or Cervix

Non-malignant: Infective, Inflammatory (sarcoidosis), lipoma, fibroma and haemangioma

Question 13

Describe follicular lymphoma.

Answer 13

• It is a neoplastic disorder of lymphoma tissue
• It is a type of Non-Hodgkin lymphoma characterised by slowly enlarged lymph nodes
• Accounts for 15% of all Non-Hodgkin Lymphoma Disease
• Incidence rises with age
• Men and Women are affected the same
• Ann Arbor Stage III or IV
• LDH above the limit of normal at diagnosed
• Polycythaemia
• 70-80% have a translation between chromosome 14 and 18. This stops B cells in lymph nodes from apoptosis leading to over production
  We don’t always need to treat the condition may need to just monitor
• Median 5YSR 72-77%

Question 14

What is the most common cancer in the IUK?

Answer 14

Chronic Lymphocytic Leukaemia - accounts for 1% of all cancers.

The presentation varies from an incidental finding (80%) to a widespread lymphadenopathy, splenomegaly, bone marrow failure and systemic symptoms - this is rare.

Question 15

What staging system is used for CLL?

Answer 15

Binet System

Question 16

What are complications of CLL?

Answer 16

• Richer’s transformation - transformation to a high grade Lymphoma which occurs in 10% of cases. this has ana cute onset of symptoms and a poor prognosis.
• Recurrent infections secondary to reduced immunoglobulin production
• Autoimmune phenomenon - ITP, haemolytic Anaemia, Pure Recd Cell Aplasia and Autoimmune Neutropenia

Question 17

Give an example of a mutation that confers a poorer prognosis in CLL?

Answer 17

17p deletion - patients experience treatment resistance or rapid relapses.