Sarcomas of the female genital tract are uncommon neoplasms with an estimated incidence ranging between 1 – 7% of all gynecologic malignancies (1). Cells that line or cover most organs are called epithelial cells and cancers that develop from these cells are called carcinomas. Cancers that develop in connective tissues, such as muscle, fat, bone and fibrous tissue (the material that forms tendons and ligaments) are called sarcomas. Most women with sarcomas of the genital tract are postmenopausal at diagnosis.

UTERINE CORPUS

Although sarcomas may arise in any organ of the female genitalia (uterine corpus, cervix, ovary, fallopian tubes, vulva and vagina) the highest occurrence is in the uterine corpus. These tumors constitute between 2 – 4% of uterine malignancies (2). Uterine sarcomas include leiomyosarcoma, endometrial stromal sarcoma and mixed mesodermal tumors.

Leiomyosarcomas account for 20 – 30% of uterine sarcomas. They arise from the smooth muscle of the uterus or result from malignant transformation of a benign leiomyoma (3). The number of mitoses in 10 high-powered fields is the criterion for the division between benign and malignant lesions. If there are greater than 10 mitoses per 10 high-powered fields then the tumor is considered malignant. Lesions with 5 – 9 mitoses per 10 high-powered fields and atypical nuclear cytology are also considered malignant, whereas those with a like number of mitoses and no atypia are of borderline malignancy (4). Cellular leiomyomas and atypical leiomyomas are benign lesions with less than 5 mitoses per 10 high-powered fields (1).

Endometrial stromal sarcomas account for about 15 – 25% of uterine sarcomas. The three types are the benign stromal nodule, the well-differentiated (low-grade) stromal sarcoma and the poorly differentiated stromal sarcoma. Benign stromal nodules have smooth, well circumscribed borders and most often appear as benign submucosal leiomyomas. No nuclear atypia or mitoses are seen in these lesions (4). Well-differentiated (low-grade) endometrial stromal sarcoma resembles proliferative endometrial stroma with small arterioles and the mitotic activity is low. There are usually less than 3 mitoses per 10 high-powered field. Poorly differentiated stromal sarcomas have high mitotic rates, lack small arterioles, exhibit extreme nuclear pleomorphism, and are highly aggressive (5). Spread typically occurs through the pelvic vasculature and eventually reaches distant sites, usually the lungs.

Three distinct groups of mixed mesodermal tumors exist. The benign category, mullerian adenofibroma, consists of benign endometrial or endocervical epithelium and somewhat hypercellular fibromuscular stroma. The second group, mullerian adenosarcoma, contains malignant homologous or heterologous stroma. This is a low-grade malignant tumor with potential for local recurrence and occasionally metastasis. The third group, carcinosarcomas (previously referred to as malignant mixed mesodermal tumor) is made up of malignant epithelial and stromal elements. These account for approximately 40 - 60% of uterine sarcomas. The stroma may be abnormally proliferative and may contain rhabdomyoblasts and/or neoplastic alterations such as cartilage and bone. Tumors of this nature are called heterologous. In contrast, the homologous lesions contain only endometrial stroma or smooth muscle. Both if these types of malignant mixed mesodermal tumors have the same prognosis. The average five year survival for all stages is about 25% (6).

Women with sarcoma tumors have a number of characteristics in common with the endometrial adenocarcinoma population. On average, 25% are nulliparous, 40% are obese and 15% are diabetic. Post menopausal estrogen use has not been implicated in the etiology of this form of uterine cancer. Peters (1984) and others report an incidence as high as 10% of women diagnosed with sarcomas have a history of prior pelvic radiation. Rarely do sarcomas originate in pelvic endometriosis.

Frequently the most common presenting symptom is vaginal bleeding (85%), abdominal pain or pelvic pain (25%), abdominal enlargement or mass (10%). The uterus is usually large and soft to palpation. Lung, abdominal, peripheral node, or aortic node metastases are found in 10 – 20% of the cases at time of diagnosis (7).

The natural history and patterns of spread vary among the histologic subtypes of uterine sarcomas. Generally, these uterine neoplasms are characterized by an aggressive growth pattern with early lymphatic dissemination or by a slow growth pattern with long disease-free intervals. Carcinosarcomas, high grade leiomyosarcomas and endometrial stromal sarcomas behave in an aggressive manner. The overall survival rate is poor, and death often occurs in 1 to 2 years from time of diagnosis. Low grade leiomyosarcomas and adenosarcomas are associated with long disease free intervals and local recurrence, if any (3).

CERVIX

The most important sarcoma of the cervix is the embryonal rhabdomyosarcoma, which occurs in children and young adults. The tumor has grapelike polypoid nodules, the so-called sarcoma botyoides, and the diagnosis depends on the recognition of rhabdomyoblasts (7). Leiomyosarcomas and mixed mesodermal tumors involving the cervix may be primary but are more likely to be secondary to uterine tumors (1).

OVARY

Malignant mixed mesodermal sarcomas of the ovary are extremely rare. Most lesions are heterologous and are biologically aggressive. The presentation is similar to that of most ovarian malignancies and the majority of patients have evidence of metastases at the time of diagnosis (2).

FALLOPIAN TUBE

Primary tubal sarcoma is extremely rare and highly malignant tumor. These lesions are usually diagnosed as leiomyosarcomas and have the same microscopic pattern as those from the uterus or ovaries. Mesodermal tissue, most frequently cartilaginous and rhabdomyoblastic, is often recognized (2).

VULVA AND VAGINA

Sarcomas of the vulva and the vagina are extremely uncommon the incidence is less than 1% of all primary malignancies. The gross lesions are both hard and nodular or ulcerative. These neoplasms spread to the regional and retroperitoneal lymph nodes (4).

Embryonal rhabdomyosarcomas are rare tumors found in the vagina during the first five years of life. These arise from the growing tip of the mullerian (paramesonephric) duct. The multicystic gapelike form of grayish red polyps fill and may extrude from the vagina. Extension to the uterus, parametrium and regional nodes is common (4).

TREATMENT

There are four basic types of treatment for sarcomas, surgery, radiation therapy, hormonal therapy, and chemotherapy. These treatments may be used alone or in combination. While radiation therapy is often the primary treatment for vaginal sarcomas, the value of radiation therapy following surgery is controversial for uterine sarcomas.

The primary treatment for sarcomas of the uterus, ovary, or fallopian tube is generally surgery. The recommended operative procedure is exploratory laparotomy via a vertical incision, total abdominal hysterectomy, and bilateral salpingo-oophorectomy, omentectomy, peritoneal cytology, and selective pelvic and aortic lymph node dissection. Removal of the ovaries is recommended for these neoplasms as they are characterized by high levels of estrogen and progesterone receptors and often respond to hormonal therapy.

The role of adjuvant radiation therapy is still debated by the experts. Most studies have not found adjuvant radiation therapy to improve survival rates in those with uterine sarcomas (6). However, radiation therapy does improve tumor control in the pelvis at time of recurrence without influencing the final outcome.

Hoskins (1997) reviews eight drugs that have been studied as single agents in the treatment of advanced or recurrent uterine sarcomas; ifosfamide, cisplatin, doxorubicin, etoposide, mitoxantrone, piperazindione, aziridinybenzoquinone (AZQ), and aminothiadiazole (ATD). The response rates range from 30% to 0%. Two active agents have been identified in mixed mesodermal sarcomas of the uterus: ifosfamide and cisplatin. In leiomyosarcomas only doxorubicin appears to have significant activity. There was no evidence to support the use of combination chemotherapy in recurrent uterine sarcomas.

CONCLUSION

Sarcomas develop in connective tissue and these neoplasms are more commonly found in the uterus than anywhere else in the female genitalia. Although sarcomas account for less than 7% of gynecological malignancies, their behavior may be very aggressive. Carcinosarcoma, malignant mixed mesodermal tumor, the most common uterine sarcoma, contains both epithelial and stromal elements. Following carcinosarcoma in order of decreasing incidence is leiomyosarcoma, endometrial stromal sarcoma and Mullerian adenosarcoma (11).

The majority of women with sarcomas are postmenopausal. The most common presenting symptom in these women is vaginal bleeding. However, of note is, a very rare embryonal rhabdomyosarcoma can be found on the cervix or in the vagina of a pediatric patient(11).

Treatment of gynecological sarcomas is dependent on the location of the sarcoma, the tumor type, and the stage of the sarcoma. Treatment may include surgery, radiation therapy, hormonal therapy, or chemotherapy.

Define sarcomas in the female genitalia.

State the incidence of gynecologic sarcomas.

List the three types of uterine sarcomas.

Distinguish between benign and malignant lesions.

Describe the presenting symptoms of uterine sarcomas.

List the four types of treatments for sarcomas.