Hepatic carcinosarcoma: evidence of polyclonal origin based on microsatellite analysis

Gu, Yijin; Zhu, Yuyao; Lu, Xinyuan; Zhao, Qian

doi:10.1016/j.prp.2015.09.007

Cited by 10 publications

(12 citation statements)

References 21 publications

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“…Several competing hypotheses have been proposed for the histogenesis of carcinosarcoma, as follows: ‘collision’ means that carcinoma and sarcoma are two independent neoplasms that invade each other; ‘combination’ means that a tumour develops from a multipotential stem cell that differentiates into carcinomatous and sarcomatous components; ‘conversion’, like ‘combination’, also means that a tumour is monoclonal in origin, but emphasises that part of a carcinoma transforms to sarcomatous elements . So far, to the best of our knowledge, only three clonality studies of HCS based on direct molecular evidence have been published . Schaefer et al .…”

Section: Introductionmentioning

confidence: 99%

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Molecular profiling of the biphasic components of hepatic carcinosarcoma by the use of targeted next‐generation sequencing

Zhang

Bai

et al. 2019

Histopathology

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Histopathology 74, 944-958. https://doi.org/10.1111/his.13822 Molecular profiling of the biphasic components of hepatic carcinosarcoma by the use of targeted next-generation sequencing Aims: To better understand the tumourogenesis and molecular features of hepatic carcinosarcoma (HCS). Methods and results: We selected 13 cases of HCS, including the clinicopathological and immunohistochemical features, and analysed the molecular alterations in separately microdissected carcinomatous and sarcomatous components in eight cases by using targeted next-generation sequencing with a panel of 329 cancer-related genes. As a result, transitional areas were observed between the two components of HCS in all cases. Concordance and overlap in genetic alterations were identified in the two histological components of the eight HCS patients, indicating the clonal relatedness of the two tumour components. The most common gene alterations found in both components were TP53 (75%, 6/8) and NF1/2 (38%, 3/8) mutations and VEGFA amplification (25%, 2/8), which may be strongly associated with HCS tumorigenesis. Unique mutations and amplifications found only in one component were also identified. Amplifications involving MET (38%, n = 3/8) and PDGFRA (25%, n = 2/8) were present only in the sarcomatous components, whereas mutation affecting ERBB4 (25%, n = 2/8) and amplifications of CCND1 and FGF3/4/19 (38%, n = 3/8) were present only in the carcinomatous components, indicating their involvement in the clonal evolution of HCS. Furthermore, multiple potential therapeutic targets were identified for HCS. Conclusions: Our findings indicate that HCS could have been of monoclonal origin, and that the diverse clonal evolution might be driven by special molecular alterations in each tumour component. Our results also identify multiple therapeutic targets of HCS, which are valuable for the personalised treatment of HCS.

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Section: Introductionmentioning

confidence: 99%

“…In contrast, Gu et al . demonstrated that HCSs were of polyclonal origin, on the basis of the analysis of loss of heterozygosity and microsatellite instability . Therefore, the histogenesis of HCS is still controversial and needs to be further elucidated.…”

Section: Introductionmentioning

confidence: 99%

Molecular profiling of the biphasic components of hepatic carcinosarcoma by the use of targeted next‐generation sequencing

Zhang

Bai

et al. 2019

Histopathology

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“…It was reported that most cases originated from normal hepatocyte without cirrhosis, supporting the hypothesis that liver carcinosarcoma begins from a pluripotent precursor cell or stem cell, then differentiates into carcinomatous element and sarcomatous element [6]. Others argue that primary hepatocellular carcinoma transforms into mesenchymal component; the presence of transitional or transformational zones between carcinoma and sarcoma in some cases supports this view [7][8][9]. According to the study by Yamamoto et al, which analyzed the reports published before 2003, more than half of the liver carcinosarcoma patients had a medical history of chronic viral hepatitis or cirrhosis [2,4], which supports that the opinion of the latter.…”

Section: Discussionmentioning

confidence: 92%

Efficacy and Safety of Nivolumab Plus Apatinib in Advanced Liver Carcinosarcoma: a Case Report

2019

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Liver carcinosarcoma is a rare malignancy usually seen in adults, majority of whom have a history of chronic hepatitis. Radical resection in early stages leads to better prognosis; however, the treatment regimen for patients at advanced stage is usually based on previously published case reports. At present, there is no report on programmed death-1 blockade and liver carcinosarcoma. Here, we report the case of a patient with advanced liver carcinosarcoma treated with nivolumab plus apatinib, which resulted in partial remission. However, grade 3 elevation of aminotransferase occurred during treatment, suggesting that the combination therapy should be recommended only after risk assessment. Nonetheless, programmed death-1 blockade plus apatinib might be a promising therapeutic approach for patients with advanced liver carcinosarcoma.

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“…Metastatic sarcomas are more common in adults. A major characteristic of metastatic sarcomas is that they are often very large heterogeneous tumors without clear borders on CT and MR images [ 10 , 22 ]. The intratumoral component of these tumors is relatively complicated, and a cystic or cystic–solid, mucinous appearance is common.…”

Section: Discussionmentioning

confidence: 99%

Primary carcinosarcoma of the liver: imaging features and clinical findings in six cases and a review of the literature

Liang

Zhang

et al. 2018

Cancer Imaging

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BackgroundCarcinosarcoma of the liver is a very rare tumor composed of a mixture of carcinomatous and sarcomatous elements. Less than 25 adequately documented cases have been reported, with inadequate description of imaging features. In order to improve the awareness of this rare tumor, this study aimed to analyze the clinicopathologic and imaging features of six cases of hepatic carcinosarcoma (HCS) confirmed by surgical pathologic evaluation.MethodsWe retrospectively studied the clinicopathologic and imaging features of six cases of HCS (matching the World Health Organization definition) and discussed the differential diagnosis on the basis of imaging findings. The patients, including five men and one woman, were 38 to 69 years of age. Five patients underwent CT scans, one underwent MRI scans.ResultsWhile 3 patients were positive for hepatitis-B surface antigen, 2 had cirrhosis. The largest tumor diameter ranged from 5.0 to 21.0 cm. Satellite nodules, venous thrombi, and organ invasion (gastric wall, gallbladder, and right adrenal gland) were identified. Pathologically, the carcinomatous components corresponded to hepatocellular carcinoma in three cases, cholangiocellular carcinoma in one case, and adenocarcinoma in two cases. The sarcomatous components exhibited complex features, with undifferentiated spindle cells in five cases and a leiomyosarcoma in one. All tumors showed heterogeneous density/intensity with extensive cystic change and necrosis; spot calcification was observed in one case. Capsule was not identified. While four tumors showed heterogeneous hypervascular enhancement, two showed hypovascular enhancement. All patients underwent surgical resection. The follow-up period ranged from 2 to 18 months. Four patients died from recurrence and metastasis.ConclusionsThe clinical and imaging features of HCS are heterogeneous. Due to the heterogenous nature and very low morbidity of HCS, combination of careful analysis of imaging findings and clinical features might be useful for a more accurate diagnosis of HCS.

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Hepatic carcinosarcoma: evidence of polyclonal origin based on microsatellite analysis

Cited by 10 publications

References 21 publications

Molecular profiling of the biphasic components of hepatic carcinosarcoma by the use of targeted next‐generation sequencing

Molecular profiling of the biphasic components of hepatic carcinosarcoma by the use of targeted next‐generation sequencing

Efficacy and Safety of Nivolumab Plus Apatinib in Advanced Liver Carcinosarcoma: a Case Report

Primary carcinosarcoma of the liver: imaging features and clinical findings in six cases and a review of the literature

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