Sarcomas, ASPHO Flashcards
1
Q
most imp somatic mutations in RMS?
A
PAX-FOX0O1 fusions in alv. RMS t(2;13)
2
Q
most common PAX_FOXO1 in RMS?
A
PAX3-FOXO1 (2;13) =60% >PAX7-FOXO1 (t;13)=20%
3
Q
PAX-FOXO1 mut is a ___ in tumorigenesis
A
driver
4
Q
give 2 genetic changes seen in fusion neg RMS
A
aneuploidy
activation muts of RAS pathway (FGF4, NRAS, KRAS, etc muts)
p53 muts= unfav
myoD muts= unfav
LOH or Loss of Imprinting at 11p15.5
NCOA2, VGLL2 rearrangements= fav in infants with spindle cell RMS
5
Q
Give 5 germline muts associted with RMS
A
Li-Fraumeni=p53 BWS=IGF2 Costello=HRAS Noonan= RAS-MAPK path NF1= NF1 Gorlin= PTCH1 PBB= Dicer 1
6
Q
bimodal peak for general sarcomas adn soft tissue sarcomas?
A
infancy and teenage years
7
Q
presentation of RMS?
A
mass
+/- pain
+/- distrubance in function like CN palasy or bladder dysfunction
8
Q
most common site of RMS?
A
head and neck>GU>extrem
9
Q
favourable H&N site for RMS
A
orbit, non-parameningeal
10
Q
parameningeal site= unfavourable in rhabdo…waht does this include?
A
base of skull, including infratemporal fossa, paranasal sinuses, parapharyngeal area
11
Q
favourable GU site for RMS?
A
paratsticular, vag, uterine
12
Q
unfavoruable GU site for rhabdo?
A
bladder, prostate
13
Q
lymphatic spread of RMS seen where?
A
paratesticular, extremity tumours
14
Q
CNS ext seen where in RMS?
A
50% parameningeal
15
Q
hematogenous mets go where in RMS?
A
lung, bone, BM, liver
16
Q
stage RMS how?
A
- MRI or Ct of priamry site adn regional nodal basin
- CT chest
- PET scan or bone scan
- bilateral BMA/bx
- CSF cytomology if parameningeal/paraspinal
- LN for paratestictular at least 10 years of age or extremity
17
Q
WHich RMS pts do NOT need bone scan, BMA/bx, possible chest CT?
A
ERMS, T1, N0 disease
18
Q
what’s the name of the MRS staging system?
A
IRS
19
Q
describe stage 1 or IRS staging for RMS
A
- favourable site: orbit, non-parameningieal head and neck, non-bladder/prosatate GU, biliary tract
- T1= confined to site of origin or T2= extension and/or fixation to surroundign tissue
- size: any
- any regional LN status
20
Q
describe stage 2 for RMS staging
A
- unfav site: parameningeal, bladder/prostate, extremity, other
- T1 or T2 (same)
- size <5 cm
- regional lymph nodes not present or unknwon
21
Q
describe stage 3 for RMS
A
- unfav site
- T1 or T2 (same)
- size: <5 cm if just regional LNs involved, vs. >5 cm for LNs not involved/regional involvement/unknown
22
Q
describe stage 4 RMS
A
- all sites with distant mets
- T1 or T2 (same)
- any size
- regional LNs involved or not
23
Q
what does RMS grouping tell you?
A
IRS grouping tells you extent of tumour remaining after SURGERY, before any other tx
24
Q
Describe RMS group 1
A
completely resected lcoal disease
25
describe group 2 in RMS
gross total resection with evdience of regional spread...
A): microscopic residual diseae
b) reigonal nodes involved AND completely researcted
C) regional nodes invovled and grossly resected but have microscopic residual disease and histo involvement of the resected regional nodes
26
describe group 3 rmS
incomplete resection with gross residual disease
27
describe gropu 4 RMS
distant mets
28
what's very prog in RMS?
staging= extent of disease
29
3 yr FFS in stages 1-4 RMS?
86%
80%
68%
25%
30
how does group impact prog?
Groups1-3 have better 5-yr FFS and 5-yr OS (73% and 84%) than group 4 (30% and 42%).....also 3-yr FFS gets worse with higher group: 83%->86%->73%->25%
31
RMS histo subtypes in fusion neg?
spiondle cell, botryoid, embryonal
32
what if you are fusion negative but alveolar RMS?
better prog, simialr to embryonal histo
33
describe RMS risk gruops (COG)
low risk has a 5 yr FFS of at lesat 85%...drops to 50-75% for intermed and 20% or less for high...to be low risk, must be stage 1-2 with group I-II diseaes, embryonal OR stage 1, group III ORBIT, embryonal....high risk: stage 4, group 4, at lesat 10 yrs of age with emrbryonal or stage 4+ group 4 wtih alv. RMS (fusion pos)...everything else= intermed
34
primary site in RMS = prognostic. best site? worst site? order?
best= orbit/head and neck
worst= extremity
order. orbit/head and neck>GU non-bladder/prostate> then GU ballder/prostate, parameningeal>other>extremity
35
other than primary site, genetic mutations, staging, group, what else is prog in RMS?
- mets...mets to lung better than to bone/bone marrow.
- and # of met sites...2 or less is better than 3 or more!
- recurrence...~20-25% 3-5 yr OS
36
if relapsed RMS, waht are good RFs?
botryoid histology
| ERMS that was stage 1 or group 1 at initial dx with local or regional recurrence adn not previously tx'ed iwth cyclophos
37
what are 3 main types of childhood RMS
embryonal, alveolar, spindle cell
38
ERMS and spindel cell RMS fall in teh category of ___ ___ tumours; what else is in this category?
spindle cell; synovial sarcoma
39
how can you differentiate synovial sarcoma from RMS (ERMS or spindle cell RMS)?
ERMS and spindle cell RMS: pos for MyoD, myogenin, Desmin, muscle specific actin...but synovial: cytokeratin, EMA, Bcl2
40
ARMS falls in teh category of what tumours?
Small round blue cell tumour
41
small round blue cell tumour pos for NSE, synaptophysin, TH, PHOX2b?
NBL
42
small round blue cell tumour + for CD99, vimentin, +/-NSE, synaptophysin?
EWS/PNET
43
SRBC tumour + for myoD, myogenin, desmin, muscle specific actin?
ALVEOLAR RMS
44
SRBCT pos for LCA< CD3, CD20, TdT?
lymphoma
45
most common type of RMS?
embryonal, ~2/3
46
ERMS has includes a ___ pattern
botryoid
47
ERMS associated with a ___ age, ___ site, ___ disease, ___ prog
younger; favourable; localized; favourable
48
spindle cell RMS: associated with ___ or ___ rearrangements in infants and a ___ prog
NCOA2; VGLL2; favourable
49
what % of alv RMS is fusion neg?
20%
50
RMS tx involves? broadly
surgery, radiotherpay, chemo
51
tx in RMS based on?
risk groups
52
RMS risk groups based on what things? 4
stage
group
histo/fusion status
age (soemtimes)
53
surgical approach in RMS?
excise pirmary tumour upfront whenever possible wihtout --> major functional or consmetic defs...sometimes wait to do surgery if think may spare radiation
54
which RMS sites reqwuire surg assessmetn of LNs?
paratesticular (retroperitoneal for boys 10 yrs+), extremity
55
who doesn't need rads in RMS?
group 1 ERMS/spindle cell RMS
56
do radiation when in RMS?
usually begins during week 3-15 of therpay
57
dose of rads in RMS
36-50.4 Gy
58
Standard= interm risk chemo in RMS?
VAC x 45 weeks = vcr, dactinomycin, cyclophos
59
low risk chemo in RMS?
VA...or shorter duration with VA + lower CPM dose
60
high risk chemo in RMS?
no standards...can add doxo, epto, ifos, irinotecan
61
image how often in RMS?
q3 months
62
response at 12 weeks: predictive of survival in RMS?
no
63
aucte tox in RMS?
heme tox, infection, VOD with dactinomyicn and cyclophos
64
late effects of RMS?
infert due to alk agents 7.5-8 mg/m2 esp in boys (standard dose and higher)...secondary maligs due to alk agents/radiation/CPS...bone growth/arrest/muscle atrophy due to radiation
65
non rhabdo soft tissue: tend to occur where? spread wehre?
extremities, trunk....lungs, bone, LNs
66
general work up for non rhabdo soft tissue tumours?
MR/Ct of primary, Ct chest, PET scan, nodal eval for select tumorus
67
non rhabdo soft tissue sarcomas: prog depends on?
stage, group (extent of resection), tumouor size (< or >5 cm), grade (mitotic rate), tumour type, age
68
ilst 3 non-rhabdo soft tissue sarcomas that are reposneive to chemo
synovial, undifferentatied, infantile fibrosarcoma
69
most common non-rhabdo soft tissue sarc?
synovial
70
transloc in synovial sarc?
t(X;18) SYT-SSX
71
tranlsoc seen in infantile fibrosarcoma?
t(12;15)= ETV-NTRK3 fusion...most common STS in children <1 yrs...give VA, VAC, or larotectinib if not resected
72
3 non rhabdo soft tissue sarcs that are poorly responsive to chemo
MPNST, leiomyosarcoma, alveolar soft part sarcoma, epithelioid sarcoma
73
MPSNT asscoiated with what CPS?
NF1
74
sarcoma associated with immunosuppression and HIV?
leiomyosarcoma
75
fusion seen in alv soft part sarcoma?
t(X;17) = ASPSCR1-TFE3 fusion
76
non rhabdo STS: tx philopshy?
surgery + radiotherpay....+/- chemo
77
general tx approach in nrSTS?
based on extent of resection...group 1: observe unless grade 3 or large, then do RT (and maybe chemo= doxo + ifos)....group 2: RT alone unless grade 3 or large, then consdier chemo (Doxo + ifos)...group 3-4: RT, delayed surgery, consider chemo
78
what's being investigated in NRSTS?
pazopanib= tki
79
give 2 cytogen changes seen in osteosarcoma
chromothripsis
| supernumary ring chromosone 12q13-15
80
3 molecular abnoramliteis seen in osteosarcoma
Rb, p53, RECQL4 helicase mutations (germline)
81
peak age for osteo?
~15
82
3 rfs for osteo?
ionizing rad, hereditary rb, li fraumeni
83
presentation of oseto?
pain +/- mass invovlign metasphyses of long bone
84
3 most common primary sites in osteo?
distal femur> prox tibia>prox humerus
85
what is a skip lesion?
pattern of spread of osteo; can be several cm from primary, in the same bone...occurs in 20% of osteo
86
how does osteo spread?
skip lesions adn hematgenous spread
87
sites of osteo mets? (2)
lung>bone
88
what % of osteo has mets at dx?
15-20%
89
stage osteo how?
plain films of primary
MRI of primary
CT chest
PET scan or bone scan
90
stage assginemnt in osteo based on waht two things?
localized or not
| resectable or not
91
localized osteo 3 yrs EFS?
65-70%
92
5 yrs EFS in met osteo?
<30%
93
in osteo, bettter to have unilateral pulm mets or bone mets?
unilateral pulm mets
94
describe role of necrosis in osteo
if at lesat 90% necrosis at 10 week of pre-op chemo, better 3-yr EFS...80% vs 60%
95
types of histo that are favorable in osteo?
parosteal, fibroblastic, telangiectatic
96
how does lcoation and size play a role in osteo prog?
extremity better than axial; 8 cm or less better
97
relapsed osteo don't do well. RFs for shorter survival after realpse?
age >10
mets at dx
lung and bone recurrence
time to relapse<2 yrs
98
pathognomic features on histo for osteo?
osteoid-producing malig cdells
99
2 major histo subtypes of osteo?
central (medullary) and surface tumours
100
```
for the following types of OS, indicate if central=medullary or surface
1-small round cell
2-low grade central
3-parosteal
4-telangiectatatic
5-conventional
6-periosteal
7-high grade surface
```
```
1-central
2-central
3-surface
4-central
5-central
6-surface
7-surface
```
101
3 features of osteo on x-ray?
- mixed osteoblatsic+ oteolytic features
- cortical destruction adn expanstion into soft tissue
- periosteal reaction, eg: codman triagle, sunburst pattern
102
ewings is more ___ than osteo
osteolytic
103
5 ddx for osteosarcoma?
```
ewing sarcoma
mets
LCH
oseomyelitis
osteoblastoma
aneurysmal bone cyst
fibrous dysplasia
```
104
tx philosophy for osteo?
SURGICAL resection of all gross tumour adn chemo
105
timing of surgery in osteosarcoma?
after 10 weeks of neoadj chemo
106
advanrages of neoadj chemo in osteo?
- allows starting therapy more rapidly
- may faciliate limb salvage surgery
- provides histo response
107
chemo in osteo?
HD-Mtx, doxo, cisplatin= MAP
108
what type of osteo doesn't need chemo?
PAROSTEAL
109
what's teh diff between parosteal and periosteal osteosarcom?
parosteal: tends to occur in distal femur, is low grade, reqwuires resection only!
periosteal: tends to occur at prox tibia, is intemdiate grade, tx with resection +/-chemo
110
3 things you may see on imaging that indicate osteo improving?
- increased ossification
- sclerosis or calcification or border
- reduction in soft tissue mass
111
late effects in osteo?
cardiomyopathy (athracyclin)...in >20%
| cisplatin-indcued ototox
112
most common fusion in EWS?
EWSR-FLI1 fusion = t(11;22), 85%!
113
2nd most common EWS fusion?and another?
21;22...2;22
114
detect EWS transloc how?
RT PCR or FISH
115
EWS: more common in black or white pts?
white
116
presenation of EWS?
pain +/- palp mass
117
EWS: what part of bone involved?
diaphyses and central axis
118
most common site in EWS (3)
pelvis>femur>rib
119
top 3 met sites in EWS?
lung>bone>BM
120
what % of EWS have mets?
20%...same as osteo
121
EWS staging how?
```
plain films
MRI or CT of primary
CT chest
PET or bone scan
bilateral BMA/bx
```
122
assign stage how in EWS?
local vs mets
123
most imp prog featuers in EWS?
stage
124
in terms of prog, worst primary site in EWS?
pelvis
125
describe how tumour size and age are import in EWS prog
better if younger
| better if <8 cm
126
2 stains used in EWS?
CD99, vimentin
127
EWS can have differentaition or not...if does have diff, see what? (3)
rosettes
NSE
synaptophysin
128
what features of EWS are seen on x-ray?
lytic lesion with a wide zone of transition and periosteal reaction...see aggressive periosteal reactions like codman triangle, sunburst pattern or onion skin pattern
129
ddx for EWS on x-ray?
osteosarcoma, mets, LCH, osteomyelitis
130
tx philosophy for EWS?
surg, radiation, neoadj chemo, (SCT)...use surg when possible
131
tx in EWS based on what 2 things?
stage, site
132
rad dose in EWS?
36-50.4 Gy
133
chemo in EWS?
VDC IE= vcr, doxo, cyclo, ifos, etop
134
other htan VDC IE, what are other active agents in EWS?
topotecan, iriontecan, temozolomide
135
role of SCT in EWS?
possibly for high risk localized EWS
136
late effects in EWS?
Radiation: --> SMNs (carcinomas, sarcomas, 10%); path fractures/limb length discrepancy/femoral head necrosis..
Chemo: leukemias, cardiomyopathy from athracyclin, ifosfamide-induced nephrotoxicity = dose-dep proximal tubular damage
137
BRIEFLY describe bio of RMS vs NRSTS vs OS vs EWS
```
ERMS: aneuploidy, point mutations
ARMS: PAX-FOXO1 fusions
NRSTS: many tumour types
OS: chrom instability
EWS: TET-ETS fusion: EWSR1-FL1
```
138
most common sites for RMS/NRSTS/OS/EWS?
RMS: head, GU tract
NRSTS: extrems, trunk
OS: metaphyseal, distal femur adn prox tibia
EWS: diaphyseal or soft tissue, pelvis and central axis most common
139
risk based on what for RMS/NRSTS/OS/EWS?
RMS: stage, group, fusion status, histo
NRSTS: stage, group, tumour size, grade, histo
OS: stage, resectability
EWS: stage, site
140
histo of RMS/OS/EWS?
```
ERMS: spindle cell tumour
ARMS: SRBCT
RMS in general: myogenin, desmin +
OS: osteoid-producing malig cells
EWS: SRBCT, CD99+, may show neural diff
```
141
tx in RMS?
upfront surgery +/- delayed RT/surgery...systemic= VAC +/- VI
142
tx in NRSTS?
local: surgery (may be dleayed) +/- RT (may be pre-op)...systemic= +/- Doxo, ifos depending on chemo sens
143
tx in OS?
```
local= delaeyd surgery
syst= MAP
```
144
EWS tx?
```
local= delayed surgery adn/or RT
syst= VDC/IE
```
