Uterine sarcomas arise from the uterine muscle (leiomyosarcoma) or endometrial glands and stroma (endometrial stromal sarcoma and carcinosarcoma). They account for about 3% of all uterine malignancies and less than 1% of all gynecologic malignancies. Uterine sarcomas have differing etiologies, clinical courses, and pathologic features, which give rise to variable treatment regimens and clinical outcomes. The leiomyosarcomas and (malignant) mixed mullerian tumors (M/MMT or carcinosarcomas) have a higher rate of occurrence in black than in white females. Carcinosarcomas are unusual before the age of 40 and have rising incidence with advancing age, while leiomyosarcomas have peak incidence between ages 35 and 55 for blacks and ages 40 and 50 for whites. The development of sarcomas also appears to be increased by previous pelvic radiation, especially the carcinosarcomas and adenosarcomas.
MMTs, leiomyosarcomas, and high-grade endometrial stromal sarcomas are clinically aggressive tumors. Metastases can occur by means of local extension or by lymphatic or hematogenous pathways. When spread has occurred, the survival rates are very low. Low-grade tumors of all histologic types have a better survival rate.
Classification of uterine sarcomas can be simplified as follows (with % of all uterine sarcomas):
- (Malignant) mixed mullerian tumor, (M)MMT, also known as carcinosarcomas (30%)
- Homologous type
- Heterologous type
- Leiomyosarcoma (27%)
- Endometrial stromal sarcoma (ESS) (26%)
- Other (17%)
A more detailed classification has been adopted by the International Society of Gynecologic Pathologists (Table 1).
The uterine sarcomas do not lend themselves to any specific screening technique, but at times a Pap smear will be abnormal in the face of a glandular lesion. A routine pelvic examination may reveal an enlarged uterus, but due to the rarity of these lesions, no screening interventions are indicated.
Abnormal bleeding with a foul discharge and/or pelvic pain from uterine distention are the most frequent symptoms. A polypoid mass or enlarged uterus is present in about 50% of patients. If there is bleeding or a foul prolapsing mass at the cervical os in a postmenopausal patient, the most likely diagnosis is an MMT. Biopsy is required to confirm the diagnosis but may be performed at the time of surgery in some instances if bleeding and symptoms dictate immediate intervention.
Due to the rarity of these lesions and the lack of a landmark for depth of invasion, no International Federation of Gynecology and Obstetrics (FIGO) staging is available. A simple modification of the staging system for endometrial carcinomas is usually used:
Stage I: Confined to the corpus
Stage II: Confined to the corpus and cervix
Stage III: Confined to the pelvis
Stage IV: Spread outside of pelvis
The leiomyosarcomas account for nearly a third of the uterine sarcomas. They tend to occur premenopausally. Most often the diagnosis is made retrospectively on hysterectomy specimens removed as treatment for fibroids. The establishment of the correct diagnosis of a leiomyosarcoma is based primarily on the quantitative evaluation of mitotic activity in the most undifferentiated portion of the tumor. In addition, cel-lular atypia is also important, for aneuploid tumors have a malignant course unrelated to their mitotic activity.
Although pathologists may differ in their opinions of a smooth muscle tumors malignant potential, there is general agreement on the mitotic activity criteria for determining malignancy. Tumors with more than 10 mitoses/10 high power fields (hpf) are malignant; those with less than 5 mitoses/10 hpf are benign, and those with 5 to 10 mitoses/10 hpf are classified as smooth muscle tumors of uncertain malignant potential. Although nodal spread can occur, lymphadenectomy is not commonly done in these patients because the malignant nature of the tumor is usually not known at the time of surgery. Direct local spread and hematogenous spread occur frequently.
Initial treatment is total abdominal hysterectomy and bilateral salpingo-oophorectomy. There is minimal clinical use for lymphadenectomy.
Mixed Mullerian Tumors (Carcinosarcomas)
MMTs are the most common type of uterine sarcomas and tend to behave aggressively, with frequent lymph-vascular space involvement and lymphatic spread at earlier stages than expected. Homologous MMTs are those in which the malignant elements are of cell types found in the normal uterus, such as glandular adenocarcinomas and smooth muscle tumors (leiomyosarcomas). Heterologous MMTs contain sarcomatous changes in cell types not found in the normal uterus: rhabdomyosarcomas, chondrosarcomas, osteosarcomas, and liposarcomas. Both the epithelial (carcinomas) and mesenchymal (sarcoma) components must be malignant to establish the diagnosis of MMT.
Stage, depth of myometrial involvement, and tumor ploidy are the most important prognostic factors. Adjuvant chemotherapy of stage I disease because of its high recurrence rates (40% to 50%) has been utilized with minimal efficacy. Current trends favor ifosfamide(Drug information on ifosfamide) (Ifex) over doxorubicin(Drug information on doxorubicin), in combination with cisplatin(Drug information on cisplatin) (Platinol) for MMTs. Radiotherapy may be important for local disease control but may not impact on overall survival.
Endometrial Stromal Sarcoma (ESS)
Traditionally endometrial stromal tumors have been divided into endometrial stromal nodule, endolymphatic stromal myosis, and endometrial stromal sarcoma. The stromal nodules are noninfiltrating and relatively benign with less than 3 mitoses/10 hpf. Endolymphatic stromal myosis is now considered more a low-grade form of ESS than a separate entity. With typically less than 10 mitoses/10 hpf, these tumors can have a protracted course with recurrences as late as 25 years. Progestins have an important role in the management of this type of ESS. The true endometrial stromal sarcoma is a high-grade sarcoma with an equally poor (25%) 5-year survival rate compared to the other uterine sarcomas.
The mainstay of treatment for high-grade ESS is surgery, with removal of the uterus, tubes, ovaries, and selective lymphadenectomy for complete surgical staging. Low-grade ESS (stromal myosis) also calls for maximal effort to remove all gross and microscopic tumor.
Many chemotherapeutic agents have been shown to have some activity in uterine sarcomas: doxorubicin, actinomycin D (dactinomycin [Cosmegan]), cyclophosphamide(Drug information on cyclophosphamide) (Cytoxan, Neosar), vincristine, and cisplatin. One of the initial Gynecologic Oncology Group (GOG) studies of sarcomas showed no clear benefit for adjunctive chemotherapy.
Radiotherapy is indicated for local-regional disease control but has not been shown to impact on overall survival.
Patients need to be followed in accordance with usual gynecologic oncology protocols, with examinations every 3 to 4 months during the first 2 years and every 4 to 6 months thereafter. The chest x-ray should be part of the follow-up process every 3 to 6 months during the first 2 years because of the propensity for lung metastases.
Uterine sarcomas typically recur at distant sites at a ratio of about 3:1 vs local recurrences. Focal recurrences may be treated surgically, and chemotherapy or radiation may be given selectively. Progestins are commonly used as an adjunct, although their benefit has mainly been demonstrated for the management of low-grade ESS.