Germ Cell Tumours and Retinoblastoma and Rare Tumours, ASPHO Flashcards
Retinoblastoma: presents when?
63% before age 2
what % of pts with retinoblastoma have the inherited form?
25%
non-heritable rb presents when? heritable?
30 months; 15 months
gene in rb?
RB1
what is the name for those with RB1 DELETIONS who also have dysmorphic features and intellectual disability?
13q deletion syndrome
1.5% of pts with retinoblastoma have ___ mutated INSTEAD of RB1
MYCN amplfication
pentrance in RB1 germline?
very high!
what percent of RB1 mutations are de novo (no fam hx)
75%
% of pts with uniteral RB who have germline mutation?
15
% of pts iwth germline mut who end up having unilateral RB
15
should do what for pts diagnoed with rb?
send to cancer genetics
do what if pt with a history of RB1 has a baby?
Exam screening at birth and every 4 weeks until genetic testing is done..if genetic testing positive, conitnue eye exams every 4 weeks
3 phys exam findings associated iwth rb?
leukocoria strabismus nsytagmus glaucoma perioribital cellultis buphtlamos proptosis + lymph nodes mets
work up for rb?
- 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!
ddx for rb? (3)
-congential cataracts
-persistent fetal vasculatory
-retinitis, toxoplasma
coats disease
etc
Rb staging 2 principles?
eye classification= group
how do we stage patient= stage
international rb classification system: based on what 4 things?:
- tumor size and burden
- tumor location in relationship to foveola and optic disc
- subretinal fluid and seeding
- vitreous seeding
describe group A Rb
small tumours away from the foveola and disc
group b rb?
all remaining tumours confined to the retina (within 3 mm of foveola or 1.5 mm of optic disc)
group c rb?
local subretinal fluid or seeding
group d rb?
diffuse subretinal fluid or seeding
group e rb?
presence of poor prog features
staging in rb- 2 key concepts?
intraocular or extra?…if intra, is it intra-retinal or extra?
stage 0 rb=?
get conservative treatment…no enucleation
stage 1-4 RB based on?
after enucleation
stage 1 rb?
complete resection, including histo
stage 2 rb?
microscopic residual tumor after resection
stage 3 rb?
regional extesnion= orbital or nodal
stage 4 rb?
mets
doctors needed to tx rb? priorities?
- multi-d team with onc, opth, rad onc
- priorities: cure-> eye salvage-> vision presevation
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?
problems with RT in RB?
- impact on orbital growth
- risk of second malig if heritable rb
intraocular rb tx: depends on?
group, potential for vision, laterality
ocular salvage highest for group _ and lowest for group _
a;e
in general ocular salvage not offered to whom?
group e and many group d–> get UPFRONT enucleation
decisions for pts with ___ rb is more conservative and decisions regarding ___ is usually ____
bilateral; enucleation; delayed
optionis for ocular salvage?
- chemoreduction
- focal treatments
- external-beam radiation thearpy
chemo used in rb?
- systemic: VCE= vcr, etop, carbopatin
- intra-arterial: melphalan, others= carboplatin, topotecan
- intra-vitreal for vitreous seeds: melphalan
rb focal tx is used to ___ repsonse __ ___; options?
consolidate; after chemo; small lesions can have cyrotherpay, thermotherapy…large can have brahcytherapy
when is external beam rads used in rb?
when other measures have failed
enucleation done when?
- upfront if group E and many group D (or alternative to ocular salvage)
- after failure of ocular salvage
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
do what if have high risk histo in rb?
- addiitonal staging studies
- risk-adpated therapy
what if you have no high risk histo in rb (intra-retinal)?
observation, <95% survival
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
ocular salvage rate in bilateral rb? survival?
90%, 90%
orbital disease in rb includes?
- overt orbital diseae
- trans-scleral diseae
- cut-end of optic nerve
orbital disease in rb associated iwth?
pre-auricular or cervical node disease
tx orbital disease how in rb?
- cispaltin-baed therpay
- enculeation
- radiation
sites of met in rb?
bone, bone marrow, liver, CNS
tx of extraorbital rb?
cisplatin based chemo
consoldiated with high dose chemo and auto transplant
what has a really bad prog in rb?
CNS disease
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!
secondary maligs in rb tend to be wehre?
head and neck
most common secondary malig in rb?
osteosarcoma>soft tissue sarcomas (esp leiomyosarcoma), melanoma, lung cancer….maligs most commonly inside rad field
trilateral rb=? develps when?
bilateral rb+ asynchromous midling intracranila tumour= pineoblastoma…35 months later
screen for trilateral rb how?
MRI q6 months until 5 yrs of age for kids with bilateral rb
GCT age distribution?
<3 yrs and adolescence
what types of GCTs are seen in <3 yrs?
extragonadal; testicular tumours
what germ cell tumours are seen in adolescence?
gonadal
2 main categories of peds GCTs?
seminomatous= germinomatous adn non-seminomatous= non-germinomatous
seminomatous/germinomatous GCTs include?
- seminoma (testes)
- dysgerminoma (ovary)
- germinoma (extra-gonadal)
non-seminomatous/non-germinomatous GCTs include? 4
Embryonal ca
yolk sac tumor
choriocarcnoma
teratoma
embryonal carcinoma: describe
undifferentiated cells that histologically resemble embryonal cells from teh blastocyst
describe YST
most common malig GCT in young kids; has components of embryonic and extraembryonic endoderm
describe choriocarcinoma
very rare, represents trophoblastic differentiaton
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
type 1 GCT: age group? usually presents as?
<4 years; teratoma or YST or a mixture of the two
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
common cytogeneic chages in type 1 GCTs?
gain of 1q, 11q, 20q, 22
loss of 1p, 6q, 16q
partial loss of genomic impriting
common cytogeni change sin type 2 GCTs?
chrom 12 amplification
X chrom amplification
loss of genomic imprinting
2 RFs for GCTs?
Klinefelter syndrome Swyer Sydnrome 46XY Turner Syndrome 47 XO Crypto-orchidism inguinal hernia hydrocele
ovarian GCT pres?
- abdo pain
- abdo/adnexal mass
- precocious puberty (granulosa cell tumour)
- amenorrhea and /or viritlization (sertoli-leydig tumor)
sacroccygeal GCT presents?
constipation, urinary retention
medisatinal GCT presents?
chest pain, resp distress
testic GCT presents/
irreg, non-tedner mass
work up for GCT?
CT/MRI primary
met work-up bone scan, chest ct
RF for metastatic disease in GCTs?
extragonadal tumours
GCTs: gonadal or extragonadal more common?
extra
children <15: gct more likely to be gonadal or extra?
extra
children 15y+: gct more likely to be gonadal or extra?
gonadal
which tumour associated with high AFP?
YST
which tumor associated with high b-hcg?
choriocarcinoma
afp and/or b-hcg could be weakly pos in waht?
embryonal ca
afp alone could be weakly pos in what?
immature teratoma
adult AFP levels (<10) normally reached when?
8-12 mos
AFP half life?
5-7 days
normal newborn AFP level?
40k
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
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
GCT staging #s?
1-4
stage 1 GCT?
commplete resection with nroamlization of tumour markers within expected half life
stage 4 GCT?
distant mets
stage 2 GCT?
microscopic residual disease: persistent marker elevation; LNs <2 cm
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
in testicular germ cell tumour, what surgical approach makes the pateint not eligible for stage 1 disease?
scrota biopsy! scrotum is contaiminated–> stage 2
boys with testicular GCTs should undergo?
radial orchiectomy…preferably inguinal (but can be scrotal)
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
ovarian GCT: high risk of what?
intraop spill
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
stage 1 GCT tx?
surgery only if copmlete resection adn tumour markers noramlized…may recur after surgery but salvage rates high
tx GCT if stage 2 or higher?
chemotherpy + surgery
…rads are NOT indicated in upfront tx of malig GCT
which GCTs are low risk?
stage 1 gonadal or immature teratoma…surg only
which GCTs are intermed risk?
stage 2-4 gonadal or stage stage 1-2 extragonadal…tx with surgery + chemo
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
chemo for GCTs?
peds= PEb= cisplat+etop+bleo…adolescents get adult tx= weekly belo (BEP)
GCTs: who gets 4 cycles of post-op chemo?
stage 1 extragonadal and stage 2
which GCT patinets get 4 cycles chemo THEN surgery?
stage 3-4
sacrococcygeal gct: most common path? tx how? outcomes?
teratoma, immature teratoma, YST…stage 1: surgery only…higher stage= surg+ chemo…outcomes excellent
late effects for GCT?
chemo–> hearing loss, neuropathy, therapy-related AML, cardiotox, renal tox, pulm toxi
tumor/surgery: bladder and bowel dysfucntion
ovarian sex-cord tumours: egs?
juvenile granulosa cell tumour, sertoli-leydig cell tumor
approx 50% of pts with a sertoli leydig cell tumour and gynandroblastoma have a germline mutation in what?
dicer1
tumour associated with peutz-jegher syndrome?
sec cord tumour with annualar tubules
lab tests for ovarian sex cord tumours?
inhibin, estradiol, testerstoner, ALP, imaging
risk factors for melanoma? 4
- giant congential melanocytic nevi
- immunosuppression
- dysplastic nevi
- exposure to UV, red hair, blue eyes
major mutations in conventional melanoma?
BRAFV600E, PTEN, TRET
clinical presenttion of melanoma?
ABCDE asymmetry border color change diameter evolution over time
when do you need LN eval in melanoma?
lesion at least 1 mm
<1 mm and high mitotic rate
<1 mm and ulcerated
tx options in melanoma?
surgery= tx of choice
-checkpoint inhibitors
BRAF/MEK inhibitors
risk factors for thyroid ca?
- ionizing radiation
- MEN2= RET mutations
- DICER1 syndrome
types iof thyroid ca in children adn teens from most to least common?
differentiated thyroid carcinoma>medullary>anaplastic
medullary ca tends to occur in ___ pts
younger (vs. differnetiated in adolescents)
eval for thyroid ca?
US of neck fine needle aspiration bx CT or MRI of primary CT chest labs: thyroglobulin (differentaied), calcitonin (medullary)
tx for medullary ca?
- genetic counseling
- ppx thryorodiectmy if MEN 2 syndrome
- RET inhibitors
nasopharyngeal carcinoma: more common in what populatioN?
- black children adn adoelscents
- endemic in SE Asia, north africa, adn mediterranean
2 risk factors for nasophayngeal ca?
- EBV infeciton
- salted fish
- HLA A2 adn HLA BSin2
eval for nasopharyngeal ca?
- nasopharyngeal scope
- MRI head and neck
- CT chest
- PET
- EBV serology and EBV DNA testing
- bx
2 ddx for nasophayrngeal ca?
RMS
NUT-midline carcinoma
nasopharyngeal ca: tx?
3 cycles x cisplatin + 5FU then radiation
late effects of nasopharyngeal ca?
hearing loss dry mouth dental problems trismus hypot4 panhypopit
pleuropulmonary blastoma associated with what gene mut?
dicer1
pleuropulmonary blastoma : who does worst?
solid tumour (not cystic), older
pleuropulmonary blastoma : tx?
type 1= cystic…surgery only…2 and 3: radical surgery adn sarcoma chemo
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
