Zamiara Paul, Shillingford Nick, Wang Larry L, Schmidt Ryan J, Raca Gordana, Zhou Shengmei
Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States; Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States; Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
Hum Pathol. 2025 Sep 12;165:105935. doi: 10.1016/j.humpath.2025.105935.
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.
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.
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.
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.
肝未分化胚胎性肉瘤（UESL）是一种罕见的侵袭性恶性肿瘤，其临床病理和基因组特征有限。本研究旨在调查一组UESL病例中的基因组异常情况。
我们分析了2018年至2025年在我院诊断的10例UESL病例。肿瘤标本使用OncoKids®检测板进行基于DNA和RNA的下一代测序，并进行染色体微阵列分析。
诊断时的中位年龄为13.0岁（范围：0.8 - 18.3岁），中位肿瘤大小为14.4 cm（范围：7.5 - 26.0 cm）。3例患者出现肺转移，6个肿瘤表现出包膜破裂。组织学显示多形性、深染的椭圆形、梭形或星状细胞，CD56呈阳性。TP53是唯一反复出现突变的基因，在10例病例中的9例中被鉴定出来。与单等位基因TP53突变（n = 2）相比，双等位基因TP53失活（突变加拷贝数丢失，n = 7）与更高的染色体复杂性相关。仅在双等位基因TP53失活的肿瘤中观察到19q13.42 - q13.43节段性增益，包括19号染色体微小RNA簇（C19MC）。未检测到具有临床意义的RNA融合。所有患者均接受了肿瘤切除术和基于ARST0332的化疗；6例肿瘤破裂患者中的4例还接受了全腹放疗。中位随访32.0个月（范围：3.0 - 81.2个月），9例有随访的患者均存活。
TP53突变是UESL的决定性分子事件，双等位基因失活与染色体复杂性增加和C19MC基因座增益有关。尽管其具有侵袭性，但多模式治疗可实现良好的预后。
