Case Conference

Maria Victoria Pertubal , MDPGY-2

St Barnabas Hospital - Pediatrics

TS 23 month old girl • --In Israel--

• March 2012

• Noted with decreased activity and seemed less happy, refused to walk

• ER: + anemia, US: + liver mass

• Transferred to Children’s Hospital: + high AFP (~ 600,000)

• CT scan : + tumor 2 lobes of liver, + pulmonary nodules

• April 2012

• Liver biopsy : + consistent with small cell hepatoblastoma

• SIOPEL 4 Cycle 1: Cisplatin + Doxorubicin

• ---flew to NYC---

July 2012Cycle 3 (SIOPEL4) Cisplatin + Doxorubicin

• Case reviewed at Tumor Board : ResectableAFP 189.4

Pathology : 95% tumor necrosisAFP 55.5

August 2012Cycle 4 (SIOPEL 4) Cisplatin

Admitted for nadir sepsis

• 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

• Admitted for nadir sepsis

• June 2012

• CT scan : regression of large pulmonary nodule

• MRI of liver : decreased size of liver tumors

• Surgical eval: unresectable needs liver transplant

• AFP 783.5 Cycle 3 (SIOPEL 4) Cisplatin + Doxorubicin

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• (angiosarcoma, ERMS)

Primary benign liver tumors:

vascular tumors:• hemangioma• hemangioepithelioma

• hepatic ademona• focal nodular hyperplasia

Histopathology

• Epithelial type• Fetal• Embryonal• Variants : macrotrabecular,

• small cell ( anaplastic type )

• Mixed epithelial + mesenchymal type

Prognosis • 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

• Systemic symptoms• Physical exam:• Abdomen__________• skin __________• Signs of precocious puberty

(3%)

Sites of metastasis

• Most common site __________• other less common_______&____

Imaging and Laboratory

• 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

• Chest ct• Bone scans only if bone mets

are suspected

Blood tests• CBC • LFT• 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• 2 approaches• COG – Children’s Oncology

Group• SIOPEL - Société Internationale

d’Oncologie Pédiatrique – Epithelial Liver Tumor Study Group.• International Society Of

Pediatric Oncology Group - (European based grp)

Staging

• • based on post-surgical findings

PreText Staging

Chemotherapy

• Cisplatin, 5- FU, vincristine• Doxorubicin – reserved for

unresponsive and recurrent tumors

• Cyclophosphamide• irinotecan

Treatment

• 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: • percussion (upper edge)• palpation (lower edge)

• Newborns: 3.5 cm• children : 2cm

• auscultation- scratch test

Normal liver span

1 week new born: 4.5 - 5 cm

12 year old: 7-8 cm (boys) • 6 to 6.5 cm (girls)

A palpable liver is NOT always hepatomegaly

Conditions that can displace the liver inferiorly:• 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 span

1 week new born: 4.5 - 5 cm

12 year old: 7-8 cm (boys) • 6 to 6.5 cm (girls)

Mechanisms for Hepatomegaly:

• inflammation • congestion• excessive storage• infiltration• obstruction

Clinical Evaluation

• History: • Birth

• perinatal infections

• maternal infections, h/o IV drug abuse

• Rh/ABO incompatibility

• Newborn

• hyperbilirubinema, NBS

• umbilical catherterization (risk of hepatic abscesses

Clinical Evaluation

• History: • Non-specific symptoms:

• fatigue

• anorexia

• weight loss

• bowel movement changes, color changes, blood in stools

• fever

• jaundice

Clinical Evaluation

• History: • Family history

• Inherited disease

• travel

• food intake

• exposure to environmental toxins

Clinical Evaluation• Physical exam:

• Liver size

• nodularity, firmness

• auscultation (bruits, increased flow)

Laboratory:

• 2 true Liver Function tests: ____, ____• PT - prolongation with loss of >80% synthetic capacity

• 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 well-developed, 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 cell count, 4.8x103/mcL (4.8x109/L)•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:

• Wolf , A, Lavine Hepatomegaly in Neonates and Children

• Pediatrics in review Vol 21 No 9. Sept 2000, pp 303-310

• Abeloff: Abeloff's Clinical Oncology, 4th ed. Chapter 99:Pediatric solid tumors

• PREP 2012