Myeloma and plasma cell dyscrasias

Question 1

Where do B cells come from

Answer 1

pluripotent HSC in bone marrow

Question 2

are B cells part of the innate or adaptive immune system

Answer 2

adaptive (slower, more specific response)

Question 3

what are immunoglobulins

Answer 3

antibodies produced by B cells and plasma cells

Question 4

what are immunoglobulins made of

Answer 4

2 heavy chains: IgG/A/M/E/D

2 light chains: k/lambda

Question 5

each antibody can recognise multiple antigens, true or false

Answer 5

false

each antibody recognises a specific antigen

Question 6

which Ig antibodies are monomeric

Answer 6

IgG, IgD, IgE

Question 7

which Ig antibody is dimeric

Answer 7

IgA

Question 8

which Ig antibody is pentameric

Answer 8

IgM

Question 9

what allows for variability in Ig

Answer 9

V-D-J region recombination

Question 10

Where do B cells in the periphery travel to

Answer 10

follicle germinal centres in lymph nodes to identify antigens

Question 11

what can happen to a B cell after it finishes in the lymph node

Answer 11

may return to the bone marrow as a plasma cell or circulate as a memory B cell

Question 12

what are plasma cells

Answer 12

factory cells that pump out antibody

Question 13

what are histological features of plasma cells

Answer 13

eccentric clock face nucleus with H&E staining
open chromatin
plentiful blue cytoplasm
pale perinuclear area

Question 14

define polyclonal

Answer 14

produced by many different plasma cell clones

Question 15

what can polyclonal proliferation be indicative of

Answer 15

infection
autoimmune condition
malignancy - as a reaction from the host to a malignant clone
liver disease

Question 16

define monoclonal

Answer 16

all derived from clonal expansion of a single B cell

Question 17

characteristics of monoclonal antibodies

Answer 17

identical structure and specificity

Question 18

what are monoclonal antibodies also known as

Answer 18

paraprotein

Question 19

what are paraproteins a marker of

Answer 19

underlying clonal B cell disorder

Question 20

what investigation is used to detect immunoglobulins

Answer 20

serum electrophoresis

Question 21

in serum electrophoresis, what causes proteins to move the way they do

Answer 21

their shape and charge

Question 22

what investigation is used to classify abnormal protein bands found in electrophoresis

Answer 22

serum immunofixation

Question 23

What are Bence Jones Proteins BJPs

Answer 23

free light chains detected by urine electrophoresis

Question 24

are light chains normally secreted into plasma

Answer 24

yes, in very small amounts 0.5g/l

Question 25

what can cause raised free light chains

Answer 25

polyclonal (infection) or monoclonal (multiple myeloma) increase in plasma cells

Question 26

causes of paraproteinaemia

Answer 26

``` myeloma lymphoma MGUS amyloidosis plasmacytoma CLL ```

Question 27

MGUS is benign/malignant

Answer 27

benign/premalignant

Question 28

asymptomatic myeloma is benign/malignant

Answer 28

malignant - but no organ damage

Question 29

what are the direct tumour effects of myeloma on the body

Answer 29

bone lesions bone pain hypercalcaemia marrow failure

Question 30

what are the paraprotein mediated effects of myeloma on the body

Answer 30

renal failure immunosuppression hyperviscosity amyloid

Question 31

how can multiple myeloma be classified

Answer 31

according to Ig Ab produced

Question 32

why do you get lytic bone lesions in myeloma

Answer 32

malignant myeloma cells suppress osteoblasts and activate osteoclasts (also the reason for hypercalcaemia)

Question 33

list consequences of hypercalcaemia

Answer 33

``` kidney stones psychiatric moans abdominal groans painful bones thirst and dehydration renal impairment ```

Question 34

how can multiple myeloma lead to renal failure by cast nephropathy

Answer 34

free light chains can filter through glomerulus proximal convoluted tubule cannot deal with light chain overload so they pass to ascending limb of loop of Henle ascending limb produces Tam-Horsfall proteins which bind to light chains and make them insoluble forming casts this blocks the nephron

Question 35

what is the prompt management for dealing with cast nephropathy

Answer 35

rehydration stop nephrotoxic drugs start chemo/steroids to reduce light chain production

Question 36

what is the median age for multiple myeloma

Answer 36

65 years old

Question 37

what is the mainstay of treatment for multiple myeloma

Answer 37

combination chemotherapy

Question 38

what can be used to monitor response to treatment in multiple myeloma

Answer 38

paraprotein levels

Question 39

what is AHSCT (autologous haemopoeitic stem cell transplant)

Answer 39

a method of administering very high dose chemotherapy relatively safely

Question 40

many patients dont tend to relapse in multiple myeloma, true or false

Answer 40

false | relapse in inevitable

Question 41

how can you control symptoms in multiple myeloma

Answer 41

opiate analgesia (not NSAIDs) local radiotherapy bisphsphonates vertebroplasty

Question 42

what does MGUS stand for

Answer 42

monoclonal gammopathy of undetermined significance

Question 43

how can you define MGUS

Answer 43

paraprotein <30g/l bone marrow plasma cells <10% no evidence of end organ damage from myeloma

Question 44

what is AL amyloidosis

Answer 44

rare disorder | slowly progressive multisystem disease

Question 45

what is the pathophysiology of AL amyloidosis

Answer 45

mutation in light chain causes abnormal structure which precipitates in tissues as insoluble pleated B sheets

Question 46

what organ damage can occur in AL amyloidosis

Answer 46

``` kidneys - nephrotic syndrome heart - cardiomyopathy liver - hepatomegaly, deranged LFTs neuropathy - ANS, PNS GI tract - malabsorption ```

Question 47

how can you diagnose AL amyloidosis

Answer 47

organ biopsy with congo red stain (positive result - apple green birefringence under polarised light) or less invasive rectal/fat biopsy

Question 48

what is a SAP scan for AL amyloidosis

Answer 48

serum amyloid P scintigraphy scan can localise amyloid deposits rapidly and specifically

Question 49

what is Waldenstroms macroglobulinaemia

Answer 49

lymphoplasmacytoid neoplasm = clonal disorders of cells which are in between a lymphocyte and a plasma cell

Question 50

what is characteristic of Waldenstroms macroglobulinaemia

Answer 50

IgM paraprotein

Question 51

what can IgM paraprotein cause in Waldenstroms macroglobulinaemia

Answer 51

hyperviscosity | neuropathy

Question 52

what is the treatment of Waldenstroms macroglobulinaemia

Answer 52

chemo | plasmapharesis

Question 53

what is plasmapharesis

Answer 53

removal of paraprotein from your circulation and replacing with donor plasma