Primary malignant hepatic tumours in childhood

Summary Twenty-four cases of hepatoblastoma, 14 cases of hepatocellular carcinoma and three cases of malignant mesenchymoma out of a total of 54 primary liver tumours were studied by light microscopy and immunohistochemistry. A remarkable finding in one case of hepatoblastoma and one case of hepatocellular carcinoma was a sarcoid-like reaction in the tumour tissue. Three cases of hepatoblastoma presented a macrotrabecular pattern. Among hepatocellular carcinomas, three cases corresponded to the fibrolamellar variant. By immunohistochemistry, the proportion of cases with positive staining for alpha₁-fetoprotein was higher in hepatoblastoma than in hepatocellular carcinoma. HB_s-antigen could be demonstrated in non-neoplastic liver cells in two cases of hepatocellular carcinoma, but not in the tumour cells. No strong correlation between histological pattern and prognosis could be established in hepatoblastoma. However, there was a tendency to more aggressive biological behavior in cases with pronounced mitotic activity. The number of mitoses in hepatoblastoma varied widely. As in previous studies, patients with the fibrolamellar variant of hepatocellular carcinoma fared better than those with the classical type of this tumour. Prognosis in malignant mesenchymoma was not as poor as suggested from previous studies.This study was supported in part by a grant from the Bundesminister für Arbeit und Sozialordnung     

“Cancer in ARID1A-Coffin-Siris syndrome: Review and report of a child with hepatoblastoma”

Coffin-Siris syndrome (CSS) is a rare neurodevelopmental and multisystemic disorder with wide genetic heterogeneity and phenotypic variability caused by pathogenic variants in the BAF complex with 341 cases enrolled in the CSS/BAF-related disorders registry by 2021. Pathogenic variants of ARID1A account for 7–8% of cases with CSS phenotype. Malignancy has been previously reported in six individuals with CSS associated with BAF mutations. Two of these malignancies including one acute lymphoid leukemia and one hepatoblastoma were reported in ARID1A-associated CSS (ARID1A-CSS). Alterations in ARID1A are among the most common molecular aberrations in human cancer. Somatic deletion of 1p and specifically of 1p36.11 containing ARID1A is frequently seen in hepatoblastoma and has been associated with high-risk features. Here we report a child with CSS Phenotype and a novel de novo variant of ARID1A with hepatoblastoma. Because hepatoblastoma has an incidence of 1 per million children, the presence of hepatoblastoma in 2 of 30 known cases of ARID1A-CSS is significant. ARID1A-CSS should be included among the cancer predisposition syndromes associated with an increased risk of hepatoblastoma and tumour surveillance considered for these patients. The role of ARID1A in the pathogenesis and outcome of hepatoblastoma deserves further investigation.     

术前经动脉化疗栓塞在肝母细胞瘤治疗中的应用

目的 探讨肝母细胞瘤术前介入性肝动脉化疗栓塞(transarterial chemoembolization，TACE)的临床可行性、疗效及适应证及在综合治疗中的地位。方法 对常规估计不能切除的13例肝母细胞瘤先行经动脉化疗栓塞，再行Ⅱ期外科手术切除，观察分析患儿临床症状的变化反应、术中情况和远期疗效。结果 TACE术后数天至1个月复查，肿瘤体积明显缩小7．5％～66．3％(平均38．0％)，AFP水平显著降低11％～61．2％(平均52．3％)，无明显的化疗毒性反应，TACE后其中11例患儿都安全地施行外科手术，手术切除标本的病理改变肿瘤明显坏死，平均坏死区域面积达70．9％。介入后2年死于肺转移1例，介入后3年死于肺、脑转移的1例，肝移植后死亡1例，3个月后肝衰竭者1例，3例复发，无瘤存活6例，其平均生存期22．3个月，平均随访时间为30个月。结论 TACE能有效杀死肿瘤细胞，控制肿瘤生长，使部分不能Ⅰ期手术的患儿重新获得手术机会，改善预后，无严重并发症，是一种安全、有效、实用的肝母细胞瘤的辅助治疗方法，而且对防止术中肿瘤细胞的扩散也有一定的作用。     

The prognostic implication of hypercholesterolemia in infants and children with hepatoblastoma

This paper reports the relationship between serum cholesterol level and hepatoblastoma in nine patients. Four of the nine patients had a high (417-544 mg%) serum cholesterol. All of these patients were less than one year of age and had tumors of the epithelial type. Three of the infants died soon after being diagnosed. Three patients had a moderately elevated serum cholesterol (206-249mg%). One underwent primary hepatic resection. Two had nonresectable tumors that became resectable after chemotherapy. One died secondary to pulmonary metastases. The remaining two patients had a normal serum cholesterol level prior to treatment. Both patients had hepatic resection after chemotherapy and had no evidence of increased cholesterol postoperatively and are alive six years after diagnosis. From these data, it is suggested that the pretreatment level of serum cholesterol may be of prognostic significance in infants and children with hepatoblastoma.     

肝母细胞瘤4例临床病理分析

目的：探讨肝母细胞瘤的临床病理特点。方法：对吉林省柳河医院病理科近30年4例肝母细胞瘤临床病理资料进行回顾性分析。结果：上皮型肝母细胞瘤2例,其中胎儿型1例,胚胎型l例;上皮间叶混合型2例。胎儿型细胞角蛋白（CK）、甲胎蛋白（AFP）阳性,波型蛋白（Vimentin）阴性;胚胎型CK阳性,AFP、Vimentin阴性;上皮间叶混合型CK、Vimentin阳性,AFP阴性。手术完整切除肿瘤4例,3例生存期超过5年。结论：肝母细胞瘤组织学类型、治疗方式与疾病的预后关系密切。     

Positron emission tomography in recurrent hepatoblastoma

Early detection of recurrent hepatoblastoma is not always possible with conventional imaging methods such as computed tomography (CT) and magnetic resonance imaging (MRI). This article describes three cases of recurrent hepatoblastoma in which positron emission tomography (PET) using F¹⁸-fluoro-deoxy-glucose (FDG-PET) was used to locate the site of recurrence. In the first two patients, FDG-PET accurately located recurrent disease where it was not detected by conventional imaging modalities, including CT and MRI. In the third patient, FDG-PET imaging also located the recurrent disease in an MRI-identified adrenal metastasis. The technique of coregistration using PET with CT and MRI scans was used in the cases described. This improves the anatomical localization of metabolically active sites and was particularly useful for determining the surgical approach. The difficulties of conventional imaging in locating early tumor recurrence or metastatic disease in hepatoblastoma make FDG-PET imaging an important investigation that may impact patient management.     

Videoscopic fluorescence diagnosis of peritoneal and thoracic metastases from human hepatoblastoma in nude rats

Background Various medical disciplines are employing photodynamic diagnosis (PDD) when searching for malignancies. It is still unknown whether pediatric solid tumors such as hepatoblastoma are susceptible to this technique as well. Methods Human hepatoblastoma cells were injected into the abdomen or right thoracic cavity of nude rats. Tumor growth was allowed for 7 weeks. Then, photosensitization was induced by peritoneal lavage with 5-aminolevulinic acid (ALA). Applying the Storz PDD system and one 4-mm scope, all animals were investigated by videoscopic white light diagnosis (WD) and PDD. Suspicious lesions were marked and analyzed by spectrometry and histology. Results Positive fluorescence was documented for every tumor seen by WD in the abdomen or right thoracic cavity. Spectrometry of lesions showed a 6.34-fold increased fluorescence intensity. Histology revealed hepatoblastoma in all specimens. Conclusions Human hepatoblastoma can be detected by PDD in a rat model. Considering the clinical success of this method in other specialties, our findings indicate that further investigations to evaluate the benefit of PDD for children with hepatoblastoma should be performed.     

Liver transplantation for childhood hepatic malignancy: a review of the United Network for Organ Sharing (UNOS) database

Background

Orthotopic liver transplantation (OLT) is the only treatment option for unresectable hepatoblastoma (HB) and hepatocellular carcinoma (HCC) in children. Aggregated outcomes of OLT for these hepatic malignancies have not been evaluated in the United Network for Organ Sharing national database.

Purpose

The purpose of this study was to evaluate graft and patient survival in pediatric OLT recipients with HB and HCC.

Methods

Data from the United Network for Organ Sharing Standard Transplant and Research Files were analyzed and included pediatric (<18 years) OLT recipients with HB or HCC from 1987 to 2004. The effects of diagnosis on pretransplant variables were evaluated using analysis of variance methods or χ² tests, as appropriate. Actuarial survival and effect of diagnosis on survival were determined using Kaplan-Meier methods and log-rank tests.

Results

Since 1987, 152 OLTs have been performed in 135 pediatric patients for HB and 43 OLTs in 41 pediatric patients for HCC. Respective 1-, 5-, and 10-year patient survival after OLT was 79%, 69%, and 66% for HB and 86%, 63%, and 58% for HCC (P = .73). The primary cause of death for both groups was metastatic or recurrent disease, accounting for 54% of deaths in the HB group and 86% in the HCC group (P = .338). Patients with hepatoblastoma were younger (mean age, 2.9 ± 2.5 vs 10.4 ± 4.8 years for the HCC group; P < .001) and more likely to receive a living donor organ (16% vs 4%, P = .03). A greater proportion of the patients with HB had previous abdominal surgery than patients with HCC (63% HB vs 37% HCC, P = .04). Pretransplant medical condition and transplant era were associated with graft and patient survival on univariate and multivariate analysis (all P < .05).

Conclusions

Orthotopic liver transplantation remains a viable option for pediatric patients with unresectable primary hepatic malignancies and results in good long-term survival. Pretransplant medical condition is an important predictor of outcome. Thus, in conjunction with better chemotherapy regimens, earlier evaluation for OLT in patients with unresectable HB and HCC may result in yet further improved long-term survival.     

肝母细胞瘤基因组不平衡性与染色体变异

目的建立稳定的比较基因组杂交（CGH）技术,探讨肝母细胞瘤（HB）染色体1p36杂合性缺失（LOH）的特点。方法应用CGH检测30例HBDNA的丢失或扩增;应用聚合酶链反应-简单重复序列多态性（SSLP）方法,对30例HB中染色体1p36上6个微卫星的杂合子丢失进行检测。结果每例HB细胞染色体均有不同程度的变异,HB常见增益的染色体区域是1q、2q、2p、8q、8p、12q和22q,常见丢失的染色体区域为1P、4q、4p、16q、17p和18q。30例HB中,1号染色体上6个基因座发生LOH的总频率为63．3％（19／30）,其中D1S199为最高（66．7％）,其次为D1S450（46．7％）。结论HB存在多条染色体DNA拷贝数扩增或丢失的区域;HB在染色体1p36上存在广泛的LOH;染色体变异引起相应瘤基因扩增和抑癌基因的丢失可能参与了HB的发生、发展。     

Preoperative chemoembolization for unresectable hepatoblastoma

 Complete surgical resection offers the only chance for cure in patients with hepatoblastoma (HB). Patients with unresectable lesions are given preoperative chemotherapy in an attempt to create a resectable lesion. We present a case of an 11-month-old with an unresectable stage III HB unresponsive to systemic chemotherapy. Transfemoral hepatic-artery chemoembolization resulted in a surgically resectable tumor. The patient underwent a right trisegmentectomy with complete resection of the tumor and remains tumor-free 24 months postoperatively. Salvage chemoembolization can be an effective preoperative modality to convert an unresectable tumor into a resectable one. Accepted: 19 January 2001