Plasma Cell Dyscrasias

Question 1

B cells are derived in the _________ from ________

Answer 1

Bone marrow

Haematopoeitic stem cells

Question 2

What is the dual role of B cells in the immune system?

Answer 2

Antibody production

Acts as antigen presenting cells

Question 3

What are immunoglobulins?

Answer 3

Antibodies produced by B cells and plasma cells, that recognize a specific antigen

Question 4

Describe the structure of an immunoglobulin

Answer 4

Two heavy chains
Two light chains
An Ig variable element at the end of each chain

Question 5

B cells in the lymph node return to the plasma after picking up an antigen. What two cells can they transform into?

Answer 5

Plasma cells

Memory B cells

Question 6

What is the role of a plasma cell?

Answer 6

A fully differentiated B cell that pumps out antibody

Question 7

List key features of the histological appearance of plasma cells

Answer 7

Eccentric ‘clock face’ or ‘fried egg’ nucleus
Blue cytoplasm (containing protein)
Coarse chromatin pattern (mRNA synthesis)
Pale perinuclear area (Golgi apparatus)

Question 8

What is the clinical marker of a clonal B cell disorder?

Answer 8

Monoclonal immunoglobulin (single B cell expansion)

Question 9

What is a paraprotein?

Answer 9

An abnormal immunoglobulin fragment that is produced in excess by an abnormal monoclonal proliferation of plasma cells

Question 10

How are abnormal protein bands on immunoglobins detected?

Answer 10

Serum electrophoresis

Question 11

How are abnormal protein bands classified after they have been detected?

Answer 11

Serum immunofixation

Question 12

What us a Bence Jones protein?

Answer 12

A monoclonal globulin protein or immunoglobulin light chain found in urine electrophoresis

Question 13

What is the pathogenesis behind multiple myeloma?

Answer 13

Abnormal plasma cell proliferation due to genetic hits causing chromosomal translocation and mutation

Question 14

What are the clinical features of multiple myeloma?

Answer 14

TUMOUR EFFECTS
Bone lesions
Bone pain
Hypercalcaemia (stones, bones, abdominal groans, psychic moans)

PARAPROTEIN EFFECTS
Renal failure
Immune suppression
Hyperviscosity
Amyloidosis

Question 15

Explain why osteolytic lesions are a characteristic feature of multiple myeloma

Answer 15

IL6 produced by plasma cells activates osteoclasts causing bone resorption and hypercalcaemia and suppresses osteoblasts

Question 16

Why does multiple myeloma lead to renal failure?

Answer 16

Tubular cell damage by deposition of light chains causing cast nephropathy

Question 17

Outline treatment of multiple myeloma

Answer 17

Stop nephrotoxins
Combination chemotherapy (switch off light chains)
CCS e.g. dexamethasone, prednisolone
Alkylating agents e.g. cyclophosphonamide
High dose chemo/stem cell transplant in fit patients

Question 18

Outline symptom control in multiple myeloma

Answer 18

Opiate analgesia (avoid NSAIDs)
Local radiotherapy (pain relief or cord compression)
Biphosphonates (correct hypercalcaemia and pain)
Vertebroplasty (inject sterile cement into fracture)

Question 19

List the characteristic features of monoclonal gammopathy of undetermined significance

Answer 19

Paraprotein <30g/l
Bone marrow plasma cells <10%
No evidence of myeloma end organ damage (normal calcium, renal function, Hb, bones, immune system)

Question 20

MGUS is at risk of progression to which haematological malignancy?

Answer 20

Multiple myeloma

Question 21

What is AL amyloidosis?

Answer 21

Rare disorder characterised by a mutation in light chain leading to altered structure and formation of insoluble beta pleated sheats that can accumulate in the body, causing organ damage

Question 22

List features of organ damage found in AL amyloidosis

Answer 22

Nephrotic syndrome
Cardiomyopathy
Hepatomegaly
Neuropathy
Malabsorption

Question 23

Outline investigations used to diagnose AL amyloidosis

Answer 23

Organ biopsy to confirm amyloid deposition via stain
SAP scan to localise amyloid deposits
Echo/cardiac MRI
Nephrotic range proteinuria

Question 24

State the characteristic clinical feature of a stained organ biopsy containing amyloid protein, and a biopsy placed under polarised light respectively

Answer 24

Congo red

Apple-green birefringence

Question 25

Outline the treatment of AL amyloidosis

Answer 25

Chemotherapy similar to myeloma to witch off light chain supply

Question 26

What is Waldenstrom’s macroglobinaemia?

Answer 26

Clonal disorder of cells intermediate between a lymphocyte and plasma cells (lymphoplasmacytoid)

Question 27

State the characteristic clinical feature of Waldenstrom’s macroglobinaemia

Answer 27

IgM pentaric paraprotein

Question 28

What are the clinical features of Waldenstrom’s macroglobinaemia?

Answer 28

TUMOUR EFFECTS
Lymphadenopathy
Splenomegaly
Marrow failure
PARAPROTEIN EFFECTS
Hyperviscosity 
Neuropathy

Question 29

List clinical features of hyperviscosity syndrome

Answer 29

Fatigue
Visual disturbance
Confusion, coma
Bleeding
Heart failure
B symptoms (night sweats, weight loss)

Question 30

Outline treatment of Waldenstrom’s macroglobinaemia

Answer 30

Chemotherapy

Plasmapheresis to remove paraprotein IgM in patient’s plasma and replace with donor plasma

Question 31

What is rouleaux formation?

Answer 31

Stacks or aggregations of red blood cells (RBCs), typically found in multiple myeloma or Waldenstrom’s macroglobinaemia

Question 32

What is the CRAB criteria for multiple myeloma?

Answer 32

C = calcium (elevated)
R = renal failure
A = anemia
B = bone lesions