Staged resection for a ruptured hepatoblastoma: a 6-year follow-up

Hepatoblastoma (HB) is a rare germ cell tumour of childhood usually presenting with progressive abdominal distention. However, presentation as acute abdomen is a rare occurrence and is secondary to spontaneous rupture. This presentation carries high mortality. To our knowledge, six cases of ruptured hepatoblastoma have previously been reported, although the long-term outcome has not been clear. We report a case of ruptured HB who was managed by initial control of haemorrhage by laparotomy followed by chemotherapy with high-risk hepatoblastoma protocol as per SIOPEL 2 (cisplatin, carboplatin and doxorubicin) and a staged hepatectomy 5 months later. Patient is currently disease free at 6-year follow-up. Staged hepatectomy after initial control of haemorrhage does not preclude a curative resection.     

Successful treatment of multifocal unresectable hepatoblastoma with chemotherapy only

We report the case of a girl with multi-focal hepatoblastoma in whom chemotherapy alone has resulted in long term event-free survival and possibly cure, without any surgical procedure apart from biopsy for initial diagnosis. At presentation she had a large tumour arising from the left lobe of liver and two other separate masses were noted in the right lobe, but the lungs were free of metastases. Histology showed a foetal type of hepatoblastoma. The serum alpha-feto protein (AFP) level was 44,000 iu/litre. Chemotherapy was started using the triple drug regime recommended for “high risk” (of relapse) patients in the SIOPEL 2 hepatoblastoma protocol of the International Society of Paedaitric Oncology (SIOP). Within a few weeks her abdominal girth decreased, the child became much more comfortable. Drug-induced cardiotoxicity, ototoxicity and nephrotoxicity were not observed. After a total of 4 courses of chemotherapy (completed at the end of August 1998) a CT scan showed that all 3 tumours were smaller but that there were residual multifocal defects in the liver neither hepatic resection nor liver transplantation were considered safe or appropriate. 6.5 years after completion of chemotherapy and now aged 8.5 years the child is in normal health and at school with normal liver size, serum AFP levels and chest imaging.     

Case-control study of perinatal factors and hepatoblastoma in children with an extremely low birthweight

BACKGROUND: There is a significant association between hepatoblastoma and low birthweight. A case-control study was conducted to reveal risk factors for hepatoblastoma in children of extremely low birthweight (< 1,000 g). METHODS: Prenatal and postnatal histories, including parental histories, of 12 hepatoblastoma cases and 75 birthweight-matched controls were compared. RESULTS: The gestational age of the hepatoblastoma cases (23-32 weeks: median 25 weeks), tended to be lower than that of the controls (23-36 weeks; median, 27 weeks; P = 0.072). The time for an infant's bodyweight to return to the same level as the birthweight also tended to be longer in hepatoblastoma cases than in controls (P = 0.055). All hepatoblastoma cases received oxygen therapy for a period of 4-508 days (median 114 days), which was significantly longer than the 0-366 days (median 62 days) in the controls (P = 0.022). Furosemide was given to all hepatoblastoma cases and was used for a significantly longer period in these infants (6460 days; median 89 days) than in the controls (0-241 days; median 44 days P = 0.027). A univariate Cox regression demonstrated that the time taken to regain bodyweight at birth and the duration of both oxygen therapy and furosemide treatment were significantly associated with the development of hepatoblastoma (hazard ratio (HR)= 1.044, P= 0.013; HR = 1.006, P= 0.001; and HR = 1.007, P= 0.001, respectively). Although there were significant correlations between the factors, a multivariate Cox regression analysis identified the duration of oxygen therapy as a significant independent risk factor (HR = 1.006, P = 0.001). CONCLUSIONS: Oxygen therapy and furosemide treatment, along with the rate of growth, are risk factors for the development of hepatoblastoma in children of extremely low birthweight, and the duration of oxygen therapy is the most important factor in predicting the development of hepatoblastoma. Further studies are necessary to determine the real reasons for the development of hepatoblastoma and to protect children of low birthweight from the development of cancer.     

Hepatoblastoma—An attempt of histological subtyping on fine‐needle aspiration material

Hepatoblastoma (HB) is classified into epithelial, mixed (epithelial/mesenchymal), and small‐cell (anaplastic) type. Wnt/β‐catenin pathway plays a key role in hepatic development, regeneration, and tumorigenesis, and HB is known to present β‐catenin mutations (50–90%). The present study was undertaken to delineate the cytomorphologic features of HB and to evaluate the feasibility of subtyping of HB on fine‐needle aspiration cytology (FNAC). The expression of β‐catenin in these tumors was also evaluated both of histopathologic sections and on the aspirated material. Thirty‐three cases with fine‐needle aspirates of HB were retrieved over a period of 12 years. Cytologic diagnosis was reviewed in the light of clinicoradiological data, response to therapy, and subsequent histopathology. Immunochemistry for β‐catenin was performed in 19 of 33 cases on histopathologic sections (n = 10)/cell blocks (n = 6)/cytosmears (n = 3). Based on the cytologic features, the cases were divided into fetal HB (n = 17), embryonal HB (n = 4), combined epithelial HB (n = 8), and mixed HB (n = 4). Four cases of histopathologically proven mixed HB were reported as pure epithelial HB on FNAC, as mesenchymal elements were not represented in the cytology smears. Cytoplasmic as well as nuclear staining for β‐catenin was noted in a total of 10 of 19 cases. FNAC can accurately categorize epithelial HB; however, in mixed type, the accuracy depends on number of areas sampled. Cell block can be of help to perform ancillary investigations especially β‐catenin for both diagnostic and therapeutic purposes. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.     

Hepatoblastoma

Hepatoblastoma is the most common liver cancer diagnosed in children, generally presenting in children under 3 years of age. They are embryonal tumors believed to arise from a hepatocyte precursor cell and are typically heterogeneous, presenting with mixed histological patterns that may recapitulate stages of liver development. Central review of liver tumors diagnosed in children enrolled in collaborative therapeutic protocols has allowed the identification of histological subtypes with distinct clinical associations. However, and despite great therapeutic advances, the prognosis is still poor for children with unresectable or disseminated hepatoblastoma, and no biomarkers or alternative therapies are currently available. International collaborative efforts are drafting common treatment protocols, and a first consensus histologic classification is now available. New therapeutic algorithms incorporating histopathology and biological parameters, such as patient characteristics and tumor genetics, will be necessary to further improve the management and outcome of these patients in the future.     

Pathobiology of hepatobiliary neoplasms in children

Abstract   Several types of malignant epithelial liver tumors are recognized in infants, children and young adolescents. These neoplasms mainly include hepatoblastoma and its types and subtypes, whereas hepatocellular carcinoma is very rare in this age group. A pathology classification of hepatoblastomas has been worked out over the years, although some of the subtypes listed are still not sufficiently defined. Moreover, reviews of cases within large clinical trials have shown that an increasing number of pediatric hepatic tumors deviate from the phenotypes found in current classifications. The present overview refers to some of these apparently novel and intriguing lesions.     

Acquired Antithrombin Type IIb Deficiency After Liver Transplantation: A Case Report

A 3‐year‐old girl with multifocal hepatoblastoma was referred to our clinic for living‐donor liver transplantation, the patient's father being the donor. Pretransplant evaluation revealed that the father presented partial asymptomatic antithrombin (AT) deficiency, with no inherited AT deficiency found in the girl. The genetic testing showed an AT type IIb deficiency responsible for a defect in the heparin‐binding region of AT which is less thrombogenic but more common than the other AT qualitative defects. Her mother was ABO incompatible. Despite the thrombophilia on the father's side, transplantation was successfully performed under replacement therapy with intravenous AT concentrate and low‐molecular‐weight heparin thromboprophylaxis given to both the recipient and the donor. No thrombotic complications occurred. In the posttransplantation course, acquired partial AT deficiency was detected in the recipient, who received adjuvant chemotherapy without thrombotic complications. This case report highlights the relevance of full thrombophilic work‐up before liver transplantation from a living donor, while illustrating that the procedure can be successfully performed in the case of AT deficiency on the donor's side provided that appropriate AT supplementation and thromboprophylaxis are administered to both the recipient and the donor.     

Gray Platelet Syndrome

Seven hepatoblastomas were studied by electron microscopy, and four of these were studied by immunohistochemistry. Five tumors were purely epithelial, and two were mixed epithelialmesenchymal. They showed a spectrum of cellular differentiation ranging from primitive epithelial cells to differentiated cells resembling adult hepatocytes. Glycogen, lipid, basal lamina, and canaliculi were present in all cases. Mitochondria with large, membrane-bound, amorphous inclusions were present in one tumor, and large, complex, basal cell processes were present in two tumors. Ultrastructural features most characteristic of hepatocytes were most common in fetal type hepatoblastomas. Immunoreactive chromogranin cells were present in two tumors, one of which also contained immunoreactive somatostatin cells. The somatostatin-positive tumor had cells with granules resembling those seen in somatostatin-containing cells of normal pancreas and somatostatin-containing neuroendocrine carcinomas. Other immunoreactive substances were present, including α₁-antitrypsin (four cases), vimentin (embryonal cells in four cases; fetal cells in three cases), low-molecular weight cytokeratin (embryonal cells in three cases; fetal cells in four cases), and high-molecular weight cytokeratin (embryonal cells in one case; fetal cells in two cases). Osteoidlike material was positive for epithelial membrane antigen, vimentin, and S-100 protein.