Wilms Tumour, ASPHO Flashcards
give 4 peds renal tumours other than wilms
RCC malignant rhabdoid clear cell sarcoma of kidney congenital mesoblastic nephroma cystic nephhoma
neprhogenic rests
= persistentce of foci of embryonic renal tissue after normal nephrogenesis
which neprhogenic rests are associated with increased risk fo progression to wilms? associated with waht mutations?
intralobar
Wt1
which neprhogenic rests are associatd with sporadic tumours? associated with what else?
perilobar;
BWS
hemihypertrophy
dysregulation at 11 p15
neprhoblastomatosis=? associated with?
multilobar or diffuse nephrogenic rests; high risk of developing WT
muts taht are most frequent in wilms? 3
WT1
WT2
WTX
where is WT1 located? function?
11p13; trx factor, tumor suppressor
WT1 mutation seen in which syndromes?
WAGR
Denys-Drash
Frasier syndrome
features seen in WT1 mutations?
- bilateral wilms
- unilateral wilms with nephrogenic rests at contralateral kidney
- stromal and rhabdomyomatous differentation
WT2 associated syndromes?
Beckwith-Wiedemann
other than WT1/2/X, 2 other genes that can be associated with wilms?
DICER1, TP53
TP53 found in what type of wilms?
anaplastic
5 features of BWS?
exomphalus *omphalocele *macroglossia *macrosomia *neonatal hypoglycemia *viscerogmegaly *hemihyperplasia cancer predispo high IGF2 expression
WAGR features?
wilms, aniridia, GU abN, range of intellectual disability
Denys-drash features?
progressive renal disease, pseudohermaphrodism
fraiser syndrome features?
focal segmental glomerulosclerosis, male gonadal dysgenesis
other than BWS, wagr, frasier, denys-drash, 2 others asscoiated with wt?
perlman bohring-opitz syndrome fanconi anemia dicer1 LFS familial WT
wilms affects M or F more?
F
median prseentation for WT?
3
% of WT= favourable histo?
95%, vs. 5% anaplastic
Risk strat factors for wilms? 5
- histo
- stage
- age
- tumour wt
- tumour genetic (LOH 1p, LOH 16q, gain 1q, 11p15 LOH)
- CPS
- resolution of pulm lesions
triphasic components of favourable histo in Wilms?
- epithelial
- blastemal
- stromal
___ predominant often seen with ___ risk pathology
blastemal; higher
SIOP psot chemo histo risk assessmetn in wilms?
-LR: completely necrotic tumour, cystic partially differenaited tumour
IR: epitehlail, stroma, mixed or regressive type, focal anaplasia
HR: bastemal predominant, diffuse anaplasia
Describe stage 1 wilms
-tumour limited to kidney and completely resected, capsule in tact, LNs are neg
stage 2 wilms?
confined to renal fossa, LNs are neg, cmpletely resected, can ext only into renal sinus/capsule
stage 3 wilms?
microscopic or gross residual disease in abdo after surgery (Non-hematogenous spread)…also if tumour removed if more than one piece (eg tumour thrombus in renal vein removed separately)
stage 4 wilms?
hematogenous sprad to lungs, liver, bone, brain…or LNs outside of abdo
stage 5 wilms?
bilateral, 5-10%
wilms pres?
- abdo mass
- abdo pain
- hematuria
- htn
- acquired vwd
- fever
- anemia
work up for wt?
US
CT/MRI
CT chest
feature seen on abdo imaging in WT?
“claw sign”= normal kidney surrounding tumour
survival rate in wt?
> 90%
COG advocates for upfront nephrectomy whenever possible: PROS of this?
BR HS…“BRian mcmahon High School”
- immediate removal of bulk disease
- establish histo dx and appropr therapy
- full upfront tumour staging
- use of tumour bio to guide therapy
if cannot do upfront nephrectomy, do what?
BIOPSY! core or open needle…NOT fine needle
SIOP recs neoadj chemo instead, why?
based on premise taht vast majority of peds renal tumours= WT adn all localzied tumours get VA (vs. VAD for met disease)
advantages of neoadj chemo in wilms?
“RCT”
- lower surgical Complication rate
- less Rupture, could –> downstaging
- ability to base Therapy off response to chemo with post-chemo histo risk stratification system
does SIOP advocate for bx?
NO…due to risk of tumour spread thru biopsy
SIOP recs upfront nephrectomy for which population?
<1 year and >10 yrs of age…less likely to have FH wilms
Very LR criteria in AREN0532?
stage 1, FH WT
neg LNs
tumour wt <550 g
pt < 2 yrs
…can’t have CPS, multicentric tumour or contralateral Nephrogenic rests
very low risk WT: manage?
obsrvation alone unless LOH 11 p15, LOI 11p15 (these pts relapsed)–> EFS 89.7%, 100% OS
AREN0532: what happened to relapsed cases?
- relapsed EARLY (4 months)
- got DD4A and radiation, which worked well
conclusion of AREN0532?
observation after surgery is recommended for Very low risk….but EE4A with vcr and actinomycin= reasonable alternative
which pts are LR wilms?
stage 1 adn 2 wtih favourable histo…can’t have LOH at 1 p or 16q
EFS and OS of LR wilms?
OS 98.4%, EFS 91.4%
standard of care for LR wilms pts?
EE4A: 19 weeks x vcr, actinomycin after upfront necphrectomy
stage 3 pts treated how on AREN0532?
DD4A= 25 weeks x vcr, actinomycin, doxorubicin with flank/whole abdo rads…this study removed those with LOH at 1p, 16 ro anaplasia…EFS 88%, OS 97%
if your LNs are negative adn no LOH, what happens?
better survival
factors associated with relapse in WT?
+ LNs, LOH at 1p or 16q
stage 4 tx for WT as per AREN0533?
if lung disease: Vcr, Actino, Doxo…assessment at 6 weeks–> complete response: continue…if incomplete: moved to Remigen M with cyclo/etop and whole lung XRT
AREN0533 outcomes for stage 4 wilms with slow response for pulm nodules?
EFS 88.5%, OS 95.4% (much better than DD4a with lung rads)…regimen M = best for pateints iwth slow incomplete response of pulmonary lesions…associated with increased tox though adn poor salvage after relapse
AREN0533: outcomes for stage 4 with complete response to pulm nodules?
got DD4a, NO lung rads–> EFS 79.5%, OS 96.1%…recurrences mostly in the lung…similar results to NWTS with lung rad results….allowed many pateints to be spared from rads! however, those who had 1q gain did MUCH worse when they looked at that…a reduction of therapy (no lung RT) is not recommended for those with 1q gain
wt stage 4: slow incomplete response and/or 1q gain: give what?
regimen M
WT stage 4 with mets OTHER than lung: DD4A x 6 weeks–> regimen M, rads to all met sites: outcomes?
no improvvement vs those who just got dd4a on NWTS…needs mroe studying
pts with LOH 1p AND 16q…if combined, they had what?
markedly lower EFS
ARENO532 and 33 offered what?
offered intesifcation of therapy…for stage 1-2, vcr, actino + DOXO….for 3-4: got regimen 4= vcr, actino, doxo + 4x Cyclo/etop, plus rad
intensifing thearpy for Stage 1-2 with LOH 1p and 16q on AREN0533 did what?
increased EFS and OS but not signif
intensifing thearpy for Stage 3-4 with LOH 1p and 16q on AREN0533 did what?
improved EFS adn OS, was signficant
conclusion for LOH 1p + 16q:
for stage 3-4, intesnification to regimen M should be standard of care
anaplastic WT associated with?
higher stage
older age
anaplasia in WT can be focal or diffuse. with intesnifiation or regimens, OS has __ __
trended up (but is still low, esp for stage 4)
most common reanl tumour in adults?
rcc
most common renal tumour in kids>15?
RCC
RCC management?
surgery= most affective! need LN dissection.
cheo, rads don’t work too well
RCC management?
-surgery= most affective! need LN dissection.
chemo, rads don’t work too well
-systemic: VEGF tyrosine kinase inhibitor (AXITINIB), mTOR inhbiition, anti-PDL1 antibodies (NIVOLUMAB)
mean age pres rCC?
12 yrs
most common histo subtype of RCC?
TFE3 or TFEB translocation associated
CPS associated with RCC?
- von Hippel-Lindau
- tuberous sclerosis
- familial RCC
- herediatary leiomyomatosis and RCC
vHL inheritance?
AD
renal medullary carcinoma seen in which pts? histo?
sickle cell trait…loss of INI-1= characteristic…very aggressive tumour with poor prog
most common sutbype of RCC?
- translocation-associated RCC, accountsfor 1/2 of RCC in kids
- Xp11.2 translcation, strong nuclear exprsesion of TFE3 or TFEb
clear cell sarcoma of kidney: tends to met or no?
tends to met! bone, brain, soft tissue
clear cell sarcoma of kidney : age? molec findings? gender?
- median age: 3
- BCOR ITD’s in 80%!
- more in males
AREN0321: tx for CCS of the kidney?
stage 1: regimen I= vcr, doxo, cyclo, etop…NO rads
stage 2-3: same as 1, with rads
stage 4: UH-1 therapy: vcr, doxo, cyclophos, etop
what about relapse in CCSK?
typically LATE relapses, including to bone and brain
malignant rhabdoid tumour of the kidney seen in what age?
<1 year mostly
malignant rhabdoid tumour of the kidney associated with what on histo?
lack of INI1 expression!
mets in malig rhabdoid tumour?
yes, often to lungs, abdo, LNs, liver, bone brain at dx
malig rhaboid tumour can also presentat same time with what?
AT/RT
prog of malignant rhabdoid tumour?
very poor
tx malig rhabdoid tumour how as per AREN0321?
vcr/irinotecan didn’t work–> UH-1 with VDC/CCyE
vcr, doxo, cyclophos, carboplat, etop
congenital mesoblastic nephroma: almost exclusively detected when?
first year of life
most prevalent renal tumour in first 3 months of life?
congenital mesoblastic nephroma
clinical pres in CMN?
htn
elevated ca (can continue after resection)
elevated renin
CMN: histo can be classic and cellular and mixed…cellular type associated with?
t(12;15)= ETV6-NTRK3..which is also found in infantile fibrosarcoma
CMN outcomes?
excellent with surgery only.
what drug is being considered for metastatic CMN with 12;15 transloc
larotrectinib (TRK inhibitor)
cystic nephroma presents when?
2.3 years
cystic neprhoma associated with what muts?
DICER1! sent to Cancer gen!
cystic nephroma: tx how?
surgery only
