{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T04:06:15Z","timestamp":1754193975850},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:p>Primary osteosarcoma (OS) of the uterus is distinctly rare. We report a case of primary uterine OS with pulmonary metastasis in a 74-yr-old woman. Histopathologic features of the uterine tumor were in keeping with a pure chondroblastic OS composed of neoplastic cells with osteoblastic\/chondroblastic differentiation and neoplastic bone formation. Despite treatment with Doxorubicin and Olaratumab and later with palliative radiation therapy, the patient died 7\u2009mo after hysterectomy due to multiple distant metastases. A targeted next-generation sequencing assay based on a 637-gene panel was performed to analyze genetic alterations in this highly aggressive tumor, but no somatic mutations that are amenable to targeted therapy were detected. Rather, a 51-nucleotide deletion mutation including partial exon 2 of <jats:italic toggle=\"yes\">mediator complex subunit 12<\/jats:italic> (<jats:italic toggle=\"yes\">MED12<\/jats:italic>), a gene commonly mutated in leiomyoma, breast fibroadenoma and phyllodes tumor, was identified. Given the <jats:italic toggle=\"yes\">MED12<\/jats:italic> mutation in this uterine OS, we propose possible mechanisms that account for the origin and development of this tumor.<\/jats:p>","DOI":"10.1097\/pgp.0000000000000511","type":"journal-article","created":{"date-parts":[[2018,4,8]],"date-time":"2018-04-08T19:37:57Z","timestamp":1523216277000},"page":"414-419","source":"Crossref","is-referenced-by-count":9,"title":["Clinicopathologic Features and Genetic Alterations of a Primary Osteosarcoma of the Uterine Corpus"],"prefix":"10.1097","volume":"38","author":[{"given":"Gang","family":"Zheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abby","family":"Richmond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengbao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Berrebi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aparna","family":"Pallavajjala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Haley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca L.","family":"Stone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"McCarthy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russell","family":"Vang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deyin","family":"Xing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-20230824","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1016\/j.humpath.2014.04.010","article-title":"Changing prognostic factors in osteosarcoma: analysis of 381 cases from two institutions","volume":"45","author":"Xing","year":"2014","journal-title":"Hum Pathol"},{"key":"R2-20230824","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-4419-0284-9_1","article-title":"The epidemiology of osteosarcoma","volume":"152","author":"Ottaviani","year":"2009","journal-title":"Cancer Treat Res"},{"key":"R3-20230824","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1002\/cncr.24121","article-title":"Osteosarcoma incidence and survival rates from 1973 to 2004: data from the Surveillance, Epidemiology, and End Results Program","volume":"115","author":"Mirabello","year":"2009","journal-title":"Cancer"},{"key":"R4-20230824","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1002\/1097-0142(19951201)76:11<2253::AID-CNCR2820761112>3.0.CO;2-8","article-title":"A review of 40 patients with extraskeletal osteosarcoma","volume":"76","author":"Lee","year":"1995","journal-title":"Cancer"},{"key":"R5-20230824","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1111\/jog.13079","article-title":"Primary osteosarcoma of the uterine corpus: a case report","volume":"42","author":"Tsukasaki","year":"2016","journal-title":"J Obstet Gynaecol Res"},{"key":"R6-20230824","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1046\/j.1440-1827.2002.01325.x","article-title":"Primary osteosarcoma of the uterine corpus: case report and review of the literature","volume":"52","author":"Su","year":"2002","journal-title":"Pathol Int"},{"key":"R7-20230824","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/0020-7292(85)90146-8","article-title":"Primary osteosarcoma of the uterine corpus. Report of a case and critical review of the literature","volume":"23","author":"Piscioli","year":"1985","journal-title":"Int J Gynaecol Obstet"},{"key":"R8-20230824","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1006\/gyno.2001.6262","article-title":"Primary osteosarcoma of the uterine corpus: report of a case with immunohistochemical and ultrastructural study","volume":"82","author":"Hardisson","year":"2001","journal-title":"Gynecol Oncol"},{"key":"R9-20230824","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.gore.2014.07.002","article-title":"Primary osteosarcoma of the uterus with cardiac and pulmonary metastases","volume":"11","author":"Abraham","year":"2014","journal-title":"Gynecol Oncol Rep"},{"key":"R10-20230824","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/0090-8258(80)90036-0","article-title":"Osteosarcoma of the uterus: case report and review of the literature","volume":"9","author":"Crum","year":"1980","journal-title":"Gynecol Oncol"},{"key":"R11-20230824","first-page":"212","article-title":"Primary osteosarcoma of the uterus: report of a case with immunohistochemical study","volume":"5","author":"De Young","year":"1992","journal-title":"Mod Pathol"},{"key":"R12-20230824","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1006\/gyno.1994.1229","article-title":"Primary osteosarcoma of the uterus: report of a case with immunohistochemical analysis","volume":"54","author":"Emoto","year":"1994","journal-title":"Gynecol Oncol"},{"key":"R13-20230824","doi-asserted-by":"crossref","first-page":"544","DOI":"10.5144\/0256-4947.2012.23.5.1111","article-title":"An unusual case of an osteosarcoma arising in a leiomyoma of the uterus","volume":"32","author":"Kefeli","year":"2012","journal-title":"Ann Saudi Med"},{"key":"R14-20230824","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1111\/jog.13443","article-title":"Primary osteosarcoma of the uterine cervix: a case report","volume":"43","author":"Tsuji","year":"2017","journal-title":"J Obstet Gynaecol Res"},{"key":"R15-20230824","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1177\/1066896908327037","article-title":"Osteosarcoma arising in a long-standing uterine leiomyoma: a case report and literature review","volume":"19","author":"Wang","year":"2011","journal-title":"Int J Surg Pathol"},{"key":"R16-20230824","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1038\/leu.2016.63","article-title":"Donor cell leukemia arising from clonal hematopoiesis after bone marrow transplantation","volume":"30","author":"Gondek","year":"2016","journal-title":"Leukemia"},{"key":"R17-20230824","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/his.12138","article-title":"SATB2 is a novel marker of osteoblastic differentiation in bone and soft tissue tumours","volume":"63","author":"Conner","year":"2013","journal-title":"Histopathology"},{"key":"R18-20230824","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/jor.1100090504","article-title":"Mesenchymal stem cells","volume":"9","author":"Caplan","year":"1991","journal-title":"J Orthop Res"},{"key":"R19-20230824","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s00428-012-1235-x","article-title":"Smooth muscle actin expression in primary bone tumours","volume":"460","author":"Hemingway","year":"2012","journal-title":"Virchows Arch"},{"key":"R20-20230824","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.stemcr.2015.05.004","article-title":"Expression of alpha-smooth muscle actin determines the fate of mesenchymal stromal cells","volume":"4","author":"Talele","year":"2015","journal-title":"Stem Cell Reports"},{"key":"R21-20230824","doi-asserted-by":"crossref","first-page":"E5564","DOI":"10.1073\/pnas.1419260111","article-title":"Complementary genomic approaches highlight the PI3K\/mTOR pathway as a common vulnerability in osteosarcoma","volume":"111","author":"Perry","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R22-20230824","doi-asserted-by":"crossref","first-page":"e1005850","DOI":"10.1371\/journal.pgen.1005850","article-title":"Exome sequencing of uterine leiomyosarcomas identifies frequent mutations in TP53, ATRX, and MED12","volume":"12","author":"Makinen","year":"2016","journal-title":"PLoS Genet"},{"key":"R23-20230824","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1111\/his.12039","article-title":"Prevalence of MED12 mutations in uterine and extrauterine smooth muscle tumours","volume":"62","author":"Matsubara","year":"2013","journal-title":"Histopathology"},{"key":"R24-20230824","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.humpath.2013.08.005","article-title":"MED12 exon 2 mutations in uterine and extrauterine smooth muscle tumors","volume":"45","author":"Schwetye","year":"2014","journal-title":"Hum Pathol"},{"key":"R25-20230824","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/bjc.2015.116","article-title":"Frequent MED12 mutations in phyllodes tumours of the breast","volume":"112","author":"Yoshida","year":"2015","journal-title":"Br J Cancer"},{"key":"R26-20230824","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/ng.2279","article-title":"Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer","volume":"44","author":"Barbieri","year":"2012","journal-title":"Nat Genet"},{"key":"R27-20230824","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1111\/bjh.14869","article-title":"MED12 mutations and NOTCH signalling in chronic lymphocytic leukaemia","volume":"179","author":"Wu","year":"2017","journal-title":"Br J Haematol"},{"key":"R28-20230824","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.stem.2016.08.004","article-title":"MED12 regulates HSC-specific enhancers independently of mediator kinase activity to control hematopoiesis","volume":"19","author":"Aranda-Orgilles","year":"2016","journal-title":"Cell Stem Cell"},{"key":"R29-20230824","first-page":"534634","article-title":"Dedifferentiated leiomyosarcoma of the uterus with heterologous elements: a potential diagnostic pitfall","volume":"2012","author":"Rawish","year":"2012","journal-title":"Case Rep Obstet Gynecol"}],"container-title":["International Journal of Gynecological Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/PGP.0000000000000511","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T01:44:52Z","timestamp":1692841492000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/PGP.0000000000000511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019]]}},"URL":"https:\/\/doi.org\/10.1097\/pgp.0000000000000511","relation":{},"ISSN":["0277-1691"],"issn-type":[{"value":"0277-1691","type":"print"}],"subject":[],"published":{"date-parts":[[2019,9]]}}}