Hepatic tumours, ASPHO Flashcards
liver tumours = what percent of tumours in kids?
1%
median age of liver tumours in kids?
19 mos…80% under 15 yrs
hepatoblastoma = ___ most common intra-abdo tumour in kids
3rd
incidence of hepatoblastoma?
11.2 per million
91% of hepatoblastoma cases occur before what age?
5
liver malig in adolescents?
hepatocellular carcinoma; >95% of liver tumours in people over age 15
hepatocellular ca is more common where? why?
asia and africa; endemic hep b
DDX for benign liver tumours in infancy? (3)
hemangioendothelioma, mesenchymal hamartoma, teratoma
ddx for malig liver tumours in infants? (4)
HEPATOBLASTOMA, rhabdoid tumour, yolk sac tumour, LCH, M7 AML, disseminated NBL
ddx of benign liver tumours age 1-3?
hemangioendothelioma, mesenchymal harmatoma
ddx for malig liver tumours age 1-3?
HBL, rhabdomyosarcoma, inflammatory myofibroblastic tumour
ddx for benign liver tumour age 3-10? (1)
perivascular epithelioid cell tumours (PE-comas)
ddx for malig liver tumours age 3-10? (4)
hepatocellular carcinoma, embryonal sarcoma, angiosarcoma, cholangiocarcinoma, endocrine (gastrin) carcinoma
ddx for benign liver tumours age 10-16? (3)
adenoma, focal nodular hyperplasia, biliary cystadenoma
ddx for malig liver tumours in age 10-16? (3)
conventional and fibrolamellar hepatocellular carcinoma, hodgkin lymphoma, leiomyosarcoma
describe bio of HBL
- activation of WNT pathway, including activating mutations of CTNNB1 (or APC) in >90% of cases; upregulation of Wnt signaling pathway genes, like DKK1, APCDD1, AXIN2, CCND1
- NFE2L2 (NRF2) mutation in 5%
- Other alterations= mutations in epigenetic modifiers like MLL2, ARID1a or variable expression of Lin-28, AFP, Notch
give 5 congenital risk factors for HBL
“Genetics For Hepatic Glitches at Birth”
- familial polyposis
- Gardner syndrome
- Beckwith-Wiedemann Syndrome
- Hemihypertrophy
- Glycogen storage disease
Give 5 enviornemntal RFs for HBL
“Other Features Predisposing GI Malignant Conditions”
- Fetal alcohol syndrome
- Prematurity and LBW
- Oral contraceptives
- Oral gonadotropins
- Parental exposure to metal/petroleum/paint
BWS: 1) involves what chrom? 2)incidence?
3) give 5 features
1) 11p15.5
2) 1 in 10k
3) abdo wall defects, macroglossia, GU malformations, organomegaly, hyperinsulinemic hypoglycemia
BWS: malig risk in first decade of life?
8-10%
Give 5 tumours associated with BWS and the incidence of the 2 most common
Wilms: 43% HBL: 20% Adrenocortical tumours (7%) NBL RMS Pancreatoblastoma Leukemia
Hemihypertrophy incidence?
1 in 86k
Hemihypertrophy can be ISOLATED or associated with which syndromes (give 3)?
BWS
Klippel-Trenaunay-Weber
McCune-Albright Syndrome
Malignancy risk with hemihypertrophy?…give 3 tumours that are associated
5%
Wilms, HBL, adrenocortical tumours
HBL: see disprorotionate increase in HBL with BW< what?
2500 g
which germline mutation is associated with familial adenomatous polyposis and gardner syndrome?
APC mutation
other than increased risk of HBL, 3 features/tumours associated with FAP?
gastric tumours, desmoids, congenital hypertrophy of retinal pigment epithelium
feature of gardner syndrome?
osteomas
what % of HBL cases have FAP syndrome?
5-10%! important to do fam hx!…APC testing recommended in sporadic HBL!
if no FAP, what’s risk of HBL? If FAP?
1 in 100k…1 in 250
presentation of HBL?
-asymptomatic abdo mass
-wt loss, anorexia, emesis, abdo pain (advanced disease)
=elevated AFP in 80-90%
-distant mostly mets in 20% (mostly to lung)
-thrombocytosis (HB cells secrete IL-1B–> induces fibroblasts and endothelial cells to produce IL-6–> hepatocyte GF secretion adn thrombopoietin secretion
-htn (rare) if secrete renin
-precocious puberty (rare) if secrete beta-hcg
where does HBL met?
LUNG=#1
intraperitoneal, LN, brain, tumour thrombus
evaluation for HBL?
- US with doppler’
- CT C/A/P and MRI
- AFP
- biopsy
half life of AFP?
5-7 days
if doing needle biopsy for HBL, what’s recommended?
MULTIPLE passes because multiple histologic types can be present and intermingled
Types of hbl histo and incidence?
Epithelial 85-90%
pure fetal histology 7-10%
small cell undifferentiated histo 5%
epithelial histo in HBL includes what?
fetal + embryonal
prog in pure fetal histo for HBL?
excellent outcome! if stage 1, may only need surgery for cure
small cell undifferentiated histo in HBL: outcome?
very poor
small cell undifferentiated histo in HBL: AFP tends to be high or low?
LOW…<100 ng/ml
small cell undifferentiated histo associated with what genetic change?
22q11 aberations (hSNF5/INI1 gene)= malig rhabdoid…get NEGATIVE INI1 immunostain
AFP high in what % of HBL? what % of HCC?
80-90% of HBL
60-70% of HCC
Other than HBL and HCC, AFP also high in what 2 tumours? also mildly elevated in what 2 benign tumours?
germ cell tumours (liver primary), pancreatoblastoma….infantile hemangioendothelioma, mesenchymal hamartoma
in what variant of HCC is AFP low or normal?
fibrolamellar variant
In HBL, LOW AFP (<100 ng/ml) is associated with ___ prog and wiht ___ ___ ___ histo
worse; small cell undifferentiated
surgical criteria for staging HBL?
1= Complete resection 2= microscopic margins 3= gross residual or nodal involvement 4= met disease
SIOPEL staging based on what? (for preop chemo in all pts)
radiographic criteria; PRETreatment EXTent of disease
Describe PRETEXT staging
PRETEXT 1: 3 contiguous sectors free
2: 2 continguous sectors free
3: 1 contiguous sector free
4: all 4 sectors involved:(
what 2 things determine HBL tx?
stage and path
what is the mainstay of curative therapy in HBL?
surgical resection
what % of pts with HBL have resectable disease at presentation?
20-30%
surgery ONLY is curative for what % of pure fetal HBL?
> 90%
Is HBL considered to be very chemosensitive?
YES
HBL chemo is ___-based
cisplatin
in HBL, chemo increases the proportion of ___ ___ ___ ___
pts achieving complete resection
in HBL, chemo is used in what settings?
both neoadjuvant and adjuvant
is radiation indicated in upfront tx of HBL?
NO
COG chemo for HBL?
Cisplatin + 5FU+ Vcr (c5v) +/- dox (C5VD)
what does SIOPEL (europe) use to tx hbl?
cisplatin alone or with doxo (PLADO)
what additional agents are used for tx for high risk/met HBL pts?
irinotecan, carboplatin, etoposide
how do COG and siopel approaches to HBL difer?
COG: surgery when feasbile, followed by chemo
SIOPEL: always preop chemo
what is the AHEP1531 trial?
HBL trial with consensus COG/SIOPEL approach using both regimens
Define Low Risk, Intermed Risk, High Risk HBL
Low Risk: Stage 1 and non-small cell undifferentiated
Intermed: Stage 1 and 2 small cell undiff + stage 3
High riskL stage 4 and all pts with AFP<100
treatment for low risk HBL?
= stage 1 and 2 (non SCU): give upfront surgery adn adjuvant chemo (2-4 cycles of CDDP=cisplatin- based therapy)
treatment for intermed risk HBL?
= stage 3= early transplant evaluation; preop chemo (2-4 cycles CDDP-based therapy)–> surgery–> postop chemo (2-4 cycles of CDDP based therapy)
high risk HBL tx?
= stage 4 and any patients with AFP<100 ….early transplant eval, preop chemo (2-4 cycles of cisplat-based hterapy)–> surgery–> postop chemo (2-4 cycles of high risk CDDP based therapy)
outcome for low risk HBL?
90%+ survival; pure fetal histo curable with surgery only!
intermed risk HBL: outcome?
70-90% survival
high risk HBL: outcome?
40-60% survival
what % of HBL pts need transplant?
10%
who needs liver transplant with HBL?
- unifocal PRETEXT 4
- multifocal PRETEXT 4
- unifocal, centrally-located tumours involving main hilar structures or main hepatic veins
if considering liver transplant, imp to do what?
refer early!!!!
2 factors associated with improved survival in liver trasnplant HBL pts?
complete resection ASAP after induction therapy (4 cycles), avoiding excessive pre-transplant chemo & good response to chemo
are lungs mets a contraindication to liver transplant in HBL?
no, can still transplant if the mets can be resected:)
HCC: makes up ___ % of liver cancer in pts over the age of ___
95%; 15
median age for hepatocellular ca?
12 yrs
2 categories of hepatocellular ca?
1) in context of underlying liver disease
2) de novo
what are the types of de novo HCC? 3
- conventional HCC
- fibrolamellar HCC
- HCC with elements of HBL (transitional cell tumour or hepatocellular neoplasm otherwise not specified
which signaling pathways are activated in HCC?
WNT/CTNNB1, EPHB2, TGFB/MTOR signaling pathways
type of fusion seen in fibrolamellar HCC?
DNAJB1-PRKACA
congenital RFs for HCC? 5
Hepatic Glitches At Birth: Hcc
- Hereditary Tyrosinemia
- Biliary cirrhosis
- Glycogen storage diseases
- alpha 1 antitrypsin def
- Hemochromatosis
envrionmental RFs for HCC? 5
crazy habits and alternative afflictions
hepatitis b and c alcohol consumption anabolic steroids aflatoxin carcinogens (pesticides, vinyl chloride, thorotrast)
HCC: fibrolamellar= what % of cases?
25%
HCC: fibrolamellar: AFP is __ to ___
low to normal (90%<20)
HCC:
% with mets?
% with extrahepatic extension or vasc invasion?
% with multifocality?
30%; 40%; 50-60%
what % of HCC is associated with liver cirrhosis?
30%
response to chemo in HCC? add waht?
usually poor:( <50%…usually add sorafenib
waht % of HCC pts can have complete resection? may use what? role of tarnsplnat?
only 30%…low:(…may use chemoembolization…almost always send pts to transplant, unless they have extrahepatic disease
HCC: 5 yrs OS and EFS?
OS:28%; EFS 17-19%
long term effects for pts with liver tumours?
CHEMO--> hearing loss therapy-related AML cardiotox renal tox
SURGERY–>
post-transplant immuno supp
Also colon ca in APC+ pts
surveillance guidelines for APC+ pts?
yearly sigmoidoscopy from age 13-15 onwards
ppx colectomy between ages 16-20
upper GI study every 3 years from age 30 to watch for small bowel ca (5-10% risk)
