Case Conference Maria Victoria Pertubal , MD PGY-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 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 • • • • 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 1 week new born: 4.5 -span 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 1 week new born: 4.5 -span 5 cm 12 year old: 7-8 cm (boys) • 6 to 6.5 cm (girls) Mechanisms for Hepatomegaly: • inflammation • congestion • excessive storage • infiltration • obstruction • Birth • perinatal infections • Clinical Evaluation maternal infections, h/o IV drug abuse • Rh/ABO incompatibility • Newborn • • hyperbilirubinema, NBS umbilical catherterization (risk of hepatic abscesses • Non-specific symptoms: • • • • fatigue Clinical Evaluation anorexia weight loss bowel movement changes, color changes, blood in stools • fever • jaundice • History: • Family history • • Clinical Evaluation Inherited disease travel • food intake • exposure to environmental toxins • Physical exam: • Clinical Evaluation 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 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: • • 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