Case Conference
Maria Victoria Pertubal , MD
PGY-2
St Barnabas Hospital - Pediatrics
TS 23 month old girl
--In Israel--
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March 2012
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Noted with decreased activity and seemed less happy, refused
to walk
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ER: + anemia, US: + liver mass
Transferred to Children’s Hospital: + high AFP (~ 600,000)
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CT scan : + tumor 2 lobes of liver, + pulmonary nodules
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April 2012
Liver biopsy : + consistent with small cell hepatoblastoma
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SIOPEL 4 Cycle 1: Cisplatin + Doxorubicin
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---flew to NYC---
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July 2012
Cycle 3 (SIOPEL4) Cisplatin + Doxorubicin
Case reviewed at Tumor Board : Resectable
AFP 189.4
Pathology : 95% tumor necrosis
AFP 55.5
August 2012
Cycle 4 (SIOPEL 4) Cisplatin
Admitted for nadir sepsis
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In NYC
May 2012
Cycle 2 delayed due to nadir sepsis
MSKCC, confirmed the diagnosis of hepatoblastoma, epithelial type with
predominant embryonal component.
AFP 39,709.9
Cycle 2 (SIOPEL4) Cisplatin + Doxorubicin
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Admitted for nadir sepsis
June 2012
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CT scan : regression of large pulmonary nodule
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MRI of liver : decreased size of liver tumors
Surgical eval: unresectable needs liver transplant
AFP 783.5
Cycle 3 (SIOPEL 4) Cisplatin + Doxorubicin
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Hepatoblastoma
Epidemiology
Primary malignant tumors of the liver
in pediatric population are _____ in
the pediatric age group
Median age of diagnosis is_____
Males to female preponderance is
______
associated with Extremely LBW
Tumor biology
Hepatoblastoma has strong
associations with which syndromes?
(____ _____)
APC gene mutation is associated
with _________
______syndrome associated with loss
of heterozygosity IFG-2 gene at
chromososme 11 p 15
Pathology
Hepatoblastoma represents _____ %
of childhood liver cancers
the remaining ____% is __________
Other Primary malignant tumors of
the liver are :
Benign tumors of the liver are:
Commonly arises from _____lobe of
liver
Primary liver cancers:
Hepatoblastoma
Hepatocellular carcinoma
extrahepatic biliary tree sarcoma
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(angiosarcoma, ERMS)
Primary benign liver tumors:
vascular tumors:
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hemangioma
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hemangioepithelioma
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hepatic ademona
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focal nodular hyperplasia
Histopathology
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Epithelial type
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Fetal
Embryonal
Variants : macrotrabecular,
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small cell ( anaplastic type )
Mixed epithelial + mesenchymal type
Prognosis
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Significance by histology is still
unresolved
Complete resection of tumor ( purely
fetal type ) + low mitotic activity =
Excelent prognosis
Small cell- anaplastic type, poor
prognosis
Often misdiagnosed due to low
AFP levels
Clinical S/sx
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Systemic symptoms
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Physical exam:
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Abdomen__________
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skin __________
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Signs of precocious puberty (3%)
Sites of metastasis
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Most common site __________
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other less common_______&____
Imaging and Laboratory
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First line modality for any child
presenting with abdominal mass___
assess the extent of involvement and
resectability of tumor ________
to define vascular involvement_____
Investigation of metastasis
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Chest ct
Bone scans only if bone mets are
suspected
Blood tests
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CBC
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LFT
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AFP - often increased in 80- 90%,
except for the _______ type
- used to monitor residual disease
or recurrence
* AFP levels are eleveated in
infancy, and will start to decline after
1 yr of age.
Management
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2 approaches
COG – Children’s Oncology Group
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SIOPEL - Société Internationale
d’Oncologie Pédiatrique – Epithelial
Liver Tumor Study Group.
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International Society Of Pediatric
Oncology Group - (European
based grp)
Staging
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based on post-surgical findings
PreText Staging
Chemotherapy
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Cisplatin, 5- FU, vincristine
Doxorubicin – reserved for
unresponsive and recurrent tumors
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Cyclophosphamide
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irinotecan
Treatment
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Complete resection – 40 – 60% long
term cure
Pre-op chemo – for large
unresectable tumors resectable
Orthotopic liver transplant – for
unresectable tumors
Hepatomegaly
True or false:
A palpable liver is always hepatomegaly.____
How to assess Liver size:
Liver span:
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percussion (upper edge)
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palpation (lower edge)
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Newborns: 3.5 cm
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children : 2cm
auscultation- scratch test
Normal
liver
1 week
new born:
4.5 -span
5 cm
12 year old: 7-8 cm (boys)
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6 to 6.5 cm (girls)
A palpable liver is NOT always hepatomegaly
Conditions that can displace the liver
inferiorly:
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fluid or air in the thorax
retroperitoneal mass (choledochal
cyst, abscess)
narow chest walls - pectus
excavatum
normal variant of R lobe of liver
(Riedel lobe)
Riedel lobe
Normal
liver
1 week
new born:
4.5 -span
5 cm
12 year old: 7-8 cm (boys)
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6 to 6.5 cm (girls)
Mechanisms for Hepatomegaly:
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inflammation
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congestion
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excessive storage
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infiltration
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obstruction
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Birth
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perinatal infections
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Clinical
Evaluation
maternal infections, h/o IV drug abuse
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Rh/ABO incompatibility
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Newborn
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hyperbilirubinema, NBS
umbilical catherterization (risk of hepatic
abscesses
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Non-specific symptoms:
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fatigue
Clinical
Evaluation
anorexia
weight loss
bowel movement changes, color
changes, blood in stools
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fever
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jaundice
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History:
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Family history
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Clinical
Evaluation
Inherited disease
travel
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food intake
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exposure to environmental toxins
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Physical exam:
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Clinical
Evaluation
Liver size
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nodularity, firmness
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auscultation (bruits, increased flow)
Laboratory:
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2 true Liver Function tests: ____, ____
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PT - prolongation with loss of >80% synthetic capacity
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Albumin
Question 176
A mother brings in her 5-week-old infant girl
because of feeding difficulties. The baby
weighed 3,300 g when born at term, and she
has breastfed exclusively. Approximately 2
weeks ago, the parents noted that the baby
became increasingly irritable, particularly
during feedings, and she began spitting-up 4
to 6 times per day.
Physical examination demonstrates a welldeveloped, alert but irritable infant whose
weight is 3.85 kg, heart rate is 180 beats/min,
and respiratory rate is 70 breaths/min. Lung
sounds are clear. On physical examination, you
note a hyperdynamic precordium and a grade
2/6 holosystolic cardiac murmur. Chest
auscultation yields normal results. You palpate
a firm liver edge 5.0 cm below the right costal
margin. The spleen is not palpable.
You also note a 2x2-cm hemangioma on the
abdominal wall.
Results of laboratory tests include:
•Hemoglobin, 9.8 g/dL (9.8 g/L)
•White blood
(4.8x109/L)
cell
count,
4.8x103/mcL
•Platelet count, 80x103/mcL (80x109/L)
•Peripheral blood smear, Burr cells and
schistocytes noted
•Electrolytes, normal
•Bilirubin, 1.6 mg/dL (27.4 mcmol/L)
Chest radiography demonstrates mild
cardiomegaly.
Of the following, the study that is
MOST likely to demonstrate the
cause of this infant’s symptoms is
A.
abdominal ultrasonography
B.
acid alpha-glucosidase assay
C.
bone marrow aspiration
D.
Coombs test
E.
echocardiography
References:
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Wolf , A, Lavine Hepatomegaly in Neonates and Children
Pediatrics in review Vol 21 No 9. Sept 2000, pp 303-310
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Abeloff: Abeloff's Clinical Oncology, 4th ed. Chapter 99:Pediatric solid tumors
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PREP 2012