{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T08:56:30Z","timestamp":1789721790895,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473150"],"award-info":[{"award-number":["82473150"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2705805"],"award-info":[{"award-number":["2023YFC2705805"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Fumarate hydratase\u2010deficient uterine leiomyomas (FHd\u2010ULMs) represent a molecularly distinct subgroup of smooth muscle tumours associated with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. This study determined the detection rate of germline pathogenic\n                    <jats:italic>FH<\/jats:italic>\n                    variants in FHd\u2010ULMs using paired tumour\u2010normal sequencing and assessed the utility of integrated morphological, immunohistochemical (FH\/2SC), genomic, and clinical features for selecting cases suspected of HLRCC. Histopathological assessment of the 252 FHd\u2010ULMs revealed consistent morphological features, whereas molecular profiling identified three biologically distinct categories. Germline\n                    <jats:italic>FH<\/jats:italic>\n                    \u2010mutated (hereditary) cases constituted 35.7% (74\/207) of this FHd\u2010ULM cohort, four of which showed concomitant somatic copy\u2010number alterations. This contrasted with the somatic\u2010mutated subgroup, which comprised 50.7% (105\/207), including 18.4% (38\/207) with isolated somatic copy\u2010number losses. The remaining 13.6% (28\/207), though lacking detectable\n                    <jats:italic>FH<\/jats:italic>\n                    mutations, were classified with somatic\u2010mutated cases as sporadic FHd\u2010ULMs based on shared clinicopathological features. Molecular analysis identified shared variant distributions across exons 2\u201310, with exons 5 and 7 in the fumarate lyase domain emerging as the predominant mutational hotspots. Notably, truncating mutations showed significantly higher prevalence in hereditary cases versus somatic variants (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01). Clinically, hereditary FHd\u2010ULMs presented at younger ages (&lt;\u200945\u2009years) and manifested more aggressive phenotypes, including elevated rates of infertility (54.1% versus 26.4%), multifocal tumour development (86.5% versus 53.4%), increased surgical interventions (44.6% versus 11.5%), and familial leiomyoma clustering (51.4% versus 24.2%). Our results identify germline FH mutations, which confer significant HLRCC risk, in 35.7% of FHd\u2010ULMs, while somatic alterations account for the majority of cases. To ensure efficient resource allocation, we propose a stratified diagnostic approach: initial universal FH\/2SC immunohistochemical screening for ULMs displaying \u2265\u20093 FH\u2010deficient morphological features, followed by confirmatory genetic testing in high\u2010risk individuals, defined by either aberrant FH\/2SC immunoreactivity or, in immunohistochemically normal cases, age &lt;\u200945\u2009years together with a personal\/family history of multiple symptomatic leiomyomas or HLRCC\u2010associated neoplasms. \u00a9 2026 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70016","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T07:33:37Z","timestamp":1767771217000},"page":"340-352","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Integrated morphological, immunohistochemical, and genomic profiling identifies uterine leiomyoma patients with hereditary leiomyomatosis and renal cell cancer syndrome: a comprehensive analysis of 252 cases"],"prefix":"10.1002","volume":"268","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4000-1273","authenticated-orcid":false,"given":"Yan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pathology Third Hospital, School of Basic Medical Sciences, Peking University Health Science Center  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology China\u2010Japan Friendship Hospital  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology Third Hospital, School of Basic Medical Sciences, Peking University Health Science Center  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Ting","sequence":"additional","affiliation":[{"name":"Department of Pathology Third Hospital, School of Basic Medical Sciences, Peking University Health Science Center  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1574-4428","authenticated-orcid":false,"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology Third Hospital, School of Basic Medical Sciences, Peking University Health Science Center  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pathology Third Hospital, School of Basic Medical Sciences, Peking University Health Science Center  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixiu","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pathology Third Hospital, School of Basic Medical Sciences, Peking University Health Science Center  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congrong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology Third Hospital, School of Basic Medical Sciences, Peking University Health Science Center  Beijing PR 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