Uterine sarcomas (US) are relatively rare malignant tumor of uterine mesenchymal origin, representing 1% of gynecologic malignancies and 3–7% of all malignant uterine tumors (1, 2). The prognosis of uterine sarcoma is worse compared with common endometrial cancer, and its clinical behavior tends to be more aggressive with early lymphovascular spreading (3, 4); which are associated with a 5-year survival rate of less than 30% for women with advanced disease (5). Uterine sarcoma classifications have traditionally included leiomyosarcoma (LMS), endometrial stromal sarcoma (ESS), and carcinosarcoma (CS) (5).
Leiomyosarcoma (LMS) is highly malignant with an adverse prognosis, and even in stage I, its 5-year survival rate is approximately 50% (6). The prognosis for uterine LMS is poor, with 5-year overall survival rates in uterine LMS around 19–65% in all stages, and 52–85% in women with stage I–II disease (7).
Carcinosarcoma (CS) is the most common type of uterine sarcoma (8.2 cases per million), typically followed by leiomyosarcoma (LMS) (6.4 cases per million) and endometrial stromal sarcoma (ESS) (1.8 cases per million) (3). Five-year overall survival rate in uterine carcinosarcoma is around 6–38% in all stages, and 44–74% in women with stage I–II disease (7). These tumors are characterized by dense uniform stromal cells with a low mitotic index and without significant atypia (8). The uterine ESS showed relatively better survival than CS and LMS, and 5-year overall survival rate in uterine ESS was around 50–65% in all stages, and 89% in women with stage I–II disease (9).
Clinical presentation patterns of uterine sarcomas differ for the histologic subtypes, such as enlarged uterine size or abdominal pain in LMS or ESS and abnormal uterine bleeding in pre- or postmenopausal women in carcinosarcoma or ESS (10).
Adenosarcomas (AS) of the uterus are rare and seen far less frequently than other more common uterine sarcomas which are composed of benign, but occasionally atypical glandular epithelium, in combination with a malignant mesenchymal component (11). Despite the fact that adenosarcomas are typically considered low-grade tumors, recurrences have been reported in up to 30–40% of patients while 20–25% of women ultimately die from their tumors (11).
The present study evaluated the outcomes of patients with different types of uterine sarcoma in Iranian women during a 5-year survey.
A case series of Twenty-three consecutive patients with uterine sarcomas who referred to Bahman hospital, Tehran, Iran during 2014-2019 were studied. The mean age of the cases was 51.69 years (range: 28-84 years). There were nine cases of ESS, three cases of AS, seven cases of CS, and four cases of LMS. The descriptions of patients in each group are presented below.
Cases of AS
Three cases were detected for adenosarcoma; only one of them needed radiotherapy and chemotherapy. This case showed a recurrence 4-years after the termination of therapies. This patient has a familial history of breast cancer (her aunt). The clinical characteristics of these cases are listed in Table 1.
Table 1. The clinical characteristics of adenosarcoma patients
Cases of CS
Seven cases of CS were studied. Two patients with stages IVB and IA had familial history of cancer in their sister (liver cirrhosis and hepatocellur carcinoma) and aunt (colon cancer), respectively. The clinical characteristics of CS cases are presented in Table 2.
Table 2. The clinical characteristics of carcinosarcoma patients
Cases of ESS
Nine cases were diagnosed with ESS all of which were alive by the end of the study duration. The mean age of these cases was 45.77 years. Cytology examination was negative for malignant cells in all ESS cases. Adjuvant radiotherapy and/or chemotherapy was done for five cases. One case who did not receive radio/chemotherapy experienced a bronchial recurrence after 3-years of ESS diagnosis. Immunohistochemistry test on tumoral cells in three patients was positive for following markers expressions: vimentin+Ki67 (30%), BCL2+CD64+Ki67 (30%), and ER+PR+WT1+Ki67 (15%), respectively. In one patient with FIGO stage IIA, ovarian, paramaterial and lymphovascular invasions were seen. In another patient with high grade ESS, myometrium and uterine-cervical stroma and vascular invasions were present. Both of these patients with tumoral invasion received adjuvant radio/ chemotherapy.
Cases of LMS
There were four detected cases of LMS during study time; two of them died. The clinical characteristics of LMS cases are listed in Table 3.
Table 3. The clinical characteristics of leiomyosarcoma patients
Compared to the more common types of endometrial cancer, women with uterine sarcomas have a poor prognosis due to the aggressive nature of this tumor (4, 12) The most frequent prognostic factors in uterine sarcomas include tumor stage, histological subtype, grade, lymphovascular invasion and menopausal status (4). As the results of the study of Putikul et al. show (13), abnormal uterine bleeding was the most common presenting symptom in the present cases.
According to the results of a study by Arend et al., patients with AS turned to be younger and were more likely to have early-stage tumors and patients with AS were 65% less likely to die from their tumors than women with CS (11). In the present study, the mean ages for AS and CS patients were 47.33 and 67 years, respectively. Two cases of AS were in IA stage and one of them was in IIA stage; while 4 cases of CS were in III and IV stages. All three cases of AS were alive by the study duration and two CS patients died in this period. Also, patients with carcinosarcoma have been reported that are more likely to receive adjuvant radiotherapy (11). In the present cases one out of three AS patients needed adjuvant radiotherapy; while 4 out of seven cases of CS received this therapy. Surgery followed by adjuvant radiotherapy with or without chemotherapy in CS cases has been significantly associated with improved overall survival (14). Three out of four CS cases who received these therapies were alive by the end of the study duration.
The LMSs are rare but aggressive tumors with poor clinical outcomes regardless of stage (15). Two-cases out of four LMS patients had IB stage in this study; which was in accordance with some other studies (16, 17). Two LMS patients received adjuvant radiotherapy and chemotherapy; one of them, with IIB stage, died during the study. It has been claimed that adjuvant radiotherapy may provide a survival benefit for uterine carcinosarcoma, but not leiomyosarcoma (18). In the studied cases, 3 out of four CS cases who received this therapy were alive at the study termination; but one of two cases of LMS undergone adjuvant radiotherapy died. On the other hand, mitotic count >10-15/HPF has been associated with poorer prognosis in patients with LMS and mitotic count was defined as the most significant predictor of overall survival in uterine sarcomas (19-21). Both LMS patients studied in the present study, had mitotic count 40/10 HPF.
Histological subtypes of LMS and CS (MMMT) have been associated with a poorer overall survival than ESS (12). Two out of four LMS cases and two out of seven CS patients in this study died before study termination; however, all nine ESS cases were alive at that time. Extra-uterine spread were associated with poorer outcome in uterine sarcomas (22). Lymphovascular invasion was the most common extra-uterine tissues involvement in patients with poor outcome in the present cases.
Comparing histological types of uterine sarcomas, ESS are related with better survival (4). All the nine cases of ESS in the present study were alive till the end of the study.
Advanced age and higher FIGO staging were observed to have poorer outcomes in patients with different histological types of uterine sarcomas. So, an early diagnosis seemed to improve the prognosis of the patients. This study is limited by small sample size and further studies with larger sample size could improve the findings.
We would like to thank the radiotherapy and chemotherapy staff of Bahman hospital and all those who participated in the implementation of the present study.
This study is with patient permission publish her medical data. The identity of the patient was confidential and not disclosed in the study.
Conflicts of Interest
The authors declared no conflict of interest regarding the publication of this article.