{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T12:12:20Z","timestamp":1792239140159,"version":"4.4.0"},"reference-count":28,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T00:00:00Z","timestamp":1630627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006383","name":"Sy\u00f6p\u00e4j\u00e4rjest\u00f6t","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Obstet Gynecol Scand"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Hereditary leiomyomatosis and renal cell cancer (HLRCC) constitute a tumor susceptibility syndrome caused by germline mutations in the fumarate hydratase (<jats:italic>FH<\/jats:italic>) gene. The most common features are leiomyomas of the uterus and the skin. The syndrome includes a predisposition to early\u2010onset, aggressive renal cell cancer. It is important to identify women with HLRCC among other uterine leiomyoma patients in order to direct them to genetic counseling and to identify other affected family members.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>We conducted a nationwide historical study to identify typical clinical characteristics, uterine leiomyoma morphology, and immunohistochemistry for diagnosing HLRCC. The study included 20 women with a known <jats:italic>FH<\/jats:italic> germline mutation and 77 women with sporadic uterine leiomyomas. The patient records of all women were reviewed to obtain clinical details regarding their leiomyomas. Uterine leiomyoma tissue specimens from 43 HLRCC\u2010related leiomyomas and 42 sporadic leiomyomas were collected and prepared for histology analysis. A morphologic description was performed on hematoxylin &amp; eosin\u2010stained tissue slides, and immunohistochemical analysis was carried out for CD34, Bcl\u20102, and p53 stainings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The women with HLRCC were diagnosed with uterine leiomyomas at a young age compared with the sporadic leiomyoma group (mean 33.8\u00a0years vs. 45.4\u00a0years, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001), and their leiomyomas occurred as multiples compared with the sporadic leiomyoma group (more than four tumors 88.9% vs. 30.8%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). Congruently, these women underwent surgical treatment at younger age compared with the sporadic leiomyoma group (mean 37.3\u00a0years vs. 48.3\u00a0years, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). HLRCC leiomyomas had denser microvasculature highlighted by CD34 immunostaining when compared with the sporadic leiomyoma group (112.6\u00a0mean count\/high\u2010power field, SD 20.8 vs. 37.4 mean count\/high\u2010power field, SD 21.0 <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) and stronger anti\u2010apoptotic protein Bcl\u20102 immunostaining when compared with the sporadic leiomyoma group (weak 4.7%, moderate 44.2%, strong 51.2% vs. 26.2%, 52.4%, 21.4%, respectively, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.003). No differences were observed in p53 staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Women with HLRCC may be identified through the distinct clinical characteristics: symptomatic and numerous leioymyomas at young age, and morphologic features of <jats:italic>FH<\/jats:italic>\u2010mutant leiomyomas, aided by Bcl\u20102 and CD34 immunohistochemistry. Further, distinguishing individuals with a germline <jats:italic>FH<\/jats:italic> mutation enables proper genetic counseling and regular renal monitoring.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aogs.14248","type":"journal-article","created":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T02:40:30Z","timestamp":1630723230000},"page":"2066-2075","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Uterine leiomyomas in hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome can be identified through distinct clinical characteristics and typical morphology"],"prefix":"10.1111","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8954-2900","authenticated-orcid":false,"given":"Outi","family":"Uimari","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Oulu University Hospital Oulu Finland"},{"name":"PEDEGO Research Unit University of Oulu and Oulu University Hospital Oulu Finland"},{"name":"Medical Research Center Oulu University of Oulu and Oulu University Hospital Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Ahtikoski","sequence":"additional","affiliation":[{"name":"Department of Pathology Oulu University Hospital and University of Oulu Oulu Finland"},{"name":"Department of Pathology Turku University Hospital and University of Turku Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kati","family":"K\u00e4mpj\u00e4rvi","sequence":"additional","affiliation":[{"name":"Research Programs Unit, Applied Tumor Genomics University of Helsinki Helsinki Finland"},{"name":"Department of Medical and Clinical Genetics University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Butzow","sequence":"additional","affiliation":[{"name":"Department of Pathology The Laboratory of Helsinki University Central Hospital (HUSLAB) Helsinki University Central Hospital and University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilkka Y.","family":"J\u00e4rvel\u00e4","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Kuopio University Hospital Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markku","family":"Ryyn\u00e4nen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Oulu University Hospital Oulu Finland"},{"name":"PEDEGO Research Unit University of Oulu and Oulu University Hospital Oulu Finland"},{"name":"Medical Research Center Oulu University of Oulu and Oulu University Hospital Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauri A.","family":"Aaltonen","sequence":"additional","affiliation":[{"name":"Research Programs Unit, Applied Tumor Genomics University of Helsinki Helsinki Finland"},{"name":"Department of Medical and Clinical Genetics University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Vahteristo","sequence":"additional","affiliation":[{"name":"Research Programs Unit, Applied Tumor Genomics University of Helsinki Helsinki Finland"},{"name":"Department of Medical and Clinical Genetics University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Outi","family":"Kuismin","sequence":"additional","affiliation":[{"name":"PEDEGO Research Unit University of Oulu and Oulu University Hospital Oulu Finland"},{"name":"Medical Research Center Oulu University of Oulu and Oulu University Hospital Oulu Finland"},{"name":"Department of Clinical Genetics Oulu University Hospital Oulu 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