Infantile hepatic hemangioma misdiagnosed by prenatal ultrasonography: A case report.

RATIONALE: The drastic differences in treatment and prognosis of infantile hepatic hemangioma (IHH) and hepatoblastoma (HBL) make accurate prenatal diagnosis imperative. The retrospective comparisons of ultrasonic features between fetal IHH and HBL have been reported before, but clinically, the differential diagnosis in utero is very difficult and can lead to prenatal misdiagnosis. PATIENT CONCERNS: A 27-year-old woman at 30 gestational weeks underwent the routine prenatal examination. A heterogeneous solid mass of the fetus, with close relationship to the liver, was recognized by ultrasound. DIAGNOSIS: A diagnosis of HBL was highly considered. INTERVENTIONS: The fetus was aborted and the autopsy was performed. OUTCOMES: The histological outcome was IHH. LESSONS: The prognosis of fetal IHH and HBL is very different, so an accurate diagnosis prenatally is crucial and indispensable. The radiologist and clinician should differentiate between IHH and HBL, especially since the fetus can have serious complications.

Claudin-1 and claudin-2 differentiate fetal and embryonal components in human hepatoblastoma.

Claudins (CLDNs), a family of transmembrane proteins, are major constituents of tight junctions (TJs). They have been shown to be differentially regulated in malignant tumors and play a role in carcinogenesis and progression. We aimed to explain the molecular mechanism underlying the main epithelial components of hepatoblastomas (HBs) based on the composition of TJs. Fourteen formalin-fixed, paraffin-embedded surgical resection specimens were analyzed by immunohistochemistry for CLDN-1, -2, -3, -4, -7; proliferating cell nuclear antigen (PCNA); Ki-67; beta-catenin; cytokeratin-7 (CK-7); and hepatocyte-specific antigen; messenger RNA was isolated for real-time reverse transcriptase polymerase chain reaction analysis of the CLDNs from dissected fetal and embryonal cell types. Significantly increased protein and messenger RNA expression of CLDN-1 and -2 was detected in the fetal compared with the embryonal component. Both cell types displayed negative or weak immunostainings for CLDN-3, -4, and -7. Hepatocyte-specific antigen was dominantly expressed in the fetal component. PCNA and Ki-67 labeling indices were significantly higher in embryonal compared with fetal cells. beta-catenin cytoplasmic/nuclear immunoreaction was frequent, although not showing significant differences between fetal and embryonal cells. Mutational analysis of beta-catenin detected mutation in two cases. Our results suggest that increased expression of CLDN-1 and -2 characterizes the more differentiated fetal component in HBs and is a reliable marker for differentiating fetal and embryonal cell types in HBs. The results proved that the embryonal and fetal components of HBs differ in such important feature as the protein composition of TJs. The expression of CLDN-1 and -2 is inversely correlated with cell proliferation. The more aggressive, rapidly proliferating embryonal phenotype is associated with the decrease/loss of CLDN-1 and -2. However, there are no data indicating association with the nuclear translocation of beta-catenin.

Activation of beta-catenin in epithelial and mesenchymal hepatoblastomas.

Wnt/beta-catenin signaling is frequently activated in cancer cells by stabilizing mutations of beta-catenin or loss-of-function mutations of the APC tumor suppressor gene. We have analysed the role of beta-catenin in the pathogenesis of hepatoblastoma (HB), an embryonic liver tumor occurring mainly in children under 2 years of age. Sequence analysis of the beta-catenin NH2-terminal domain in 18 epithelial and mixed HBs revealed missense mutations in the GSK3beta phosphorylation motif or interstitial deletions in 12 tumors (67%). In the remaining cases, no truncating mutation of APC could be evidenced. Immunohistochemical analysis of beta-catenin in 11 HBs demonstrated nuclear/cytoplasmic accumulation of the protein in all tumors analysed, with predominant nuclear beta-catenin immunostaining in undifferentiated cells. Membranous beta-catenin localization was preserved only in fetal-type tumoral hepatocytes and was associated with E-cadherin expression. Moreover, we show that beta-catenin is aberrantly overexpressed in a large spectrum of tumor components, including hepatocyte-like cells at various differentiation stages and heterologous elements such as squamous, osteoid and chrondroid tissues, and in occasional other mesenchymally-derived cells. These data strongly suggest that activation of beta-catenin signaling is an obligatory step in HB pathogenesis, and raise the possibility that it interferes with developmental signals that specify different tissue types at early stages of hepatic differentiation.

Hepatoblastoma.

Hepatoblastoma is the most frequently occurring liver tumor in children, accounting for over 25% pediatric hepatic tumors and nearly 50% of those that are malignant. Histologically, the tumor can be divided into the following six patterns: (1) fetal epithelial; (2) embryonal and fetal epithelial; (3) macrotrabecular; (4) small cell undifferentiated; and (5) mixed epithelial and mesenchymal type with teratoid features or (6) without teratoid features. Immunohistochemical studies display a wide variety of immunostaining with monoclonal antibodies particularly those specific for epithelial-derived components. Tumor cytogenetics show a high incidence of trisomy 20 and trisomy of all or part of chromosome 2. The developing liver displays many features similar to those seen in hepatoblastoma, including uniform hepatocytes and cords two cells thick separated by sinusoids displaying hematopoiesis. Hepatoblastomas display only minimal ductular differentiation, similar to the fetal development of the liver that does not display significant ductular development until well into the second trimester.