Common and Rare Histological Variants of Hepatoblastoma in Children: A Pathological Diagnosis and Review of the Literature

Bharti, Jyotsna Naresh; Sinha, Arvind; Yadav, Taruna

doi:10.1159/000512236

Cited by 11 publications

(19 citation statements)

References 11 publications

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“…In recent studies, some authors defined MRTL as liver tumors with loss of INI1 independent of the presence of rhabdoid or small undifferentiated tumor cells [ 2 , 5 ]. Others still adhered to the classification of small cell undifferentiated HB for tumors without rhabdoid tumor cells, but INI1-negativity of undifferentiated cells [ 10 , 28 , 29 ].…”

Section: Resultsmentioning

confidence: 99%

“…Recently, expert liver pathologists re-analyzed small patient cohorts or tissue biobanks and showed that SCUD share the important loss of INI1 with MRTL [ 1 , 2 , 10 , 11 ]. Furthermore, they found a vast predominance of small undifferentiated cells and absence of typical HB histology.…”

Section: Introductionmentioning

confidence: 99%

“…The current unclear situation leads to unstandardized diagnoses and therapies of these tumors. For example, some authors classify tumors with non-rhabdoid morphology but negative INI1-staining as MRTL, whereas others still adhere to the classification as SCUD [ 5 , 10 , 13 , 14 ]. Overall, there is an evident lack of clinical data on both MRTL and SCUD.…”

Section: Introductionmentioning

confidence: 99%

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A Systematic Review and Meta-Analysis of Malignant Rhabdoid and Small Cell Undifferentiated Liver Tumors: A Rational for a Uniform Classification

Fuchs

Murtha-Lemekhova

Keßler

et al. 2022

Cancers

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Background: Rhabdoid liver tumors in children are rare and have a devastating prognosis. Reliable diagnosis and targeted treatment approaches are urgently needed. Immunohistochemical and genetic studies suggest that tumors formerly classified as small cell undifferentiated hepatoblastoma (SCUD) belong to the entity of malignant rhabdoid tumors of the liver (MRTL), in contrast to hepatoblastomas with focal small cell histology (F-SCHB). This may have relevant implications on therapeutic approaches. However, studies with larger cohorts investigating the clinical relevance of the histological and genetic similarities for patients are lacking. Purpose: To analyze possible similarities and differences in patient characteristics, tumor biology, response to treatment, and clinical course of patients with MRTL, SCUD and F-SCHB. Applied therapeutic regimens and prognostic factors are investigated. Methods: A systematic literature search of MEDLINE, Web of Science, and CENTRAL was performed for this PRISMA-compliant systematic review. All studies of patients with MRTL, SCUD and F-SCHB that provided individual patient data were included. Demographic, histological, and clinical characteristics of the three subgroups were compared. Overall survival (OS) was estimated with the Kaplan–Meier method and prognostic factors investigated in a multivariable Cox regression model. Protocol registered: PROSPERO 2021 CRD42021258760. Results: Fifty-six studies with a total of 118 patients were included. The two subgroups MRTL and SCUD did not differ significantly in baseline patient characteristics. However, heterogenous diagnostic and therapeutic algorithms were applied. Large histological and clinical overlap between SCUD and MRTL could be shown. Two-year OS was 22% for MRTL and 13% for SCUD, while it was significantly better in F-SCHD (86%). Chemotherapeutic regimens for hepatoblastoma proved to be ineffective for both SCUD and MRTL, but successful in F-SCHB. Soft tissue sarcoma chemotherapy was associated with significantly better survival for MRTL and SCUD, but was rarely applied in SCUD. Patients who did not undergo surgical tumor resection had a significantly higher risk of death. Conclusions: While F-SCHB is a subtype of HB, SCUD should be classified and treated as a type of MRTL. Surgical tumor resection in combination with intensive, multi-agent chemotherapy is the only chance for cure of these tumors. Targeted therapies are highly needed to improve prognosis. Currently, aggressive regimens including soft tissue sarcoma chemotherapy, extensive resection, radiotherapy or even liver transplantation are the only option for affected children.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Systematic Review and Meta-Analysis of Malignant Rhabdoid and Small Cell Undifferentiated Liver Tumors: A Rational for a Uniform Classification

Fuchs

Murtha-Lemekhova

Keßler

et al. 2022

Cancers

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“…In addition, hepatoblastoma brings about 80% of primary liver malignancies in children [4]. The first-line treatment for early-stage hepatoblastoma is complete resection of the liver [5,6]. Nevertheless, preoperative chemotherapy is the major requirement for many patients with unresectable advanced-stage hepatoblastoma [7].…”

Section: Introductionmentioning

confidence: 99%

miR-126 in Extracellular Vesicles Derived from Hepatoblastoma Cells Promotes the Tumorigenesis of Hepatoblastoma through Inducing the Differentiation of BMSCs into Cancer Stem Cells

Zai

Jiang

et al. 2021

Journal of Immunology Research

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Background. Extracellular vesicles (EVs) can deliver miRNAs between cells and play a crucial role in hepatoblastoma progression. In this study, we explored the differentially expressed miRNAs related to tumor cell-derived EVs and the mechanism by which EVs regulate hepatoblastoma progression. Methods. Bioinformatics analysis was performed to explore the differentially expressed miRNAs between the hepatoblastoma and adjacent normal tissues. TEM, NTA, and western blotting were conducted to identify EVs. The expression of miR-126-3p, miR-126-5p, miR-30b-3p, miR-30b-3p, SRY, IL-1α, IL-6, and TGF-β was detected by RT-qPCR. Immunofluorescence (IF) was used to analyze the expression of PKH67, and flow cytometry was applied to assess the ratio of CD44+ CD90+ CD133+ cells. ELISA was used to evaluate the levels of IL-6 and TGF-β. A xenograft mouse model was constructed to detect the function of EVs with downregulated miR-126. IHC was performed to calculate β-catenin levels in tumor tissues. Results. miR-126 was upregulated in hepatoblastoma. EVs derived from hepatoblastoma cells significantly increased the ratio of CD44+ CD90+ CD133+ cells and increased the expression of IL-6, Oct4, SRY, and TGF-β in bone marrow mesenchymal stem cells (BMSCs), while EVs with downregulated miR-126 reversed these phenomena. miR-126 downregulation notably attenuated hepatoblastoma tumor growth and decreased the ratio of CD44+ CD90+ CD133+ cells and increased the expression of IL-6, Oct4, SRY, TGF-β, and β-catenin in tumor tissues of mice. Furthermore, EVs with downregulated miR-126 inhibited the differentiation of BMSCs into cancer stem cells. Conclusions. Exosomal miR-126 derived from hepatoblastoma cells promoted the tumorigenesis of liver cancer through inducing the differentiation of BMSCs into cancer stem cells.

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“…Hepatoblastoma (HB) is one of the most regularly seen malignant tumors of the liver in children, accounting for about 1% of childhood malignant tumors. 1 , 2 Physicians avoid surgery as the primary treatment for HB because most patients are diagnosed before the age of two. 3 , 4 According to the statistics, about 40% of HB patients could not undergo surgery immediately after being diagnosed.…”

Section: Introductionmentioning

confidence: 99%

Down-Regulation of Activating Transcription Factor 3 (ATF3) in Hepatoblastoma and Its Relationship with Ferroptosis

Li¹,

Pang²,

Yin³

et al. 2021

IJGM

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Purpose The molecular mechanisms and signal pathways of ferroptosis in hepatoblastoma (HB) have not yet been clarified. In previous studies, activating transcription factor 3 (ATF3) was reported to be correlated with several tumors, but the clinical significance of ATF3 has never been determined. Herein, we investigated the clinicopathological value and mechanisms of ATF3 in regulating ferroptosis in HB. Methods The mRNA microarray and RNA-sequencing data of 402 samples from our hospital and public databases were used to estimate ATF3 expression and assess its clinical role in HB. The standard mean difference (SMD) and summary receiver operating characteristic curves were utilized to judge the discrimination ability of ATF3 between HB and non-HB liver tissues. We examined the expression variation of ATF3 in HB cells after the treatment with erastin. We also predicted the target genes of ATF3 as a transcriptional factor from public Chromatin Immunoprecipitation-sequencing data and selected the ferroptosis-related genes for a signaling pathway analysis. Results In ten series, the pooled SMD for ATF3 was −0.91, demonstrating that ATF3 expression was predominantly lower in HB than in non-HB liver tissues. ATF3 down-regulation showed moderate potential to distinguish HB from non-HB liver tissues (area under curves = 0.83, 95% confidence interval = 0.79–0.86). Altogether, 4855 putative targets of ATF3 as a transcriptional factor were collected, among which, 60 genes were ferroptosis-related. Conclusion The down-regulated ATF3 expression may play a vital role in the occurrence of HB possible partially by regulating ferroptosis.

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Common and Rare Histological Variants of Hepatoblastoma in Children: A Pathological Diagnosis and Review of the Literature

Cited by 11 publications

References 11 publications

A Systematic Review and Meta-Analysis of Malignant Rhabdoid and Small Cell Undifferentiated Liver Tumors: A Rational for a Uniform Classification

A Systematic Review and Meta-Analysis of Malignant Rhabdoid and Small Cell Undifferentiated Liver Tumors: A Rational for a Uniform Classification

miR-126 in Extracellular Vesicles Derived from Hepatoblastoma Cells Promotes the Tumorigenesis of Hepatoblastoma through Inducing the Differentiation of BMSCs into Cancer Stem Cells

Down-Regulation of Activating Transcription Factor 3 (ATF3) in Hepatoblastoma and Its Relationship with Ferroptosis

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