Uterine sarcoma: Classification, clinical manifestations, and diagnosis
- Sanaz Memarzadeh, MD, PhD
Sanaz Memarzadeh, MD, PhD
- Associate Professor
- Department of Obstetrics and Gynecology
- Division of Gynecologic Oncology
- David Geffen School of Medicine at UCLA
- Director G.O. Discovery Laboratory
- Jonathan S Berek, MD, MMS
Jonathan S Berek, MD, MMS
- Laurie Kraus Lacob Professor
- Director, Stanford Women's Cancer Center
- Stanford Comprehensive Cancer Institute
- Chair, Department of Obstetrics & Gynecology
- Stanford University School of Medicine
- Section Editors
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Professor of Gynecologic Oncology
- University of Washington
- Rochelle L Garcia, MD
Rochelle L Garcia, MD
- Section Editor — Obstetric and Gynecologic Pathology
- Professor of Pathology
- Adjunct Professor of Obstetrics & Gynecology
- University of Washington Medical Center
- Don S Dizon, MD, FACP
Don S Dizon, MD, FACP
- Section Editor – Gynecologic Oncology
- Clinical Co-Director, Gynecologic Oncology
- Founder and Director, The Oncology Sexual Health Clinic
- Massachusetts General Hospital Cancer Center
- Associate Professor of Medicine
- Harvard Medical School
Uterine sarcoma accounts for 3 to 9 percent of all uterine malignant neoplasms [1,2]. Uterine sarcomas arise from dividing cell populations in the myometrium or connective tissue elements within the endometrium. Compared with the more common endometrial carcinomas (epithelial neoplasms), uterine sarcomas, particularly leiomyosarcomas (connective tissue neoplasms), behave aggressively and are associated with a poorer prognosis. (See "Endometrial carcinoma: Pretreatment evaluation, staging, and surgical treatment".)
The classification, clinical manifestations, and staging of uterine sarcomas that arise in adults (eg, endometrial stromal sarcomas, leiomyosarcoma, adenosarcoma) are reviewed here. Staging and treatment of endometrial stromal tumors and leiomyosarcoma are discussed separately. Carcinosarcoma, which is no longer classified as a sarcoma, and rhabdomyosarcoma, which typically arises in children and adolescents, are also discussed separately. (See "Treatment and prognosis of uterine leiomyosarcoma" and "Classification and treatment of endometrial stromal sarcoma and uterine adenosarcoma" and "Clinical features, diagnosis, staging, and treatment of uterine carcinosarcoma" and "Rhabdomyosarcoma in childhood and adolescence: Epidemiology, pathology, and molecular pathogenesis".)
The World Health Organization (table 1) and College of American Pathologists (table 2) have published classification systems for uterine sarcomas. The histologic classification of these neoplasms is based upon the differentiation/growth pattern of the neoplastic cells and their presumed cell of origin.
Uterine sarcomas are referred to as homologous or heterologous. The majority are homologous (ie, differentiate in ways similar to normal uterine tissues), including endometrium (endometrial stromal sarcomas), muscle (leiomyosarcoma), or sarcomas of nonspecific supporting tissue (eg, connective tissue, blood vessels, lymphatics). In contrast, heterologous tumors contain elements with non-native differentiation (eg, skeletal muscle, cartilage, bone).
Historically, uterine carcinosarcoma was classified as a type of uterine sarcoma and was termed malignant mixed müllerian tumor or mixed mesodermal sarcoma. However, these neoplasms are now classified as carcinomas since they derive from a monoclonal neoplastic cell, which has more characteristics of epithelial than stromal neoplasms. In addition, the epidemiology, risk factors, and clinical behavior associated with carcinosarcoma suggest a closer relationship to endometrial carcinoma than to sarcoma. (See "Clinical features, diagnosis, staging, and treatment of uterine carcinosarcoma".)
- Nordal RR, Thoresen SO. Uterine sarcomas in Norway 1956-1992: incidence, survival and mortality. Eur J Cancer 1997; 33:907.
- Tropé CG, Abeler VM, Kristensen GB. Diagnosis and treatment of sarcoma of the uterus. A review. Acta Oncol 2012; 51:694.
- Bell SW, Kempson RL, Hendrickson MR. Problematic uterine smooth muscle neoplasms. A clinicopathologic study of 213 cases. Am J Surg Pathol 1994; 18:535.
- Silverberg SG, Kurman RJ. Tumors of the uterine corpus and gestational trophoblastic disease. In: Atlas of Tumor Pathology - Armed Forces Institute of Pathology, electronic fascicle version 2.0, Washington DC.
- Kurma RJ. Pathology of the Female Genital Tract, 4th, Springer Verlag, New York p.499.
- Sandberg AA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: leiomyosarcoma. Cancer Genet Cytogenet 2005; 161:1.
- Sandberg AA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: leiomyoma. Cancer Genet Cytogenet 2005; 158:1.
- Morton CC. Genetic approaches to the study of uterine leiomyomata. Environ Health Perspect 2000; 108 Suppl 5:775.
- Bodner K, Bodner-Adler B, Kimberger O, et al. Estrogen and progesterone receptor expression in patients with uterine leiomyosarcoma and correlation with different clinicopathological parameters. Anticancer Res 2003; 23:729.
- Wade K, Quinn MA, Hammond I, et al. Uterine sarcoma: steroid receptors and response to hormonal therapy. Gynecol Oncol 1990; 39:364.
- Moinfar F, Azodi M, Tavassoli FA. Uterine sarcomas. Pathology 2007; 39:55.
- Karpathiou G, Sivridis E, Giatromanolaki A. Myxoid leiomyosarcoma of the uterus: a diagnostic challenge. Eur J Gynaecol Oncol 2010; 31:446.
- Oliva E, Clement PB, Young RH, Scully RE. Mixed endometrial stromal and smooth muscle tumors of the uterus: a clinicopathologic study of 15 cases. Am J Surg Pathol 1998; 22:997.
- Kir G, Gurbuz A, Karateke A, Dayicioglu V. Stromomyomas of the uterus-- importance of total circumferential evaluation of the margin. Eur J Gynaecol Oncol 2004; 25:489.
- 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.
- Krivak TC, Seidman JD, McBroom JW, et al. Uterine adenosarcoma with sarcomatous overgrowth versus uterine carcinosarcoma: comparison of treatment and survival. Gynecol Oncol 2001; 83:89.
- Toro JR, Travis LB, Wu HJ, et al. Incidence patterns of soft tissue sarcomas, regardless of primary site, in the surveillance, epidemiology and end results program, 1978-2001: An analysis of 26,758 cases. Int J Cancer 2006; 119:2922.
- Brooks SE, Zhan M, Cote T, Baquet CR. Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999. Gynecol Oncol 2004; 93:204.
- Ueda SM, Kapp DS, Cheung MK, et al. Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths. Am J Obstet Gynecol 2008; 198:218.e1.
- Norris HJ, Taylor HB. Mesenchymal tumors of the uterus. I. A clinical and pathological study of 53 endometrial stromal tumors. Cancer 1966; 19:755.
- Sherman ME, Devesa SS. Analysis of racial differences in incidence, survival, and mortality for malignant tumors of the uterine corpus. Cancer 2003; 98:176.
- Mourits MJ, De Vries EG, Willemse PH, et al. Tamoxifen treatment and gynecologic side effects: a review. Obstet Gynecol 2001; 97:855.
- Yildirim Y, Inal MM, Sanci M, et al. Development of uterine sarcoma after tamoxifen treatment for breast cancer: report of four cases. Int J Gynecol Cancer 2005; 15:1239.
- Wysowski DK, Honig SF, Beitz J. Uterine sarcoma associated with tamoxifen use. N Engl J Med 2002; 346:1832.
- Wickerham DL, Fisher B, Wolmark N, et al. Association of tamoxifen and uterine sarcoma. J Clin Oncol 2002; 20:2758.
- http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm154510.htm (Accessed on October 12, 2010).
- Committee Opinion No. 601: Tamoxifen and uterine cancer. Obstet Gynecol 2014; 123:1394.
- Fang Z, Matsumoto S, Ae K, et al. Postradiation soft tissue sarcoma: a multiinstitutional analysis of 14 cases in Japan. J Orthop Sci 2004; 9:242.
- Giuntoli RL 2nd, Metzinger DS, DiMarco CS, et al. Retrospective review of 208 patients with leiomyosarcoma of the uterus: prognostic indicators, surgical management, and adjuvant therapy. Gynecol Oncol 2003; 89:460.
- Launonen V, Vierimaa O, Kiuru M, et al. Inherited susceptibility to uterine leiomyomas and renal cell cancer. Proc Natl Acad Sci U S A 2001; 98:3387.
- Toro JR, Nickerson ML, Wei MH, et al. Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America. Am J Hum Genet 2003; 73:95.
- Yu CL, Tucker MA, Abramson DH, et al. Cause-specific mortality in long-term survivors of retinoblastoma. J Natl Cancer Inst 2009; 101:581.
- Koivisto-Korander R, Butzow R, Koivisto AM, Leminen A. Clinical outcome and prognostic factors in 100 cases of uterine sarcoma: experience in Helsinki University Central Hospital 1990-2001. Gynecol Oncol 2008; 111:74.
- Liao Q, Wang J, Han J. [Clinical and pathological analysis on 106 cases with uterine sarcoma]. Zhonghua Fu Chan Ke Za Zhi 2001; 36:104.
- Schwartz Z, Dgani R, Lancet M, Kessler I. Uterine sarcoma in Israel: a study of 104 cases. Gynecol Oncol 1985; 20:354.
- Parker WH, Fu YS, Berek JS. Uterine sarcoma in patients operated on for presumed leiomyoma and rapidly growing leiomyoma. Obstet Gynecol 1994; 83:414.
- Leung F, Terzibachian JJ, Gay C, et al. [Hysterectomies performed for presumed leiomyomas: should the fear of leiomyosarcoma make us apprehend non laparotomic surgical routes?]. Gynecol Obstet Fertil 2009; 37:109.
- Leibsohn S, d'Ablaing G, Mishell DR Jr, Schlaerth JB. Leiomyosarcoma in a series of hysterectomies performed for presumed uterine leiomyomas. Am J Obstet Gynecol 1990; 162:968.
- Takamizawa S, Minakami H, Usui R, et al. Risk of complications and uterine malignancies in women undergoing hysterectomy for presumed benign leiomyomas. Gynecol Obstet Invest 1999; 48:193.
- Leung F, Terzibachian JJ. Re: "The impact of tumor morcellation during surgery on the prognosis of patients with apparently early uterine leiomyosarcoma". Gynecol Oncol 2012; 124:172.
- Durand-Réville M, Dufour P, Vinatier D, et al. [Uterine leiomyosarcomas: a surprising pathology. Review of the literature. Six case reports]. J Gynecol Obstet Biol Reprod (Paris) 1996; 25:710.
- Seidman MA, Oduyebo T, Muto MG, et al. Peritoneal dissemination complicating morcellation of uterine mesenchymal neoplasms. PLoS One 2012; 7:e50058.
- Theben JU, Schellong AR, Altgassen C, et al. Unexpected malignancies after laparoscopic-assisted supracervical hysterectomies (LASH): an analysis of 1,584 LASH cases. Arch Gynecol Obstet 2013; 287:455.
- Sinha R, Hegde A, Mahajan C, et al. Laparoscopic myomectomy: do size, number, and location of the myomas form limiting factors for laparoscopic myomectomy? J Minim Invasive Gynecol 2008; 15:292.
- Hagemann IS, Hagemann AR, LiVolsi VA, et al. Risk of occult malignancy in morcellated hysterectomy: a case series. Int J Gynecol Pathol 2011; 30:476.
- Goto A, Takeuchi S, Sugimura K, Maruo T. Usefulness of Gd-DTPA contrast-enhanced dynamic MRI and serum determination of LDH and its isozymes in the differential diagnosis of leiomyosarcoma from degenerated leiomyoma of the uterus. Int J Gynecol Cancer 2002; 12:354.
- Huang GS, Chiu LG, Gebb JS, et al. Serum CA125 predicts extrauterine disease and survival in uterine carcinosarcoma. Gynecol Oncol 2007; 107:513.
- Hoskins PJ, Le N. Preoperative tumor markers at diagnosis in women with malignant mixed müllerian tumors/carcinosarcoma of the uterus. Int J Gynecol Cancer 2008; 18:1200.
- Rha SE, Byun JY, Jung SE, et al. CT and MRI of uterine sarcomas and their mimickers. AJR Am J Roentgenol 2003; 181:1369.
- Kitajima K, Murakami K, Kaji Y, Sugimura K. Spectrum of FDG PET/CT findings of uterine tumors. AJR Am J Roentgenol 2010; 195:737.
- Shah SH, Jagannathan JP, Krajewski K, et al. Uterine sarcomas: then and now. AJR Am J Roentgenol 2012; 199:213.
- Sagae S, Yamashita K, Ishioka S, et al. Preoperative diagnosis and treatment results in 106 patients with uterine sarcoma in Hokkaido, Japan. Oncology 2004; 67:33.
- Jin Y, Pan L, Wang X, et al. Clinical characteristics of endometrial stromal sarcoma from an academic medical hospital in China. Int J Gynecol Cancer 2010; 20:1535.
- 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.
- Kawamura N, Ichimura T, Ito F, et al. Transcervical needle biopsy for the differential diagnosis between uterine sarcoma and leiomyoma. Cancer 2002; 94:1713.
- Quade BJ. Pathology, cytogenetics and molecular biology of uterine leiomyomas and other smooth muscle lesions. Curr Opin Obstet Gynecol 1995; 7:35.
- Quade BJ, Wang TY, Sornberger K, et al. Molecular pathogenesis of uterine smooth muscle tumors from transcriptional profiling. Genes Chromosomes Cancer 2004; 40:97.
- Nonepithelial neoplasms
- - Endometrial stromal and undifferentiated sarcoma
- - Leiomyosarcoma
- - Mixed endometrial stromal and smooth muscle tumor
- Mixed epithelial-nonepithelial tumors
- - Adenosarcoma
- RISK FACTORS
- Increasing age
- Pelvic radiation
- Hereditary conditions
- Other risk factors
- CLINICAL PRESENTATION
- DIAGNOSTIC EVALUATION
- History and physical examination
- Laboratory evaluation
- DIFFERENTIAL DIAGNOSIS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS