Myeloma & Paraproteins

Question 1

Describe the basic structure of an antibody?

Answer 1

Y shaped with 2 heavy and 2 light chains

“Trunk” = FC portion (constant & defines subclass)

“Branches” = FAB portion (variable & defines antigen binding)

Question 2

What’s the most common antibody?

Answer 2

IgG - 75% of total

Question 3

So the heavy chain determines an immunoglobulins subclass. What does the light chain do?

Answer 3

Each cell randomly selects if it will have Kappa or Lambda light chains

Some free light chains can be tested for in the blood to indicate which is more common

Question 4

What is a paraprotein?

Answer 4

A monoclonal Ab in blood or urine (i.e. lots of the same Ab) indicating monoclonal proliferation of a B-cell type

Question 5

How can we test antibody levels?

Answer 5

Total Immunoglobulin levels

Question 6

How do we assess for antibody diversity & paraproteins?

Answer 6

Serum Protein Electrophoresis

Seperates the proteins incl antibodies by size/charge

Question 7

How do we determine which class of paraprotein is present?

Answer 7

Immunofixation

Question 8

Light chains aren’t detected in electrophoresis but can cause myeloma, how do we test for them?

Answer 8

Light Chain Assay

Question 9

What if we find a paraprotein in someone with no illness?

Answer 9

Diagnose with MGUS

Monoclonal Gammopathy of Uncertain Significance

Question 10

How do we diagnose a myeloma?

Answer 10

Usually indicated by a paraprotein

Then we must find Excess Plasma Cells in the marrow (>10% of total marrow cell pop)

Question 11

How do we stage myeloma?

Answer 11

BAsed on Albumin & Beta2 Microglobulin levels

Question 12

What is a myeloma?

Answer 12

A neoplasm of plasma cells –> Excessive production of a single immunoglobulin

Question 13

Who gets myeloma?

Answer 13

Peaks in the 7th decade

And is commonest amongst black people

Question 14

Presentations of myeloma can occur through Plasma cells or the paraprotein. what could the plasma cells cause?

Answer 14

• Bone disease (Lytic lesions, path fractures, cord compression & hypercalcaemia)
• Marrow failure (esp anaemia)
• Infections

Question 15

What presentations of myeloma can be caused by the paraprotein?

Answer 15

Renal failure (Cast Nephropathy)

Hyperviscosity Syndrome –> Bleeding e.g. retinal, oral, nasal or cutaneous. Sometimes HF, confusion or renal failure

Hypogammaglobulinaemia –> Infections

Amyloidosis

Question 16

How can we treat Myeloma?

Answer 16

Chemo
RT
Bisphosphonate
Steroids
Surgery
Autologous Stem Cell Transplant

Question 17

Why use bisphosphonates in myeloma?

Answer 17

Treat the bone disease, very like osteoporosis

Question 18

What is surgery used for in myeloma?

Answer 18

Pinning long bones and decompressing the spinal cord

Question 19

How does an autologous stem cell transplant work?

Answer 19

ITs not the transplant that treats you, its the chemo:

1) Shrink myeloma as much as possible
2) Harvest healthy stem cells
3) Hardcore chemo destroys myeloma & normal marrow
4) Stem cell transplant (prevents you dying from the marrow damage of chemo)

Question 20

Which immunoglobulins are present in myeloma?

Answer 20

IgA & IgG

IgM paraproteins can be found instead in lymphoma

Question 21

So what is the most common presentation of myeloma?

Answer 21

Bone pain & anaemia

Sometimes with infection, fatigue or renal impairment

Question 22

What tests can you do in myeloma?

Answer 22

Serum protein electrophoresis to identify presence of a paraprotein
Bone marrow aspirate/biopsy (>10% B cells)

Serum Ca, FBC, skeletal survey & U&Es + creatinine are all to assess complications

Albumin & B2 Microglobulins for Staging

Question 23

How does an IgM lymphoma present?

Answer 23

• Bone marrow failure
• lymphadenopathy
• hepatosplenomegaly
• B symptoms
• poor protein related symptoms

Question 24

what does chemo in myelomas include?

Answer 24

• Monoclonal antibodies
• Proteosome inhibitors
• Immudolatory amide drugs