NBl/Renal Flashcards by Kyle Mendonça

Hereditary NBl epi and mutations/syndromes

1-2% are familial

ALK
PHOX2B
Predispositions: Turner, NF1, BWS, LFS, Noonan

How well did you know this?

Not at all

Perfectly

NBl genetics (top 3 and others) and px significance

MYCN amplification (>4-10 copies by FISH; 20%)
- strongest px factor

Poor cytogenetics:
- LOH 1p36 (20-30%)
- del14q
- del11q
- gain 17q

DNA index
- near diploid/tetraploid is unfavourable
- hyperdiploid favourable

Others
- ATRX inactivating mutation: aggressive, poor px
- TERT (10%)
- ALK amplification (4%) or activating mutations (15%); traget crizotinib, lorlatinib
- rare: p53, PTPN11, Ras/MAPK

How well did you know this?

Not at all

Perfectly

NBl IHC

small round blue cells
NSE, synaptophysin, chromogranin A, PGP 9.5, GD2

How well did you know this?

Not at all

Perfectly

what proportion of NBl are HVA/VMA neg? MIBG nonavid?

10-15%
10% MIBG non-avid

How well did you know this?

Not at all

Perfectly

NBl path types (3)

Neuroblastoma: neuropil, more differentiated
Ganglioneuroblastoma: Schwannian background with random distribution of cells
Ganglioneuroma: little neuropil, individually scattered cells

How well did you know this?

Not at all

Perfectly

NBl Shimada Classification elements

age
stromal component
degree of differentiation
MKI

How well did you know this?

Not at all

Perfectly

Sites for NBl

40% adrenal
25% abdo
15% thoracic
5% cervical
5% pelvic sympathetic ganglia

How well did you know this?

Not at all

Perfectly

2 NBl paraneoplastic syndromes

OMAS
- opsoclonus: rapid chaotic eye movements
- ataxia
- myoclonus
- behaviour changes

VIP: intractible watery diarrhea

How well did you know this?

Not at all

Perfectly

NBl % metastatic, and sites

70% metastatic (lymph and hematog spread)

LN (1/3 local LN invasion)
bone
BM
skin
liver
Rare: CNS, lung

How well did you know this?

Not at all

Perfectly

OMAS epi, pathophys, tx

2-4% of NBl, 50-70% of OMAS has NBl

anti-NBl Ab cross-reactive with Purkinje cells

Tx: tx neuroblastoma, steroid, IVIG, ritux, cyclophosphamide

How well did you know this?

Not at all

Perfectly

NBl staging ix

CBCD, LDH
HVA/VMA
CT/MRI local/met sites
MIBG (10% nonavid)
bilat BMA/B (biopsy not required <6mo)

How well did you know this?

Not at all

Perfectly

NBl INRG staging

L1: localized in 1 body compartment, not involving vital structures
- isolated intraspinal extension
L2: ipsilateral locoregional with 1+ IDRF
M: distant mets
MS: mets (skin, liver, BM) <18mo

How well did you know this?

Not at all

Perfectly

NBl INRG px features

stage
age
histologic category
grade
MYCN
11q aberration
ploidy

How well did you know this?

Not at all

Perfectly

NBl RT indications

HR: tumor bed and residual metastatic disease at end of induction

LR/IR: organ/life-threatening symptoms

How well did you know this?

Not at all

Perfectly

NBl chemo

cyclo/topo
cisplat/etop
VDC

thio/cyclo
CEM: carbo, etop, melphalan

isotretinoin
dinutuximab

How well did you know this?

Not at all

Perfectly

NBl risk stratification

LR:
- L1
- MS <12mo fav bio

IR:
- L2 <18 mo or >18 mo fav histo
- M <12 mo or 12-18 fav bio
- MS <120 w sympto or unfav bio, or 12-18 mo fav bio

HR:
- MYCNA
- L2 18m-5y UH or <5y undiff/poorly diff
- M 12-18m unfav bio or >18 mo
- MS 12-18m unfav bio

unfav bio: UH, ploidy=1, SCA (-1p or -11q)

How well did you know this?

Not at all

Perfectly

Tx schema LR NBl

observe MS
Resection only
chemo or RT for organ/life threatening

How well did you know this?

Not at all

Perfectly

Tx schema IR NBl

2-8 cycles VDC
resection
RT for organ/life threatening

How well did you know this?

Not at all

Perfectly

Tx schema HR NBl

induction: chemo x5 (VDC, cisplat/etop, cyclo/topo)
consolidation:
- tandem HSC+SC (cyclo/thio, CEM)
- RT 21.6 to 1o bed and EOI mets
Maintenance: dinutuximab, isotretinoin

How well did you know this?

Not at all

Perfectly

ANBL0532 results

tandem HSCT 3yEFS 73%
single HSCT 3yEFS 54%

relapse NBl tx

131-I-MIBG
dinutuximab
ALK inhibition (crizotinib, lorlatinib)
topo, temozolamide

Do we screen for NBl

No
Quebec study
screening increased detection rate but not EFS/OS

NBl MS organs

skin, liver, BM

PHOX2B mutation associations

NBl
Hirschsprung
CCHS

NBl px by risk

5yEFS LR >90% IR >85% HR 63% (from ANBL0532)

OMAS px

long term neuro complications 20-60% - ataxia, tremor - dysarthria - decreased cognition - behavioural: hyperactivity, impulsivity, irritability

WT predisposition syndromes and risk

Denys Drash: >70% Perlman: >60% (DIS3L2 mutation, overgrowth) WAGR: 50% (often bilat - wilm, aniridia, GU, dev delay) BWS: 10% Other: Bohring-Opitz, FA, DICER1, LFS, Bloom, Sotos, Familial (WT1)

WT mutations (incl incidence) and cytogenetics

WT1 (15%) WT2 (30%) WTX (30%) CTNNB1 (15%) - WNT activating TP53 (5% of anaplastic) DICER1, DIS3L2, DROSHA - miRNA processing gene mutation 1q gain (30%, poor px) LOH 1p and 16q MYCN (13%)

WT 3 histologic components

blastemal: small round blue cells Epithelial stromal

nephrogenic rests intralobar vs perilobar

intralobar: WT1 mutation, WT (b/l), largely stromal Perilobar: BWS, blastema predominant, 50% develop WT

congenital mesoblastic nephroma: epi, genetics, tx

#1 renal tumor <3mo ETV6-NTRK3, t(12;15) Stage I/II: resection (OS 95%) Stage III/IV: chemo, larotrectinib (TRK inhibitor)

renal tumor with sickle cell trait, and hallmark IHC

renal medullary carcinoma loss of INI-1

RCC mutations

TFE3 gene Xp11.2 TFEB gene 6p21

WT px factors

stage >2yo histology (favourable vs anaplastic) cytogenetics (LOH 1p and 16q) lung nodule response predisposition syndrome tumor weight (<550g associated with VLR)

WT staging

I: localized, completely resected II: completely resected, extension outside kidney (capsule/sinus), LN neg III: residual abdo disease IV: residual disease outside abdo V: bilateral

WT staging

CT/MR abdo CXR/CT chest

WT chemo regimens

EE4A: VCR, actinomycin DD4a: VCR, actinomycin, doxo Reg M: VCR, actinomycin, doxo, cyclo, etop UH-1: VDC, carbo, etop UH-2: VDC, carbo, etop; VCR/irenotecan

WT EFS by risk stratification

4yEFS/OS VLR: 90/100 LR: 90/98 SR: 88/97 HR: 75/85

WT RT indications

III: flank; whole abdo if spill/rupture, peritoneal implant, + cytology IV: as above but + met sites whole lung RT if incomplete response at 6w anaplastic relapse

WT % anaplastic

WT common metastatic sites

lung, liver

BWS WT screening

AUS + AFP q3mo until age 4 then renal US q3mo until age 7

WT anaplasia features

nuclei 3+x diameter hyperchromasia nuclear atypia atypical mitoses often TP53

frequency of nephrogenic rests in WT

unilateral: 30-45% bilateral: 100%

WT heme association

acquired VWD, <10%

WT COG vs SIOP approach

COG: - resection - risk directed therapy SIOP: - neoadj VCR/actino +-doxo - resection

RCC predisposition syndrome

Von Hippel Lindau aut dom TS gene mutation 60% develop RCC

Renal tumors loss of INI-1

renal medullary carcinoma (sickle cell trait) malignant rhabdoid tumor of kidney

cystic nephroma predisposition

germline DICER mutation