Refractory Pneumothorax Due to Cystic Pulmonary Metastasis of a Lowgrade Endometrial Stromal Sarcoma: A Case Report.

Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine neoplasm. Computed tomography (CT) revealed the presence of multiple small bilateral pulmonary nodules in a 58-year-old woman 1 year after surgery for LG-ESS; the clinical diagnosis was pulmonary metastasis. Hormone therapy with progesterone was initiated, after which most of the solid nodules disappeared and some transformed into cystic lesions. Seven years after hormone therapy, the patient experienced repeated pneumothorax. The cause of the pneumothorax was perforation of a metastatic focus within the wall of a small subpleural cyst that was not evident on CT images.

Endometrial stromal tumors: A clinico-histomorphological spectrum of endometrial stromal tumors with review of literature.

BACKGROUND: Endometrial stromal tumors (ESTs) are rare subset of mesenchymal uterine neoplasms. There are heterogeneous morphological, immunohistochemical, and genetic features. Approximately 50% of ESTs occur in perimenopausal women. In 2020, WHO sub-categorized ESTs into four groups: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LGESS), high-grade endometrial stromal sarcoma (HGESS), and undifferentiated uterine sarcoma (UUS). OBJECTIVE: To review the morphological spectrum of endometrial stromal tumors. METHOD: This retrospective study reviewed the histomorphological features of 15 endometrial stromal tumors with respect to atypia, necrosis, mitosis, collagen bands, whorling around vessels, myometrial invasion, and inflammatory cells. Immunohistochemistry markers (CD10, SMA, and ER) along with special stains (Masson's trichrome, toluidine blue) were also studied. RESULTS: The age of the patients ranged from 32 to 60 years. Three patients were postmenopausal. The most common presenting symptom was vaginal bleeding. Five patients were operated with a clinical diagnosis of uterine fibroid. One patient presented with prolapse with no other complaint. All the 15 patients had total abdominal hysterectomy and salpingo-oophorectomy. One case showed necrosis, eight cases showed collagen bands, all the 15 cases showed whorling around vessels, one case showed vascular emboli, and seven cases showed inflammatory cells. In low-grade cases, one case showed focal atypia and one case showed focal coagulative necrosis indicating infarction. Thirteen cases were LGESS, and one case of ESN and HGESS. All cases were positive for ER and CD10. CONCLUSION: Endometrial stromal tumors demonstrate extensive permeation of the myometrium as irregular islands with frequent vascular invasion, whorling around vessels, collagen bands, and inflammatory cells. All these features should be observed thoroughly on microscopy by pathologists to clearly differentiate the low-grade and high-grade endometrial stromal tumors, and to understand the overlapping gray areas morphologically as it affects the prognosis of the patient.

Prognosis of uterine and extrauterine low-grade endometrial stromal sarcoma: an observational cohort study.

OBJECTIVE: Little is known about the survival differences between uterine and extrauterine low-grade endometrial stromal sarcoma (LGESS). Survival outcomes, consisting of disease-free survivals and overall survivals (OS), were compared in these two entities. METHODS: From February 2012 to June 2019, all primary LGESS cases and LGESS cases with first recurrence in the study center were reviewed. The clinicopathological characteristics and survival outcomes of extrauterine and uterine LGESS patients were compared for both primary and recurrent diseases. RESULTS: During the study period, 143 patients with primary LGESS and 56 patients with recurrent LGESS were included and followed up to 1 June 2020, among whom 8 (5.6%) and 10 (17.8%) patients were identified as having extrauterine LGESS. Patients with primary and recurrent extrauterine LGESS had similar clinicopathological characteristics to those of patients with uterine LGESS. In primary or in recurrent LGESS cases, in univariate analysis, patients with uterine and extrauterine LGESS had similar disease-free intervals after the last treatment, and they also had similar OSs after the diagnosis. Ovarian preservation led to significantly increased recurrence for primary LGESS [hazard ratio (HR) 4.9, 95% CI: 2.3-10.1, P <0.001) and repeated recurrence for recurrent LGESS (HR 3.1, 95% CI: 1.3-7.3, P =0.009). Surgical treatment for recurrent LGESS decreased repeated recurrence after the first recurrence (HR 0.2, 95% CI: 0.1-0.7, P =0.006). No factors were found to be associated with the OS of primary or recurrent LGESS. CONCLUSION: The clinical characteristics and survival outcomes of extrauterine LGESS are similar to those of uterine LGESS. Surgery is the treatment of choice for recurrent LGESS. Ovarian preservation is detrimental to disease-free survival but not to OS in both uterine and extrauterine LGESS.

ZC3H7B-BCOR Fusion High-grade Endometrial Stromal Sarcoma With Morphologic Features of Low-grade Endometrial Stromal Sarcoma. A Case Report and Review of Literature.

High-grade endometrial stromal sarcomas with ZC3H7B-BCOR fusion are rare. They are predominantly located in the endomyometrium, with morphologic features characterized as haphazardly arranged fascicles of spindle cells with mild to moderate atypia, abundant myxoid matrix, high mitotic index, and tongue-like/pushing patterns of myometrial invasion. Furthermore, conventional or variant low-grade endometrial stromal sarcomas are often not present. Clinically, they present at a higher stage and are associated with worse prognosis compared with low-grade endometrial stromal sarcoma. Given the limited number of reported cases, we describe the case of a ZC3H7B-BCOR fusion high-grade endometrial stromal sarcoma initially diagnosed on the hysterectomy specimen as low-grade endometrial stromal sarcoma based on an endometrial stromal tumor showing tongue-like myometrial and lymphovascular invasion, minimal cytologic atypia, low-mitotic activity (0-1/10 high-power field), round/spindle cell component and immunohistochemical stain results (positive for CD10, estrogen receptor, progesterone receptor, and focally positive for cyclin D1). At the time of pathologic diagnosis, she was Stage Ia and managed conservatively. Subsequent molecular analysis revealed a ZC3H7B (exon 10)- BCOR (BCL-6 corepressor) (exon 7) gene fusion. On follow-up, she showed no evidence of disease at 37 months from the time of diagnosis. This case report expands the morphologic spectrum of ZC3H7B-BCOR fusion high-grade ESS, which includes an intramural location, morphologic and immunophenotypic features similar to LG-ESS, as well as the presence of round and spindle cell components. This case also underscores the value of molecular analysis in the proper classification of ESS.

Endometrial/Endometrioid Stromal Tumors With Extensive Whorling and CTNNB1 Translocation : A Report of 3 Cases.

Endometrial/endometrioid stromal tumors are rare and morphologically heterogenous, and their diagnosis may be challenging. We identified 3 endometrial/endometrioid stromal tumors with identical and previously undescribed histologic features and herein report their morphologic, immunohistochemical, and molecular profiles. Patients were 53, 62, and 79 years. Tumors were well-circumscribed, tan-yellow solid masses measuring 10.0, 11.0, and 18.7 cm, and were intramyometrial (n=2) or in the broad ligament (n=1). All showed small, tight whorls of epithelioid to slightly spindled tumor cells with minimal cytoplasm and negligible mitoses, multifocally associated with hyalinization and myxoid change set in a loose fibroblastic background with small, delicate vessels. This morphology was seen throughout in 1 tumor and in ∼20% and 70% of the 2 others with the remaining areas showing sex cord-like differentiation. Tumor cells expressed CD10 (3/3, 1 focal), calretinin (3/3 diffuse), WT1 (3/3 diffuse), estrogen receptor (1/1, diffuse). RNA-sequencing was successful in 1 tumor and revealed a GREB1-CTNNB1 in-frame fusion. All 3 tumors harbored a CTNNB1 translocation by fluorescence in situ hybridization correlating with nuclear ß-catenin expression. Whole-genome DNA methylation analysis classified all 3 tumors within the low-grade endometrial stromal sarcoma reference class with flat copy number profiles. One patient (79-y-old) died of unrelated causes 2 months after surgery and the other 2 were alive without disease after 13 and 75 months. We have described a rare subset of endometrial/endometrioid stromal tumors with extensive whorling and a CTNNB1 translocation, expanding the morphologic and molecular spectrum of these neoplasms.

Clinical features of uterine sarcomas presenting mainly with uterine masses: a retrospective study.

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.

Rare case of high-grade endometrial stromal sarcoma metastasising to inferior vena cava and right atrium.

Endometrial stromal sarcomas (ESSs) are a rare form of uterine malignancy representing <10% of all uterine sarcomas and <1% of all primary malignant tumours of the uterus. Invasion of the vascular system by low-grade ESS has been reported in the literature. Here we report the first case of a high-grade ESS invading the pelvic and gonadal vein and extending through the inferior vena cava to the right atrium, the diagnostic challenges and multidisciplinary management of the case.

[Endometrial stromal sarcoma: French Guidelines from the French Sarcoma Group and the Rare Malignant Gynecologic Tumors Group]. / Sarcomes du stroma endométrial de bas grade : référentiels de prise en charge du GSF-GETO/NETSARC+ et du groupe TMRG.

Low-grade endometrial stromal sarcoma (LG-ESS) accounts for approximately 15% of all uterine sarcomas. Median age of patients is around 50 years and half of the patients are premenopausal. In all, 60% of cases present with FIGO stage I disease. Preoperatively radiologic findings of ESS are not specific. Pathological diagnosis remains essential. This review aimed to present the French guidelines for low grade ESS treatment within the Groupe sarcome français - Groupe d'étude des tumeurs osseuse (GSF-GETO)/NETSARC+ and tumeur maligne rare gynécologique (TMRG) networks. Treatments should be validated in multidisciplinary team involved in sarcomas or rare gynecologic tumors. Hysterectomy is the cornerstone of treatment for localized ESS, and morcellation should be avoided. Systematic lymphadenectomy in ESS does not improve the outcome and is not recommended. Leaving the ovaries in situ in stage I tumors could be discussed for young women. Adjuvant hormonal treatment could be considered, for two years for stage I with morcellation or stage II and livelong for stages III or IV. Nevertheless, several questions remain, such as optimal doses, regimens (progestins or aromatase inhibitors) and duration of therapy. Tamoxifen is contraindicated. Secondary cytoreductive surgery if feasible for recurrent disease, appears to be an acceptable approach. Systemic treatment for recurrent or metastatic disease is mainly hormonal, with or without surgery.

Primary ovarian endometrial stromal sarcoma after hysterectomy associated with multiple organ invasion: A case report.

RATIONALE: Endometrial stromal sarcoma (ESS) is a rare disease in patients with uterine malignancies, accounting for <1%. Low-grade endometrial stromal sarcoma (LGESS) accounts merely 0.2% of gynecologic malignant tumor. Primary low-grade extrauterine endometrioid stromal sarcomas (LGEESS) is even more uncommon, with only a few documented case reports. We report a case of primary LGEESS exhibiting widely invasion in multiple organs after hysterectomy, which is the first case reported in Jiangsu Province of China. PATIENT CONCERNS: A 42-year-old nulliparous female with dysgnosia presented with a moderate amount of irregular vaginal bleeding, abdominal pain and distension, and frequent urination for 2 days. Her surgical history included a total hysterectomy and bilateral salpingectomy for uterine fibroids 6 years ago. Ultrasonography and the abdominal and pelvic computed tomography scan detected some solid polycystic masses in the pelvic and abdominal cavities. DIAGNOSES: The histopathology of the specimen confirmed the diagnosis of LESS in the absence of florid endometriosis. The patient was diagnosed with primary extrauterine endometrial stromal sarcoma at FIGO stage III. INTERVENTIONS: Surgery and histopathology were performed. OUTCOME: After surgery, the patient was maintained on leuprorelin acetate microspheres with sustained release for injection at 3.75 mg once every 4 weeks while refusing further radiotherapy. LESSONS: The diagnosis of primary LGEESS is challenging mainly because of their unforeseen location and nongynecologic signs and symptoms. Total hysterectomy and bilateral salpingo-oophorectomy are recommended to LGESS, while additional resection for extrauterine disease depends on disease extent and resectability.

Expanding the molecular spectrum of gene fusions in endometrial stromal sarcoma: Novel subunits of the chromatin remodeling complexes PRC2 and NuA4/TIP60 as alternative fusion partners.

Endometrial stromal sarcomas (ESS) are morphologically and molecularly heterogeneous. We report novel gene fusions (EPC1::EED, EPC1::EZH2, ING3::PHF1) identified by targeted RNA sequencing in five cases. The ING3::PHF1-fusion positive ESS presented in a 58-year-old female as extrauterine mesocolonic, ovarian masses, and displayed large, monomorphic ovoid-to-epithelioid cells arranged in solid sheets. The patient remained alive with disease 13 months after surgery. The three ESS with EPC1::EED occurred in the uterine corpus in patients with a median age of 58 years (range 27-62 years). One tumor showed a uniform epithelioid nested morphology, while the other two were composed of monomorphic spindle cells in fascicles with elevated mitotic figures, focal tumor cell necrosis, and lymphovascular invasion. At a median follow-up of 20 months, two patients developed local recurrence, including one with concomitant distant metastasis, while one patient remained free of disease. All three patients were alive at the last follow-up. The EPC1::EZH2-fusion positive ESS presented in a 52-year-old female in the uterus, and displayed uniform spindled cells arranged in short fascicles, with focally elevated mitotic activity but without necrosis. The patient remained free of disease 3 months after surgery. All cases were diffusely positive for CD10; four diffusely express estrogen and progesterone receptors. Our study expands the molecular spectrum of EPC1 and PHF1-related gene fusions in ESS to include additional novel subunits of the PRC2 and/or NuA4/TIP60 complexes. These cases displayed a monomorphic epithelioid or spindled phenotype, spanning low-grade and high-grade cytomorphology, all expressing CD10 and commonly ER and PR, and are prone to local and/or distant spread.

Low-grade endometrial stromal sarcoma with intravenous thrombus extension: a multidisciplinary surgical challenge.

Low-grade endometrial stromal sarcoma (LG-ESS) usually exhibits indolent behavior, often misdiagnosed and is associated with a favorable prognosis [1]. Despite the indolent nature of LG-ESS, recurrence is common, the risk is as high as 1 in 3 to 1 in 2 [2]. The behavior of such tumors can lead to invade blood vessels [3]. An intravascular tumor is associated with direct risk of sudden death from pulmonary embolism. There are very few reported cases with clinically obvious intravascular extension. Chemotherapy, radiotherapy and hormone therapy are adjuvant treatments that have not been able to demonstrate a definitive benefit in survival [4]. We want to take advantage of the opportunity, so far unpublished, to demonstrate with this case the surgical challenge described step by step, as well as to demonstrate the importance of surgery as the only curative treatment even in extended intravascular disease [5]. Here in, we present the surgical challenge of a LG-ESS in a 59-year old woman with iliac and cava vein tumoral thrombus extension. We performed a tumoral thrombectomy and vascular repair, with a pelvic exenteration and double barrel wet colostomy. After performing pelvic exenteration, the thrombus with intravascular involvement was addressed at 2 points: inferior cava vein and right common iliac vein with the extraction of the entire thrombus. These defects are corrected by angioplasty and venorrhaphy, respectively. The surgery got a complete cytoreduction. It lasted 290 minutes, with 430 mL blood loss. In patients with LG-ESS, cytoreduction is a reliable option even in extended metastatic disease.

A Rare Case of Extrauterine Endometrial Stromal Sarcoma Arising from Deep Pelvic Endometriosis: Role of Multidisciplinary Team Meeting.

INTRODUCTION: Extrauterine endometrial stromal sarcoma (EESS) arising from Deep pelvic endometriosis (DPE) has a poor life quality and is difficult to diagnose pre-operatively. However, the patient's quality of life can be improved when it is diagnosed precisely and managed successfully. CASE REPORT: A 35-year-old woman presented to our hospital with a 3-month history of hematochezia and anal pain. Initially, she was misdiagnosed as a rectal stromal tumor and then precisely diagnosed as having EESS from DPE following several multidisciplinary team (MDT) meetings. The lesion was shrunk by gonadotrophin-releasing hormone agonist (GnRH-α) treatment and then resected with minimal trauma. CONCLUSION: MDT is crucial in the treatment of the patient. It can promote individualized treatment and improve patient's quality of life.

Primary ovarian endometrioid stromal sarcoma presenting with reno-ureteral colic.

BACKGROUND: Endometrioid Stromal Sarcomas are an infrequent group of mesenchymal tumors that we must take into account in the differential diagnosis despite representing only 0.2% of tumors of the female genital tract, as they can go unnoticed until advanced stages. CASE PRESENTATION: Fifty-fourth year-old woman referred from the Urology department due to incidental finding of adnexal mass in MRI during examination after renoureteral colic, in the case of a 50 mm solid cystic mass in LE. MT were within the normal range, and the CT scan observed this mass in contact with the left ureter. The surgery was completed with hysterectomy and contralateral adnexectomy without incident and chemotherapy treatment was not added. The pathological result was ovarian tissue with low-grade endometrial sarcoma. Currently, after two years of follow-up, the patient remains stable without any recurrence of disease. CONCLUSIONS: Endometrioid stromal sarcomas are rare tumors that originate in the endometrial stroma, the ovarian location being rare. Management lies in surgical treatment, and adjuvant therapy is sometimes necessary in advanced stages.