Myeloma and Other Plasma Cell Disorders

Question 1

what are B cells derived from

Answer 1

pluripotent haematopoietic stem cells in the bone marrow

Question 2

what is the roles of B cells

Answer 2

part of the adaptive immune system

• antibody production
• antigen presenting cells

Question 3

what are immunoglobulins

Answer 3

Antibodies produced by B-cells and plasma cells

Proteins made up of 2 heavy and 2 light chains

Each antibody recognizes a specific antigen

Question 4

what are the monomer shaped immunoglobulins

Answer 4

IgD
IgE
IgG

Question 5

what are the dimer shaped immunoglobulins

Answer 5

IgA

Question 6

what is the pentamer shaped immunoglobulin

Answer 6

IgM

Question 7

what is the normal pathway of lymphocyte maturation

Answer 7

stem cell&raquo_space; lymphoid progenitors&raquo_space; Pro B cells (IgM)&raquo_space; Pre B cells (IgM & IgD)&raquo_space; IgM B cells

Question 8

what do IgM B cells divided to make normally

Answer 8

IgM plasma cells
IgA
IgE
IgG

Question 9

what does IgG eventually go on to become

Answer 9

plasma cells

Question 10

what is the function of a plasma cell

Answer 10

to produce large quantities of antibodies when needed

Question 11

how does the nucleus appear in a plasma cell

Answer 11

“clock face nucleus”

nucleus off to one side, can look like a fried egg

Question 12

what is meant when a blood film is described as polyclonal or monoclonal

Answer 12

polyclonal - multiple types of blood cells seen; can be seen as part of normal function

monoclonal - one type of cell seen overwhelming; suggests pathology

Question 13

what are the causes of a polyclonal increase in immunoglobulins

Answer 13

infection
autoimmune
malignancy
liver disease

Question 14

what does a monoclonal increase in immunoglobulins imply

Answer 14

implies that the antibody is all identical and produced by a single B cell

Question 15

what is a monoclonal immunoglobulin also called and what is it a marker of

Answer 15

paraprotein

underlying clonal B-cell disorder

Question 16

how can you detect immunoglobulins

Answer 16

serum electrophoresis

Question 17

what area is immunoglobulins seen in

Answer 17

gamma region

Question 18

what is bence-jones protein (BJP)

Answer 18

excess immunoglobulin light chains leaking into the urine
» paraproteinaemia

detected by urine electrophoresis

Question 19

what are causes of paraproteinaemia

Answer 19

1st - MGUS (completely harmless)
2st - myeloma
3rd - Amyloidosis
4th - lymphoma

• asymptomatic myeloma
• chronic lymphocytic leukaemia

Question 20

essentially what is myeloma

Answer 20

clone of a malignant plasma cell

Question 21

what are direct tumour effects of myeloma

Answer 21

bone lesions
increased calcium
bone pain
bone marrow failure

Question 22

what are the effects of paraprotein seen in myeloma

Answer 22

renal failure
immune suppression
hyperviscosity
amyloid

Question 23

how is myeloma classified

Answer 23

by type of antibody produced

Question 24

what are the most to least common type of myeloma

Answer 24

Most to least:

• IgG
• IgA
• Bence Jones Myeloma
• Nonsecretory
• IgD
• Biclonal
• IgE

Question 25

what is myeloma's affect on bone and what is commonly seen on x-ray

Answer 25

lytic bone disease "punched-out lesions" Pepper pot skull

Question 26

what are Sx of hypercalcaemia

Answer 26

``` Stones Bones Abdominal groans Psychiatric moans Thirst Dehydration Renal impairment ```

Question 27

how can myeloma cause kidney failure

Answer 27

free light chains first accumulate in the proximal tubules before entering the loop of Henle. Here they can combined with Tamm-Horsfall protein to produce insoluble casts blocking the nephron i.e. cast nephropathy This can lead to renal failure

Question 28

what is the Tx of myeloma

Answer 28

Chemotherapy with +/- prednisolone +/- Thalidomide or bortezomib or lenalidomide If asymptomatic may just observe

Question 29

how is response to Tx monitored in myeloma

Answer 29

paraprotein

Question 30

what is symptomatic control of myeloma

Answer 30

opiate analgesia local radiotherapy biphosphonates - corrects hypercalcaemia vertebroplasty - stabilises fractured bone

Question 31

what is MGUS

Answer 31

Monoclonal Gammopathy of Uncertain Significance

Question 32

what is the definition of MGUS

Answer 32

Paraprotein <30g/l Bone marrow plasma cells <10% No evidence of myeloma end organ damage; - Normal calcium - Normal renal function - Normal Hb - No lytic lesions - No increase in infections

Question 33

what is amyloidosis

Answer 33

accumulation of protein in abnormal fibrillar form - in tissues can cause organ damage caused by mutations in the light chain

Question 34

what can amyloidosis cause

Answer 34

nephrotic syndrome

Question 35

how is amyloid deposition confirmed

Answer 35

congo red staining | - causes “Apple-green” birefringence under polarised light

Question 36

what is Waldenstrom’s Macroglobulinaemia

Answer 36

Clonal disorder of cells intermediate between a lymphocyte and a plasma cell Characteristic IgM paraprotein

Question 37

what are the Sx of Waldenstrom’s Macroglobulinaemia

Answer 37

``` lymphadenopathy splenomegaly marrow failure hyperviscosity neuropathy ```

Question 38

what are features of hyper viscosity syndrome

Answer 38

``` Fatigue, visual disturbance, confusion, coma Bleeding Cardiac failure Night sweats Weight loss ```

Question 39

Tx of WM

Answer 39

``` chemotherapy plasmapheresis (removes paraprotein from the circulation) ```