{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:51:15Z","timestamp":1786978275606,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Leiomyoma with bizarre nuclei (LM\u2010BN) is a rare variant of leiomyoma with a benign clinical course. In contrast, leiomyosarcoma (LMS) is a high\u2010grade, malignant neoplasm characterized by high recurrence rates and poor survival. While LM\u2010BN and LMS show distinct morphologies, they share similar immunoprofiles and molecular alterations, with both considered \u2018genomically unstable\u2019. Rare cases of LM\u2010BN 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\u2010BN confirmed by histology and immunohistochemistry (IHC), further analyzed by clinical, histologic, and molecular characteristics of these distinct components. LM\u2010BN and LMS had similar p16 and p53 IHC patterns, but LMS had a higher Ki\u201067 index and lower estrogen and progesterone eceptor expression. Digital image analysis based on cytologic features revealed spatial relationships between LMS and LM\u2010BN. Genomic copy number alterations (CNAs) demonstrated the same clonal origin of LMS arising from existing LM\u2010BN through conserved CNAs. LMS harbored highly complex CNAs and more frequent losses of the\n                    <jats:italic>TP53<\/jats:italic>\n                    ,\n                    <jats:italic>RB1<\/jats:italic>\n                    , and\n                    <jats:italic>PTEN<\/jats:italic>\n                    genomic regions than LM\u2010BN (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0031), with\n                    <jats:italic>CDKN2A\/B<\/jats:italic>\n                    deletion identified in LMS only. Mutational profiling revealed many shared oncogenic alterations in both LM\u2010BN 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\u2010BN, LMS, and other cell types. Our findings indicate for the first time that a subset of LMS arises from an existing LM\u2010BN, and highly complex genomic alterations could be potential high risks associated with disease progression in LM\u2010BN. \u00a9 2024 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6379","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T04:49:18Z","timestamp":1734497358000},"page":"211-225","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Genomic characterization and histologic analysis of uterine leiomyosarcoma arising from leiomyoma with bizarre nuclei"],"prefix":"10.1002","volume":"265","author":[{"given":"Christopher","family":"Felicelli","sequence":"first","affiliation":[{"name":"Department of Pathology Northwestern University Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pathology Northwestern University Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Coty\u2010Fattal","sequence":"additional","affiliation":[{"name":"Department of Pathology Northwestern University Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pathology Northwestern University Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Northwestern University Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew John","family":"Schipma","sequence":"additional","affiliation":[{"name":"Lurie Cancer Center Northwestern University, Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie J","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Northwestern University Feinberg School of Medicine  Chicago IL USA"},{"name":"Lurie Cancer Center Northwestern University, Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence J","family":"Jennings","sequence":"additional","affiliation":[{"name":"Department of Pathology Northwestern University Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serdar E","family":"Bulun","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Northwestern University Feinberg School of Medicine  Chicago IL USA"},{"name":"Lurie Cancer Center Northwestern University, Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0281-2793","authenticated-orcid":false,"given":"Jian\u2010Jun","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pathology Northwestern University Feinberg School of Medicine  Chicago IL USA"},{"name":"Department of Obstetrics and Gynecology Northwestern University Feinberg School of Medicine  Chicago IL USA"},{"name":"Lurie Cancer Center Northwestern University, Feinberg School of Medicine  Chicago IL 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