Genomic characterization and histologic analysis of uterine leiomyosarcoma arising from leiomyoma with bizarre nuclei.

IF 5.6 2区 医学 Q1 ONCOLOGY The Journal of Pathology Pub Date : 2024-12-18 DOI:10.1002/path.6379
Christopher Felicelli, Xinyan Lu, Zachary Coty-Fattal, Yue Feng, Ping Yin, Matthew John Schipma, Julie J Kim, Lawrence J Jennings, Serdar E Bulun, Jian-Jun Wei
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引用次数: 0

Abstract

Leiomyoma with bizarre nuclei (LM-BN) is a rare variant of leiomyoma with a benign clinical course. In contrast, leiomyosarcoma (LMS) is a high-grade, malignant neoplasm characterized by high recurrence rates and poor survival. While LM-BN and LMS show distinct morphologies, they share similar immunoprofiles and molecular alterations, with both considered 'genomically unstable'. Rare cases of LM-BN associated with LMS have been reported; however, the histogenesis and molecular relationship between these two tumors remains unclear. In this study, we assessed 11 cases of LMS arising in conjunction with LM-BN confirmed by histology and immunohistochemistry (IHC), further analyzed by clinical, histologic, and molecular characteristics of these distinct components. LM-BN and LMS had similar p16 and p53 IHC patterns, but LMS had a higher Ki-67 index and lower estrogen and progesterone eceptor expression. Digital image analysis based on cytologic features revealed spatial relationships between LMS and LM-BN. Genomic copy number alterations (CNAs) demonstrated the same clonal origin of LMS arising from existing LM-BN through conserved CNAs. LMS harbored highly complex CNAs and more frequent losses of the TP53, RB1, and PTEN genomic regions than LM-BN (p = 0.0031), with CDKN2A/B deletion identified in LMS only. Mutational profiling revealed many shared oncogenic alterations in both LM-BN and LMS; however, additional mutations were present within LMS, indicative of tumor progression through progressive genomic instability. Analysis of spatial transcriptomes defined uniquely expressed gene signatures that matched the geographic distribution of LM-BN, LMS, and other cell types. Our findings indicate for the first time that a subset of LMS arises from an existing LM-BN, and highly complex genomic alterations could be potential high risks associated with disease progression in LM-BN. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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来源期刊
The Journal of Pathology
The Journal of Pathology 医学-病理学
CiteScore
14.10
自引率
1.40%
发文量
144
审稿时长
3-8 weeks
期刊介绍: The Journal of Pathology aims to serve as a translational bridge between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The main interests of the Journal lie in publishing studies that further our understanding the pathophysiological and pathogenetic mechanisms of human disease. The Journal of Pathology welcomes investigative studies on human tissues, in vitro and in vivo experimental studies, and investigations based on animal models with a clear relevance to human disease, including transgenic systems. As well as original research papers, the Journal seeks to provide rapid publication in a variety of other formats, including editorials, review articles, commentaries and perspectives and other features, both contributed and solicited.
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