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Background: Endometrial stromal sarcoma (ESS) is a rare type of uterine malignancy typically classified into low-grade ESS (LG-ESS) and high-grade ESS. LG-ESS is characterized by low malignancy and limited metastasis, primarily to the lungs. Metastasis of the breast is extremely rare, posing significant challenges in clinical diagnosis and treatment. Case demonstration: A 33-year-old female with a history of two cesarean sections was diagnosed with uterine LG-ESS five months prior. She was admitted for the excision of a left breast mass discovered during a routine examination. A histopathological biopsy confirmed the mass as a breast metastasis of LG-ESS. Postoperatively, she underwent radiotherapy and chemotherapy at a cancer hospital. She has been followed up on for two years with no recurrence. Conclusions: ESS with breast metastasis is extremely rare. The morphological features of ESS with breast metastasis can resemble mesenchymal and sex cord-stromal tumors, complicating imaging and pathological diagnosis, especially if there is no known history of uterine ESS. This study highlights the clinicopathological features of LG-ESS with breast metastasis, including clinical manifestations, imaging features, histopathology, immunohistochemistry, molecular genetic features, and treatment prognosis. It aims to provide new insights for the clinical diagnosis and treatment of ESS with breast metastasis. [ABSTRACT FROM AUTHOR]

Simple Summary: We analyzed the clinicopathological characteristics, management, and survival trends in women diagnosed with uterine sarcoma at our tertiary institute over ten years. We studied the recurrence trends and their management, with a further focus on patterns of the follow-up. This study generates meaningful real-world data to help offer more insight into these rare gynecological cancers. Uterine sarcomas are rare and aggressive gynecological malignancies. We evaluated the epidemiology, treatment outcomes and survival rates in uterine sarcoma patients managed in our institute. The medical records of women with histology proven uterine sarcoma, including leiomyosarcoma (LMS), adenosarcoma (ADS), and endometrial stromal sarcoma (ESS), treated at our institution from February 2010 to February 2022, were analyzed. In total, 41 patients were identified. In detail, LMS, ADS, and high-grade and low-grade ESS were identified, respectively, in 60.9%, 19.5%, 12.1%, and 7.3% of the cases. The majority of women affected by LMS (72%) underwent primary surgery and 40% of them also received adjuvant chemotherapy. A surgical approach was the preferred mode of treatment in 83% of the recurrences. The median OS (overall survival), DFS (disease free survival), and PFS (progression free survival) for the LMS group were 25, 44.5, and 8 months, respectively. The 5-year survival rates for LMS, ADS, and ESS groups were 30.5%, 100% and 37.5%, respectively. The 5-year survival for LMS was found to be significantly worse than for other histology types (p = 0.016). Our study provides valuable data for the evaluation of treatment strategies and survival trends among these rare cancers. The management and follow-up planning of each subtype requires a thorough patient-focused multidisciplinary discussion. [ABSTRACT FROM AUTHOR]

Abstract Low grade endometrial stromal sarcoma (LGESS) typically presents as a solid intracavitary or intramural uterine mass. On imaging, LGESS is usually seen as an endometrial or myometrial solid mass. Cystic change is unusal and may lead to a differential diagnosis of an ovarian mass as was seen in the present case. Here we present a case of a 38 year old woman who presented with a cystic ovarian mass clinically and radiologically. Per-operatively, it was found to be a multiloculated cystic mass, filled with serosanguinous fluid, in the uterine fundus. Histopathological examination showed a tumor mass composed of mainly spindle cells arranged in fascicular pattern showing marked myxoid degeneration and cystic areas. On immunohistochemistry(IHC), tumor cells showed positivity for CD 10, ER, PR, SMA and desmin while HMB45 was negative. Based on histopathological and IHC, a diagnosis of LGESS was made. Most cases of cystic uterine masses have a benign course but, LGESS exhibits a relatively poorer outcome and a risk of metastasis. Hence, we present this case for its unusual presentation which mimics an ovarian mass but has worse prognosis.

Opinion statement: The cornerstone of treatment for uterine sarcoma, regardless of histologic type, remains en bloc surgical resection with total hysterectomy. In the case of incidental diagnosis during another procedure, such as myomectomy, where a hysterectomy was not performed initially, completion hysterectomy or cervical remnant removal is recommended. The completion of additional surgical procedures, including bilateral salpingo-oophorectomy and lymphadenectomy, remains nuanced. Bilateral salpingo-oophorectomy remains controversial in the setting of most subtypes of uterine sarcoma, except in the case of hormone-receptor positivity, such as in low grade endometrial stromal sarcoma, where it is indicated as part of definitive surgical treatment. In the absence of apparent nodal involvement, we do not recommend performing universal lymphadenectomy for patients with sarcoma. We recommend systemic therapy for patients with extra-uterine or advanced stage disease, high-grade histology, and recurrence. The most active chemotherapy regimens for advanced, high-grade disease remain doxorubicin or gemcitabine and docetaxol combination therapy. A notable exception is low grade endometrial stromal sarcoma, where we recommend anti-hormonal therapy in the front-line setting. Radiation therapy is reserved for selected cases where it can aid in palliating symptoms. [ABSTRACT FROM AUTHOR]

Endometrial stromal tumors are rare uterine mesenchymal neoplasms. Endometrial stromal sarcomas (ESSs) are of endometrial stromal origin that accounts for approximately 1% of all uterine malignant neoplasms. ESS is classified into endometrial stromal nodule (ESN), low-grade ESS (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and undifferentiated uterine sarcoma (UUS). The usual clinical presentation of ESS is abnormal uterine bleeding in about 90% of women and uterine enlargement in about 70%, followed by dysmenorrhea and pain in the abdomen in some patients. Clinically, leiomyoma, endometrial polyp, and other malignant entities enter the differential diagnosis. Gross presentation and microscopic examination, along with immunohistochemistry marker expression and clinical correlation, are mandatory to understand their biological nature, prognosis, and treatment outcome.

OBJECTIVES: To elucidate prognostic factors, determine the best course of treatment methods, and assess oncological results in individuals diagnosed with uterine sarcoma. STUDY DESIGN: Between January 2001 and August 2023, 30 patients with uterine sarcomas (US) were included and analyzed in this cross-sectional study. Sixteen patients (53.3%) had uterine leiomyosarcoma, 6 patients (20%) had high-grade endometrial stromal sarcoma, 8 patients (26.7%) had low-grade endometrial stromal sarcoma. RESULTS: The median follow-up of all participants was 50 months. Recurrence was detected in 43.3% of the patients. 5-year survival ratio was 73.3%, 5-year disease-free survival ratio was 66.7%, the overall survival ratio was 70% and the overall disease-free survival rate was 56.6%. No difference was observed between groups in terms of survival comparisons. No statistically significant effect of adjuvant systemic chemotherapy, adjuvant radiotherapy, and combined treatments on median overall survival and median disease-free survival was detected (p>0.05). CONCLUSION: Uterine sarcomas are uncommon malignancies characterized by a poor prognosis, even in early stages, and they are associated with a high recurrence ratio. The most effective treatment method remains unclear to date. [ABSTRACT FROM AUTHOR]

Introduction: Endometrial stromal sarcoma (ESS) is a rare tumor that remains a diagnostic and therapeutic challenge to physicians worldwide. The metastatic setting implies a poor prognosis, with a 5-year survival rate below 40%. Patients with advanced-stage high-grade ESS (HG-ESS) have limited therapeutic options, often involving various chemotherapy regimens. Case Presentation: This report depicts the case of a 47-year-old female diagnosed with HG-ESS. She underwent several lines of treatment starting with radiotherapy and brachytherapy, followed by multiple lines of treatment including trabectedin over several months. After retreatment with trabectedin and achieving disease stabilization for 10 months, treatment was optimized by trabectedin combined with radiotherapy, leading to stable disease that is still ongoing and lasts for over 17 months. Conclusion: Our case underscores the challenging nature of treating patients with HG-ESS and highlights the safety of long-term retrial with trabectedin, coupled with radiotherapy administration. This approach maintained a durable stable disease response in the metastatic setting.

Extrauterine endometrial stromal sarcoma arising from malignant transformation of the vagina is an extremely rare condition. The diagnosis is often difficult as the symptomatology and pathological features overlap with that of pelvic endometriosis. A 38 years old female presented with complaints of dyspareunia, dysmenorrhea, and painful defecation along with blood-stained vaginal discharge for a year. Examination revealed the presence of multiple brownish irregular nodules in posterior vaginal fornix and fixed tender nodules which on biopsy revealed florid vaginal endometriosis. She improved symptomatically on medical therapy. After 18 months of diagnosis, she presented again with a necrotic growth in posterior fornix, which on repeat biopsy revealed a low-grade endometrial stromal sarcoma. Laparotomy revealed a 7×5 cm mass in the pouch of Douglas, infiltrating the posterior vaginal wall and rectum. A complete cytoreductive surgery with retrograde hysterectomy, excision of posterior vaginal wall and rectosigmoid resection was done. The patient is disease-free at a follow-up of 65 months.

Uterine sarcomas are rare and aggressive gynecological malignancies. We evaluated the epidemiology, treatment outcomes and survival rates in uterine sarcoma patients managed in our institute. The medical records of women with histology proven uterine sarcoma, including leiomyosarcoma (LMS), adenosarcoma (ADS), and endometrial stromal sarcoma (ESS), treated at our institution from February 2010 to February 2022, were analyzed. In total, 41 patients were identified. In detail, LMS, ADS, and high-grade and low-grade ESS were identified, respectively, in 60.9%, 19.5%, 12.1%, and 7.3% of the cases. The majority of women affected by LMS (72%) underwent primary surgery and 40% of them also received adjuvant chemotherapy. A surgical approach was the preferred mode of treatment in 83% of the recurrences. The median OS (overall survival), DFS (disease free survival), and PFS (progression free survival) for the LMS group were 25, 44.5, and 8 months, respectively. The 5-year survival rates for LMS, ADS, and ESS groups were 30.5%, 100% and 37.5%, respectively. The 5-year survival for LMS was found to be significantly worse than for other histology types (p = 0.016). Our study provides valuable data for the evaluation of treatment strategies and survival trends among these rare cancers. The management and follow-up planning of each subtype requires a thorough patient-focused multidisciplinary discussion.

Introduction: Endometrial stromal sarcoma (ESS) is a rare tumor that remains a diagnostic and therapeutic challenge to physicians worldwide. The metastatic setting implies a poor prognosis, with a 5-year survival rate below 40%. Patients with advanced-stage high-grade ESS (HG-ESS) have limited therapeutic options, often involving various chemotherapy regimens. Case Presentation: This report depicts the case of a 47-year-old female diagnosed with HG-ESS. She underwent several lines of treatment starting with radiotherapy and brachytherapy, followed by multiple lines of treatment including trabectedin over several months. After retreatment with trabectedin and achieving disease stabilization for 10 months, treatment was optimized by trabectedin combined with radiotherapy, leading to stable disease that is still ongoing and lasts for over 17 months. Conclusion: Our case underscores the challenging nature of treating patients with HG-ESS and highlights the safety of long-term retrial with trabectedin, coupled with radiotherapy administration. This approach maintained a durable stable disease response in the metastatic setting. [ABSTRACT FROM AUTHOR]

An 11-year-old female Persian cat underwent ovariohysterectomy due to dilation of the uterine cavity with irregular thickening of the wall. Macroscopically, the middle and distal regions of the left uterine horn were swollen and the uterine wall was irregularly thickened due to the development of multiple coalescent, variably sized nodules. Microscopically, the nodules had originated in the endometrium and were composed of round to polygonal neoplastic cells arranged in dense sheets or ill-defined fascicles. The neoplastic cells had locally invaded the myometrium and reached the subserosa, with lymphovascular invasion. Immunohistochemically, the neoplastic cell population was partially positive for CD10, an established marker of endometrial stromal sarcoma (ESS) in humans, with focal and diffuse nuclear immunopositivity for oestrogen and progesterone receptors and immunonegativity for desmin and α-smooth muscle actin. Based on these findings, the uterine tumour was diagnosed as ESS and was considered to correspond morphologically to high-grade ESS in humans. [Display omitted] [ABSTRACT FROM AUTHOR]

Reporting clinical cases of high-grade endometrial stromal sarcoma tumors is essential for a better understanding of their natural course and for the development of appropriate diagnostic and treatment strategies. To date, only a few cases have been studied in this regard.In the present study, the authors present the case of a 69-year-old Iranian woman diagnosed with high-grade endometrial stromal sarcoma involving the myometrium and ovaries. The diagnosis was confirmed after pathology, which revealed myometrial and vascular involvement. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and adjuvant chemotherapy with chemotherapy regimens.

Endometrial stromal sarcoma (ESS) is an uncommon uterine mesenchymal neoplasm. The primary extra-uterine location of ESS is a very rare occurrence.We present a case of a 39-year-old woman presented with severe abdominal pain, MRI showed bilateral ovarian tumors with heterogeneous intensity on T2-weighted imaging (T2WI) and T1-weighted imaging (T1WI), with restricted diffusion, including hyperintense areas on T1WI, not erased on T1-weighted fat-suppressed imaging, hypointense on T2WI, and not enhanced after contrast. This mass extended to the Douglas and invaded the uterine and the rectum serosa suggesting an underlying endometriosis. No abnormalities were suspected in the endometrium.The exploration revealed a friable mass arising from ovaries associated with nodules in the small intestine and sigmoid. The patient underwent bilateral adnexectomy and the anatomopathological study revealed a low-grade endometrial stromal sarcoma.This is one of the few reports covering the radiological features of low-grade extra-uterine ESS in the ovary which is probably secondary to degeneration of endometriosis with no evidence of primary uterine ESS.

The benign tumor uterine leiomyoma (UL) develops from the smooth muscle tissue that constitutes the uterus, whereas malignant tumor uterine sarcoma develops from either the smooth muscle tissue or stroma and is different from UL and endometrial cancer. Uterine sarcoma is broadly classified into three types: uterine leiomyosarcoma, endometrial stromal sarcoma (ESS), and carcinosarcoma. Although uterine leiomyosarcoma and ESS are both classified as uterine sarcoma, they significantly differ in terms of their sites of occurrence, symptoms, and treatment methods. Uterine leiomyosarcoma develops from the muscle tissue constituting the wall of the uterus and accounts for approximately 70% of all uterine sarcoma cases. In contrast, ESS develops from the stromal tissue beneath the endometrium and accounts for approximately 25% of all uterine sarcoma cases. ESS is classified as either low grade (LG) or high grade (HG). This case report aimed to highlight the importance of histopathologic examinations based on surgical specimens. Herein, we reported the case of a 45-year-old woman suspected of having submucosal leiomyoma of the uterus based on imaging results. Transvaginal ultrasonography and endometrial biopsy or partial dilation and curettage were performed. Contrast-enhanced magnetic resonance imaging (MRI) revealed a 32-mm mass projecting from the posterior wall of the uterus into the uterine cavity. T2-weighted imaging revealed a low signal within the mass; thus, submucosal UL was suspected. Histopathologic examination of surgical specimens obtained from a patient suspected of having submucosal UL after contrast-enhanced MRI indicated that the patient had ESS. Despite the remarkable advancements in medical imaging technology, the accuracy of contrast-enhanced MRI for detecting uterine mesenchymal tumors is limited. Therefore, histopathologic diagnosis based on surgical specimens should be performed when medical grounds for diagnosing a benign tumor on contrast-enhanced MRI are lacking.

Background: Endometrial stromal sarcoma (ESS) is extremely rare in pregnancy. It shares clinical and imaging features with more common pregnancy findings such as leiomyoma and molar gestations, which makes diagnosis challenging. Case: A 36-year-old patient presented at 8 weeks and 1 day gestation for vaginal bleeding. An intrauterine pregnancy with an appropriately sized embryo with heart motion and a 9.5 cm complex uterine mass was found on ultrasound. MRI showed an 11.4 cm cystic mass with nodular septations causing mass effect on the endometrial cavity. After extensive counseling, the patient underwent a gravid abdominal hysterectomy and bilateral salpingectomy. Final pathology showed low grade ESS. Conclusion: This case highlights the importance of evaluating suspicious uterine masses in pregnancy and the necessity for safe abortion access.

Abstract Background The ZC3H7B-BCOR fusion gene has recently been described in tumours with kinship to so-called high grade endometrial stromal sarcoma (HG-ESS). This subset of tumour behaves similarly to YWHAE-NUTM2A/B HG-ESS, however, they are both morphologically and immunophenotypically distinct neoplasms. The identified rearrangements in the BCOR gene have been accepted as both the driver and requisite feature in creating a novel sub-entity within the category of HG-ESS. Preliminary investigations into BCOR HG-ESS have shown similar outcomes to YWHAE-NUTM2A/B HG-ESS, with patients typically presenting with high stage disease. Clinical recurrences and metastases to lymph nodes, sacrum/bone, pelvis/peritoneum, lung, bowel and skin have been identified. In this report, we describe a case of BCOR HG-ESS, that is deeply myoinvasive and widely metastatic. Metastatic deposits include a mass in the breast discovered on self-examination; a metastatic site that has yet to be reported in the literature. Case presentation A 59-year-old female underwent biopsy for post-menopausal bleeding, yielding a diagnosis of “low-grade spindle cell neoplasm with myxoid stroma and endometrial glands”, favouring endometrial stromal sarcoma (ESS). She was then referred for total hysterectomy and bilateral salpingo-oophorectomy. The resected uterine neoplasm was both intracavitary and deeply myoinvasive with morphology consistent with that of the biopsy specimen. Characteristic immunohistochemistry (IHC) was noted, and fluorescence in situ hybridization confirmed BCOR rearrangement, supporting a diagnosis of BCOR HG-ESS. A few months postoperatively, the patient underwent needle core biopsy of the breast which revealed metastatic HG-ESS. Conclusions This case highlights some of the diagnostic challenges posed by uterine mesenchymal neoplasms, and exemplifies the emerging histomorphologic, immunohistochemical, molecular and clinicopathologic features of the recently described HG-ESS with ZC3H7B-BCOR fusion. It adds to the body of evidence supporting the inclusion of BCOR HG-ESS as a sub-entity of HG-ESS within the endometrial stromal and related tumours subcategory of uterine mesenchymal tumors, as well as the poor prognosis and high metastatic potential of this tumor.

Leiomyoma is the most common benign uterine tumor, whereas endometrial stromal tumors are rare uterine tumors with limited clinical experience. The distinction between highly cellular leiomyoma and endometrial stromal sarcoma can pose a diagnostic challenge to the pathologists as both these tumors have considerable overlapping features on histology. [ABSTRACT FROM AUTHOR]

Introduction. High-grade endometrial stromal sarcomas (HGESS) are rare malignant mesenchymal tumors of the uterus with aggressive poor clinical outcome, which frequently exhibit YWHAE::NUTM2 and ZC3H7B::BCOR fusions. In this study, we aimed to investigate HGESSs with YWHAE and BCOR translocations through our archive materials, and to identify morphological, immunohistochemical and molecular features of these tumors. We also assessed the diagnostic value of BCOR immunohistochemistry (IHC) in HGESSs, low-grade endometrial stromal sarcomas (LGESS) and uterine leiomyosarcomas. Methods. One hundred fifty-one uterine sarcomas diagnosed between 2000-2019 were reevaluated, and tumors of 39 patients with specific features were included in the study. Fluorescence in situ hybridization (FISH) studies using YWHAE and BCOR break-apart probes and BCOR IHC were performed. BCOR IHC was also performed in 20 leiomyosarcomas and 19 LGESSs. Results. In six HGESSs, translocations involving YWHAE or BCOR were detected. Five tumors showed high-grade morphology and revealed YWHAE translocation. One HGESS with myxoid morphology revealed BCOR translocation. In immunohistochemistry, three (3/4) YWHAE translocated HGESSs showed BCOR expression. However, the BCOR translocated HGESS was BCOR negative. The study showed that all LGESSs were immunohistochemically negative with BCOR. Although 15% (3/20) leiomyosarcomas reveal focal weak-moderate BCOR expression. Conclusion. BCOR IHC is a useful marker to distinguish LGESS from HGESS. A small percentage of uterine leiomyosarcomas reveal BCOR expression; however, it is not as diffuse and strong as in HGESSs. Strong and diffuse BCOR IHC expression is highly suggestive for HGESS. The diagnosis of HGESS should be supported by molecular studies such as FISH. [ABSTRACT FROM AUTHOR]

Several defining molecular alterations have recently been identified underlying high-grade endometrial stromal sarcomas, such as YWHAE: NUTM2A/B fusions, ZC3H7B: BCOR fusions, and BCOR internal tandem duplication (ITD). BCOR is a useful immunohistochemical marker for identifying these tumors. A 37-year-old lady was presented with a 10-cm-sized tumor in the pouch of Douglas, involving the vaginal vault, bilateral adnexa, and peritoneum. A 53-year-old lady with a prior hysterectomy was presented with a 12-cm-sized tumor in the vault with abdominal deposits. Histopathological examination of both tumors revealed atypical cells comprising oval to spindle-shaped nuclei, a variable amount of myxoid stroma, and mitotic figures exceeding 10/10 high power fields. Immunohistochemically, the former tumor was diffusely positive for CD10, and the second tumor displayed patchy staining. Both tumors were positive for BCOR. Estrogen receptor (ER) showed variable staining in both tumors. By fluorescence in-situ hybridization (FISH), both tumors lacked YWHAE gene rearrangement. Both tumors had an aggressive clinical course, including extensive involvement This constitutes the first report of BCOR-positive high-grade sarcomas involving the female genital tract from our subcontinent. BCOR is a useful immunostain for identifying these relatively aggressive tumors. The differential diagnoses and the prognosis of these ultra-rare tumors are discussed herewith.

Objective: We report a low-grade endometrial stromal sarcoma (ESS) with a novel CDKN1A-JAZF1 fusion gene arising from abdominal wall endometrioma. Case report: A 40-year-old woman presented with a 5.5-cm abdominal wall mass juxtaposed to the postoperative scar of two cesarean sections. Histologically, the tumor exhibited obvious tongue-like protrusions into the surrounding tissue, showed spindle cells with multinodular growth pattern that occasionally rotate around small arteries. Immunohistochemically, the tumor cells were positive for CD10, estrogen receptor (ER), progesterone receptor (PR), negatively stained for smooth muscle actin (SMA), CD117, CyclinD1. In addition, a previously undescribed gene fusion between CDNK1A 5′ end of exon 1(NM_000389.5) and JAZF1 3′ end of exon 5 (NM_175,061,3) was reported in this case. Conclusion: This report of ESS suggesting that rapidly growing abdominal wall masses without menstruation-related should be promptly evaluated and treated aggressively. In addition, we have expanded the molecular landscape of low-grade ESS.

Endometrial stromal tumors (EST) are uterine mesenchymal tumors, which histologically resemble endometrial stroma of the functioning endometrium. The majority of EST are malignant tumors classified as low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and undifferentiated uterine sarcoma (UUS). Overall, ESTs are rare malignancies, with an annual incidence of approximately 0.30 per 100′000 women, mainly affecting peri- or postmenopausal women. The most common genetic alteration identified in LG-ESS is the JAZF1-SUZ12 rearrangement, while t(10;17)(q23,p13) translocation and BCOR gene abnormalities characterize two major subtypes of HG-ESS. The absence of specific genetic abnormalities is the actual hallmark of UUS. Unlike HG-ESSs, LG-ESSs usually express estrogen and progesterone receptors. Total hysterectomy without morcellation and bilateral salpingo-oophorectomy (BSO) is the first-line treatment of early-stage LG-ESS. Ovarian preservation, fertility-sparing treatment, and adjuvant hormonal therapy ± radiotherapy may be an option in selected cases. In advanced or recurrent LG-ESS, surgical cytoreduction followed by hormonal treatment, or vice versa, are acceptable treatments. The standard treatment for apparently early-stage HG-ESS and UUS is total hysterectomy without morcellation with BSO. Ovarian preservation and adjuvant chemotherapy ± radiotherapy may be an option. In advanced or recurrent HG-ESS, surgical cytoreduction and neoadjuvant or adjuvant chemotherapy can be considered. Alternative treatments, including biological agents and immunotherapy, are under investigation. LG-ESSs are indolent tumor with a 5-year overall survival (OS) of 80–100% and present as stage I-II at diagnosis in two third of patients. HG-ESSs carry a poor prognosis, with a median OS ranging from 11 to 24 months, and 70% of patients are in stage III-IV at presentation. UUS median OS ranges from 12 to 23 months and, at diagnosis, 70% of patients are in stage III-IV. The aim of this review is to assess the clinical, pathological, and biological features and the therapeutic options for malignant ESTs. • ESTs are rare malignancies, mainly affecting peri- or postmenopausal women. • Most common genetic alteration identified in LG-ESS is the JAZF1-SUZ12 rearrangement. • YWHAE-NUTM2A/B and BCOR rearrangements characterize two subtypes of HG-ESS. • The absence of specific genetic abnormalities is the actual hallmark of UUS. • LG-ESSs usually express estrogen and progesterone receptors. [ABSTRACT FROM AUTHOR]

MEIS1::NCOA1/2 sarcomas are a newly recognized group of exceedingly rare low-grade spindle cell sarcomas that often involve the genitourinary and gynecologic tracts. Due to its deceptively low-grade morphology and the non-specific immunoprofile, these neoplasms may pose a diagnostic challenge by histologically mimicking other entities such as endometrial stromal sarcoma, smooth muscle tumor, or uterine perivascular epithelioid cell tumor (PEComa). Histologically, MEIS1::NCOA1/2 sarcomas typically show spindle cell proliferation with hyperchromatic nuclei and a generalized cytologic uniformity, arranged in short fascicles and exhibiting alternating zones of hypo- and hypercellularity. Among the previously reported cases, molecular analysis revealed the MEIS1::NCOA2 fusion as the most commonly detected fusion gene, whereas the MEIS1::NCOA1 fusion gene has been reported in only a single case that involved kidney. Herein we report the first case of uterine sarcoma harboring the MEIS1::NCOA1 fusion gene that was initially misclassified as low-grade endometrial stromal sarcoma, demonstrating its clinicopathologic features, and highlighting the essential role of molecular pathology to arrive at the accurate diagnosis that may alter disease classification and inform therapy. [ABSTRACT FROM AUTHOR]

Uterine sarcomas are a rare, heterogenous, group of cancers with limited data on optimal adjuvant treatment. We examined patterns of care for leiomyosarcomas (LMS), endometrial stromal sarcomas (ESS), adenosarcomas (AS), and mixed uterine sarcomas and assessed the utilization of adjuvant therapy for each histology. The National Cancer Database (NCDB) was queried for patients with non-metastatic uterine sarcoma diagnosed between 2004 and 2018 treated with surgery. Uterine carcinosarcomas were excluded. Adjuvant patterns of care and temporal treatment trends are evaluated, stratified by histology. Multivariable logistic regression model was constructed to identify predictors of receipt of radiation adjuvant therapy. Among 12,806 patients, 88% received a total hysterectomy and bilateral salpingo-oophorectomy (TH+BSO) and 42% received lymph node sampling (LNS). Surgery alone was the most common treatment modality for all histology groups (59.0%). Surgery with chemotherapy was the second most common form of treatment for LMS (33.1%) and mixed type tumors (29.6%). Surgery with radiation was the second most common treatment for high-grade ESS (10.8%) and AS (11.8%). External beam radiation therapy (EBRT) was the most common type of adjuvant radiation therapy utilized. Adjuvant radiation therapy (RT) has declined in LMS, from 27% in 2004 to 3% in 2018. Adjuvant chemotherapy for all histology groups has increased in use from 10% in 2004 to 28% in 2018. For uterine sarcomas, TH+BSO without LNS was the main surgical modality. Adjuvant therapy for uterine sarcomas is not commonly used, however high risk features including stage II/III, high grade, and more extensive lymph node sampling appear to increase the likelihood of adjuvant RT. The utilization of adjuvant chemotherapy in uterine sarcomas has increased over time, while RT has been decreasing. [ABSTRACT FROM AUTHOR]

Uterine sarcomas are very infrequent and heterogeneous entities. Due to its rarity, pathological diagnosis, surgical management, and systemic treatment are challenging. Treatment decision process in these tumors should be taken in a multidisciplinary tumor board. Available evidence is low and, in many cases, based on case series or clinical trials in which these tumors have been included with other soft tissue sarcoma. In these guidelines, we have tried to summarize the most relevant evidence in the diagnosis, staging, pathological disparities, surgical management, systemic treatment, and follow-up of uterine sarcomas. [ABSTRACT FROM AUTHOR]

Background: The ZC3H7B-BCOR fusion gene has recently been described in tumours with kinship to so-called high grade endometrial stromal sarcoma (HG-ESS). This subset of tumour behaves similarly to YWHAE-NUTM2A/B HG-ESS, however, they are both morphologically and immunophenotypically distinct neoplasms. The identified rearrangements in the BCOR gene have been accepted as both the driver and requisite feature in creating a novel sub-entity within the category of HG-ESS. Preliminary investigations into BCOR HG-ESS have shown similar outcomes to YWHAE-NUTM2A/B HG-ESS, with patients typically presenting with high stage disease. Clinical recurrences and metastases to lymph nodes, sacrum/bone, pelvis/peritoneum, lung, bowel and skin have been identified. In this report, we describe a case of BCOR HG-ESS, that is deeply myoinvasive and widely metastatic. Metastatic deposits include a mass in the breast discovered on self-examination; a metastatic site that has yet to be reported in the literature. Case presentation: A 59-year-old female underwent biopsy for post-menopausal bleeding, yielding a diagnosis of "low-grade spindle cell neoplasm with myxoid stroma and endometrial glands", favouring endometrial stromal sarcoma (ESS). She was then referred for total hysterectomy and bilateral salpingo-oophorectomy. The resected uterine neoplasm was both intracavitary and deeply myoinvasive with morphology consistent with that of the biopsy specimen. Characteristic immunohistochemistry (IHC) was noted, and fluorescence in situ hybridization confirmed BCOR rearrangement, supporting a diagnosis of BCOR HG-ESS. A few months postoperatively, the patient underwent needle core biopsy of the breast which revealed metastatic HG-ESS. Conclusions: This case highlights some of the diagnostic challenges posed by uterine mesenchymal neoplasms, and exemplifies the emerging histomorphologic, immunohistochemical, molecular and clinicopathologic features of the recently described HG-ESS with ZC3H7B-BCOR fusion. It adds to the body of evidence supporting the inclusion of BCOR HG-ESS as a sub-entity of HG-ESS within the endometrial stromal and related tumours subcategory of uterine mesenchymal tumors, as well as the poor prognosis and high metastatic potential of this tumor. [ABSTRACT FROM AUTHOR]

High-grade endometrial stromal sarcoma (HGESS) is a very rare kind of uterine tumor that accounts for less than 2% of all uterine cancers. The usual sites of metastasis are the abdomen and lung, while bone metastasis is very rare, with only a few cases reported till now. We present a case of HGESS with bone metastasis and review the literature. [ABSTRACT FROM AUTHOR]

Objective: Distinguishing uterine sarcomas from leiomyomas preoperatively poses a significant challenge. This study aims to analyze patient characteristics in cases where uterine sarcoma was suspected prior to surgery. Methods: A retrospective review of medical records (2018-2023) was conducted, focusing on patients who underwent pelvis magnetic resonance imaging (MRI) for uterine masses with suspected sarcoma or due to clinical indications of the disease. Analyzed factors included age, preoperative imaging (particularly pelvis MRI), and preoperative and postoperative diagnoses. Results: Out of the 95 patients meeting inclusion criteria, 52 were suspected of sarcoma via pelvis MRI for uterine mass, while 43 underwent MRI due to clinical suspicion. Postoperative diagnoses revealed 15 malignant cases, including endometrial stromal sarcoma (n=6), leiomyosarcoma (n=3), poorly differentiated sarcoma (n=1), endometrial cancer (n=2), and lymphoma (n=3). During the same period, 21 patients were diagnosed with uterine sarcoma postoperatively. Misdiagnoses as leiomyoma were common in younger patients, with an age difference observed between those suspected (50.1 years) and not suspected (44.9 years) of sarcoma preoperatively. Single, large tumors (>5 cm) were significant predictors of sarcoma (p<0.05). MRI proved the most effective in diagnosing sarcoma, with 60% accuracy, compared to a 76.4% misdiagnosis rate when solely relying on ultrasonography. Six patients required re-staging surgery due to incomplete initial staging following myomectomy, revealing peritoneal seeding in two leiomyosarcoma cases. Conclusion: Uterine sarcomas, often misdiagnosed as leiomyomas, tended to be in younger patients with smaller (<5 cm) or multiple tumors, primarily evaluated using only ultrasonography. Comprehensive assessments, including MRI, are recommended for accurate differentiation of uterine sarcomas in women with uterine mass. [ABSTRACT FROM AUTHOR]

Sarcomas in cytology fluids are uncommon, accounting for an estimated 3-6% of malignant effusions. High-grade endometrial stromal sarcomas are uncommon malignancies, whose true frequency is not well defined. We present a case of high-grade endometrial stromal sarcoma with a BCOR translocation metastatic to the pleural fluid. A 31-year-old female with a long-standing history of abnormal uterine bleeding underwent needle core biopsy, which showed a high-grade endometrial stromal sarcoma with a BCOR translocation. In the months following her diagnosis, the patient underwent multiple cycles of chemotherapy along with radiation therapy, but had disease progression. She then presented with bilateral pleural effusions. Cytology from the pleural effusions showed single cells and three-dimensional clusters of spindle-shaped to epithelioid cells. The cell block showed many groups of the atypical cells. The histologic and immunophenotypic features were consistent with metastatic endometrial stromal sarcoma. Ten months after initial diagnosis and two months after positive pleural fluid cytology the patient was deceased. Malignant pleural fluids with sarcoma metastases are not common. Endometrial stromal sarcomas are infrequent malignancies and those with BCOR translocations are recently described with a small number of cases reported. Pleural fluid metastasis of high-grade endometrial stromal sarcoma with BCOR translocation has not, to our knowledge, been described in the literature. [ABSTRACT FROM AUTHOR]

The clinical value of lymph node dissection remains controversial. This study aimed to evaluate the impact of lymphadenectomy on the prognosis of patients with uterine leiomyosarcomas (uLMS) or endometrial stromal sarcomas (ESS). PubMed, EMBASE and the Cochrane Library were searched for studies describing the prognostic significance of lymphadenectomy in uLMS or ESS. Quality assessments were performed using the Newcastle-Ottawa Scale, relative hazard ratios and a random-effects model. Thirty-two retrospective cohort studies that included 26,693 patients in total were enrolled. Patients with uLMS or low-grade ESS (LG-ESS) had no survival benefits from lymphadenectomy. However, patients with high-grade ESS (HG-ESS), did show survival benefits of lymphadenectomy, with no heterogeneity. No significant evidence of publication bias was found. Lymphadenectomy had little prognostic effect on patients with early-stage uLMS or LG-ESS. The best treatment for HG-ESS is early, comprehensive hysterectomy with lymph node dissection. [ABSTRACT FROM AUTHOR]

We report on a 50-year-old postmenopausal woman who presented with abnormal uterine bleeding and pelvic pain due to a uterine solid mass grew from the uterine fundus to the cervix and with so far undescribed obviously gelatinous grossly change, which was suspected of myxoid leiomyosarcoma in intraoperative diagnosis. Morphologically, the tumor cells displayed haphazard fascicles of uniform mild-to-moderate heteromorphic spindle cell component with significant and abundant myxoid stroma, forming signet ring cells and microcysts. Immunohistochemically, the tumour cells were diffusely positivefor CD10 and cyclin D1 and negative for Desmin and SMA, but the expression of BCOR staining was not present. The FISH study showed a positive BCOR gene break probe, and the RNA sequencing revealed an identified reciprocal fusion gene ZC3H7B-BCOR. The case was finally diagnosed as ZC3H7B-BCOR high-grade endometrial stromal sarcoma. Tumor recurrence occurred rapidly on the pelvic peritoneal and vaginal 2 months after resection. In conclusion, these findings further support ZC3H7B-BCOR HGESS has a poor prognosis and molecular testing of uterine mesenchymal tumors with myxoid matrix and unusual grossly presentation is recommended to avoid misdiagnosis. [ABSTRACT FROM AUTHOR]

This article, published in the European Heart Journal, discusses a case of endometrial stromal sarcoma (LGESS) with intracardiac extension through the inferior vena cava. A 48-year-old woman presented with a cardiac mass and lower limb edema, and imaging revealed a cystic mass in the right atrium that extended from the inferior vena cava. The patient underwent surgical intervention, confirming the diagnosis of LGESS. The extension of LGESS to the inferior vena cava and heart is rare, and this case highlights the importance of vigilance among clinicians for unusual presentations of LGESS. [Extracted from the article]

Background: Endometrial stromal sarcoma is a relatively rare malignant tumor that derives from the malignant transformation of primitive uterine mesenchymal cells. It can lead to distant metastases. High-grade endometrial stromal sarcoma is extremely rare. The adrenal glands are an unreported site of metastasis. Case summary: A 71-year-old woman with a diagnosis of endometrial stromal sarcoma 30 months ago. After receiving treatment with radiotherapy and chemotherapy, the patient was kept asymptomatic during the follow-up until 2 years later, when she complained of dyspnea. Pulmonary and right adrenal gland metastases were detected by 18F-FDG PET/CT. The right upper lobe mass was diagnosed as a high-grade endometrial stromal sarcoma metastasis after postoperative pathology. Due to the patient’s high risk of surgery, as she had many underlying diseases, we performed adequate preoperative preparation. The physical examination revealed that a hard mass was palpable in the right renal area. The right adrenal mass was resected in our hospital. Immunohistochemistry showed ER (-), PR (-), CD10 (+), P16 (+), Ki-67 (50%). The final diagnosis on pathological examination was a high-grade ESS metastatic to the right adrenal gland. The patient continued treatment in other hospitals after surgical resection. After four months of postoperative follow-up, metastasis was detected again during a PET/CT examination at an outside hospital. Conclusion: Endometrial stromal sarcoma is rare, and the adrenal glands are an unreported site of metastasis. It has no specific clinical symptoms and mainly found for other reasons. The diagnosis still depends on pathology and immunohistochemistry. If there is no relevant past history, it is difficult to exclude a primary adrenal tumor. [ABSTRACT FROM AUTHOR]

The landscape of uterine sarcomas is becoming increasingly complex with the description of new entities associated with recurrent molecular alterations. Uterine sarcomas, as well as soft tissue sarcomas, can be distinguished into complex genomic sarcomas and simple genomic sarcomas. Leiomyosarcoma and pleomorphic type undifferentiated uterine sarcoma belong to the first group. Low-grade and high-grade endometrial stromal sarcomas, NTRK, COL1A1 :: PDGFB, ALK, RET, ROS1 associated sarcomas, and SMARCA4 deficient uterine sarcoma belong to the second group. Leiomyosarcoma is the most common uterine sarcoma followed by endometrial stromal sarcomas. Three different histologic subtypes of leiomyosarcomas are recognized with distinct diagnostic criteria and different clinical outcomes, the myxoid and epithelioid leiomyosarcomas being even more aggressive than the fusiform type. The distinction between low-grade and high-grade endometrial stromal sarcoma is based first on morphology and immunohistochemistry. The detection of fusion transcripts helps in the diagnosis. Definitely recognized as a separate entity, uterine PEComa is a rare tumor whose diagnostic criteria are being recently defined. Uterine PEComa has a specific algorithm stratifying the tumors into uncertain malignant potential and malignant tumors. Embryonal rhabdomyosarcomas of the uterine cervix are not restricted to children but can also be observed in adult women and are almost always DICER1 mutated, unlike embryonal rhabdomyosarcoma of the vagina which are DICER1 wild-type, and adenosarcoma which can be DICER1 mutated but with less frequency. As sarcomas associated with fusion transcripts involving the NTRK, ALK, COL1A1 :: PDGFB genes can benefit from targeted therapy, systematic detection are now relevant especially for patients with high risk of relapse or in recurrent setting. The integration of molecular data with dedicated expert pathology review for histology and clinical data allows better identification of uterine sarcomas in order to better treat them. • Uterine sarcomas are divided into complex and simple genomic sarcomas. • Leiomyosarcoma and pleomorphic undifferentiated sarcoma belong to the first group. • Endometrial stromal sarcomas, NTRK, and COL1A1 fused sarcomas belong to the second. • sarcomas with NTRK, ALK, COL1A1-PDGFB fusions can benefit from targeted therapy. • Integration of molecular results with histology improve diagnosis and treatment. [ABSTRACT FROM AUTHOR]

There is a consensus that epigenetic alterations play a key role in cancer initiation and its biology. Studies evaluating the modification in the DNA methylation and chromatin remodeling patterns, as well as gene regulation profile by non-coding RNAs (ncRNAs) have led to the development of novel therapeutic approaches to treat several tumor types. Indeed, despite clinical and translational challenges, combinatorial therapies employing agents targeting epigenetic modifications with conventional approaches have shown encouraging results. However, for rare neoplasia such as uterine leiomyosarcomas (LMS) and endometrial stromal sarcomas (ESS), treatment options are still limited. LMS has high chromosomal instability and molecular derangements, while ESS can present a specific gene fusion signature. Although they are the most frequent types of "pure" uterine sarcomas, these tumors are difficult to diagnose, have high rates of recurrence, and frequently develop resistance to current treatment options. The challenges involving the management of these tumors arise from the fact that the molecular mechanisms governing their progression have not been entirely elucidated. Hence, to fill this gap and highlight the importance of ongoing and future studies, we have cross-referenced the literature on uterine LMS and ESS and compiled the most relevant epigenetic studies, published between 2009 and 2022. [ABSTRACT FROM AUTHOR]

The World Health Organization currently divides endometrial stromal sarcomas into 4 different entities, based on their clinical and pathological features: endometrial stromal nodule, low-grade endometrial stromal sarcomas (LG-ESS), Highgrade endometrial stromal sarcomas, and undifferentiated uterine sarcoma. The fibroblastic variant of LG-ESS is rare and is usually made of small tumoral cells of oval to fusiform shape, demonstrating low cytologic atypia and low mitotic activity, which can lead to confusion with a benign myofibroblastic proliferation. We hereby report a rare case of a fibroblastic variant of LG-ESS in a 37-year-old woman presenting abundant metrorrhagia, which was initially misdiagnosed as an inflammatory pseudotumor before proofreading in our laboratory, along with a review of a histological and immunohistochemical findings, aiming to help pathologists avoid this diagnosis pitfall. [ABSTRACT FROM AUTHOR]

Background and Objectives: Uterine sarcomas represents only 3% of all the female genital tract ones. The tumoral stage is the most significant prognostic factor. The role of the bilateral salpingo-oophorectomy (BSO) in the surgical management of FIGO stage IA and IB appears still controversial. This review aims to investigate the impact of bilateral adnexectomy in the treatment of uterine sarcoma. Methods: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the PubMed, Scopus, Cochrane, Medline, and Medscape databases in February 2022. We applied no language or geographical restrictions, but we considered only English studies. We included the studies containing data about Recurrence Rate (RR), Disease-free Survival (DFS), and Overall Survival (OS). We used comparative studies for meta-analysis. Results: Seventeen studies fulfilled the inclusion criteria; 2 retrospective observational studies, and 15 retrospective comparative studies, And 14 out of the 15 comparative studies were enrolled in meta-analysis. A total of 3743 patients were analyzed concerning the use of adnexectomy with hysterectomy in patients with uterine sarcoma and compared with those who did not. Meta-analysis highlighted a non-significant worsening of the OS in the BSO group compared to the OP group and showed that adnexectomy does not improve the DFS (BSO OR 1.23 (95% CI 0.81–1.85) p = 0.34; I2 = 24% p = 0.22). Conclusions: Most studies selected for our review showed that adnexectomy does not significantly affect the RR, OS, and PFS in treating FIGO stage I uterine sarcomas. Therefore, even if there is a unanimous consensus about bilateral adnexectomy in menopausal patients, preservation of ovarian tissue may be considered in premenopausal women. Nonetheless, there are not enough cases in the literature to recommend this procedure. [ABSTRACT FROM AUTHOR]

Uterine carcinosarcoma (UCS) is a rare and highly aggressive gynecological malignancy characterized by poor prognosis. Due to its rarity, UCS remains relatively unexplored, and specific treatment guidelines are scarce. Despite standard treatments, including surgery, adjuvant chemotherapy, and radiotherapy, UCS has a high recurrence rate and poor overall prognosis. The aggressive nature of UCS is attributed to the metaplastic transformation of carcinomatous elements into sarcoma. This "biphasic" neoplasm features a mixture of epithelial and mesenchymal/tumor components, which partially share molecular signatures and exhibit a typical epithelial-to-mesenchymal transition (EMT) gene expression profile. Recent scientific advancements have highlighted the pivotal role of EMT in UCS progression and mortality. This review covers the epidemiology of UCS, theories regarding its origin, and the current state of clinical trials with more emphasis on the role of EMT drivers in UCS progression and scope of targeting these molecules. By shedding light on the molecular mechanisms supporting UCS, particularly emphasizing the importance of EMT, we aim to provide a more comprehensive understanding of the disease to support the development of more effective therapeutic strategies., (© 2024 Federation of American Societies for Experimental Biology.)

Background: Endometrial stromal sarcoma (ESS) is a rare type of uterine malignancy typically classified into low-grade ESS (LG-ESS) and high-grade ESS. LG-ESS is characterized by low malignancy and limited metastasis, primarily to the lungs. Metastasis of the breast is extremely rare, posing significant challenges in clinical diagnosis and treatment., Case Demonstration: A 33-year-old female with a history of two cesarean sections was diagnosed with uterine LG-ESS five months prior. She was admitted for the excision of a left breast mass discovered during a routine examination. A histopathological biopsy confirmed the mass as a breast metastasis of LG-ESS. Postoperatively, she underwent radiotherapy and chemotherapy at a cancer hospital. She has been followed up on for two years with no recurrence., Conclusions: ESS with breast metastasis is extremely rare. The morphological features of ESS with breast metastasis can resemble mesenchymal and sex cord-stromal tumors, complicating imaging and pathological diagnosis, especially if there is no known history of uterine ESS. This study highlights the clinicopathological features of LG-ESS with breast metastasis, including clinical manifestations, imaging features, histopathology, immunohistochemistry, molecular genetic features, and treatment prognosis. It aims to provide new insights for the clinical diagnosis and treatment of ESS with breast metastasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tian, Luo, Xu and Wang.)

Objective: To evaluate the disease course of patients with low grade endometrial stromal sarcoma (LG-ESS) and compare oncologic outcomes associated with hormonal therapy in primary and recurrent disease., Methods: This is a retrospective study of patients with LG-ESS who underwent active treatment between January 2000 and July 2023. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier product-limit estimator and modeled via Cox proportional hazards regression., Results: A total of 221 patients were included; 58 % of patients (91/157) were stage I, 12 % (19/157) stage II, 13 % (20/157) stage III, and 17 % (27/157) stage IV. Surgery was the primary treatment for 98 % (213/218). Only 79 patients received hormonal adjuvant therapy, 58 % (46/79) Megace, 24 % (19/79) Letrozole, and 18 % (14/79) received other hormonal therapy. There was no significant difference in RFS (p = 0.159) and OS (p = 0.167) between patients receiving Megace versus Letrozole as adjuvant therapy. At first recurrence, patients given Megace had a similar RFS to those on Letrozole (p = 0.302), but a better OS (27 vs 10 months, p = 0.018).  Negative status of estrogen, smooth muscle actin, and desmin were associated with lower RFS (p = 0.039, p = 0.002, and p = 0.015, respectively) and OS (p = 0.008, p = 0.012, and p = 0.013, respectively). Lymphovascular invasion was associated with lower RFS (p = 0.033), and negative status of progesterone was associated with lower OS (p = 0.003)., Conclusion: There was no difference in oncologic outcomes between Megace and Letrozole in patients who received adjuvant therapy for LG-ESS. Megace may have potential survival advantage in recurrent disease. Further study is warranted to determine the most effective agents and their sequence in the treatment of LG-ESS., Competing Interests: Declaration of competing interest Michael Frumovitz – Consulting/speaking Stryker; Consulting Astellas; Research funding AkesoBio. Pamela Soliman – Consulting GSK, Aadi Research funding Merck, GSK, Leap Therapeutics. All other authors have no conflict of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Low-grade endometrial stromal sarcomas (LGESSs) are indolent tumors with a slow progression rate that tend to recur locally. They represent up to 10% of all primary sarcomas of the uterus and endometrium and only 0.2% of all genital tract tumors. They are commonly present in a younger demographic compared to other uterine tumors, with patients' ages typically between 42 and 58 years old. Although the overall 5-year survival rate is excellent, it has a natural history of delayed metastases which may manifest even decades after the disease was first diagnosed. They typically present as poorly defined lesions infiltrating the myometrium, along with extensive engagement of surrounding vascular structures. LGESS may display variants of different morphologies such as smooth muscle, fibromyxoid, sex cord-like, and endometrioid-type gland differentiation. These variations can pose a diagnostic challenge. The occurrence of this differentiation in a metastatic focus rather than in the primary tumor is seldom recorded in the literature. We present a case of a 51-year-old lady with a history of LGESS who was treated with surgery and radiotherapy and then presented after 12 years with an inferior vena cava (IVC) mass, which was confirmed histologically to be metastatic LGESS. Immunohistochemistry studies reveal strong positivity for CD10, WT1, and PR. These markers were negative in the sex cord and endometrioid gland-like differentiation counterparts. The patient had her initial follow-up appointment after the IVC mass resection, and she was in good health with no complications. To the best of our knowledge, this case represents a unique instance of metastatic LGESS exhibiting both sex cord and endometrioid gland-like differentiation that has not been observed in the primary tumor., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Haneen Al-Maghrabi et al.)