Myeloma and Plasma Cell Disorders

Question 1

Where are B cells derived from?

Answer 1

Derived in bone marrow from pluripotent haemopoietic stem cells

Question 2

What are the functions of B cells?

Answer 2

Antibody production, act as antigen presenting cell

Question 3

What are immunoglobulins?

Answer 3

Antibodies produced by B cells and plasma cells = made of 2 heavy and 2 light chains

Question 4

What influences B cells?

Answer 4

The microenvironment

Question 5

Where is the Ig variable element of B cells generated from?

Answer 5

The VDJ region recombination = occurs early in development

Question 6

What happens once self reactive cells are removed during B cell development?

Answer 6

Immature B cells with Ig on their surface exit the bone marrow

Question 7

What do B cells do once they are released into the periphery?

Answer 7

Travel to follicle germinal centre of lymph node

Identify antigen and improve fit by somatic mutation or be deleted

Question 8

What is the fate of B cells once they have identified an antigen?

Answer 8

May return to marrow as plasma cell or circulate as memory B cell

Question 9

What is the function of plasma cells?

Answer 9

Pump out antibody

Question 10

What are the histological features of plasma cells?

Answer 10

Clock face nucleus on H & E
Open chromatin = synthesise mRNA
Plentiful blue cytoplasm full of protein and pale perinuclear area

Question 11

How does polyclonal Ig arise?

Answer 11

Ig produced by many different plasma cell clones

Question 12

What causes polyclonal increase in Ig?

Answer 12

Reactive = infection, autoimmune, malignancy, liver disease

Question 13

How does monoclonal Ig arise?

Answer 13

All derived from clonal expansion of a single B cell = identical antibody structure and specificity

Question 14

What is the other name for monoclonal Ig?

Answer 14

Paraprotein = marker of underlying B cell disorder

Question 15

What is used to detect Ig?

Answer 15

Serum electrophoresis = proteins move at different rates determined by size and charge, detects abnormal protein band

Question 16

What is serum immunofixation used for?

Answer 16

Classifying abnormal protein band

Question 17

What is Bence Jones protein?

Answer 17

Ig light chains = excess produced by plasma cells, leaks into urine and detected by urine electrophoresis

Question 18

What are the causes of paraproteinaemia?

Answer 18

MGUS, myeloma, amyloidosis, lymphoma, plasmacytoma, chronic lymphocytic leukaemia, Waldenstrom’s macroglobinaemia

Question 19

What is the progression of cells to myeloma?

Answer 19

Normal plasma cell - MGUS clone (premalignant) - asymptomatic myeloma (malignant but no organ damage) - myeloma

Question 20

What are the features of myeloma?

Answer 20

Bone lesion, increased calcium, bone pain, marrow failure, amyloid, immune suppression, hyperviscosity, renal failure

Question 21

How is myeloma classified?

Answer 21

By the type of antibody produced = IgG (59%), IgA (21%), Bence Jones (15%)

Question 22

What are the symptoms of hypercalcaemia?

Answer 22

Stones, bone pain, abdominal pain, psychiatric issues, thirst, dehydration, renal impairment

Question 23

How common is renal failure in myeloma?

Answer 23

30% have renal impairment at diagnosis = tubular cell damage by light chain deposition occurs causing cast nephropathy

Question 24

How is cast nephropathy treated?

Answer 24

Damage may be reversible with prompt treatment = hydration, stop nephrotoxic drugs, steroids/chemo to stop light chain production

Question 25

What is the mainstay of myeloma treatment?

Answer 25

Combination chemotherapy | High dose chemo or stem cell transplant used in fit patients

Question 26

What are some chemotherapy agents used to treat myeloma?

Answer 26

Corticosteroids, dexamethasone or prednisolone Alkylating agents = cyclophosphamide Novel agents = thalidomide, bortezomib, lenalidomide

Question 27

What is used to monitor myeloma treatment response?

Answer 27

Paraprotein levels

Question 28

What is used for symptomatic control in myeloma?

Answer 28

``` Opiate analgesia (avoid NSAIDs) Local radiotherapy = pain relief, spinal cord compression Bisphosphonates = corrects hypercalcaemia Vertebroplasty ```

Question 29

What is the purpose of a vertebroplasty?

Answer 29

Stabilises fractured bone = sterile cement injected into bone

Question 30

How is MGUS defined?

Answer 30

Paraprotein <30g/l and bone marrow plasma cell <10% | No evidence of myeloma end organ damage

Question 31

What does MGUS stand for?

Answer 31

Monoclonal gammopathy of undetermined significance

Question 32

What test results would you expect in MGUS?

Answer 32

Normal Hb, normal Ca2+, normal renal function, no lytic lesion, no increase in infection

Question 33

What causes AL amyloidosis?

Answer 33

Small plasma cell clone with mutation in light chain = altered structure

Question 34

How does AL amyloidosis appear in tissues?

Answer 34

Precipitates as beta pleated sheets = causes slowly progressive organ damage

Question 35

What feature conveys poor prognosis of AL amyloidosis?

Answer 35

Cardiac amyloid

Question 36

What organ damage may occur due to AL amyloidosis?

Answer 36

Nephrotic syndrome, cardiomyopathy, hepatomegaly, neuropathy, malabsorption

Question 37

How is AL amyloidosis treated?

Answer 37

Chemotherapy

Question 38

How is AL amyloidosis diagnosed?

Answer 38

Organ biopsy for amyloid deposition | SAP scan, echocardiogram, cardiac MRI

Question 39

How is amyloid identified on biopsy?

Answer 39

Use congo red stain = causes apple green birefringence (may do fat or rectal biopsy)

Question 40

What is the purpose of SAP scans in AL amyloidosis?

Answer 40

Used to monitor disease burden = Indium 23-labelled SAP localises rapidly to amyloid deposits

Question 41

What paraprotein is associated with Waldenstrom's microglobinaemia?

Answer 41

IgM paraprotein = pentameric structure

Question 42

What is Waldenstrom's microglobinaemia?

Answer 42

Lymphoplasmacytoid neoplasm = clonal disorder of cells intermediate between a lymphocyte and plasma cell

Question 43

What are the features of Waldenstrom's microglobinaemia?

Answer 43

Lymphadenopathy, splenomegaly, marrow failure, hyperviscosity, neuropathy

Question 44

What kind of syndrome does Waldenstrom's microglobinaemia cause?

Answer 44

Hyperviscosity syndrome = fatigue, visual disturbance, confusion, coma, bleeding, cardiac failure

Question 45

How is Waldenstrom's microglobinaemia treated?

Answer 45

Chemotherapy and plasmapheresis