OBJECTIVE: To investigate the clinicopathological characteristics and prognosis of patients with uterine sarcoma treated following surgery for presumed benign disease.
METHODS: We identified all patients with uterine sarcoma found incidentally after primary surgery for presumed benign disease who presented to our institution and received re-exploration for completion surgery from January 1, 2004 to January 1, 2021. We analyzed the clinicopathological characteristics and prognosis.
RESULTS: Overall, 95 patients were included in our study. For the initial surgery, myomectomy was performed in 50 (52.6%, 50/95) patients, hysterectomy was performed in 45 (47.4%, 45/95) patients. All patients were re-explored to complete the staging operation. The median time to the staging surgery was 40 days (range 15-90 days). There were 29 patients (30.5%, 29/95) had remnant sarcomas, with 17 patients (17/95, 17.9%) on the remaining uterus, 9 patients (9/95, 9.5%) had disseminated diseases, and 4 patients (4/95, 4.2%) had positive lymph nodes. About 40 patients (42.1%) received adjuvant chemotherapy, 55.2% (16/29) and 36.4% (24/66) patients with/without remnant diseases received adjuvant chemotherapy, respectively (P = 0.087). The median follow-up duration was 76.7 months (IQR: 34.8-118.1 months). And 17 patients (17.9%) had recurrence following re-exploration surgery. 5-year progression-free survival (PFS) and 5-year overall survival (OS) for the entire cohort was 81.7% and 92.1%, respectively. Patients with remnant sarcomas had a tendency towards a worse 5-year PFS and 5-year OS, compared with those without (5-year PFS: 75.6% vs. 84.5%, P = 0.224; 5-year OS: 85.5% vs. 95.1%, P = 0.217). Patients with disseminated diseases had a worse 5-year OS (62.5% vs. 95.1%, P = 0.007) and non-significantly worse 5-year PFS (64.8% vs. 83.4%, P = 0.153) compared with those without.
CONCLUSIONS: Patients with uterine sarcoma treated following surgery for presumed benign disease have a favorable survival. Patients with disseminated diseases had a worse 5-year OS compared with those without. Surgical re-exploration may be valuable for removing remnant sarcomas and disseminated diseases.

OBJECTIVE: To determine prognosis and factors associated with survival of women with uterine sarcoma found incidentally after myomectomy.
METHODS: We performed a retrospective study for patients who had previously undergone myomectomy for presumed benign uterine fibroid disease and were found to have uterine confined sarcoma after myomectomy surgery.
RESULTS: In total, 50 patients were identified. There were 23 (46.0 %) patients undergoing myomectomy were performed by minimal invasive surgery: laparoscopic (Lap, n = 22, 44.0 %) or transvaginal (TV, n = 1, 2.0 %) approach; while, 24 (48.0 %) and 3 (6.0 %) patients had myomectomy through abdominal (Abd) or hysteroscopic (Hys) approach. All patients received the re-exploration and staging surgery in our center. The median time from myomectomy to the staging surgery was 43 days (range 15-90 days). 17 patients had remnant sarcomas on the remaining uterus and 6 patients had disseminated disease after re-exploration. In the entire cohort, 5-year RFS and 5-year OS was 79.4 % and 88.0 %, respectively. Patients who received initial Lap/TV myomectomy had a tendency towards a worse 5-year RFS compared with Abd/Hys approach (63.0 % vs 88.9 %, P = 0.080). No difference in 5-year OS was found between the two groups (90.3 % vs 91.8 %, P = 0.768). For stage I disease (n = 44), patients who received Lap/TV myomectomy had a worse 5-year RFS compared with Abd/Hys approach (58.3 % vs 95.7 %, P = 0.009). No difference in 5-year OS was found (P = 0.121).
CONCLUSIONS: Patients with incidental uterine sarcoma who received primary Lap/TV myomectomy may have a worse RFS. Re-exploration can detect remnant or disseminated sarcomas.

OBJECTIVE: To explore the feasibility of multiparametric MRI-based habitat imaging for distinguishing uterine sarcoma (US) from atypical leiomyoma (ALM).
METHODS: This retrospective study included the clinical and preoperative MRI data of 69 patients with US and 225 patients with ALM from three hospitals. At both the individual and cohort levels, the K-means and Gaussian mixture model (GMM) algorithms were utilized to perform habitat imaging on MR images, respectively. Specifically, T2-weighted images (T2WI) and contrast-enhanced T1-weighted images (CE-T1WI) were clustered to generate structural habitats, while apparent diffusion coefficient (ADC) maps and CE-T1WI were clustered to create functional habitats. Parameters of each habitat subregion were extracted to construct distinct habitat models. The integrated models were constructed by combining habitat and clinical independent predictors. Model performance was assessed using the area under the curve (AUC).
RESULTS: Abnormal vaginal bleeding, lactate dehydrogenase (LDH), and white blood cell (WBC) counts can serve as clinical independent predictors of US. The GMM-based functional habitat model at the cohort level had the highest mean AUC (0.766) in both the training and validation cohorts, followed by the GMM-based structural habitat model at the cohort level (AUC = 0.760). Within the integrated models, the K-means functional habitat model based on the cohort level achieved the highest mean AUC (0.905) in both the training and validation cohorts.
CONCLUSIONS: Habitat imaging based on multiparametric MRI has the potential to distinguish US from ALM. The combination of clinical independent predictors with the habitat models can effectively improve the performance.

UNASSIGNED: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the USs.
UNASSIGNED: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients.
UNASSIGNED: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), 3 adenosarcomas, 2 carcinosarcomas, and 1 uterine tumor resembling an ovarian sex-cord tumor (UTROSCT). ESS (including high-grade ESS and low-grade ESS) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A - PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uDEGs were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named MMN-MIL showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804.
UNASSIGNED: USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

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 Xi\'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.
CONCLUSIONS: 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.

BACKGROUND: Uterine sarcoma (US) is a highly malignant cancer with poor prognosis and high mortality in women. In this study, we evaluated the expression of human fibroblast growth factor 23 (FGF23) in different US subtypes and the relationship between survival and clinicopathological characteristics.
METHODS: We conducted a comparative analysis of FGF23 gene expression in different pathological types of US. Utilizing a cohort from The Cancer Genome Atlas of 57 patients, a 50-patient microarray dataset (GSE119043) from the Gene Expression Omnibus and a Suining cohort of 44 patients, we analyzed gene expression profiles and corresponding clinicopathological information. Immunohistochemistry was used to examine the expression level of FGF23 in four US subtypes. Survival analysis was used to assess the relationship between FGF23 expression and prognosis in US patients.
RESULTS: Compared with uterine normal smooth muscle and uterine leiomyoma, FGF23 expression was significantly upregulated in US and was differentially expressed in four US subtypes. Uterine carcinosarcoma exhibited the highest expression of FGF23 among the subtypes. Survival analysis revealed no correlation between FGF23 expression and either overall survival or progression-free survival in US (P > 0.05). Similar results were obtained from the validation cohorts. Univariate and multivariate analyses showed no significant correlation between FGF23 expression and the US prognosis. Tumor stage, CA125, and tumor recurrence were independent prognostic factors for survival of US patients.
CONCLUSIONS: FGF23 was highly expressed in US and was promising as a novel potential biomarker for the diagnosis and prognosis of US.

Intravascular leiomyoma (IVL) is usually defined as a histologically benign leiomyoma that originates in a uterine fibroid or the intrauterine vein wall and grows and expands intravenously. We report a case in which pelvic IVL was detected early and discuss the early diagnosis of and best treatment for this tumor.

COL1A1::PDGFB fusion uterine sarcoma is a rare uterine mesenchymal tumor with some clinicopathological features that overlap with those of soft tissue dermatofibrosarcoma protuberans. However, the varied clinicopathologic and genetic characteristics have not been fully revealed, which may be a potential pitfall for diagnosis. Here, we present a case of COL1A1::PDGFB fusion-positive uterine sarcoma in a 49-years-old female. Histologically, the tumor from the initial marginal excision predominantly exhibited high-grade fibrosarcomatous and myxofibrosarcoma-like appearances, while a low-grade focal area displaying storiform growth was identified in the residual tumor after subsequently extended resection. Immunohistochemically, the high-grade components mainly exhibited focal positivity for CD34 and mutated-type p53 immunoreactivity, whereas the low-grade component showed diffuse positivity for CD34 and wild-type p53 staining. The COL1A1::PDGFB fusion was confirmed by fluorescence in situ hybridization and next-generation sequencing. In addition, the TERT-124 C > T mutation was further identified in this lesion\'s fibrosarcomatous and classic storiform components. To the best of our knowledge, this is the first described case of COL1A1::PDGFB fusion uterine sarcoma with a TERT promoter mutation, which might be a novel genetic finding associated with tumorigenesis of this rare tumor.

BACKGROUND: Uterine sarcomas are uncommon mesenchymal tumors of the uterus. The clinical problem is that the features of uterine sarcomas can sometimes mimic uterine fibroids. This study aims to investigate the clinical characteristics of patients with uterine sarcomas who were preoperative presenting mainly with uterine masses.
METHODS: A retrospective analysis of patients who underwent gynecological surgery for uterine sarcomas at the Obstetrics & Gynecology Hospital of Fudan University, between January 2016 and December 2021.
RESULTS: Over the 5-year period, 277 patients were final diagnosed of uterine sarcomas. A total of 162 patients were preoperatively diagnosed as uterine fibroids for surgical treatment, the majority of whom were diagnosed of uterine leiomyosarcoma (uLMS) (49/162) and low-grade endometrial stromal sarcoma (LG-ESS) (100/162). Ninety people underwent total hysterectomy and bilateral salpingo-oophorectomy (TH + BSO), while 72 underwent myomectomy followed by supplemental TH + BSO. The group with direct hysterectomy had a higher average age than the group with prior myomectomy (47.20 ± 8.94 vs. 40.86 ± 5.88, p < 0.001). Among patients preoperatively diagnosed as uterine fibroids, patients with uLMS had a higher proportion of previous myomectomy (26.53% vs. 5.00%, p < 0.001), a larger uterine mass diameter on ultrasound (8.38 ± 3.39 cm vs. 6.41 ± 1.92 cm, p < 0.001), and richer hypervascularity (34.69% vs. 18%, p = 0.024) compared with LG-ESS.
CONCLUSIONS: Analysis of our data showed that a large proportion of uterine sarcomas, especially uLMS and LG-ESS, present mainly with uterine masses. Ultrasound features including a large uterine mass diameter and rich hypervascularity, and with a history of myomectomy may alert clinicians in suspicion of uLMS when compared with LG-ESS.

Adjuvant radiotherapy has been commonly performed in uterine sarcoma patients, but its role in overall survival (OS) remains controversial. Therefore, our study aimed to build a nomogram-based prognostic stratification to identify uterine sarcoma patients who might benefit from adjuvant radiotherapy.
Uterine sarcoma patients without distant metastases between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The LASSO Cox regression was performed to identify essential prognostic predictors and a nomogram was built to predict the 1-, 3-, and 5-year OS. Receiver operating characteristic (ROC), calibration curves, and decision curve analysis (DCA) were used to validate the nomogram. Finally, prognostic stratification was performed by decision tree analysis based on the total points of the nomogram.
2871 patients with uterine sarcoma were included. Preliminary analysis suggested that adjuvant radiotherapy failed to provide an OS benefit for the total population without our nomogram. The built nomogram showed good discrimination and calibration abilities to predict the OS in uterine sarcoma patients and the patients were stratified into three risk groups based on the nomogram. For patients in the high-risk group, adjuvant radiotherapy significantly improved the 5-year OS and median survival time by 26.4% and 17 months, respectively (P < 0.001); while radiotherapy failed to improve the survival outcomes of patients in the low- and intermediate-risk groups.
The nomogram-based prognostic stratification provides preliminary characterization of uterine sarcoma patients who may benefit from radiotherapy. The newly defined high-risk patients may gain significant OS benefit from adjuvant radiotherapy.