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Pathology > Ha - Multiple Myeloma > Flashcards

Ha - Multiple Myeloma Flashcards

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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
list primary events that can cause myeloma
hyperdiploidy IGH rearrangements - Chr14q32
26
which is the most common primary cause of myeloma
hyperdiploidy 60%
27
list chr14q32 IGH rearrangments that can cause myeloma
t(11,14) t(4,14) t(14,16)
28
list secondary events that can cause myeloma
KRAS, NRAS t(8,14) 1q gain / deletion deletion of 17p (TP53) 13-/del 13q
29
how does myeloma affect the bone
anaemia bone destruction immunosuppression and infections angiogenesis
30
why does myeloma cause bone destruction
myelome plasma cells stimulate osteoclast interaction
31
sx / signs of myeloma
CRAB - high Ca - renal disease - anaemia - bone disease - fractures, lytic lesions, pain
32
diagnostic criteria of myeloma
>10% plasma cells in BM plasmacytoma and 1+ CRAB Sx
33
list myeloma defining events
BM plasma cells >60% involved:uninvolved FLC ratio >100 1+ focal lesion in MRI >5mm
34
what % of myeloma patients have bone disease
80%
35
list bone disease Sx of myeloma
proximal skeleton issues osteolytic not osteoblastic (salt and pepper skull) osteopenia high ca
36
Ix for myeloma bone issues & why
CT / PET MRI - can see BM cellularity and active/Tx effect on disease
37
list 2 medical emergencies that can occur as a consequence of MM
cord compression high calcium
38
Ix for ?cord compression due to MM
MRI Ig and FLC studies +/- biopsy
39
Mx of ?cord compression due to MM
dexamethasone radiotherapy surgery (rare)
40
Sx of high calcium due to MM
drowsy constipated tired muscle weakness AKI
41
Tx of high calcium due to MM
IV fluids steroids zolendronic acid
42
define kidney disease in MM
serum creatanine >177umol/L or eGFR <40ml/min
43
what % of MM patients have AKI at presentation
20-50%
44
what causes kidney problems in MM
cast nephropathy due to high serum FLC and bence jones proteinuria
45
consequences of kidney disease in MM
high mortality - 12% early death increases hospital stays infections reduced drug suitability as many drugs renally excreted
46
Mx of kidney disease in MM
bortezomib Tx to remove FLC
47
why do MM patients get infections
reduced serum normal IgGs - immunoparesis myeloid and T cell impairment chemotherapy reduces immunity
48
which infections in particular affect MM patients
gram + and viruses - esp HSV
49
Ix for MM
Ig studies - serum / urine protein electrophoresis - 24hr BJP collection BM biopsy and aspiration FISH analysis flow cytometry immuniphenotyping
50
Name a risk stratification score of myeloma
R-ISS
51
what does R-ISS use to stage MM
microglobulin albumin genetic abnormalities high LDH
52
pathogenesis of amyloidosis
misfolded light chains aggregate into amyloid fibrils in target organs
53
what stain is used to visualise amyloidosis
congo red
54
what effects does amyloidosis have on organs
nephrotic syndrome unexplained HF sensory neuropathy abnormal LFTs macroglosia
55
what % of amyloidosis patients have nephrotic syndrome
70%
56
what is MGRS
monoclonal gammaopathy of renal significance - Ig LCs damage nephron
57
what is the key MM histopath marker
CD138
58
Drug Tx of MM
belantamab ventoclax BiTE CAR-T cells
59
prognosis of MM
usually >10 year survival
60
new drug Tx of MM
cereblon E3 ligase modulators proteasome inhibitors
61
name 3 proteasome inhibitors
bortezomib carfilozomib ixazomib
62
name the 1st monoclonal AB for MM
daratumab
63
what does daratumab target
CD38 - a marker in normal plasma cells
64
describe transplant process for eligible MM patients
induction --> SCT --> consolidation --> maintenance
65
Tx for transplant ineligible MM patients
dartumumad + lenolimide + dex OR bortezomib + cyclophosphamide + dex OR dara - borte - cyclo - pred
66
side effects of CAR T cells
cytokine release syndrome neurotoxicity prolonged cytopenias and infections
67
what is BiTE
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
diagnostic criteria of myeloma
>10% plasma cells in BM plasmacytoma and 1+ CRAB Sx

Pathology (87 decks)

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