Department of Pathology (G.Z., A.R., C.L., A.B., A.P., L.H., E.M., R.V., D.X.) Department of Gynecology and Obstetrics (R.L.S, R.V.), The Johns Hopkins Medical Institute, Baltimore, Maryland.
Int J Gynecol Pathol. 2019 Sep;38(5):414-419. doi: 10.1097/PGP.0000000000000511.
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 mo 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 mediator complex subunit 12 (MED12), a gene commonly mutated in leiomyoma, breast fibroadenoma and phyllodes tumor, was identified. Given the MED12 mutation in this uterine OS, we propose possible mechanisms that account for the origin and development of this tumor.
原发性子宫骨肉瘤（OS）极为罕见。我们报告了一例 74 岁女性原发性子宫骨肉瘤伴肺转移。子宫肿瘤的组织病理学特征与由具有成骨/软骨分化和成骨形成的肿瘤细胞组成的纯软骨母细胞性 OS 一致。尽管接受多柔比星和奥拉单抗治疗，后来还接受姑息性放射治疗，但该患者在子宫切除术后 7 个月因多发远处转移而死亡。对这种高度侵袭性肿瘤进行了基于 637 个基因panel 的靶向下一代测序分析，但未检测到可进行靶向治疗的体细胞突变。相反，发现了一个 51 个核苷酸缺失突变，包括中介复合物亚基 12（MED12）的部分外显子 2，该基因在平滑肌瘤、乳腺纤维腺瘤和叶状肿瘤中经常发生突变。鉴于该子宫骨肉瘤中的 MED12 突变，我们提出了可能的机制来解释该肿瘤的起源和发展。
