低级别子宫内膜间质肉瘤

doi:10.12280/gjfckx.20220277

摘要/Abstract

摘要：

低级别子宫内膜间质肉瘤（low-grade endometrial stromal sarcoma，LG-ESS）是一类罕见的间叶源性恶性肿瘤，也是子宫内膜间质肉瘤最常见的亚型。LG-ESS作为遗传异质性疾病具有许多特征性的染色体易位，融合基因表达的异常融合蛋白是LG-ESS发展的重要驱动因素，同时也为其提供了潜在的治疗靶点。LG-ESS为低度恶性肿瘤，以生长缓慢、晚期复发为特征，骨盆辐射和长期使用他莫昔芬或雌激素为其重要危险因素。由于临床表现的不典型性，目前尚缺乏有效的术前诊断，形态学及联合应用免疫组织化学抗体有助于提高检出率，但价值有限。因此其诊治对于临床医师而言，仍是一个巨大挑战。综述LG-ESS的分子机制、临床表现、病理诊断、治疗及预后的研究进展。

关键词: 肉瘤，子宫内膜间质, 易位，遗传, 免疫组织化学, 妇科外科手术, 治疗, 预后

Abstract:

Low-grade endometrial stromal sarcoma (LG-ESS) is a rare type of malignant tumor of mesenchymal origin, which is also known as the most common subtype of endometrial stromal sarcoma. As a genetically heterogeneous disease, LG-ESS has many characteristic chromosomal translocations. Abnormal fusion proteins expressed by fusion genes are an important driving factor for the development of LG-ESS and also provide potential therapeutic targets for LG-ESS. LG-ESS is a low-grade malignant tumor characterized by slow growth and late recurrence, with pelvic radiation and long-term use of tamoxifen or estrogen as important risk factors. Due to the atypial of clinical manifestations, there is still a lack of effective preoperative diagnosis. Morphology and combined application of immunohistochemical antibodies can improve the detection rate, but their value is limited. Therefore, its diagnosis and treatment remains a great challenge for clinicians. This article reviews the molecular mechanisms, clinical manifestations, pathological diagnosis, treatment and prognosis of LG-ESS.

Key words: Sarcoma, endometrial stromal, Translocation, genetic, Immunohistochemistry, Gynecologic surgical procedures, Therapy, Prognosis

季安璇, 张群, 王晴, 赵淑华. 低级别子宫内膜间质肉瘤[J]. 国际妇产科学杂志, 2022, 49(6): 611-615.

JI An-xuan, ZHANG Qun, WANG Qing, ZHAO Shu-hua. Low-Grade Endometrial Stromal Sarcoma[J]. Journal of International Obstetrics and Gynecology, 2022, 49(6): 611-615.

参考文献 36

[1]	Ali RH, Rouzbahman M. Endometrial stromal tumours revisited: an update based on the 2014 WHO classification[J]. J Clin Pathol, 2015, 68(5):325-332. doi: 10.1136/jclinpath-2014-202829. doi: 10.1136/jclinpath-2014-202829 pmid: 25595274
[2]	Norris HJ, Taylor HB. Mesenchymal tumors of the uterus. I. A clinical and pathological study of 53 endometrial stromal tumors[J]. Cancer, 1966, 19(6):755-766. doi: 10.1002/1097-0142(196606)19:6<755::aid-cncr2820190604>3.0.co;2-u.. doi: 10.1002/1097-0142(196606)19:6<755::aid-cncr2820190604>3.0.co;2-u. pmid: 5939046
[3]	Micci F, Heim S, Panagopoulos I. Molecular pathogenesis and prognostication of "low-grade" and "high-grade" endometrial stromal sarcoma[J]. Genes Chromosomes Cancer, 2021, 60(3):160-167. doi: 10.1002/gcc.22907. doi: 10.1002/gcc.22907
[4]	Lee CH, Nucci MR. Endometrial stromal sarcoma--the new genetic paradigm[J]. Histopathology, 2015, 67(1):1-19. doi: 10.1111/his.12594. doi: 10.1111/his.12594
[5]	Female Genital Tumours: WHO Classification of Tumours[M]. 5th ed. Lyon, France: IARC Publications, 2020.
[6]	Sreekantaiah C, Li FP, Weidner N, et al. An endometrial stromal sarcoma with clonal cytogenetic abnormalities[J]. Cancer Genet Cytogenet, 1991, 55(2):163-166. doi: 10.1016/0165-4608(91)90073-4. doi: 10.1016/0165-4608(91)90073-4
[7]	Oliva E, de Leval L, Soslow RA, et al. High frequency of JAZF1-JJAZ1 gene fusion in endometrial stromal tumors with smooth muscle differentiation by interphase FISH detection[J]. Am J Surg Pathol, 2007, 31(8):1277-1284. doi: 10.1097/PAS.0b013e318031f012. doi: 10.1097/PAS.0b013e318031f012 pmid: 17667554
[8]	Ma X, Wang J, Wang J, et al. The JAZF1-SUZ12 fusion protein disrupts PRC2 complexes and impairs chromatin repression during human endometrial stromal tumorogenesis[J]. Oncotarget, 2017, 8(3):4062-4078. doi: 10.18632/oncotarget.13270. doi: 10.18632/oncotarget.13270 pmid: 27845897
[9]	D′Angelo E, Ali RH, Espinosa I, et al. Endometrial stromal sarcomas with sex cord differentiation are associated with PHF1 rearrangement[J]. Am J Surg Pathol, 2013, 37(4):514-521. doi: 10.1097/PAS.0b013e318272c612. doi: 10.1097/PAS.0b013e318272c612 pmid: 23211293
[10]	Han L, Liu YJ, Ricciotti RW, et al. A novel MBTD1-PHF1 gene fusion in endometrial stromal sarcoma: A case report and literature review[J]. Genes Chromosomes Cancer, 2020, 59(7):428-432. doi: 10.1002/gcc.22845. doi: 10.1002/gcc.22845
[11]	Dermawan JK, Zhang L, Singer S, et al. Low-grade endometrial stromal sarcoma-like tumors in male with JAZF1 gene fusions[J]. Genes Chromosomes Cancer, 2022, 61(2):63-70. doi: 10.1002/gcc.23003. doi: 10.1002/gcc.23003
[12]	Li C, Wang C. LG-ESSs and HG-ESSs: underlying molecular alterations and potential therapeutic strategies[J]. J Zhejiang Univ Sci B, 2021, 22(8):633-646. doi: 10.1631/jzus.B2000797. doi: 10.1631/jzus.B2000797
[13]	Przybyl J, Kidzinski L, Hastie T, et al. Gene expression profiling of low-grade endometrial stromal sarcoma indicates fusion protein-mediated activation of the Wnt signaling pathway[J]. Gynecol Oncol, 2018, 149(2):388-393. doi: 10.1016/j.ygyno.2018.03.007. doi: S0090-8258(18)30177-X pmid: 29544705
[14]	Wang Z, Li Z, Ji H. Direct targeting of β-catenin in the Wnt signaling pathway: Current progress and perspectives[J]. Med Res Rev, 2021, 41(4):2109-2129. doi: 10.1002/med.21787. doi: 10.1002/med.21787 pmid: 33475177
[15]	Denny L, Quinn M. FIGO Cancer Report 2015[J]. Int J Gynaecol Obstet, 2015, 131(Suppl 2):S75. doi: 10.1016/j.ijgo.2015.06.024. doi: 10.1016/j.ijgo.2015.06.024
[16]	Rebegea LF, Firescu D, Anghel RM, et al. Clinical, histological and therapeutical aspects in the management of uterine and extrauterine stromal sarcomas: Case reports[J]. Exp Ther Med, 2021, 22(6):1456. doi: 10.3892/etm.2021.10891. doi: 10.3892/etm.2021.10891 pmid: 34737796
[17]	陈涛, 罗霄, 李灵晶, 等. 子宫内膜间质肿瘤伴平滑肌分化1例[J]. 浙江实用医学, 2020, 25(4):298-299,305. doi: 10.16794/j.cnki.cn33-1207/r.2020.04.023. doi: 10.16794/j.cnki.cn33-1207/r.2020.04.023
[18]	Kim HS, Yoon G, Jung YY, et al. Fibromyxoid variant of endometrial stromal sarcoma with atypical bizarre nuclei[J]. Int J Clin Exp Pathol, 2015, 8(3):3316-3321.
[19]	Subbaraya S, Murthy SS, Devi GS. Immunohistochemical and Molecular Characterization of Endometrial Stromal Sarcomas[J]. Clin Pathol, 2020, 13:2632010X20916736. doi: 10.1177/2632010X20916736. doi: 10.1177/2632010X20916736
[20]	Alan S, Yilmaz E, Tecellioglu F, et al. Multifocal low-grade endometrial stromal sarcoma arising from pre-existing endometriosis in a hysterectomised patient: a case report[J]. J Obstet Gynaecol, 2019, 39(8):1177-1180. doi: 10.1080/01443615.2019.1587599. doi: 10.1080/01443615.2019.1587599 pmid: 31195864
[21]	Akaev I, Yeoh CC, Rahimi S. Update on Endometrial Stromal Tumours of the Uterus[J]. Diagnostics (Basel), 2021, 11(3):429. doi: 10.3390/diagnostics11030429. doi: 10.3390/diagnostics11030429
[22]	Behtash N, Akhavan S, Gilani MM, et al. Low grade endometrial stromal sarcoma of uterine: review of 17 cases[J]. Acta Med Iran, 2011, 49(9):619-624. pmid: 22052146
[23]	Ali SI, Sayyed RH, Bakar MA, et al. A retrospective study of endometrial stromal sarcoma: an institutional review[J]. J Pak Med Assoc, 2020, 70(5):926-929. doi: 10.5455/JPMA.299808. doi: 10.5455/JPMA.299808 pmid: 32400756
[24]	Zheng Y, Yin Q, Yang X, et al. Fertility-sparing management of low-grade endometrial stromal sarcoma: analysis of an institutional series, a population-based analysis and review of the literature[J]. Ann Transl Med, 2020, 8(21):1358. doi: 10.21037/atm-20-2180. doi: 10.21037/atm-20-2180 pmid: 33313103
[25]	Gu YZ, Duan NY, Cheng HX, et al. Fertility-sparing surgeries without adjuvant therapy through term pregnancies in a patient with low-grade endometrial stromal sarcoma: A case report[J]. World J Clin Cases, 2021, 9(4):983-991. doi: 10.12998/wjcc.v9.i4.983. doi: 10.12998/wjcc.v9.i4.983
[26]	Dai Q, Xu B, Wu H, et al. The prognosis of recurrent low-grade endometrial stromal sarcoma: a retrospective cohort study[J]. Orphanet J Rare Dis, 2021, 16(1):160. doi: 10.1186/s13023-021-01802-8. doi: 10.1186/s13023-021-01802-8 pmid: 33827628
[27]	Li N, Wu LY, Zhang HT, et al. Treatment options in stage I endometrial stromal sarcoma: a retrospective analysis of 53 cases[J]. Gynecol Oncol, 2008, 108(2):306-311. doi: 10.1016/j.ygyno.2007.10.023. doi: 10.1016/j.ygyno.2007.10.023 pmid: 18061249
[28]	Nasioudis D, Ko EM, Kolovos G, et al. Ovarian preservation for low-grade endometrial stromal sarcoma: a systematic review of the literature and meta-analysis[J]. Int J Gynecol Cancer, 2019, 29(1):126-132. doi: 10.1136/ijgc-2018-000063. doi: 10.1136/ijgc-2018-000063 pmid: 30640694
[29]	Nasioudis D, Chapman-Davis E, Frey M, et al. Safety of ovarian preservation in premenopausal women with stage I uterine sarcoma[J]. J Gynecol Oncol, 2017, 28(4):e46. doi: 10.3802/jgo.2017.28.e46. doi: 10.3802/jgo.2017.28.e46
[30]	Wang W, Sun S, Miao Z, et al. Adjuvant Radiotherapy Improved Survival in Stage I to II Low-Grade Endometrial Stromal Sarcoma: A Retrospective Study of 152 Cases[J]. Front Oncol, 2020, 10:608152. doi: 10.3389/fonc.2020.608152. doi: 10.3389/fonc.2020.608152
[31]	Wu J, Zhang H, Li L, et al. A nomogram for predicting overall survival in patients with low-grade endometrial stromal sarcoma: A population-based analysis[J]. Cancer Commun(Lond), 2020, 40(7):301-312. doi: 10.1002/cac2.12067. doi: 10.1002/cac2.12067
[32]	Deshmukh U, Black J, Perez-Irizarry J, et al. Adjuvant Hormonal Therapy for Low-Grade Endometrial Stromal Sarcoma[J]. Reprod Sci, 2019, 26(5):600-608. doi: 10.1177/1933719118778801. doi: 10.1177/1933719118778801 pmid: 29843577
[33]	Abu-Rustum NR, Yashar CM, Bradley K, et al. NCCN Guidelines Insights: Uterine Neoplasms, Version 3.2021[J]. J Natl Compr Canc Netw, 2021, 19(8):888-895. doi: 10.6004/jnccn.2021.0038. doi: 10.6004/jnccn.2021.0038
[34]	Altal OF, Al Sharie AH, Halalsheh OM, et al. Complete remission of advanced low-grade endometrial stromal sarcoma after aromatase inhibitor therapy: a case report[J]. J Med Case Rep, 2021, 15(1):262. doi: 10.1186/s13256-021-02838-x. doi: 10.1186/s13256-021-02838-x
[35]	Seagle BL, Shilpi A, Buchanan S, et al. Low-grade and high-grade endometrial stromal sarcoma: A National Cancer Database study[J]. Gynecol Oncol, 2017, 146(2):254-262. doi: 10.1016/j.ygyno.2017.05.036. doi: 10.1016/j.ygyno.2017.05.036
[36]	Spring LM, Wander SA, Andre F, et al. Cyclin-dependent kinase 4 and 6 inhibitors for hormone receptor-positive breast cancer: past, present, and future[J]. Lancet, 2020, 395(10226):817-827. doi: 10.1016/S0140-6736(20)30165-3. doi: S0140-6736(20)30165-3 pmid: 32145796