Glypican-3 (GPC3) is an oncofetal protein that has been demonstrated to be a useful diagnostic immunomarker for hepatocellular carcinoma and hepatoblastoma. Its expression in mesenchymal tumors of the liver, particularly undifferentiated embryonal sarcoma (UES) and mesenchymal hamartoma (MH), has not been investigated. In this study, a total of 24 UESs and 18 MHs were immunohistochemically stained for GPC3 expression. The results showed cytoplasmic staining for GPC3 in 14 (58%) UESs, of which 6 exhibited diffuse immunoreactivity and the remaining 8 showed focal positivity. The patients with GPC3-positive UES tended to be younger (mean 18 years; median 11 years) than those with GPC3-negative tumors (mean 39.4 years; median 27 years), although the difference did not reach statistical significance (P = .06). Eight MHs also exhibited GPC3 immunoreactivity (44%; 4 diffuse and 4 focal). Positive staining in all 8 cases was primarily seen in entrapped nonlesional hepatocytes with a canalicular and cytoplasmic staining pattern. In only 4 cases (22%) was GPC3 immunoreactivity also observed in the mesenchymal component. The patients with positive staining also tended to be younger (mean 2.6 years; median 1.1 years) compared with those with negative staining (mean 16.3 years; median 4.5 years), but the difference was not statistically significant (P = .15). Our data demonstrate that GPC3 is expressed in a subset of UES and MH of the liver. Caution should thus be exercised when evaluating a GPC3-expressing hepatic neoplasm, particularly on a needle biopsy when the differential diagnosis includes poorly differentiated hepatocellular carcinoma or hepatoblastoma.
"Although UESL exhibits aggressive behavior, UESL usually shows expansive growth with an incomplete, fibrous capsule, or only slight invasion   . Levy et al. reported a series of UESL, in which only 3 of 24 cases showed entrapment of hepatocytes in the tumor periphery . UESL with both massive sinusoidal invasion and hepatocyte entrapment, as in the present case, has not been reported yet. "
[Show abstract][Hide abstract] ABSTRACT: Undifferentiated embryonal sarcoma of the liver (UESL) is a malignant mesenchymal tumor that occurs typically in children and rarely in adults. Here we describe a case of UESL in a 51-year-old woman who presented with a cystic lesion in the liver. Because it grew slowly, the anterior segment of the liver was resected to check the lesion. Histologically, the lesion looked like a telangiectatic hepatic adenoma. Two years after resection, the tumor recurred, and she died 3 years later due to liver failure. The autopsy revealed that these lesions were UESL with massive sinusoidal invasion, and a review of the case indicated the primary lesion was also UESL. We also confirmed these tumor cells by staining with CD56, alpha-smooth muscle actin (SMA), and adipophilin, suggesting that they have a character similar to that of stellate cells in the space of Disse. The histological result of our patient revealed atypical UESL. Therefore, UESL should be considered when a hepatic lesion with degeneration is seen, even in an adult. In addition, the immunohistochemical appearance of this case implies that UESL is perhaps derived from stellate cells or stellate cells with myofibroblast differentiation in the space of Disse.
International journal of clinical and experimental pathology 10/2012; 5(8):824-9. · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatoblastoma (HB), the most common hepatic neoplasm in children is associated with germline mutations in adenomatous polyposis coli tumor-suppressor gene that cause familial adenomatous polyposis syndrome. Individuals with familial adenomatous polyposis have a 750 to 7500× the risk of developing HB. We report 3 children with APC gene mutation, who underwent resection or liver transplant for HB. In addition to HB, all 3 patients had multiple independent adenoma-like nodules lacking qualities of intrahepatic metastases. Twenty-five nodules were subjected to immunohistochemical analysis using a panel of antibodies including glypican-3 (GPC3), β-catenin, cytokeratin AE1/AE3, CD34, Ki-67, glutamine synthetase (GS), and fatty acid binding protein. The nodules were round, ranged in size from 0.2 to 1.5 cm, and paler than the background liver. All lacked the chemotherapy effect. The nodules were circumscribed but nonencapsulated and composed of well-differentiated hepatocytes with occasional minor atypical features and absent or rare portal tracts. One lesion displayed a "nodule-within-nodule" pattern. The nodules demonstrated diffuse GS overexpression. Nine (36%) nodules were focally reactive for GPC3, and 1 (4%) displayed focal nuclear β-catenin expression. The associated HB showed diffuse expression of GS, GPC3, and β-catenin nuclear staining. We interpret these nodules as neoplastic with most being adenomas (GPC3 negative) that show features of independent origin and represent early stages of carcinogenesis, implying potential to progress to HB or hepatocellular carcinoma. To our knowledge, this is the first report of multifocal neoplasms in patients with HB and APC gene mutation.
The American journal of surgical pathology 05/2013; 37(7). DOI:10.1097/PAS.0b013e31828aeb18 · 5.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Liver tumors are rare in children, and their diagnoses may be challenging particularly because of the lack of a current consensus classification system. Systematic central histopathological review of these tumors performed as part of the pediatric collaborative therapeutic protocols has allowed the identification of histologic subtypes with distinct clinical associations. As a result, histopathology has been incorporated within the Children's Oncology Group (COG) protocols, and only in the United States, as a risk-stratification parameter and for patient management. Therefore, the COG Liver Tumor Committee sponsored an International Pathology Symposium in March 2011 to discuss the histopathology and classification of pediatric liver tumors, and hepatoblastoma in particular, and work towards an International Pediatric Liver Tumors Consensus Classification that would be required for international collaborative projects. Twenty-two pathologists and experts in pediatric liver tumors, including those serving as central reviewers for the COG, European Société Internationale d'Oncologie Pédiatrique, Gesellschaft für Pädiatrische Onkologie und Hämatologie, and Japanese Study Group for Pediatric Liver Tumors protocols, as well as pediatric oncologists and surgeons specialized in this field, reviewed more than 50 pediatric liver tumor cases and discussed classic and newly reported entities, as well as criteria for their classification. This symposium represented the first collaborative step to develop a classification that may lead to a common treatment-stratification system incorporating tumor histopathology. A standardized, clinically meaningful classification will also be necessary to allow the integration of new biological parameters and to move towards clinical algorithms based on patient characteristics and tumor genetics, which should improve future patient management and outcome.
Modern Pathology 09/2013; 27(3). DOI:10.1038/modpathol.2013.80 · 6.19 Impact Factor
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