Variable Antigen Expression in Hepatoblastomas

Abstract

Hepatoblastoma is a malignant tumor that typically presents as a mass in the liver of a child less than 5 years of age. The diagnosis is usually established by means of a needle core biopsy before the treatment is commenced. The pathologic diagnosis of hepatoblastoma relies on the microscopic identification of typical morphologic features, but these may not be present in a needle core biopsy, and in this setting immunohistochemical staining has an important role in the exclusion of other childhood malignancies. We have studied 12 needle core biopsies from cases of hepatoblastoma, all of which had the diagnosis confirmed by subsequent resection of the tumor, to determine if these tumors show a diagnostic phenotype. The needle biopsies were immunostained with a standard panel of antibodies normally used in the characterization of childhood small round blue cell tumors, with the addition of antibodies directed against alpha-fetoprotein and alpha-1-antitrypsin. Our results indicate that the majority of hepatoblastomas expressed cytokeratins (10/12) and that alpha-1-antitrypsin and alpha-fetoprotein staining were positive in approximately half the cases (5/12 and 7/12, respectively). We also observed frequent expression of antigens normally expressed on other childhood tumors. A significant number of hepatoblastomas (8/12) expressed MIC-2 (CD99) an antigen normally associated with primitive neuroectodermal tumor, 4 cases showed positive staining with the neural-associated antigen NCAM (CD56), and 3 were positive with the neuroblastoma marker NB84. Occasional cases showed expression of the muscle marker desmin (2/12) and 2 cases stained with BCL2. Vimentin expression was seen in 1 case, and a single case also expressed the neural markers PGP9.5 and neurone-specific enolase. In all cases, the tumor cells were negative with CD45, WT1, and S-100. These findings indicate that the primitive cells in hepatoblastoma have a variable immunophenotype and can express antigens normally seen in other childhood malignancies. In the clinical setting of the differential diagnosis of childhood abdominal mass, hepatoblastoma shows no distinct immunohistochemical profile, and the diagnosis requires a combination of the clinical, imaging, and pathologic findings.

Equine Primary Liver Tumors: A Case Series and Review of the Literature

“…3,8,13,21,22,31,38,40 However, no IHC panel is distinctive for HB, as other tumors, including HCC, may also express markers such as AFP. 6,31 Human HB of the fetal and embryonal subtypes tend to have strong immunoreactivity for AFP, areas of mixed tumors may have some positive staining, and small cell undifferentiated forms do not stain. 37 Immunoreactivity for AFP in equine tumors is faint to strongly positive in wholly epithelial type HB, and variably positive in mixed epithelial and mesenchymal tumors.…”

“…12,37 Commonly used markers include low-molecular-weight cytokeratin, AFP, and a-1-antitrypsin, among others. Hepatocyte paraffin-1 (HepPar-1), though not commonly used in childhood tumor IHC panels, 31 is a sensitive and specific marker of differentiated hepatocytes that reacts with liver cell mitochondria and has been used to identify primary hepatic neoplasms. 20 HepPar-1 has also been shown to stain some HB.…”

Teratoid Hepatoblastoma With Abundant Neuroendocrine and Squamous Differentiation With Extensive Parenchymal Metastasis

“…Rare mixed tumors classified as hepatoblastomas with teratoid features show variable amounts of other heterologous elements such as stratified squamous, mucinous, and ductular cholangioblastic epithelium, immature neuroepithelium, neuroendocrine differentiation, and melanin pigment. [2][3][4] This category of hepatoblastomas was first recognized by Manivel et al 1 in 1986. Some reports describe mixed hepatoblastoma and teratoma as combined tumors that probably represent teratoid hepatoblastomas.…”

“…5,6 This divergent differentiation is thought to be related to the pluripotential stem cell precursors, which have the ability to differentiate into all of these different components. 4,7 Neoadjuvant chemotherapy for hepatoblastoma usually results in considerable reduction of tumor. Typical changes include tumor necrosis, a fibrohistiocytic response, peliosislike areas, cytoarchitectural differentiation mimicking nonneoplastic hepatocytes and bile ducts, and hepatocellular carcinoma-like changes.…”

Downregulation of transcription factor GATA4 sensitizes human hepatoblastoma cells to doxorubicin-induced apoptosis

“…28 It has been shown that BCL2 is, however, expressed in a subset of HBs. 29 The HB cell line, HUH6, expresses high levels of both BCL2 and BCLX L , further implicating these apoptosis inhibitors in HB pathophysiology. 30 BH3-mimetic drugs, antagonists of the anti-apoptotic BCL2 molecules, have been shown to intensify the intrinsic apoptotic pathway, thus enhancing the effects of cytotoxic drugs, including Dox, in HB cells.…”