Germ Cell Tumours and Retinoblastoma and Rare Tumours, ASPHO Flashcards
1
Q
Retinoblastoma: presents when?
A
63% before age 2
2
Q
what % of pts with retinoblastoma have the inherited form?
A
25%
3
Q
non-heritable rb presents when? heritable?
A
30 months; 15 months
4
Q
gene in rb?
A
RB1
5
Q
what is the name for those with RB1 DELETIONS who also have dysmorphic features and intellectual disability?
A
13q deletion syndrome
6
Q
1.5% of pts with retinoblastoma have ___ mutated INSTEAD of RB1
A
MYCN amplfication
7
Q
pentrance in RB1 germline?
A
very high!
8
Q
what percent of RB1 mutations are de novo (no fam hx)
A
75%
9
Q
% of pts with uniteral RB who have germline mutation?
A
15
10
Q
% of pts iwth germline mut who end up having unilateral RB
A
15
11
Q
should do what for pts diagnoed with rb?
A
send to cancer genetics
12
Q
do what if pt with a history of RB1 has a baby?
A
Exam screening at birth and every 4 weeks until genetic testing is done..if genetic testing positive, conitnue eye exams every 4 weeks
13
Q
3 phys exam findings associated iwth rb?
A
leukocoria strabismus nsytagmus glaucoma perioribital cellultis buphtlamos proptosis + lymph nodes mets
14
Q
work up for rb?
A
- eye exam under anestehsia of both eyes
- ocular ultrasound
- MRI orbits + brain (look at optic nerve+ rule out trilaternal RB)
- if advanced diseae, high risk histo after enculeation or extraoccular rb: bone sca BMA/bx and CSF cytology
- genetic counseling!
15
Q
ddx for rb? (3)
A
-congential cataracts
-persistent fetal vasculatory
-retinitis, toxoplasma
coats disease
etc
16
Q
Rb staging 2 principles?
A
eye classification= group
how do we stage patient= stage
17
Q
international rb classification system: based on what 4 things?:
A
- tumor size and burden
- tumor location in relationship to foveola and optic disc
- subretinal fluid and seeding
- vitreous seeding
18
Q
describe group A Rb
A
small tumours away from the foveola and disc
19
Q
group b rb?
A
all remaining tumours confined to the retina (within 3 mm of foveola or 1.5 mm of optic disc)
20
Q
group c rb?
A
local subretinal fluid or seeding
21
Q
group d rb?
A
diffuse subretinal fluid or seeding
22
Q
group e rb?
A
presence of poor prog features
23
Q
staging in rb- 2 key concepts?
A
intraocular or extra?…if intra, is it intra-retinal or extra?
24
Q
stage 0 rb=?
A
get conservative treatment…no enucleation
25
stage 1-4 RB based on?
after enucleation
26
stage 1 rb?
complete resection, including histo
27
stage 2 rb?
microscopic residual tumor after resection
28
stage 3 rb?
regional extesnion= orbital or nodal
29
stage 4 rb?
mets
30
doctors needed to tx rb? priorities?
- multi-d team with onc, opth, rad onc
| - priorities: cure-> eye salvage-> vision presevation
31
major concepts in tx fo rb?
- ocular presevation vs enucleation
- risk adapted therapies depnding on if intraocular or orbital or extra-orbital
- unilat or bilat
- can you avoid or delay RT for ocular salvage?
32
problems with RT in RB?
- impact on orbital growth
| - risk of second malig if heritable rb
33
intraocular rb tx: depends on?
group, potential for vision, laterality
34
ocular salvage highest for group _ and lowest for group _
a;e
35
in general ocular salvage not offered to whom?
group e and many group d--> get UPFRONT enucleation
36
decisions for pts with ___ rb is more conservative and decisions regarding ___ is usually ____
bilateral; enucleation; delayed
37
optionis for ocular salvage?
- chemoreduction
- focal treatments
- external-beam radiation thearpy
38
chemo used in rb?
- systemic: VCE= vcr, etop, carbopatin
- intra-arterial: melphalan, others= carboplatin, topotecan
- intra-vitreal for vitreous seeds: melphalan
39
rb focal tx is used to ___ repsonse __ ___; options?
consolidate; after chemo; small lesions can have cyrotherpay, thermotherapy...large can have brahcytherapy
40
when is external beam rads used in rb?
when other measures have failed
41
enucleation done when?
- upfront if group E and many group D (or alternative to ocular salvage)
- after failure of ocular salvage
42
give 3 egs of high risk histo in Rb
```
iris infiltration
ciliary body infiltration
scleral invasion
optic nerve involvement
ant chamber seeding
massive choroidal replacmeent >3 mm
```
43
do what if have high risk histo in rb?
- addiitonal staging studies
| - risk-adpated therapy
44
what if you have no high risk histo in rb (intra-retinal)?
observation, <95% survival
45
what if you do have high risk histo?
- bone scan, bm, csf
- if neg, vcr/etop/cbp x 6...>95% survival
- if pos, tx for mets
46
ocular salvage rate in bilateral rb? survival?
90%, 90%
47
orbital disease in rb includes?
- overt orbital diseae
- trans-scleral diseae
- + cut-end of optic nerve
48
orbital disease in rb associated iwth?
pre-auricular or cervical node disease
49
tx orbital disease how in rb?
- cispaltin-baed therpay
- enculeation
- radiation
50
sites of met in rb?
bone, bone marrow, liver, CNS
51
tx of extraorbital rb?
cisplatin based chemo
| consoldiated with high dose chemo and auto transplant
52
what has a really bad prog in rb?
CNS disease
53
late effects in rb?
- hearing (carboplat)
- therapy related AML
- cardiotox
- facial deformity from rads
- secondary malig from radiation
- decreased vision from tumour and tx
- retinal vasculopaty from tumour, rads, intra-art chemo
- dry eye from rt
- secondary malignancies! from rads!
54
secondary maligs in rb tend to be wehre?
head and neck
55
most common secondary malig in rb?
osteosarcoma>soft tissue sarcomas (esp leiomyosarcoma), melanoma, lung cancer....maligs most commonly inside rad field
56
trilateral rb=? develps when?
bilateral rb+ asynchromous midling intracranila tumour= pineoblastoma...35 months later
57
screen for trilateral rb how?
MRI q6 months until 5 yrs of age for kids with bilateral rb
58
GCT age distribution?
<3 yrs and adolescence
59
what types of GCTs are seen in <3 yrs?
extragonadal; testicular tumours
60
what germ cell tumours are seen in adolescence?
gonadal
61
2 main categories of peds GCTs?
seminomatous= germinomatous adn non-seminomatous= non-germinomatous
62
seminomatous/germinomatous GCTs include?
- seminoma (testes)
- dysgerminoma (ovary)
- germinoma (extra-gonadal)
63
non-seminomatous/non-germinomatous GCTs include? 4
Embryonal ca
yolk sac tumor
choriocarcnoma
teratoma
64
embryonal carcinoma: describe
undifferentiated cells that histologically resemble embryonal cells from teh blastocyst
65
describe YST
most common malig GCT in young kids; has components of embryonic and extraembryonic endoderm
66
describe choriocarcinoma
very rare, represents trophoblastic differentiaton
67
describe teratoma:
disordered mixture of differentiated cell types from all 3 soamtic cell layers (ectoderm, endoderm, mesoderm)...if a component acquires neuronal differentation, it becomes immautre teratoma
68
type 1 GCT: age group? usually presents as?
<4 years; teratoma or YST or a mixture of the two
69
type 2 GCT: age group? often associated with?
puberty-young adulthood; presumptive precursor lesion known as germ cell neoplasia in situ (GNCIS), usually seen in normal tissue adjacent to tumour
70
common cytogeneic chages in type 1 GCTs?
gain of 1q, 11q, 20q, 22
loss of 1p, 6q, 16q
partial loss of genomic impriting
71
common cytogeni change sin type 2 GCTs?
chrom 12 amplification
X chrom amplification
loss of genomic imprinting
72
2 RFs for GCTs?
```
Klinefelter syndrome
Swyer Sydnrome 46XY
Turner Syndrome 47 XO
Crypto-orchidism
inguinal hernia
hydrocele
```
73
ovarian GCT pres?
- abdo pain
- abdo/adnexal mass
- precocious puberty (granulosa cell tumour)
- amenorrhea and /or viritlization (sertoli-leydig tumor)
74
sacroccygeal GCT presents?
constipation, urinary retention
75
medisatinal GCT presents?
chest pain, resp distress
76
testic GCT presents/
irreg, non-tedner mass
77
work up for GCT?
CT/MRI primary
| met work-up bone scan, chest ct
78
RF for metastatic disease in GCTs?
extragonadal tumours
79
GCTs: gonadal or extragonadal more common?
extra
80
children <15: gct more likely to be gonadal or extra?
extra
81
children 15y+: gct more likely to be gonadal or extra?
gonadal
82
which tumour associated with high AFP?
YST
83
which tumor associated with high b-hcg?
choriocarcinoma
84
afp and/or b-hcg could be weakly pos in waht?
embryonal ca
85
afp alone could be weakly pos in what?
immature teratoma
86
adult AFP levels (<10) normally reached when?
8-12 mos
87
AFP half life?
5-7 days
88
normal newborn AFP level?
40k
89
reaosns why pt with YST may continue to have high AFP on tx?
- not responding
- jumps with Tumor lysis
- altered liver function, eg viral hepatitis
- other malig: eg hepatoblastoma
90
reason for why pt with choriocarcinoma might continue to have high beta-hcg on tx?
- not responding
- cross reaction with LH due to iatrogenic hypogonadism
- multiple myeloma
91
GCT staging #s?
1-4
92
stage 1 GCT?
commplete resection with nroamlization of tumour markers within expected half life
93
stage 4 GCT?
distant mets
94
stage 2 GCT?
microscopic residual disease: persistent marker elevation; LNs <2 cm
95
stage 3 GCT?
gross residual disease; LNs 2 cm+ (or 1-2 cm that fail to resolve within 4-6 weeks), no extra-abdo or visceral mets
96
in testicular germ cell tumour, what surgical approach makes the pateint not eligible for stage 1 disease?
scrota biopsy! scrotum is contaiminated--> stage 2
97
boys with testicular GCTs should undergo?
radial orchiectomy...preferably inguinal (but can be scrotal)
98
which LNs need to be assessed in testicular tumours for staging? how?
retroperitoneal; by CT...<1 cm= negative...2 cm+ = metastatic disease...in btween, f/u/explore options
99
ovarian GCT: high risk of what?
intraop spill
100
what's required in surgical staging of ovarian tumours?
- cytological assessment of peritoneal fluid
- inspirection adn bx of any abnormal appearing peritoneal surface LNs, omentum, contraleteral ovary
- removal of the primary tumour without violation fo the tumour capsule
101
stage 1 GCT tx?
surgery only if copmlete resection adn tumour markers noramlized...may recur after surgery but salvage rates high
102
tx GCT if stage 2 or higher?
chemotherpy + surgery
| ...rads are NOT indicated in upfront tx of malig GCT
103
which GCTs are low risk?
stage 1 gonadal or immature teratoma...surg only
104
which GCTs are intermed risk?
stage 2-4 gonadal or stage stage 1-2 extragonadal...tx with surgery + chemo
105
which GCTs are high risk? who has better prog iwthin this group? wrose?
advnced extragonadal tumours= stage 3-4 extragonadal...older age= post-pubertal = most predictive of poor outcome...better= young pts with sacrococcygeal tumours...worse= older pts with mediastinal tumours
106
chemo for GCTs?
peds= PEb= cisplat+etop+bleo...adolescents get adult tx= weekly belo (BEP)
107
GCTs: who gets 4 cycles of post-op chemo?
stage 1 extragonadal and stage 2
108
which GCT patinets get 4 cycles chemo THEN surgery?
stage 3-4
109
sacrococcygeal gct: most common path? tx how? outcomes?
teratoma, immature teratoma, YST...stage 1: surgery only...higher stage= surg+ chemo...outcomes excellent
110
late effects for GCT?
chemo--> hearing loss, neuropathy, therapy-related AML, cardiotox, renal tox, pulm toxi
tumor/surgery: bladder and bowel dysfucntion
111
ovarian sex-cord tumours: egs?
juvenile granulosa cell tumour, sertoli-leydig cell tumor
112
approx 50% of pts with a sertoli leydig cell tumour and gynandroblastoma have a germline mutation in what?
dicer1
113
tumour associated with peutz-jegher syndrome?
sec cord tumour with annualar tubules
114
lab tests for ovarian sex cord tumours?
inhibin, estradiol, testerstoner, ALP, imaging
115
risk factors for melanoma? 4
- giant congential melanocytic nevi
- immunosuppression
- dysplastic nevi
- exposure to UV, red hair, blue eyes
116
major mutations in conventional melanoma?
BRAFV600E, PTEN, TRET
117
clinical presenttion of melanoma?
```
ABCDE
asymmetry
border
color change
diameter
evolution over time
```
118
when do you need LN eval in melanoma?
lesion at least 1 mm
<1 mm and high mitotic rate
<1 mm and ulcerated
119
tx options in melanoma?
surgery= tx of choice
-checkpoint inhibitors
BRAF/MEK inhibitors
120
risk factors for thyroid ca?
- ionizing radiation
- MEN2= RET mutations
- DICER1 syndrome
121
types iof thyroid ca in children adn teens from most to least common?
differentiated thyroid carcinoma>medullary>anaplastic
122
medullary ca tends to occur in ___ pts
younger (vs. differnetiated in adolescents)
123
eval for thyroid ca?
```
US of neck
fine needle aspiration bx
CT or MRI of primary
CT chest
labs: thyroglobulin (differentaied), calcitonin (medullary)
```
124
tx for medullary ca?
- genetic counseling
- ppx thryorodiectmy if MEN 2 syndrome
- RET inhibitors
125
nasopharyngeal carcinoma: more common in what populatioN?
- black children adn adoelscents
| - endemic in SE Asia, north africa, adn mediterranean
126
2 risk factors for nasophayngeal ca?
- EBV infeciton
- salted fish
- HLA A2 adn HLA BSin2
127
eval for nasopharyngeal ca?
- nasopharyngeal scope
- MRI head and neck
- CT chest
- PET
- EBV serology and EBV DNA testing
- bx
128
2 ddx for nasophayrngeal ca?
RMS
| NUT-midline carcinoma
129
nasopharyngeal ca: tx?
3 cycles x cisplatin + 5FU then radiation
130
late effects of nasopharyngeal ca?
```
hearing loss
dry mouth
dental problems
trismus
hypot4
panhypopit
```
131
pleuropulmonary blastoma associated with what gene mut?
dicer1
132
pleuropulmonary blastoma : who does worst?
solid tumour (not cystic), older
133
pleuropulmonary blastoma : tx?
type 1= cystic...surgery only...2 and 3: radical surgery adn sarcoma chemo
134
adrenocortical ca: almost always associated iwth what? other syndromes? tx?
TP53 mutation...BWS, hemihypertrophy, NF1, MEN1....surgery!!!!! if not completely resected, mitotane and cisplatin-based chemo
