Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Classification and treatment of endometrial stromal sarcoma and uterine adenosarcoma

Stéphanie Gaillard, MD, PhD
Angeles Alvarez Secord, MD
Section Editors
Barbara Goff, MD
Rochelle L Garcia, MD
Don S Dizon, MD, FACP
Deputy Editors
Sadhna R Vora, MD
Sandy J Falk, MD, FACOG


Endometrial stromal neoplasms are a subset of uterine mesenchymal neoplasms that account for less than 10 percent of uterine sarcomas and approximately 1 percent of all uterine malignant neoplasms [1]. The World Health Organization classifies endometrial stromal neoplasms into three categories: endometrial stromal nodule (ESN), endometrial stromal sarcoma (ESS), and undifferentiated endometrial sarcoma (UES). ESN is a benign neoplasm that is cured with simple hysterectomy. Therefore, much of this discussion will focus on ESS and UES, which are neoplasms with metastatic potential.

Uterine adenosarcoma is a rare mixed epithelial-nonepithelial neoplasm that accounts for 5 to 9 percent of all uterine sarcomas [2].

An overview on the classification, clinical manifestations, diagnosis, and treatment of these and other uterine sarcomas, including leiomyosarcoma, is covered separately. (See "Uterine sarcoma: Classification, clinical manifestations, and diagnosis".)


Endometrial stromal neoplasms were historically characterized as either low-grade or high-grade neoplasms, and this classification is used in older literature (some of which is cited in this topic) [3]. However, high-grade endometrial stromal neoplasms are more commonly referred to as undifferentiated endometrial sarcomas (UES) or high-grade undifferentiated uterine sarcomas (HGUS), reflecting their composition of anaplastic cells with little or no evidence of endometrial stromal differentiation [4,5]. The term endometrial stromal sarcoma (ESS) is limited to neoplasms previously referred to as "low grade." In this topic review, when possible, we will use contemporary terminology.


The pathologic diagnosis of endometrial stromal neoplasms generally requires the evaluation of vasculature and borders for infiltration and invasion; thus, superficial endometrial biopsies are typically not sufficient to distinguish between benign and malignant neoplasms. A variant of uterine sarcomas comprised of non-neoplastic glandular epithelium associated with sarcoma is termed adenosarcoma. Because the approach to these neoplasms mirrors that of endometrial stromal neoplasms, they are included here.


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Jan 12, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Chan JK, Kawar NM, Shin JY, et al. Endometrial stromal sarcoma: a population-based analysis. Br J Cancer 2008; 99:1210.
  2. Tse KY, Crawford R, Ngan HY. Staging of uterine sarcomas. Best Pract Res Clin Obstet Gynaecol 2011; 25:733.
  3. Oliva E, Clement PB, Young RH. Endometrial stromal tumors: an update on a group of tumors with a protean phenotype. Adv Anat Pathol 2000; 7:257.
  4. Evans HL. Endometrial stromal sarcoma and poorly differentiated endometrial sarcoma. Cancer 1982; 50:2170.
  5. Chang KL, Crabtree GS, Lim-Tan SK, et al. Primary uterine endometrial stromal neoplasms. A clinicopathologic study of 117 cases. Am J Surg Pathol 1990; 14:415.
  6. Xue WC, Cheung AN. Endometrial stromal sarcoma of uterus. Best Pract Res Clin Obstet Gynaecol 2011; 25:719.
  7. Fdili Alaoui FZ, Chaara H, Bouguern H, et al. Endometrial stromal nodule: report of a case. Case Rep Med 2011; 2011:260647.
  8. Hendrickson MR, Tavassoli FA, Kempson RL, et al. Mesenchymal tumors and related lesions. In: World Health Organization Classication of Tumors: Pathology and Genetics- Tumors of the Breast and Female Genital Organs, FA Tavassoli and P Devilee. (Ed), International Agency for Research on Cancer, Lyon, France 2003. p.233.
  9. Amant F, Coosemans A, Debiec-Rychter M, et al. Clinical management of uterine sarcomas. Lancet Oncol 2009; 10:1188.
  10. Clement PB, Scully RE. Mullerian adenosarcoma of the uterus: a clinicopathologic analysis of 100 cases with a review of the literature. Hum Pathol 1990; 21:363.
  11. Verschraegen CF, Vasuratna A, Edwards C, et al. Clinicopathologic analysis of mullerian adenosarcoma: the M.D. Anderson Cancer Center experience. Oncol Rep 1998; 5:939.
  12. Arend R, Bagaria M, Lewin SN, et al. Long-term outcome and natural history of uterine adenosarcomas. Gynecol Oncol 2010; 119:305.
  13. Santos P, Cunha TM. Uterine sarcomas: clinical presentation and MRI features. Diagn Interv Radiol 2015; 21:4.
  14. Huang PS, Chang WC, Huang SC. Müllerian adenosarcoma: a review of cases and literature. Eur J Gynaecol Oncol 2014; 35:617.
  15. Blom R, Guerrieri C. Adenosarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53 and mdm-2 analysis of 11 cases. Int J Gynecol Cancer 1999; 9:37.
  16. Clement PB. Müllerian adenosarcomas of the uterus with sarcomatous overgrowth. A clinicopathological analysis of 10 cases. Am J Surg Pathol 1989; 13:28.
  17. Kaku T, Silverberg SG, Major FJ, et al. Adenosarcoma of the uterus: a Gynecologic Oncology Group clinicopathologic study of 31 cases. Int J Gynecol Pathol 1992; 11:75.
  18. Carroll A, Ramirez PT, Westin SN, et al. Uterine adenosarcoma: an analysis on management, outcomes, and risk factors for recurrence. Gynecol Oncol 2014; 135:455.
  19. Rush DS, Tan J, Baergen RN, Soslow RA. h-Caldesmon, a novel smooth muscle-specific antibody, distinguishes between cellular leiomyoma and endometrial stromal sarcoma. Am J Surg Pathol 2001; 25:253.
  20. Chiang S, Ali R, Melnyk N, et al. Frequency of known gene rearrangements in endometrial stromal tumors. Am J Surg Pathol 2011; 35:1364.
  21. Koontz JI, Soreng AL, Nucci M, et al. Frequent fusion of the JAZF1 and JJAZ1 genes in endometrial stromal tumors. Proc Natl Acad Sci U S A 2001; 98:6348.
  22. Li H, Ma X, Wang J, et al. Effects of rearrangement and allelic exclusion of JJAZ1/SUZ12 on cell proliferation and survival. Proc Natl Acad Sci U S A 2007; 104:20001.
  23. Micci F, Panagopoulos I, Bjerkehagen B, Heim S. Consistent rearrangement of chromosomal band 6p21 with generation of fusion genes JAZF1/PHF1 and EPC1/PHF1 in endometrial stromal sarcoma. Cancer Res 2006; 66:107.
  24. Kruse AJ, Croce S, Kruitwagen RF, et al. Aggressive behavior and poor prognosis of endometrial stromal sarcomas with YWHAE-FAM22 rearrangement indicate the clinical importance to recognize this subset. Int J Gynecol Cancer 2014; 24:1616.
  25. Lee CH, Mariño-Enriquez A, Ou W, et al. The clinicopathologic features of YWHAE-FAM22 endometrial stromal sarcomas: a histologically high-grade and clinically aggressive tumor. Am J Surg Pathol 2012; 36:641.
  26. Lee CH, Ou WB, Mariño-Enriquez A, et al. 14-3-3 fusion oncogenes in high-grade endometrial stromal sarcoma. Proc Natl Acad Sci U S A 2012; 109:929.
  27. D'Angelo E, Prat J. Uterine sarcomas: a review. Gynecol Oncol 2010; 116:131.
  28. Tanner EJ, Garg K, Leitao MM Jr, et al. High grade undifferentiated uterine sarcoma: surgery, treatment, and survival outcomes. Gynecol Oncol 2012; 127:27.
  29. Kurihara S, Oda Y, Ohishi Y, et al. Endometrial stromal sarcomas and related high-grade sarcomas: immunohistochemical and molecular genetic study of 31 cases. Am J Surg Pathol 2008; 32:1228.
  30. D'Angelo E, Spagnoli LG, Prat J. Comparative clinicopathologic and immunohistochemical analysis of uterine sarcomas diagnosed using the World Health Organization classification system. Hum Pathol 2009; 40:1571.
  31. Howitt BE, Sholl LM, Dal Cin P, et al. Targeted genomic analysis of Müllerian adenosarcoma. J Pathol 2015; 235:37.
  32. Bansal N, Herzog TJ, Burke W, et al. The utility of preoperative endometrial sampling for the detection of uterine sarcomas. Gynecol Oncol 2008; 110:43.
  33. Gandolfo N, Gandolfo NG, Serafini G, Martinoli C. Endometrial stromal sarcoma of the uterus: MR and US findings. Eur Radiol 2000; 10:776.
  34. Tamai K, Koyama T, Saga T, et al. The utility of diffusion-weighted MR imaging for differentiating uterine sarcomas from benign leiomyomas. Eur Radiol 2008; 18:723.
  35. Tirumani SH, Ojili V, Shanbhogue AK, et al. Current concepts in the imaging of uterine sarcoma. Abdom Imaging 2013; 38:397.
  36. Chourmouzi D, Boulogianni G, Zarampoukas T, Drevelengas A. Sonography and MRI of tamoxifen-associated müllerian adenosarcoma of the uterus. AJR Am J Roentgenol 2003; 181:1673.
  37. Leath CA 3rd, Huh WK, Hyde J Jr, et al. A multi-institutional review of outcomes of endometrial stromal sarcoma. Gynecol Oncol 2007; 105:630.
  38. Shah JP, Bryant CS, Kumar S, et al. Lymphadenectomy and ovarian preservation in low-grade endometrial stromal sarcoma. Obstet Gynecol 2008; 112:1102.
  39. Gadducci A, Cosio S, Romanini A, Genazzani AR. The management of patients with uterine sarcoma: a debated clinical challenge. Crit Rev Oncol Hematol 2008; 65:129.
  40. Park JY, Kim DY, Kim JH, et al. The impact of tumor morcellation during surgery on the outcomes of patients with apparently early low-grade endometrial stromal sarcoma of the uterus. Ann Surg Oncol 2011; 18:3453.
  41. Riopel J, Plante M, Renaud MC, et al. Lymph node metastases in low-grade endometrial stromal sarcoma. Gynecol Oncol 2005; 96:402.
  42. Dos Santos LA, Garg K, Diaz JP, et al. Incidence of lymph node and adnexal metastasis in endometrial stromal sarcoma. Gynecol Oncol 2011; 121:319.
  43. Goff BA, Rice LW, Fleischhacker D, et al. Uterine leiomyosarcoma and endometrial stromal sarcoma: lymph node metastases and sites of recurrence. Gynecol Oncol 1993; 50:105.
  44. Signorelli M, Fruscio R, Dell'Anna T, et al. Lymphadenectomy in uterine low-grade endometrial stromal sarcoma: an analysis of 19 cases and a literature review. Int J Gynecol Cancer 2010; 20:1363.
  45. Kim WY, Lee JW, Choi CH, et al. Low-grade endometrial stromal sarcoma: a single center's experience with 22 cases. Int J Gynecol Cancer 2008; 18:1084.
  46. Amant F, De Knijf A, Van Calster B, et al. Clinical study investigating the role of lymphadenectomy, surgical castration and adjuvant hormonal treatment in endometrial stromal sarcoma. Br J Cancer 2007; 97:1194.
  47. Malouf GG, Duclos J, Rey A, et al. Impact of adjuvant treatment modalities on the management of patients with stages I-II endometrial stromal sarcoma. Ann Oncol 2010; 21:2102.
  48. Li N, Wu LY, Zhang HT, et al. Treatment options in stage I endometrial stromal sarcoma: a retrospective analysis of 53 cases. Gynecol Oncol 2008; 108:306.
  49. Bai H, Yang J, Cao D, et al. Ovary and uterus-sparing procedures for low-grade endometrial stromal sarcoma: a retrospective study of 153 cases. Gynecol Oncol 2014; 132:654.
  50. Ozmen B, Uzum N, Unlu C, et al. Surgical conservation of both ovaries in an adolescent with uterine müllerian adenosarcoma: a case report. J Minim Invasive Gynecol 2007; 14:375.
  51. NCCN Clinical Practice Guidelines in Oncology. Uterine Neoplasms. Version 3.2012. http://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf (Accessed on January 14, 2013).
  52. Tropé CG, Abeler VM, Kristensen GB. Diagnosis and treatment of sarcoma of the uterus. A review. Acta Oncol 2012; 51:694.
  53. Pink D, Lindner T, Mrozek A, et al. Harm or benefit of hormonal treatment in metastatic low-grade endometrial stromal sarcoma: single center experience with 10 cases and review of the literature. Gynecol Oncol 2006; 101:464.
  54. Chu MC, Mor G, Lim C, et al. Low-grade endometrial stromal sarcoma: hormonal aspects. Gynecol Oncol 2003; 90:170.
  55. Yamaguchi M, Erdenebaatar C, Saito F, et al. Long-Term Outcome of Aromatase Inhibitor Therapy With Letrozole in Patients With Advanced Low-Grade Endometrial Stromal Sarcoma. Int J Gynecol Cancer 2015; 25:1645.
  56. Reich O, Regauer S. Hormonal therapy of endometrial stromal sarcoma. Curr Opin Oncol 2007; 19:347.
  57. Reed NS, Mangioni C, Malmström H, et al. Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: an European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874). Eur J Cancer 2008; 44:808.
  58. Barney B, Tward JD, Skidmore T, Gaffney DK. Does radiotherapy or lymphadenectomy improve survival in endometrial stromal sarcoma? Int J Gynecol Cancer 2009; 19:1232.
  59. NCCN Guidelines Version 3.2012: Uterine Neoplasms. http://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf (Accessed on October 02, 2012).
  60. Brenner DJ, Hall EJ. Computed tomography--an increasing source of radiation exposure. N Engl J Med 2007; 357:2277.
  61. Chew I, Oliva E. Endometrial stromal sarcomas: a review of potential prognostic factors. Adv Anat Pathol 2010; 17:113.
  62. Kosary CL. Cancer of the Corpus Uteri. In: SEER Survival Monograph: Cancer Survival Among Adults: U.S. SEER Program, 1988-2001, Patient and Tumor Characteristics, NCI, SEER Program. (Eds), National Cancer Institute, Bethesda, MD 2007. p.123.
  63. Cheng X, Yang G, Schmeler KM, et al. Recurrence patterns and prognosis of endometrial stromal sarcoma and the potential of tyrosine kinase-inhibiting therapy. Gynecol Oncol 2011; 121:323.
  64. Beck TL, Singhal PK, Ehrenberg HM, et al. Endometrial stromal sarcoma: analysis of recurrence following adjuvant treatment. Gynecol Oncol 2012; 125:141.
  65. Batista LM, Carvalho CH, Acioly MA, et al. Spinal metastasis of endometrial stromal sarcoma: clinicopathological features and management. Surg Oncol 2011; 20:e78.
  66. Huang MI, Debernardo RL, Rodgers M, Hart DJ. Endometrial stromal sarcoma metastasis to the lumbar spine and sphenoid bone. Rare Tumors 2011; 3:e27.
  67. Thomas MB, Keeney GL, Podratz KC, Dowdy SC. Endometrial stromal sarcoma: treatment and patterns of recurrence. Int J Gynecol Cancer 2009; 19:253.
  68. Dahhan T, Fons G, Buist MR, et al. The efficacy of hormonal treatment for residual or recurrent low-grade endometrial stromal sarcoma. A retrospective study. Eur J Obstet Gynecol Reprod Biol 2009; 144:80.
  69. Nakayama K, Ishikawa M, Nagai Y, et al. Prolonged long-term survival of low-grade endometrial stromal sarcoma patients with lung metastasis following treatment with medroxyprogesterone acetate. Int J Clin Oncol 2010; 15:179.
  70. Altman AD, Nelson GS, Chu P, et al. Uterine sarcoma and aromatase inhibitors: Tom Baker Cancer Centre experience and review of the literature. Int J Gynecol Cancer 2012; 22:1006.
  71. Burke C, Hickey K. Treatment of endometrial stromal sarcoma with a gonadotropin-releasing hormone analogue. Obstet Gynecol 2004; 104:1182.
  72. Mesia AF, Demopoulos RI. Effects of leuprolide acetate on low-grade endometrial stromal sarcoma. Am J Obstet Gynecol 2000; 182:1140.
  73. Anraku M, Yokoi K, Nakagawa K, et al. Pulmonary metastases from uterine malignancies: results of surgical resection in 133 patients. J Thorac Cardiovasc Surg 2004; 127:1107.
  74. Leitao MM, Brennan MF, Hensley M, et al. Surgical resection of pulmonary and extrapulmonary recurrences of uterine leiomyosarcoma. Gynecol Oncol 2002; 87:287.
  75. Levenback C, Rubin SC, McCormack PM, et al. Resection of pulmonary metastases from uterine sarcomas. Gynecol Oncol 1992; 45:202.
  76. Giuntoli RL 2nd, Garrett-Mayer E, Bristow RE, Gostout BS. Secondary cytoreduction in the management of recurrent uterine leiomyosarcoma. Gynecol Oncol 2007; 106:82.
  77. Friedlander ML, Covens A, Glasspool RM, et al. Gynecologic Cancer InterGroup (GCIG) consensus review for mullerian adenosarcoma of the female genital tract. Int J Gynecol Cancer 2014; 24:S78.
  78. Tanner EJ, Toussaint T, Leitao MM Jr, et al. Management of uterine adenosarcomas with and without sarcomatous overgrowth. Gynecol Oncol 2013; 129:140.
  79. del Carmen MG, Lovett D, Goodman A. A case of Müllerian adenosarcoma of the uterus treated with liposomal doxorubicin. Gynecol Oncol 2003; 88:456.
  80. Schroeder BA, Rodler ET, Loggers ET, et al. Clinical benefit of trabectedin in uterine adenosarcoma. Med Oncol 2013; 30:501.