Paul Zamiara , Nick Shillingford , Larry L. Wang , Ryan J. Schmidt , Gordana Raca , Shengmei Zhou
{"title":"未分化胚胎性肝肉瘤:来自同一机构的10例临床病理和基因组研究。","authors":"Paul Zamiara , Nick Shillingford , Larry L. Wang , Ryan J. Schmidt , Gordana Raca , Shengmei Zhou","doi":"10.1016/j.humpath.2025.105935","DOIUrl":null,"url":null,"abstract":"<div><h3>Aims</h3><div>Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive malignancy with limited clinicopathological and genomic characterization. This study aimed to investigate the genomic abnormalities in a cohort of UESL cases.</div></div><div><h3>Methods</h3><div>We analyzed ten UESL cases diagnosed at our institution from 2018 to 2025. Tumor specimens underwent DNA and RNA-based next-generation sequencing using the OncoKids® panel, along with chromosomal microarray analysis.</div></div><div><h3>Results</h3><div>The median age at diagnosis was 13.0 years (range: 0.8–18.3), and the median tumor size was 14.4 cm (range: 7.5–26.0). Lung metastases were present in three patients, and six tumors exhibited capsule rupture. Histology revealed pleomorphic, hyperchromatic oval, spindle, or stellate-shaped cells, with CD56 positivity. <em>TP53</em> was the sole recurring mutated gene, identified in nine of ten cases. Biallelic <em>TP53</em> inactivation (mutation plus copy number loss, <em>n</em> = 7) correlated with greater chromosomal complexity compared to monoallelic <em>TP53</em> mutations (<em>n</em> = 2). Segmental gain at 19q13.42-q13.43, including chromosome 19 microRNA cluster (C19MC), was observed only in tumors with biallelic <em>TP53</em> inactivation. No clinically significant RNA fusions were detected. All patients underwent tumor resection and ARST0332-based chemotherapy; four of six patients with tumor rupture also received whole abdominal radiation. At a median follow-up of 32.0 months (range: 3.0–81.2), all nine patients with follow-up were alive.</div></div><div><h3>Conclusions</h3><div><em>TP53</em> mutation is a defining molecular event in UESL, with biallelic inactivation linked to increased chromosomal complexity and C19MC locus gain. Despite its aggressive nature, favorable outcomes are achievable with multimodal therapy.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"165 ","pages":"Article 105935"},"PeriodicalIF":2.6000,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Undifferentiated embryonal sarcoma of the liver: A clinicopathological and genomic study of 10 cases from a single institution\",\"authors\":\"Paul Zamiara , Nick Shillingford , Larry L. Wang , Ryan J. Schmidt , Gordana Raca , Shengmei Zhou\",\"doi\":\"10.1016/j.humpath.2025.105935\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Aims</h3><div>Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive malignancy with limited clinicopathological and genomic characterization. This study aimed to investigate the genomic abnormalities in a cohort of UESL cases.</div></div><div><h3>Methods</h3><div>We analyzed ten UESL cases diagnosed at our institution from 2018 to 2025. Tumor specimens underwent DNA and RNA-based next-generation sequencing using the OncoKids® panel, along with chromosomal microarray analysis.</div></div><div><h3>Results</h3><div>The median age at diagnosis was 13.0 years (range: 0.8–18.3), and the median tumor size was 14.4 cm (range: 7.5–26.0). Lung metastases were present in three patients, and six tumors exhibited capsule rupture. Histology revealed pleomorphic, hyperchromatic oval, spindle, or stellate-shaped cells, with CD56 positivity. <em>TP53</em> was the sole recurring mutated gene, identified in nine of ten cases. Biallelic <em>TP53</em> inactivation (mutation plus copy number loss, <em>n</em> = 7) correlated with greater chromosomal complexity compared to monoallelic <em>TP53</em> mutations (<em>n</em> = 2). Segmental gain at 19q13.42-q13.43, including chromosome 19 microRNA cluster (C19MC), was observed only in tumors with biallelic <em>TP53</em> inactivation. No clinically significant RNA fusions were detected. All patients underwent tumor resection and ARST0332-based chemotherapy; four of six patients with tumor rupture also received whole abdominal radiation. At a median follow-up of 32.0 months (range: 3.0–81.2), all nine patients with follow-up were alive.</div></div><div><h3>Conclusions</h3><div><em>TP53</em> mutation is a defining molecular event in UESL, with biallelic inactivation linked to increased chromosomal complexity and C19MC locus gain. Despite its aggressive nature, favorable outcomes are achievable with multimodal therapy.</div></div>\",\"PeriodicalId\":13062,\"journal\":{\"name\":\"Human pathology\",\"volume\":\"165 \",\"pages\":\"Article 105935\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-09-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Human pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0046817725002229\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human pathology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0046817725002229","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}
Undifferentiated embryonal sarcoma of the liver: A clinicopathological and genomic study of 10 cases from a single institution
Aims
Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive malignancy with limited clinicopathological and genomic characterization. This study aimed to investigate the genomic abnormalities in a cohort of UESL cases.
Methods
We analyzed ten UESL cases diagnosed at our institution from 2018 to 2025. Tumor specimens underwent DNA and RNA-based next-generation sequencing using the OncoKids® panel, along with chromosomal microarray analysis.
Results
The median age at diagnosis was 13.0 years (range: 0.8–18.3), and the median tumor size was 14.4 cm (range: 7.5–26.0). Lung metastases were present in three patients, and six tumors exhibited capsule rupture. Histology revealed pleomorphic, hyperchromatic oval, spindle, or stellate-shaped cells, with CD56 positivity. TP53 was the sole recurring mutated gene, identified in nine of ten cases. Biallelic TP53 inactivation (mutation plus copy number loss, n = 7) correlated with greater chromosomal complexity compared to monoallelic TP53 mutations (n = 2). Segmental gain at 19q13.42-q13.43, including chromosome 19 microRNA cluster (C19MC), was observed only in tumors with biallelic TP53 inactivation. No clinically significant RNA fusions were detected. All patients underwent tumor resection and ARST0332-based chemotherapy; four of six patients with tumor rupture also received whole abdominal radiation. At a median follow-up of 32.0 months (range: 3.0–81.2), all nine patients with follow-up were alive.
Conclusions
TP53 mutation is a defining molecular event in UESL, with biallelic inactivation linked to increased chromosomal complexity and C19MC locus gain. Despite its aggressive nature, favorable outcomes are achievable with multimodal therapy.
期刊介绍:
Human Pathology is designed to bring information of clinicopathologic significance to human disease to the laboratory and clinical physician. It presents information drawn from morphologic and clinical laboratory studies with direct relevance to the understanding of human diseases. Papers published concern morphologic and clinicopathologic observations, reviews of diseases, analyses of problems in pathology, significant collections of case material and advances in concepts or techniques of value in the analysis and diagnosis of disease. Theoretical and experimental pathology and molecular biology pertinent to human disease are included. This critical journal is well illustrated with exceptional reproductions of photomicrographs and microscopic anatomy.