General Information About Uterine Sarcoma
Uterine sarcomas comprise less than 1% of gynecologic malignancies and 2% to 5% of all uterine malignancies. The following tumors arise primarily from three distinct tissues:
- Carcinosarcomas arising in the endometrium, in other organs of mullerian origin, and accounting for 40% to 50% of all uterine sarcomas.
- Leiomyosarcomas arising from myometrial muscle, with a peak incidence occurring at age 50, and accounting for 30% of all uterine sarcomas.
- Sarcomas arising in the endometrial stroma, with a peak incidence occurring before menopause for the low-grade tumors and after menopause for the high-grade tumors, and accounting for 15% of all uterine sarcomas.
The three distinct entities are often grouped under uterine sarcomas; however, each type of tumor is currently being studied in separate clinical trials.
Carcinosarcomas (the preferred designation by the World Health Organization [WHO]) are also referred to as mixed mesodermal sarcomas or mullerian tumors. Controversy exists about the following issues:
- Whether they are true sarcomas.
- Whether the sarcomatous elements are actually derived from a common epithelial-cell precursor that also gives rise to the usually more abundant adenocarcinomatous elements.
The stromal components of the carcinosarcomas are further characterized by whether they contain homologous elements, such as malignant mesenchymal tissue considered possibly native to the uterus, or heterologous elements, such as striated muscle, cartilage, or bone, which are foreign to the uterus. Carcinosarcomas parallel endometrial cancer in its postmenopausal predominance and in other of its epidemiologic features; increasingly, the treatment of carcinosarcomas is becoming similar to combined modality approaches for endometrial adenocarcinomas.
Other rare forms of uterine sarcomas also fall under the WHO classification of mesenchymal and mixed tumors of the uterus. These include:[2,3]
- Mixed endometrial stromal and smooth muscle tumors.
- Adenosarcomas, in which the epithelial elements appear benign within a malignant mesenchymal background.
- Embryonal botryoides or rhabdomyosarcomas, which are found almost exclusively in infants.
- PEComa—a perivascular epithelial-cell tumor that may behave in a malignant fashion, which is the latest to be added.
(Refer to the PDQ summary on Childhood Rhabdomyosarcoma for more information.)
The only documented etiologic factor in 10% to 25% of these malignancies is prior pelvic radiation therapy, which is often administered for benign uterine bleeding that began 5 to 25 years earlier. An increased incidence of uterine sarcoma has been associated with tamoxifen in the treatment of breast cancer. Subsequently, increases have also been noted when tamoxifen was given to prevent breast cancer in women at increased risk—a possible result of the estrogenic effect of tamoxifen on the uterus. Because of this increase, patients on tamoxifen should have follow-up pelvic examinations and should undergo endometrial biopsy if there is any abnormal uterine bleeding.[4-6]
The prognosis for women with uterine sarcoma is primarily dependent on the extent of disease at the time of diagnosis.For women with carcinosarcomas, significant predictors of metastatic disease at initial surgery include:
- Isthmic or cervical location.
- Lymphatic vascular space invasion.
- Serous and clear cell histology.
- Grade 2 or 3 carcinoma.
The above factors in addition to the following ones correlate with a progression-free interval:
- Adnexal spread.
- Lymph node metastases.
- Tumor size.
- Peritoneal cytologic findings.
- Depth of myometrial invasion.
Factors that bear no relationship to the presence or absence of metastases at surgical exploration are:
- The presence or absence of stromal heterologous elements.
- The types of such elements.
- The grade of the stromal components.
- The mitotic activity of the stromal components.
In one study, women with a well-differentiated sarcomatous component or carcinosarcomas had significantly longer progression-free intervals than those with moderately to poorly differentiated sarcomas for the homologous and heterologous types. The recurrence rate was 44% for homologous tumors and 63% for heterologous tumors. The type of heterologous sarcoma had no effect on the progression-free interval.
For women with leiomyosarcomas, some investigators consider tumor size to be the most important prognostic factor; women with tumors greater than 5.0 cm in maximum diameter have a poor prognosis. However, in a Gynecologic Oncology Group study, the mitotic index was the only factor significantly related to progression-free interval. Leiomyosarcomas matched for other known prognostic factors may be more aggressive than their carcinosarcoma counterparts. The 5-year survival rate for women with stage I disease, which is confined to the corpus, is approximately 50% versus 0% to 20% for the remaining stages.
Surgery alone can be curative if the malignancy is contained within the uterus. The value of pelvic radiation therapy is not established. Current studies consist primarily of phase II chemotherapy trials for patients with advanced disease. Adjuvant chemotherapy following complete resection for patients with stage I or II disease was not established to be effective in a randomized trial. Yet, other nonrandomized trials have reported improved survival following adjuvant chemotherapy with or without radiation therapy.[11-13]
Other PDQ summaries containing information related to uterine sarcoma include the following:
- Adult Soft Tissue Sarcoma Treatment
- Childhood Soft Tissue Sarcoma Treatment
- Endometrial Cancer Prevention
- Endometrial Cancer Screening
- Endometrial Cancer Treatment
- Genetics of Breast and Gynecologic Cancers
- Forney JP, Buschbaum HJ: Classifying, staging, and treating uterine sarcomas. Contemp Ob Gyn 18(3):47, 50, 55-56, 61-62, 64, 69, 1981.
- Gershenson D, McGuire W, Gore Martin, et al.: Gynecologic Cancer: Controversies in Management. 3rd ed. New York, NY: Churchill Livingstone, 2004.
- Tavassoéli F, Devilee P, et al.: Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon, France: International Agency for Research on Cancer, 2004.
- Bergman L, Beelen ML, Gallee MP, et al.: Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres’ ALERT Group. Assessment of Liver and Endometrial cancer Risk following Tamoxifen. Lancet 356 (9233): 881-7, 2000. [PUBMED Abstract]
- Cohen I: Endometrial pathologies associated with postmenopausal tamoxifen treatment. Gynecol Oncol 94 (2): 256-66, 2004. [PUBMED Abstract]
- Wickerham DL, Fisher B, Wolmark N, et al.: Association of tamoxifen and uterine sarcoma. J Clin Oncol 20 (11): 2758-60, 2002. [PUBMED Abstract]
- Major FJ, Blessing JA, Silverberg SG, et al.: Prognostic factors in early-stage uterine sarcoma. A Gynecologic Oncology Group study. Cancer 71 (4 Suppl): 1702-9, 1993. [PUBMED Abstract]
- Evans HL, Chawla SP, Simpson C, et al.: Smooth muscle neoplasms of the uterus other than ordinary leiomyoma. A study of 46 cases, with emphasis on diagnostic criteria and prognostic factors. Cancer 62 (10): 2239-47, 1988. [PUBMED Abstract]
- Oláh KS, Dunn JA, Gee H: Leiomyosarcomas have a poorer prognosis than mixed mesodermal tumours when adjusting for known prognostic factors: the result of a retrospective study of 423 cases of uterine sarcoma. Br J Obstet Gynaecol 99 (7): 590-4, 1992. [PUBMED Abstract]
- Omura GA, Blessing JA, Major F, et al.: A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study. J Clin Oncol 3 (9): 1240-5, 1985. [PUBMED Abstract]
- Piver MS, Lele SB, Marchetti DL, et al.: Effect of adjuvant chemotherapy on time to recurrence and survival of stage I uterine sarcomas. J Surg Oncol 38 (4): 233-9, 1988. [PUBMED Abstract]
- van Nagell JR Jr, Hanson MB, Donaldson ES, et al.: Adjuvant vincristine, dactinomycin, and cyclophosphamide therapy in stage I uterine sarcomas. A pilot study. Cancer 57 (8): 1451-4, 1986. [PUBMED Abstract]
- Peters WA 3rd, Rivkin SE, Smith MR, et al.: Cisplatin and adriamycin combination chemotherapy for uterine stromal sarcomas and mixed mesodermal tumors. Gynecol Oncol 34 (3): 323-7, 1989. [PUBMED Abstract]