Small Cell Undifferentiated Variant of Hepatoblastoma: Adverse Clinical and Molecular Features Similar to Rhabdoid Tumors

Department of Hematology/Oncology, Sacred Heart Children's Hospital, Spokane, Washington 99204, USA.
Pediatric Blood & Cancer (Impact Factor: 2.39). 03/2009; 52(3):328-34. DOI: 10.1002/pbc.21834
Source: PubMed


Small cell undifferentiated (SCU) histology in patients with stage I hepatoblastoma (HB) predicts an increased risk of relapse. We sought to determine the significance of SCU histology in patients with unresectable HB.
Patients enrolled on the pediatric Intergroup (INT0098) trial for HB and patients from the personal consultation files of two of the authors (MF, LG) were reviewed for cases with SCU histology. These patients were compared with SCU HB patients identified by literature review.
Eleven patients were studied. All patients with reported AFP results exhibited normal or minimally increased serum AFP levels. None of the patients survived: 10 died of disease progression, and 1 died from treatment complications. Immunostaining revealed that tumors from six of six patients tested were INI1 negative. Cytogenetic and molecular abnormalities in one patient (and two patients from the literature review) were similar to those described in rhabdoid tumors. Comparison with patients from the literature review revealed similar results except that 4 of 29 patients survived without evidence of disease.
SCU histology in HB patients is associated with an adverse outcome. These tumors appear to be biologically different from non-SCU HB. Evaluation of patient characteristics and outcomes for children with SCU HB and/or those with low AFP levels should be determined from large cooperative group studies. In the meantime, we suggest patients with unresectable HB containing SCU elements have careful cytogenetic, molecular, and immunohistochemical evaluation to ascertain rhabdoid features and receive treatment that differs from that provided for other HB patients.

Download full-text


Available from: Gail E Tomlinson
  • Source
    • "The presence of lung metastases was assessed by a chest X-ray (posteroanterior and lateral views) and lung CT scan. Infants with pure fetal HB at the initial biopsy were excluded because these tumors appear to have a different biology [20]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The combination of high-intensity focused ultrasound (HIFU) and transarterial chemoembolization (TACE) has been experimentally performed in a variety of malignant tumors, and its validity has not yet been evaluated for hepatoblastoma (HB). We evaluated the disease-response rate, resection rate, and toxicity in children with unresectable or metastatic HB (stage III and stage IV HB) after sequential treatment with TACE plus HIFU in a controlled clinical trial. The 35 patients with unresectable or metastatic HB were nonrandomly assigned to HIFU ablation (n = 12) or C5V chemotherapy (n = 23). The rates of complete resection, tumor response, and treatment toxicity were evaluated for both regimens. Nine patients who received C5V and 10 patients who received TACE plus HIFU became operable (P = .02). The 3-year event-free survival and overall survival rates were 43.03% and 56.68% in the C5V group and 38.57% and 57.86% in the TACE plus HIFU group, respectively. Acute grade 3 or 4 adverse events, including neutropenia, thrombocytopenia, and anemia, were more frequent in patients treated with C5V therapy than in patients receiving TACE plus HIFU. HIFU ablation achieved a higher rate of complete resection and a lower rate of severe complications compared with C5V treatment in children with advanced HB (Chinese Clinical Trials Registry No. ChiCTR-PRCH-08000182). Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Dec 2014 · Translational oncology
  • Source
    • "Outcomes for patients with MRTL are very poor. Multiagent chemotherapy including vincristine , doxorubicin, cyclophosphamide, ifosfamide and etoposide in combination with complete surgical resection is the mainstay of treatment[65]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: During the first year of life, most of the liver neoplasms are benign in origin, but some of these histologically benign lesions may be challenging in their management. Although most hepatic hemangiomas can be safely observed until involution is documented, some patients will need treatment due to progressive hepatomegaly, hypothyroidism and/or cardiac failure. Large mesenchymal hamartomas may require extensive hepatic resection and an appropriate surgical plan is critical to obtain good results. For malignant neoplasms such as hepatoblastoma, complete surgical resection is the mainstay of curative therapy. The decision about whether to perform an upfront or delayed resection of a primary liver malignant tumor is based on many considerations, including the ease of resection, surgical expertise, tumor histology and stage, and the likely chemosensitivity of the tumor. This article reviews the initial management of the more common hepatic tumors of infancy, focusing on the differential diagnosis and treatment options.
    Preview · Article · Jul 2014 · World Journal of Hepatology
  • Source
    • "Interestingly, SNF5 has been recently implicated in the development of familial schwannomatosis at high frequency [40]–[43] and is inactivated in a couple of tumor types besides MRTs. For instance, homozygous deletions of the SNF5 locus 22q11.2 are found in small-cell hepatoblastomas and poorly differentiated chordomas [44], [45] and inactivating mutations and/or deletion of SNF5 are observed in extraskeletal myxoid chondrosarcomas [46], undifferentiated sarcomas [47], epitheliod sarcomas [48] and meningiomas [41], [49]. It will be interesting to investigate in future studies whether FGFR signaling is up-regulated in these tumor types as well. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Malignant rhabdoid tumors (MRTs) are aggressive pediatric cancers arising in brain, kidney and soft tissues, which are characterized by loss of the tumor suppressor SNF5/SMARCB1. MRTs are poorly responsive to chemotherapy and thus a high unmet clinical need exists for novel therapies for MRT patients. SNF5 is a core subunit of the SWI/SNF chromatin remodeling complex which affects gene expression by nucleosome remodeling. Here, we report that loss of SNF5 function correlates with increased expression of fibroblast growth factor receptors (FGFRs) in MRT cell lines and primary tumors and that re-expression of SNF5 in MRT cells causes a marked repression of FGFR expression. Conversely, siRNA-mediated impairment of SWI/SNF function leads to elevated levels of FGFR2 in human fibroblasts. In vivo, treatment with NVP-BGJ398, a selective FGFR inhibitor, blocks progression of a murine MRT model. Hence, we identify FGFR signaling as an aberrantly activated oncogenic pathway in MRTs and propose pharmacological inhibition of FGFRs as a potential novel clinical therapy for MRTs.
    Full-text · Article · Oct 2013 · PLoS ONE
Show more