Myeloma + Other Plasma Cell Disorders

Question 1

where are B cells derived from

Answer 1

pluripotent haematopoietic stem cells in the bone marrow

Question 2

role of B cells

Answer 2

part of adaptive immune system

• antibody production
• act as antigen presenting cells

Question 3

what are immunoglobulins

Answer 3

antibodies produced by B cells and plasma cells

proteins made up 2 heavy and 2 light chains

each antibody recognises a specific antigen

Question 4

what immunoglobulins are monomer shaped

Answer 4

IgG
IgD
IgE

Question 5

what immunoglobulins are dimer shaped

Answer 5

IgA

Question 6

what immunoglobulins are pentamer shaped

Answer 6

IgM

Question 7

normal pathway of lymphocyte maturation

Answer 7

stem cells – lymphoid progenitors – pro B cells – pre B cells – IgM B cells

Question 8

what do IgM B cells divide to make

Answer 8

IgM plasma cells
IgA
IgE
IgG

Question 9

what does IgG eventually go on to become

Answer 9

plasma cells

Question 10

function of 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

Question 12

role of B cells in the periphery

Answer 12

travel to follicle germinal centre of the lymph node
identify the antigen
may return to the marrow as a plasma cell or circulate as a memory cell

Question 13

what is meant if a blood film is described as

• polyclonal
• monoclonal

Answer 13

polyclonal = multiple types of blood cells, can be seen as a part of normal function

monoclonal = one type of cell seen, suggests pathology

Question 14

what are the causes of polyclonal increase in immunoglobulins

Answer 14

infection
autoimmune
malignancy
liver disease

Question 15

what does a monoclonal increase in immunoglobulins imply

Answer 15

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

Question 16

what can monoclonal immunoglobulins also be called

Answer 16

paraprotein

Question 17

what are paraproteins a marker of

Answer 17

underlying clonal B cell disorder

Question 18

how can you detect immunoglobulins

Answer 18

serum electrophoresis

- separated serum proteins appear as distinct bands/zones

Question 19

what zone are immunoglobulins seen in on electrophoresis

Answer 19

gamma

Question 20

what is bence-jones protein

Answer 20

excess immunoglobulin light chains leaking into the urine
– paraproteinaemia

detected by urine electrophoresis

Question 21

what happens to amount of free light chains in the plasma when a person is unwell (i.e. infection/monocloncal disease)

Answer 21

increase in free light chains in the plasma

Question 22

causes of paraproteinaemia

Answer 22

monoclonal gammopathy of undetermined significance (MGUS- completely harmless)
myeloma
amyloidosis
lymphoma

Question 23

what is a myeloma

Answer 23

plasma cell malignancy - clonal proliferation of plasma cells resulting in increased monoclonal antibody (usually IgG or IgA)

Question 24

direct tumour effects of a myeloma

Answer 24

bone lesions - lytic lesions
increased calcium
bone pain/ pathological fractures
bone marrow failure - anaemia, bleeding, infections

Question 25

effects of paraprotein seen in myeloma

Answer 25

renal failure immunosuppression hyperviscosity amyloid

Question 26

how is myeloma classified

Answer 26

by type of antibody produced

Question 27

most common myeloma

Answer 27

IgG

Question 28

types of myeloma from most to least common

Answer 28

- IgG - IgA - Bence Jones - non secretory - IgD - biclonal - IgE

Question 29

what is a myelomas affect on bone

Answer 29

lytic bone disease | clones produce IL-6 which activates osteoclasts and inhibits osteoblasts -- bone destruction

Question 30

what is seen on x ray of myeloma

Answer 30

"punched out" lytic lesions | pepper pot skull

Question 31

symptoms of hypercalcaemia

Answer 31

``` stones bones abdominal groans psychiatric moans thirst/dehydration renal impairement ```

Question 32

how can a myeloma cause kidney failure

Answer 32

free light chains accumulate in the proximal tubules before entering loop of henle combine with Tamm-horsfall protein to produce insoluble casts blocking the nephron -- cast nephropathy this leads to renal failure

Question 33

where in the loop of henle is Tamm-Horsfall protein produced

Answer 33

thick ascending limb

Question 34

what is the significance of Tamm-Horsfall protein in renal failure

Answer 34

free light chains bind with the protein causing insoluble casts that block the nephron this causes cast nephropahty resulting in renal failure

Question 35

mean age of myeloma diagnosis

Answer 35

65

Question 36

treatment of myeloma

Answer 36

bone pain -- analgesia + biphosphonates anaemia -- transfusions/ EPO hypercalcaemia -- adequate hydration hyper viscosity -- plasmapheresis chemo: melphalan + prednisone + lenalidomide young patients may receive allogenic bone marrow transplant

Question 37

how is response to treatment monitored

Answer 37

paraprotein level

Question 38

symptom control in myeloma

Answer 38

- opiate analgesia - local radiotherapy - good pain relief for spinal cord compression - biphosphonates - correct hypercalcaemia + bone pain - vertebroplasty - infection of sterile cement into fractured bone to stabilise it

Question 39

what does MGUS stand for

Answer 39

monoclonal gammopathy of uncertain significance

Question 40

definition of MGUS

Answer 40

``` paraprotein < 30 g/l bone marrow plasma cells <10% no evidence of myeloma end organ damage : - normal calcium - normal renal function - normal Hb - no lytic lesions ```

Question 41

what is amyloidosis

Answer 41

accumulation of protein in abnormal fibrillar form - precipitates in tissues as an insoluble beta pleated sheet caused by mutations in the light chain -- causes organ damage

Question 42

what can amyloidosis cause

Answer 42

nephrotic syndrome | cardiomyopthay

Question 43

how is amyloidosis deposition confirmed

Answer 43

congo red staining - causes apple green birefringence under polarised light

Question 44

what is waldenstrom macroglobulinaemia

Answer 44

lymphoplasmacytoid neoplasm - clonal disorder of cells intermediate between a lymphocyte and a plasma cell - characteristic IgM paraprotein

Question 45

what is characteristic of waldenstroms macroglobulinaemia

Answer 45

IgM paraprotein

Question 46

tumour effects of waldenstroms macroglobulinaemia

Answer 46

lymphadenopathy splenomegaly marrow failure

Question 47

IgM paraprotein effects in waldenstroms macroglobulinaemia

Answer 47

hyper viscosity | neuropathy

Question 48

features of hyper viscosity

Answer 48

``` fatigue visual disturbance confusion bleeding cardiac failure night sweats weight loss ```

Question 49

treatment of waldenstroms macroglobulinaemia

Answer 49

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

Question 50

effects of zolendronate in myeloma

Answer 50

this is a biphosphonate that inhibits osteoclast activity so halts the progression of bone disease

Question 51

what drug regime is used in relapsed myeloma

Answer 51

lenalidomide + bortezomib (protesome inhibitor)

Question 52

blood results in myeloma

Answer 52

anaemia, thrombocytopenia, leucopenia increased calcium, increased urea, increased creatinine, increased ESR