Myeloma and plasma cell dyscrasias

Question 1

Where are B cells derived from?

Answer 1

Pluripotent haemopoietic stem cells in the marrow

Question 2

What are immunoglobulins?

Answer 2

Antibodies produced by B cells and plasma cells

Question 3

What are immunoglobulins made up of?

Answer 3

2 heavy and 2 light chains

Question 4

What are the two types of light chain in an immunoglobulin?

Answer 4

Kappa

Lambda

Question 5

What are V D J and C regions in an immunoglobulin heavy chain?

Answer 5

Variable region

Diversity region

Joining region

Constant region

Question 6

How are different proteins produced from immunoglobulins?

Answer 6

Immunoglobulins have randomised regions (V D and J regions) that are ‘picked at random’

Question 7

Where do B cells encounter antigens?

Answer 7

The follicle germinal centre of the lymph node

Question 8

What is somatic hypermutation?

Answer 8

Identification of an antigen by B cells that improve their fit

Question 9

What is class switching?

Answer 9

A process that determines which isotype of antibody is produced

Question 10

What two things may a B cell do after identifying antigens?

Answer 10

Return to the marrow as a plasma cell

Circulate as a memory cell

Question 11

Give the characteristic appearance of a plasma cell?

Answer 11

Plentiful dark blue cytoplasm

‘Clock-face’ nucleus

Pale perinuclear area - golgi apparatus

Question 12

What is polyclonal increase of immunoglobulin production?

Answer 12

When they are produced by many different plasma cell clones

Question 13

What is monoclonal increase in immunoglobulin production?

Answer 13

They are all derived from clonal expansion of a single B-cell

Question 14

What is a monoclonal increase in immunoglobulins a marker of?

Answer 14

Underlying clonal B-cell or plasma cell disorder

Question 15

How are immunoglobulins identified?

Answer 15

Serum electrophoresis

Question 16

What is used to classify abnormal protein bands?

Answer 16

Serum immunofixation

Question 17

What is Bence Jones protein?

Answer 17

Excessive immunoglobulin light chains that may leak into the urine

Question 18

What are the top three causes of paraproteinaemia?

Answer 18

Monoclonal Gammopathy of Undetermined Significance - MGUS

Myeloma

Amyloidosis

Question 19

What is myeloma?

Answer 19

A plasma cell malignancy

Question 20

What is monoclonal gammopathy of undetermined significance?

Answer 20

A small amount of paraprotein with no evidence of myeloma end organ damage

It is very common

Question 21

What are the direct tumour cell effects of myeloma?

Answer 21

Bone lesions, bone pain

Hypercalcaemia

Marrow failure

Question 22

What are paraprotein mediated effects of myeloma?

Answer 22

Renal failure

Immune suppression

Hyperviscosity

Question 23

What is lytic bone disease?

Answer 23

When bones erode and eat into the surrounding bone causing weakened bones

Question 24

What is the pathophysiology of lytic bone disease?

Answer 24

Osteoblasts are suppressed

Osteoclasts are activated

Question 25

What is the common presentation of hypercalcaemia in myeloma?

Answer 25

'Stones, groans and psychiatric moans' Kidney stones Sore bones Abdominal groans Thirst Dehydration

Question 26

What is used to correct hypercalcaemia?

Answer 26

Bisphosphates e.g. pamidronate

Question 27

How do bisphosphates act to correct hypercalcaemia and reduce bone disease?

Answer 27

They inhibit osteoclasts

Question 28

What symptom is present in 1/3 patients with myeloma at diagnosis?

Answer 28

Renal impairment

Question 29

How do you treat myeloma in fit patients?

Answer 29

High dose chemotherapy / autologous stem cell transplant

Question 30

How is myeloma typically managed?

Answer 30

Combination novel agent chemotherapy

Question 31

Give examples of symptom control in myeloma patients?

Answer 31

Opiate analgesia Local radiotherapy Bisphosphonates Vertebroplasty

Question 32

What is amyloidosis?

Answer 32

A group of disorders characterised by faulty misfolded proteins which clump together to form insoluble aggregates in tissue

Question 33

What is AL amyloidosis?

Answer 33

A rare disorder caused by a mutation in the light chain - altered structure The misfolded light chains precipitate in tissues as an insoluble beta pleated sheet

Question 34

What is the main clinical symptom in AL amyloidosis?

Answer 34

Organ damage due to amyloid accumulation in tissues

Question 35

How is AL amyloidosis diagnosed?

Answer 35

An organ biopsy will confirm AL amyloid deposition

Question 36

What stain is used in the diagnosis of AL amyloidosis?

Answer 36

Congo red stain Apple green birefringence

Question 37

What is the treatment of AL amyloidosis?

Answer 37

Chemotherapy - switches off abnormal light chain supply

Question 38

What is Waldenstrom's macroglobulinaemia?

Answer 38

A lymphoblastic neoplasm with characteristic IgM paraproteins

Question 39

What are tumour effects of Waldenstrom's macroglobulinaemia?

Answer 39

Lymphadenopathy Splenomegaly Marrow failure

Question 40

What are paraprotein effects of Waldenstrom's macroglobulinaemia?

Answer 40

Hyperviscosity Neuropathy

Question 41

What is the main clinical feature of Waldenstrom's macroglobulinaemia?

Answer 41

Hyperviscosity syndrome

Question 42

What are the symptoms of hyperviscosity syndrome?

Answer 42

B symptoms - night sweats, weight loss Fatigue Confusion Bleeding Cardiac failure

Question 43

How is hyperviscosity treated?

Answer 43

Removing patient plasma rich in IgM paraprotein and replacing it with donor plasma