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Pathology > Ha - Multiple Myeloma > Flashcards

Ha - Multiple Myeloma Flashcards

1
Q

what is MM

A

ca of plasma cells of bone marrow

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2
Q

describe the MM plasma cells

A

terminally differentiated
monoclonal IgG secreting

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3
Q

what do MM plasma cells make (3)

A

monoclonal IgG or IgA
excess kappa or lamda serum free light chains
bence jones proteins

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4
Q

what is waldenstroms

A

lymphoplastic lymphoma

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5
Q

MM is the ___ most common cancer and ___ most common blood cancer

A

19th
2nd

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6
Q

median age of MM

A

67
incidence increases with age

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7
Q

MM is higher in what sex / race ?

A

higher in males / black

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8
Q

RFs of MM

A

obesity
genetics - black, sporadic family myeloma
premalignant conditions

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9
Q

when is MM preceded by a pre malignant condition

A

ALWAYS

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10
Q

what premalignant condition preceeds MM

A

MGUS - monoclonal gammopathy of uncertain significance

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11
Q

what is MGUS

A

presence of monoclonal IgG in the blood

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12
Q

age preference of MGUS

A

incidence increases with age
1-3.5% elderly population

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13
Q

what % of MGUS progress to MM each year

A

1%

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14
Q

what does MGUS IgG/A type progress to?
MGUS IgM type?

A

IgG/A –> myeloma
IgM –> lymphoma

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15
Q

what does MGUS increase your risk of, other than MM

A

osteoporosis
thrombosis
bacterial infection

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16
Q

criteria for diagnosing MGUS

A

serum M < 30g/L
BM clonal cells >10%
no lytic bone lesions / myeloma related tissue damage / B cell proliferative disease

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17
Q

how is the risk of MGUS progression stratified

A

Mayo criteria

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18
Q

RFs for MGUS

A

non IgG M spike
M spike >15g/L
abnormal serum free light chain ratio

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19
Q

describe how number of RFs relates to risk of progression to MM

A

0 RFs = 2%
1 RF = 10%
2 RFs = 18%
3 RFs = 27%

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20
Q

does everyone that has MGUS get MM?

A

NO - most people are fine and never get myeloma

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21
Q

diagnostic criteria for smouldering myeloma

A

serum IgG or IgA >30g/L
BM clonal plasma cells 10-60%
no myeloma events

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22
Q

is mouldering myeloma malignant

A

no - premalignant

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23
Q

RFs for developing myeloma from smouldering myeloma

A

BM myeloma cells >20%
M spike >20g/L
serum FLC ratio >20

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24
Q

what is the Tx for myeloma

A

no treatment
only sx mx to prevent relapse

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25
Q

list primary events that can cause myeloma

A

hyperdiploidy
IGH rearrangements - Chr14q32

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26
Q

which is the most common primary cause of myeloma

A

hyperdiploidy 60%

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27
Q

list chr14q32 IGH rearrangments that can cause myeloma

A

t(11,14)
t(4,14)
t(14,16)

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28
Q

list secondary events that can cause myeloma

A

KRAS, NRAS
t(8,14)
1q gain / deletion
deletion of 17p (TP53)
13-/del 13q

29
Q

how does myeloma affect the bone

A

anaemia
bone destruction
immunosuppression and infections
angiogenesis

30
Q

why does myeloma cause bone destruction

A

myelome plasma cells stimulate osteoclast interaction

31
Q

sx / signs of myeloma

A

CRAB
- high Ca
- renal disease
- anaemia
- bone disease - fractures, lytic lesions, pain

32
Q

diagnostic criteria of myeloma

A

> 10% plasma cells in BM
plasmacytoma and 1+ CRAB Sx

33
Q

list myeloma defining events

A

BM plasma cells >60%
involved:uninvolved FLC ratio >100
1+ focal lesion in MRI >5mm

34
Q

what % of myeloma patients have bone disease

A

80%

35
Q

list bone disease Sx of myeloma

A

proximal skeleton issues
osteolytic not osteoblastic (salt and pepper skull)
osteopenia
high ca

36
Q

Ix for myeloma bone issues & why

A

CT / PET MRI
- can see BM cellularity and active/Tx effect on disease

37
Q

list 2 medical emergencies that can occur as a consequence of MM

A

cord compression
high calcium

38
Q

Ix for ?cord compression due to MM

A

MRI
Ig and FLC studies
+/- biopsy

39
Q

Mx of ?cord compression due to MM

A

dexamethasone
radiotherapy
surgery (rare)

40
Q

Sx of high calcium due to MM

A

drowsy
constipated
tired
muscle weakness
AKI

41
Q

Tx of high calcium due to MM

A

IV fluids
steroids
zolendronic acid

42
Q

define kidney disease in MM

A

serum creatanine >177umol/L
or
eGFR <40ml/min

43
Q

what % of MM patients have AKI at presentation

A

20-50%

44
Q

what causes kidney problems in MM

A

cast nephropathy due to high serum FLC and bence jones proteinuria

45
Q

consequences of kidney disease in MM

A

high mortality - 12% early death
increases hospital stays
infections
reduced drug suitability as many drugs renally excreted

46
Q

Mx of kidney disease in MM

A

bortezomib Tx to remove FLC

47
Q

why do MM patients get infections

A

reduced serum normal IgGs - immunoparesis
myeloid and T cell impairment
chemotherapy reduces immunity

48
Q

which infections in particular affect MM patients

A

gram + and viruses - esp HSV

49
Q

Ix for MM

A

Ig studies
- serum / urine protein electrophoresis
- 24hr BJP collection
BM biopsy and aspiration
FISH analysis
flow cytometry immuniphenotyping

50
Q

Name a risk stratification score of myeloma

A

R-ISS

51
Q

what does R-ISS use to stage MM

A

microglobulin
albumin
genetic abnormalities
high LDH

52
Q

pathogenesis of amyloidosis

A

misfolded light chains aggregate into amyloid fibrils in target organs

53
Q

what stain is used to visualise amyloidosis

A

congo red

54
Q

what effects does amyloidosis have on organs

A

nephrotic syndrome
unexplained HF
sensory neuropathy
abnormal LFTs
macroglosia

55
Q

what % of amyloidosis patients have nephrotic syndrome

A

70%

56
Q

what is MGRS

A

monoclonal gammaopathy of renal significance
- Ig LCs damage nephron

57
Q

what is the key MM histopath marker

A

CD138

58
Q

Drug Tx of MM

A

belantamab
ventoclax
BiTE
CAR-T cells

59
Q

prognosis of MM

A

usually >10 year survival

60
Q

new drug Tx of MM

A

cereblon E3 ligase modulators
proteasome inhibitors

61
Q

name 3 proteasome inhibitors

A

bortezomib
carfilozomib
ixazomib

62
Q

name the 1st monoclonal AB for MM

A

daratumab

63
Q

what does daratumab target

A

CD38 - a marker in normal plasma cells

64
Q

describe transplant process for eligible MM patients

A

induction –> SCT –> consolidation –> maintenance

65
Q

Tx for transplant ineligible MM patients

A

dartumumad + lenolimide + dex
OR
bortezomib + cyclophosphamide + dex
OR
dara - borte - cyclo - pred

66
Q

side effects of CAR T cells

A

cytokine release syndrome
neurotoxicity
prolonged cytopenias and infections

67
Q

what is BiTE

A

bispecific AB
- one part binds CD3 of T cell, other recognises TSA of tumour cell therefore bringing the 2 together to encourage T cell destruction of cancer cell

68
Q

diagnostic criteria of myeloma

A

> 10% plasma cells in BM
plasmacytoma and 1+ CRAB Sx

Pathology (87 decks)

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