Intravenous metastasis of unexpected uterine sarcoma in the context of uterine fibroids: case report and literature review.

Objective: Endometrial stromal tumors are rare and complex mesenchymal tumors that often present with clinical symptoms similar to uterine leiomyomas. Due to their atypical nature, they are prone to be misdiagnosed or overlooked by healthcare professionals. This study presents a case report of an incidentally discovered endometrial stromal sarcoma with venous metastasis, which was initially misdiagnosed as a uterine leiomyoma. In addition, this study reviews previously documented cases of similar tumors. Case report: During a routine medical examination in 2016, a 50-year-old woman was diagnosed with uterine fibroids. In June 2020, she began experiencing moderate, irregular vaginal bleeding. Nevertheless, a histopathological examination indicated an endometrial stromal sarcoma with a striking amalgamation of both low-grade and high-grade features. Molecular analysis identified a rare MED12 gene mutation. The patient underwent total hysterectomy, bilateral salpingectomy, and resection of the metastatic lesions. Postoperative management included radiotherapy, chemotherapy, and hormone therapy. After completion of chemotherapy, the patient was followed up for 27 months with no evidence of tumor recurrence. Conclusion: This case report highlights the importance of pathological, immunohistochemical, and molecular aspects of this rare tumor involving the inferior vena cava and showing the presence of atypical gene mutations. The successful treatment outcome further emphasizes the importance of advances in diagnostic modalities for managing rare tumors like this.

Case Report: Low-grade endometrial stromal sarcoma with intravenous and intracardiac extension: a case after misdiagnosis of endometrial stromal nodule as submucosal fibroid.

We present herein a rare case of large vascular and cardiac metastases of low-grade endometrial stromal sarcoma (LG-ESS) in a female patient, which occurred after misdiagnosis of endometrial stromal nodule (ESN) as submucosal leiomyoma 7 years ago. Preoperative three-dimensional CT reconstruction was used to assess the extent of the lesion. The patient underwent radical resection: thrombectomy and total hysterectomy with bilateral salpingo-oophorectomy without establishing the cardiopulmonary bypass. Intraoperative transesophageal ultrasound (TEE) was used to monitor whether the intracardiac mass was removed completely. To date, this patient is alive without any evidence of recurrence 3 years after surgery. The differential diagnosis of ESN and LG-ESS is often difficult. A clear distinction can only be reliably made after histological analysis of the tumor's entire interface with the neighboring myometrium. This case highlights that follow-ups of patients with ESN are important. Regular follow-up can detect metastasis and recurrence of misdiagnosed LG-ESS as early as possible. Distant metastasis of LG-ESS is rare, especially involving large vessels or the heart. The treatment should largely rely on multidisciplinary cooperation. Although the surgery is traumatic, the perioperative mortality rate is low, and patients can avoid death from congestive heart failure or sudden death.

A case of a recurrent low-grade endometrial stromal sarcoma extending to the inferior vena cava (IVC) after the primary fertility-sparing surgery.

INTRODUCTION AND IMPORTANCE: A case of Low-grade endometrial stromal sarcoma (LG-ESS) invading the great vessels is rare. CASE PRESENTATION: A 34-year-old female who had no past history presented to a previous hospital with abdominal distension. Magnetic resonance imaging revealed a 15 cm pelvic mass beside the uterus, and only the pelvic mass was removed at the surgery. The tumor was judged to be a LG-ESS. The patient chose to be observed to preserve her fertility, and no adjuvant treatment was undertaken. Two years later, she was referred to our hospital due to recurrence of the pelvic mass. Enhanced computed tomography revealed a large tumor in the vena cava which extended from the left internal iliac vein and which originated from the pelvic tumor. An operation was performed by a multidisciplinary team. Complete resection of the tumor was achieved with a radical hysterectomy, bilateral salpingo-oophorectomy, removal of recurrent pelvic masses and the intravascular tumor. We diagnosed a recurrence of LG-ESS. She received a postoperative adjuvant therapy of LG-ESS. CLINICAL DISCUSSION: Patients with fertility-sparing treatment had higher recurrence rates. In cases of tumor intravenous extension, we should make every effort to extract the tumor to avoid sudden death. CONCLUSION: This case highlights the importance of a multidisciplinary approach in treating this rare tumor with intravascular extension. In particular, patients with LG-ESS who receive fertility-sparing surgery should undertake postoperative chemotherapy or radiotherapy in order to reduce the risk of recurrence, as was in this case.

Utero-ovarian low grade endometrial stromal sarcoma, a case report.

INTRODUCTION: Endometrial stromal sarcoma (ESS) is a rare malignancy of uterine in middle aged women. There are numerous subtypes for ESS which share the same clinical picture of uterine bleeding and pelvic pain. Consequently, diagnosis and treatment modalities of LG-ESS with metastasis are challenging. However, both molecular and immunological study of samples can be useful. CASE PRESENTATION: In this case study, we report a 52-year-old woman presenting with the chief complaint of unusual uterine bleeding. There was no specific finding in her past medical history. The CT study revealed enlarged bilateral ovary with a significantly large left ovarian mass and suspicious mass in uterus. By the diagnosis of ovarian mass, patient went under total abdominal hysterectomy with bilateral salpingo-oophorectomy (BSO), greater omentectomy, and appendectomy followed by post-op hormone therapy. Her follow-up was uneventful. The IHC and pathological study of samples revealed incidental LG-ESS uterus mass with metastasis to ovaries despite her primary diagnosis. DISCUSSION: LG-ESS has low metastasis rate. Surgical modalities and neoadjuvant therapies are recommended base on the stage of ESS. In the following study, we represent a case of incidental LG-ESS with bilateral ovarian invasion who was initially diagnosed as an ovarian mass. CONCLUSION: Our patient was successfully managed by surgical intervention. Despite scarcity of LG-ESS, it is advised to consider LG-ESS as a differential diagnosis in management of patients with a uterus mass with bilateral ovarian involvement.

Computer-aided diagnosis of low grade endometrial stromal sarcoma (LGESS).

Low grade endometrial stromal sarcoma (LGESS) accounts for about 0.2% of all uterine cancer cases. Approximately 75% of LGESS patients are initially misdiagnosed with leiomyoma, which is a type of benign tumor, also known as fibroids. In this research, uterine tissue biopsy images of potential LGESS patients are preprocessed using segmentation and stain normalization algorithms. We then apply a variety of classic machine learning and advanced deep learning models to classify tissue images as either benign or cancerous. For the classic techniques considered, the highest classification accuracy we attain is about 0.85, while our best deep learning model achieves an accuracy of approximately 0.87. These results clearly indicate that properly trained learning algorithms can aid in the diagnosis of LGESS.

LG-ESSs and HG-ESSs: underlying molecular alterations and potential therapeutic strategies.

Endometrial stromal tumors (ESTs) include endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and undifferentiated uterine sarcoma (UUS). Since these are rare tumor types, there is an unmet clinical need for the systematic therapy of advanced LG-ESS or HG-ESS. Cytogenetic and molecular advances in ESTs have shown that multiple recurrent gene fusions are present in a large proportion of LG-ESSs, and HG-ESSs are identified by the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon (YWHAE)-family with sequence similarity 22 (FAM22) fusion. Recently, a group of ESSs harboring both zinc finger CCCH domain-containing protein 7B (ZC3H7B)-B-cell lymphoma 6 corepressor(BCOR) fusion and internal tandem duplication (ITD) of the BCOR gene have been provisionally classified as HG-ESSs. In this review, we firstly describe current knowledge about the molecular characteristics of recurrent aberrant proteins and their roles in the tumorigenesis of LG-ESSs and HG-ESSs. Next, we summarize the possibly shared signal pathways in the tumorigenesis of LG-ESSs and HG-ESSs, and list potentially actionable targets. Finally, based on the above discussion, we propose a few promising therapeutic strategies for LG-ESSs and HG-ESSs with recurrent gene alterations.

Update on Endometrial Stromal Tumours of the Uterus.

Endometrial stromal tumours (ESTs) are rare, intriguing uterine mesenchymal neoplasms with variegated histopathological, immunohistochemical and molecular characteristics. Morphologically, ESTs resemble endometrial stromal cells in the proliferative phase of the menstrual cycle. In 1966 Norris and Taylor classified ESTs into benign and malignant categories according to the mitotic count. In the most recent classification by the WHO (2020), ESTs have been divided into four categories: Endometrial Stromal Nodules (ESNs), Low-Grade Endometrial Stromal Sarcomas (LG-ESSs), High-Grade Endometrial Stromal Sarcomas (HG-ESSs) and Undifferentiated Uterine Sarcomas (UUSs). ESNs are clinically benign. LG-ESSs are tumours of low malignant potential, often with indolent clinical behaviour, with some cases presented with a late recurrence after hysterectomy. HG-ESSs are tumours of high malignant potential with more aggressive clinical outcome. UUSs show high-grade morphological features with very aggressive clinical behavior. With the advent of molecular techniques, the morphological classification of ESTs can be integrated with molecular findings in enhanced classification of these tumours. In the future, the morphological and immunohistochemical features correlated with molecular categorisation of ESTs, will become a robust means to plan therapeutic decisions, especially in recurrences and metastatic disease. In this review, we summarise the morphological, immunohistochemical and molecular features of ESTs with particular reference to the most recent molecular findings.

Fertility-sparing management of low-grade endometrial stromal sarcoma: analysis of an institutional series, a population-based analysis and review of the literature.

BACKGROUND: Low-grade endometrial stromal sarcoma (LGESS) is the second most common malignant mesenchymal tumor of the uterus which usually affects young women. However, the researches on the safety and feasibility of the fertility-sparing management of it are limited. METHODS: A retrospective analysis was performed including 5 women diagnosed with LGESS treated with fertility-sparing management at Qilu Hospital of Shandong University from 2010 to 2019. Besides that, 1,070 patients diagnosed with LGESS in SEER database from 1973 to 2016 were examined. By using the Kaplan-Meier method, survival curves were estimated, and comparisons of statistical significance were performed with the stratified log-rank test within each group. RESULTS: Five patients with LGESS were enrolled in this study. All patients were submitted to fertility-sparing surgeries, after surgery, they all continued hormonal therapy for one year. Four out of the 5 patients recurred, to be more exact, 3 of them recurred in uterus and the other one in the uterus and iliac vascular region. They all suffered further surgery and all 5 patients were alive at the time of last contact. Besides, among these patients, two conceived naturally and delivered a healthy baby by cesarean section. Among 1,070 patients in SEER database, only 28 (2.6%) patients underwent local tumor excision, including excisional biopsy (39%), myomectomy (25%), laser ablation or excision (4%) and polypectomy (4%). There was no statistical significance was observed among TH±BSO, radical hysterectomy, subtotal hysterectomy and local tumor excision (P=0.29). CONCLUSIONS: Our analysis indicated that for those young LGESS patients who wish to preserve their fertility, the feasibility and safety of fertility-sparing management should be considered after gynecological oncologist and gynecological pathologist making professional decisions.

A nomogram for predicting overall survival in patients with low-grade endometrial stromal sarcoma: A population-based analysis.

BACKGROUND: Low-grade endometrial stromal sarcoma (LG-ESS) is a rare tumor that lacks a prognostic prediction model. Our study aimed to develop a nomogram to predict overall survival of LG-ESS patients. METHODS: A total of 1172 patients confirmed to have LG-ESS between 1988 and 2015 were selected from the Surveillance, Epidemiology and End Results (SEER) database. They were further divided into a training cohort and a validation cohort. The Akaike information criterion was used to select variables for the nomogram. The discrimination and calibration of the nomogram were evaluated using concordance index (C-index), area under time-dependent receiver operating characteristic curve (time-dependent AUC), and calibration plots. The net benefits of the nomogram at different threshold probabilities were quantified and compared with those of the International Federation of Gynecology and Obstetrics (FIGO) criteria-based tumor staging using decision curve analysis (DCA). Net reclassification index (NRI) and integrated discrimination improvement (IDI) were also used to compare the nomogram's clinical utility with that of the FIGO criteria-based tumor staging. The risk stratifications of the nomogram and the FIGO criteria-based tumor staging were compared. RESULTS: Seven variables were selected to establish the nomogram for LG-ESS. The C-index (0.814 for the training cohort and 0.837 for the validation cohort) and the time-dependent AUC (> 0.7) indicated satisfactory discriminative ability of the nomogram. The calibration plots showed favorable consistency between the prediction of the nomogram and actual observations in both the training and validation cohorts. The NRI values (training cohort: 0.271 for 5-year and 0.433 for 10-year OS prediction; validation cohort: 0.310 for 5-year and 0.383 for 10-year OS prediction) and IDI (training cohort: 0.146 for 5-year and 0.185 for 10-year OS prediction; validation cohort: 0.177 for 5-year and 0.191 for 10-year OS prediction) indicated that the established nomogram performed significantly better than the FIGO criteria-based tumor staging alone (P < 0.05). Furthermore, DCA showed that the nomogram was clinically useful and had better discriminative ability to recognize patients at high risk than the FIGO criteria-based tumor staging. CONCLUSIONS: A prognostic nomogram was developed and validated to assist clinicians in evaluating prognosis of LG-ESS patients.

Adjuvant Hormonal Therapy for Low-Grade Endometrial Stromal Sarcoma.

OBJECTIVE: To compare aromatase inhibitors (AIs) with progestins as adjuvant hormonal therapy(AHT) for low-grade endometrial stromal sarcomas (LGESSs). METHODS: We reviewed cases with LGESS at our institution from 1984 to 2017. Disease recurrence and recurrence-free survival (RFS) were assessed among patients who received AI, progestins, or no AHT. RESULTS: Among 39 patients with LGESS, 18 received progestins, 13 received AI, and 8 received no AHT. Thirty patients had stage I disease, and 9 had stage II to IV disease. All underwent hysterectomies. Disease recurred in 70% (7/10) of stage I patients who received no AHT, compared to 14.3% (1/7) receiving AI, and 7.7% (1/13) receiving progestins ( P = .003). Among stage I patients taking AI, mean RFS was 153.1 months (95% confidence interval [CI]: 110-195.6) versus 306.2 months (95% CI: 259.7-352.6) for progestin patients and 90.8 months (95% CI: 56.8-124.9) for those who received no AHT. In stage II to IV patients, mean RFS was 148.5 months (95% CI: 148.5-148.5) and 120.8 months (95% CI: 55.8-185.9) for the AI and progestin groups, respectively. All stage II to IV patients received AHT. Among stage I patients, median follow-up time for RFS was 159.1 months for progestin patients, 52.6 months for AI, and 53.1 months for those who received no AHT. Of this, 69% of stage I patients taking progestins reduced/stopped treatment prematurely due to side effects. None of the patients taking AI discontinued treatment early. CONCLUSION: Aromatase inhibitor is associated with longer RFS in patients with advanced LGESS, is better tolerated than progestins, and can be primary AHT for LGESS.

Ovarian mucinous borderline tumor accompanied by LGESS with myxoid change: a case report and literature review.

OBJECTIVES: To report an extremely rare case of ovarian borderline mucinous cystic tumor accompanied by low-grade endometrial stromal sarcoma (LGESS) with myxoid change. CASE PRESENTATION: A 42-year-old woman complained of lower left abdominal fullness. Her serum carcinoembryonic antigen, cancer antigen (CA) 125, and CA19-9 levels were normal. Magnetic resonance imaging showed a 10-cm cystic mass with a 5-cm nodule in its wall, and a laparoscopy indicated a cystic mass at the left adnexa. Histology indicated a cystic lesion consisting of proliferative gastrointestinal-type epithelium; the mural nodule had a characteristic of striking myxoid change, preservation of arteriolar pattern, and a "tongue-like" infiltration. CONCLUSIONS: The diagnosis of ovarian mucinous borderline tumor accompanied by LGESS with myxoid change was appropriate.