Myeloma and other plasma cell disorders

Question 1

Where are B cells derived from and what is their role?

Answer 1

• Derived in bone marrow from pluripotent haemopoietic stem cells
• Part of the adaptive immune system
• Dual roles - antibody production, acting as antigen presenting cells

Question 2

What are immunoglobulins?

Answer 2

• Antibodies produced by B cells and plasma cells
• Proteins made up of 2 heavy and 2 light chains
• Each antibody recognises a specific antigen

Question 3

Where do B cells travel in the periphery?

Answer 3

• Travel to the follicle germinal centre of the lymph node
• Identify the antigen and improve the fit by somatic mutation or be deleted
• May return to the marrow as plasma cell or circulate as memory B cell

Question 4

What is a plasma cell and what are some of its features?

Answer 4

• A factory cell
• Pumps out antibody
• Eccentric clock face nucleus on H&E
• Open chromatin - synthesising mRNA
• Plentiful blue cytoplasm - laden with protein
• Pale perinuclear area - Golgi apparatus

Question 5

There is an associated rise in monoclonal immunoglobulins in myeloma. What are monoclonal immunoglobulins?

Answer 5

• Monoclonal immunoglobulin = paraprotein
• All derived from clonal expansion of a single B cell
• Identical antibody structure and specificity

Question 6

What does serum electrophoresis do?

Answer 6

Separates serum proteins into distinct bands or zones which allows detection of abnormal proteins

Question 7

What does serum immunofixation do?

Answer 7

Classifies the abnormal protein band

Question 8

What paraprotein is shown in this serum immunofixation?

Answer 8

IgGK - band of IgG kappa

Question 9

What paraprotein is shown in this serum immunofixation?

Answer 9

IgAK - band of IgA kappa

Question 10

What is Bence-Jones protein?

Answer 10

• Immunoglobulin light chains (excess)
• Detected by urine electrophoresis

Question 11

What is the major cause of paraproteinaemia?

Answer 11

MGUS - monoclonal gammopathy of undetermined significance

Question 12

What are some of the direct tumour cell effects of myeloma?

Answer 12

• Bone lesions
• Hypercalcaemia
• Bone pain
• Replace normal bone marrow -> marrow failure

Question 13

What are some paraprotein mediated effects of myeloma?

Answer 13

Renal failure, immune suppression, hyperviscocity, amyloid

Question 14

What are the symptoms of hypercalcaemia?

Answer 14

Stones, bones, abdominal groans, psychiatric moans, thirst, dehydration, renal impairment

Question 15

Myeloma can cause renal impairment, what are the features of this?

Answer 15

• Tubular cell damage by light chains
• Light chain deposition - cast nephropathy
• Sepsis
• Hypercalcaemia and dehydration
• Hyperuricaemia
• Amyloid

Question 16

How can cast nephropathy be treated?

Answer 16

• Damage may be reversible with prompt treatment
• Hydration, stop nephrotoxic drugs
• Switch off light chain production with steroids/chemo

Question 17

How is myeloma treated?

Answer 17

• Combination chemotherapy the mainstay
• Corticosteroids e.g. dexamethasone, alkylating agents e.g. cyclophosphamide, novel agents e.g. thalidomide
• High dose chemo/autologous stem cell transplant in suitable patients

Question 18

What is used to monitor response in myeloma?

Answer 18

Paraprotein level

Question 19

What are some medications used for symptom control?

Answer 19

• Opiate analgesia - avoid NSAIDs
• Local radiotherapy - good for pain relief or spinal cord compression
• Bisphosphonates - corrects hypercalcaemia and bone pain
• Vertebroplasty - inject sterile cement into fractured bone to stabilise

Question 20

How is MGUS defined?

Answer 20

• Paraprotein <30g/L
• Bone marrow plasma cells <10%
• No evidence of myeloma end organ damage - normal calcium, renal function, Hb, no lytic lesions or increase in infections

Question 21

What is AL amyloidosis and how is it treated?

Answer 21

• Rare disorder
• Small plasma cell clone
• Mutation in the light chain -> altered structure
• Precipitates in tissues as an insoluble beta pleated sheet
• Often presents late with organ damage
• Slowly progressive
• Multi-system disease
• Poor prognosis especially if cardiac amyloid
• Treatment with chemo similar to myeloma to switch off light chain supply

Question 22

What organ damage can occur in AL amyloid?

Answer 22

• Kidney - nephrotic syndrome
• Heart - cardiomyopathy
• Liver - organomegaly deranged LFTs
• Neuropathy - autonomic, peripheral
• GI tract - malabsorption

Question 23

How is AL amyloid diagnosed and staged?

Answer 23

• Organ biopsy confirming AL amyloid deposition - congo red stain, rectal or fat biopsy may be done if high clinical suspicion
• Evidence of deposition in other organs - echo/cardiac MRI, nephrotic range proteinuria

Question 24

What is used to measure disease burden in AL amyloid?

Answer 24

SAP scan - localises rapidly and specifically to amyloid deposits in proportion to the quantity of amyloid present

Question 25

What is Waldenstrom’s macroglobulinaemia?

Answer 25

• Lymphoplasmactoid neoplasm - clonal disorder of cells intermediate between a lymphocyte and a plasma cell
• Characterstic IgM paraprotein

Question 26

What are the tumour effects and paraprotein effects of Waldenstrom’s macroglobulinaemia?

Answer 26

• Tumour effects - lymphadenopathy, splenomegaly, marrow failure
• Paraprotein effects - hyper-viscosity, neuropathy

Question 27

What are the clinical features of Waldenstrom’s?

Answer 27

• Hyper-viscosity syndrome - fatigue, visual disturbance, confusion, coma, bleeding, cardiac failure
• B symptoms - night sweats, weight loss

Question 28

How is Waldenstrom’s treated?

Answer 28

• Chemo
• Plasmapheresis - removes paraprotein (IgM) from the circulation and replaces it with donor plasma