Abstract
Background
Uterine sarcoma is a rare and heterogeneous gynecological malignancy characterized by aggressive progression and poor prognosis. The current study aimed to investigate the relationship between clinicopathological characteristics and the prognosis of uterine sarcoma in Chinese patients.
Methods
In this single-center retrospective study, we reviewed the medical records of 75 patients with histologically verified uterine sarcoma treated at the First Affiliated Hospital of **’an Jiaotong University between 2011 and 2020. Information on clinical characteristics, treatments, pathology and survival was collected. Progression-free survival (PFS) and overall survival (OS) were visualized in Kaplan-Meier curves. Prognostic factors were identified using the log-rank test for univariate analysis and Cox-proportional hazards regression models for multivariate analysis.
Results
The histopathological types included 36 endometrial stromal sarcomas (ESS,48%), 33 leiomyosarcomas (LMS,44%) and 6 adenosarcomas (8%). The mean age at diagnosis was 50.2 ± 10.7 years. Stage I and low-grade accounted for the majority. There were 26 recurrences and 25 deaths at the last follow-up. The mean PFS and OS were 89.41 (95% CI: 76.07-102.75) and 94.03 (95% CI: 81.67-106.38) months, respectively. Univariate analysis showed that > 50 years, post-menopause, advanced stage, ≥ 1/2 myometrial invasion, lymphovascular space invasion and high grade were associated with shorter survival (P < 0.05). Color Doppler flow imaging positive signals were associated with shorter PFS in the LMS group (P = 0.046). The ESS group had longer PFS than that of the LMS group (99.56 vs. 76.05 months, P = 0.043). The multivariate analysis showed that post-menopause and advanced stage were independent risk factors of both PFS and OS in the total cohort and LMS group. In the ESS group, diagnosis age > 50 years and high-grade were independent risk factors of PFS, while high-grade and lymphovascular space invasion were independent risk factors of OS.
Conclusion
In Chinese patients with uterine sarcoma, post-menopause and advanced stage were associated with a significantly poorer prognosis. The prognosis of ESS was better than that of LMS. Color Doppler flow imaging positive signals of the tumor helped to identify LMS, which needs to be further tested in a larger sample in the future.
Similar content being viewed by others
Introduction
Uterine sarcoma is a rare and aggressive heterogeneous malignant tumor originating from the mesodermal tissues (muscle and supportive tissues) [1]. It is characterized by nonspecific clinical presentations, high recurrence rates and poor prognosis, accounting for about 1% of female genital tract malignancies and 3–7% of uterine cancers [2]. The incidence of uterine sarcoma increases with age and is reported to be about 6.4 per 100,000 in women aged above 50 years in America [3].
According to the traditional histological classification, uterine sarcoma mainly included carcinosarcoma (CS), leiomyosarcoma (LMS), endometrial stromal sarcoma (ESS), undifferentiated sarcoma (UUS) and other less frequent histological subtypes, such as adenosarcoma. In 2009, the International Federation of Gynecology and Obstetrics (FIGO) revised the staging system and reclassified CS as endometrial cancer due to its similar dedifferentiated or metaplastic form to endometrial cancer [2]. The new uterine sarcoma classification mainly contains three pathological subtypes: LMS, ESS, adenosarcoma and undifferentiated endometrial sarcoma, of which LMS is the most common [4].
Diagnosis of uterine sarcoma is generally difficult before surgery because of nonspecific symptoms, such as irregular vaginal bleeding, abdominal or pelvic mass and pain, or even no symptom [4, 5]. Ultrasonography, magnetic resonance imaging, computed tomography and cancer antigen 125 (CA125) level are useful preoperative diagnostic methods. However, distinguishing uterine sarcoma from benign uterine lesions such as fibroids is difficult due to the lacking specific symptoms or diagnostic techniques, resulting in high misdiagnosis rates, which may lead to serious consequences [6, 7].
There is no standardized treatment for uterine sarcoma due to its rarity and heterogeneity. Early-stage uterine sarcoma is mainly treated by surgery according to different pathological types, including total hysterectomy with bilateral sal**o-oophorectomy (TH-BSO) [3, 17]. Our research presented is a comprehensive analysis of uterine sarcoma and examines 75 Chinese patients over a 10-year period using the latest classification system for more detailed results.
Our findings revealed that LMS had a poorer prognosis than that of ESS. Specifically, for the ESS group, we determined post-menopausal, high-grade and LVSI as key factors associated with reduced survival. Furthermore, the study highlighted the potential diagnostic value of CDFI, enabling it to distinguish between benign and malignant tumors and representing a new research topic.
CDFI provide a new direction for distinguishing uterine sarcoma from uterine fibroids. In our research, 62.9% of patients had CDFI during the examination. CDFI positive signals had a negative effect on survival of LMS group. This suggests the potentially important role of CDFI in the evaluation of the malignant transformation of uterus myoma, which is similar to a finding reported by Yang Hua [18]. Asim Kurjak reported that a cutoff in resistance index (RI) of 0.4 of tumoral blood vessels could distinguish uterine sarcoma from uterus myoma with a higher RI [19]. The diagnostic value of this cutoff is 90.91%, 99.82%, 71.43% and 99.96% in sensitivity, specificity, positive predictive value and negative predictive value, respectively [19]. However, the study had small sample sizes (n = 10). Sun et al. found that increased vascularity on color Doppler ultrasound could sometimes favor malignancy, especially when combined with a large size and degenerative cystic changes [20]. Further studies are needed to figure out the clinical significance of CDFI for uterine sarcoma.
Univariate analysis demonstrated that over 50 years, post-menopause, advanced stage and ≥ 1/2 myometrial invasion were significantly associated with poorer survival; while multivariable analysis identified that post-menopause and advanced stage were independent prognostic factors for survival of the total cohort and the LMS group. These findings were consistent with previous studies [14, 21,22,23]. Thus, they were not limited by race or traditional classification systems.
Studies showed that prognoses of different pathological types of uterine sarcoma varied a lot [24,25,26,27]. Our study showed that ESS had a significantly lower recurrence and a higher 5-year survival rate than LMS, and the survival of LG-ESS is prior to those of LMS and HG-ESS, which was in agreement with previous studies [28,29,30,31]. It’s reported that pathological subtype is a significant prognostic factor for OS [30]. However, pathological type isn’t a prognostic factor for survival in our study, which may be related to the merger of LG-ESS and HG-ESS into ESS because of small sample size. The proportion of FIGO I stage in the ESS group is higher than that in the LMS group (86.11% vs. 72.73%). Otherwise, misdiagnosis of LMS as uterine leiomyoma because of the same symptoms and delayed treatment due to minimally invasive therapy as well as inadvertent dissemination [32]. Alexandra Huss’s study reported that three cases LMS were diagnosed at tumor recurrence [30]. LG-ESS grew slowly and had a good prognosis in initial stages than that of HG-ESS in our study. Recently several studies have shown that chromosomal rearrangments and gene amplifications can provide new ideas for the diagnosis and treatment of HG-ESS [33, 34], However, our study lacks exploration on relevant molecular markers because of the earlier diagnosed patients.
Compared with previous studies, our investigation is distinctive in several aspects. (1) Geographical and racial backgrounds. Our study is based on certain Chinese patients in a way. It thus considerably complements the currently available literatures that focus on the clinicopathological features and prognosis of uterine sarcomas conducted in Western population. It significantly increases the global knowledge database regarding potential ethnic and geographic differences in sarcomas. (2) Utilization of the new classification system. This study uses the new classification of uterine sarcomas from 2014 in an attempt to provide an up-to-date exploration of their clinicopathological characteristics and prognosis. (3) Detailed subtype analysis. Given the evident heterogeneity within uterine sarcomas, subgroup analysis was performed separately and most survival factors were developed for each sarcoma group, namely ESS and LMS respectively. This is a valuable supplement that should be deserving of clinical attention because different pathological types of sarcomas present their exclusive influential factors and prognoses, which agents nation planning and judgement prognosis. (4) The usage of CDFI, as a potential malignant myoma indicator, offer an innovation that it may play an important role in novel non-invasive diagnostic techniques.
Our study had some limitations. First, the small sample sizes of adenosarcoma limits the statistical power and generalizability of the findings. This constraint makes it challenging to conduct comprehensive subgroup analyses or to conclude the prognostic implications for rare sarcoma types definitively. Second, the retrospective nature of the study design made it subject to selection and recall bias. These biases could affect accuracy of the collected data and interpretation of the study’s findings. Third, the study was performed in a single center. Its findings may not be broadly applicable to all populations. Forth, the study suggests CDFI as a potentially valuable tool for identifying malignant myomas, which is preliminary and requires further validation through larger, prospective studies to determine its clinical utility and accuracy.
Conclusion
According to our results, LMS is more aggressive than ESS. Post-menopause and advanced stage are independent risk factors of survival for the total patients and LMS, which were not limited to race or traditional classification system. Meanwhile, post-menopause, high-grade and LVSI are independently related to decreased survival in the ESS group. Uterine myoma with blood flow signal may be a useful indicator of malignant myoma, which needs to further validate its diagnostic utility in large-scale, multi-center studies and refine protocols for the management of uterine sarcomas.
Data availability
No datasets were generated or analysed during the current study.
Abbreviations
- PFS:
-
Progression-free survival
- OS:
-
Overall survival
- CS:
-
Carcinosarcoma
- ESS:
-
Endometrial stromal sarcomas
- LMS:
-
Leiomyosarcomas
- UUS:
-
Undifferentiated sarcoma
- LG-ESS:
-
Low-grade ESS
- HG-ESS:
-
High-grade ESS
- FIGO:
-
International Federation of Gynecology and Obstetrics
- CA125:
-
Cancer antigen 125
- TH-BSO:
-
Total hysterectomy with bilateral sal**o-oophorectomy
- CDFI:
-
Color Doppler flow imaging
- LVSI:
-
Lymphovascular space invasion
- SD:
-
Standard deviations
- PT:
-
Paclitaxel and platinum
- IAP:
-
Ifosfamide + epirubicin + cisplatin
- CI:
-
Confidence interval
References
Desar IME, Ottevanger PB, Benson C, van der Graaf WTA. Systemic treatment in adult uterine sarcomas. Crit Rev Oncol Hematol. 2018;122:10–20.
Mbatani N, Olawaiye AB, Prat J. Uterine sarcomas. Int J Gynaecol Obstet. 2018;143(Suppl 2):51–8.
Hosh M, Antar S, Nazzal A, Warda M, Gibreel A, Refky B. Uterine sarcoma: analysis of 13,089 cases based on Surveillance, Epidemiology, and end results database. Int J Gynecol Cancer. 2016;26(6):1098–104.
Santos P, Cunha TM. Uterine sarcomas: clinical presentation and MRI features. Diagn Interv Radiol. 2015;21(1):4–9.
Lentz SE, Zaritsky E, Tucker LY, Lee C, Lazo IM, Niihara A, Yamamoto M, Raine-Bennett T. Prediction of Occult Uterine Sarcoma before Hysterectomy for women with leiomyoma or abnormal bleeding. J Minim Invasive Gynecol. 2020;27(4):930–e937931.
Wais M, Tepperman E, Bernardini MQ, Gien LT, Jimenez W, Murji A. A Multicentre Retrospective Review of clinical characteristics of Uterine Sarcoma. J Obstet Gynaecol Can. 2017;39(8):652–8.
Kho KA, Lin K, Hechanova M, Richardson DL. Risk of Occult Uterine Sarcoma in Women undergoing hysterectomy for Benign indications. Obstet Gynecol. 2016;127(3):468–73.
Bi Q, **ao Z, Lv F, Liu Y, Zou C, Shen Y. Utility of clinical parameters and multiparametric MRI as predictive factors for differentiating uterine sarcoma from Atypical Leiomyoma. Acad Radiol. 2018;25(8):993–1002.
Moinfar F, Azodi M, Tavassoli FA. Uterine sarcomas. Pathology. 2007;39(1):55–71.
Rojas C, Tian C, Powell MA, Chan JK, Bateman NW, Conrads TP, Rocconi RP, Jones NL, Shriver CD, Hamilton CA, et al. Racial disparities in uterine and ovarian carcinosarcoma: a population-based analysis of treatment and survival. Gynecol Oncol. 2020;157(1):67–77.
Li N, Wu LY, Zhang HT, An JS, Li XG, Ma SK. Treatment options in stage I endometrial stromal sarcoma: a retrospective analysis of 53 cases. Gynecol Oncol. 2008;108(2):306–11.
Huss A, Klar M, Hasanov MF, Juhasz-Boss I, Bossart M. Prognostic factors and survival of patients with uterine sarcoma: a German unicenter analysis. Arch Gynecol Obstet 2022.
Sucu M, Kucukgoz Gulec U, Paydas S, Guzel AB, Kilic Bagir E, Vardar MA. Clinicopathologic characteristics and prognosis comparison of the uterine high grade endometrial carcinomas. Ginekol Pol. 2021;92(4):278–83.
Cabrera S, Bebia V, Acosta U, Franco-Camps S, Manalich L, Garcia-Jimenez A, Gil-Moreno A. Survival outcomes and prognostic factors of endometrial stromal sarcoma and undifferentiated uterine sarcoma. Clin Transl Oncol. 2021;23(6):1210–9.
Ayhan A, Gungorduk K, Khatib G, Firat Cuylan Z, Boran N, Gokcu M, Celik H, Ozgul N, Akbayir O, Simsek T, et al. Prognostic factors and survival outcomes of women with uterine leiomyosarcoma: a Turkish uterine Sarcoma Group Study-003. Curr Probl Cancer. 2021;45(5):100712.
Chantharasamee J, Wong K, Potivongsajarn P, Qorbani A, Motamed N, Brackert S, Cohen J, Chmielowski B, Kalbasi A, Rao J, et al. Retrospective analysis of adjuvant treatment for localized, operable uterine leiomyosarcoma. Cancer Med. 2022;11(15):2906–12.
Kapp DS, Shin JY, Chan JK. Prognostic factors and survival in 1396 patients with uterine leiomyosarcomas: emphasis on impact of lymphadenectomy and oophorectomy. Cancer. 2008;112(4):820–30.
Yang H, Li XC, Yao C, Lang JH, ** HM, ** MR, Wang G, Wang LW, Hao M, Ding Y, et al. Proportion of uterine malignant tumors in patients with laparoscopic myomectomy: a National Multicenter Study in China. Chin Med J (Engl). 2017;130(22):2661–5.
Kurjak A, Kupesic S, Shalan H, Jukic S, Kosuta D, Ilijas M. Uterine sarcoma: a report of 10 cases studied by transvaginal color and pulsed Doppler Sonography. Gynecol Oncol. 1995;59(3):342–6.
Sun S, Bonaffini PA, Nougaret S, Fournier L, Dohan A, Chong J, Smith J, Addley H, Reinhold C. How to differentiate uterine leiomyosarcoma from leiomyoma with imaging. Diagn Interv Imaging. 2019;100(10):619–34.
Durnali A, Tokluoglu S, Ozdemir N, Inanc M, Alkis N, Zengin N, Sonmez OU, Kucukoner M. Anatolian Society of Medical O: prognostic factors and treatment outcomes in 93 patients with uterine sarcoma from 4 centers in Turkey. Asian Pac J Cancer Prev. 2012;13(5):1935–41.
Ishidera Y, Yoshida H, Oi Y, Katayama K, Miyagi E, Hayashi H, Shigeta H. Analysis of uterine corporeal mesenchymal tumors occurring after menopause. BMC Womens Health. 2019;19(1):13.
Momtahan M, Emami F, Sari Aslani F, Akbarzadeh-Jahromi M. Evaluation of treatment results and prognostic factors of uterine sarcoma: a single-center experience. J Chin Med Assoc. 2020;83(1):84–8.
Amant F, Mirza MR, Koskas M, Creutzberg CL. Cancer of the corpus uteri. Int J Gynaecol Obstet. 2018;143(Suppl 2):37–50.
Thangappah RBP. Uterine sarcoma: a clinico-pathological study. J Obstet Gynaecol India. 2019;69(Suppl 2):147–52.
Li K, Yin R, Li L, Wang D, Li L, Ma C, Ren Q, Wang G, Fan Y, Zhou H, et al. Diagnosis and treatment of uterine sarcoma: a multicenter, real-world study in western China. Med (Baltim). 2021;100(51):e28220.
Burghaus S, Halmen S, Gass P, Mehlhorn G, Schrauder MG, Lux MP, Renner SP, Beckmann MW, Hein A, Thiel FC. Outcome and prognosis in uterine sarcoma and malignant mixed mullerian tumor. Arch Gynecol Obstet. 2016;294(2):343–51.
Park JY, Kim DY, Suh DS, Kim JH, Kim YM, Kim YT, Nam JH. Prognostic factors and treatment outcomes of patients with uterine sarcoma: analysis of 127 patients at a single institution, 1989–2007. J Cancer Res Clin Oncol. 2008;134(12):1277–87.
Wang L, Li S, Zhang Z, Jia J, Shan B. Prevalence and occult rates of uterine leiomyosarcoma. Med (Baltim). 2020;99(33):e21766.
Huss A, Klar M, Hasanov MF, Juhasz-Boss I, Bossart M. Prognostic factors and survival of patients with uterine sarcoma: a German unicenter analysis. Arch Gynecol Obstet. 2023;307(3):927–35.
Nordal RN, Kjorstad KE, Stenwig AE, Trope CG. Leiomyosarcoma (LMS) and endometrial stromal sarcoma (ESS) of the uterus. A survey of patients treated in the Norwegian Radium Hospital 1976–1985. Int J Gynecol Cancer. 1993;3(2):110–5.
Sizzi O, Manganaro L, Rossetti A, Saldari M, Florio G, Loddo A, Zurawin R, van Herendael B, Djokovic D. Assessing the risk of laparoscopic morcellation of occult uterine sarcomas during hysterectomy and myomectomy: literature review and the ISGE recommendations. Eur J Obstet Gynecol Reprod Biol. 2018;220:30–8.
Micci F, Heim S, Panagopoulos I. Molecular pathogenesis and prognostication of low-grade’’ and high-grade endometrial stromal sarcoma. Genes Chromosomes Cancer. 2021;60(3):160–7.
Kommoss FK, Chang KT, Stichel D, Banito A, Jones DT, Heilig CE, Frohling S, Sahm F, Stenzinger A, Hartmann W, et al. Endometrial stromal sarcomas with BCOR-rearrangement harbor MDM2 amplifications. J Pathol Clin Res. 2020;6(3):178–84.
Funding
This work was supported by the General projects of the Key Research and Development program in the Natural Foundation of Shaanxi Province, China (Grant numbers. 2017SF-015).
Author information
Authors and Affiliations
Contributions
All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by JF W, CL and JY Y. The first draft of the manuscript was written by JF W, YL W, and JJ and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
The requirement for written informed consent from participants was waived due to the retrospective nature of the study. Verbal informed consent was obtained from surviving patients and the family members of deceased patients during phone call follow-up. They were approved by the ethics committee of the First Affiliated Hospital of **’an Jiaotong University (No. XJTU1AF2023LSK-275). All participants agreed to this study.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Statement
All methods were carried out in accordance with relevant guidelines and regulations in the study.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Wang, Jf., Li, C., Yang, Jy. et al. Clinicopathological characteristics and prognosis of uterine sarcoma: a 10-year retrospective single-center study in China. Diagn Pathol 19, 94 (2024). https://doi.org/10.1186/s13000-024-01517-x
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s13000-024-01517-x