Regular ArticleEndometrial Stromal Sarcoma: Analysis of Treatment Failures and Survival
Abstract
The objective of this retrospective multicenter study was to assess the rates, times, and sites of recurrences of 26 patients with low-grade endometrial stromal sarcomas (ESS) (<10 mitoses per 10 high-power fields (HPF) and 40 patients with high-grade ESS (≥10 mitoses/10 HPF). Surgery was the initial therapy for all patients. Postoperative treatment was given without well-defined protocols. The median follow-up of survivors was 92 months (range, 4–167). Low-grade ESS: Of the 20 patients with disease confined to the uterus, 5 (25.0%) developed pelvic recurrence after a median of 36 months (range, 4–108). Of the 6 patients with disease outside the uterus, only one recurred in the pelvis after 93 months. High-grade ESS: Of the 20 patients with disease confined to the uterus, 11 (55.0%) developed recurrent disease after a median of 5 months (range, 2–76). The relapse occurred in the pelvis in 3 patients, in upper abdomen in 3, in upper abdomen and extraabdominal sites in 1, and in the pelvis and upper abdomen or extraabdominal sites in 4. Of the 12 patients with extrauterine disease confined to the pelvis, 9 (75.0%) developed recurrent disease after a median of 12 months (range, 1–49). The relapse occurred in the pelvis in 3 patients, in extraabdominal sites in 3, and in the pelvis and upper abdomen or extraabdominal sites in 3. Of the 8 patients with extrauterine disease outside the pelvis, 7 died of disease and 1 is currently alive with progressive disease after 24 months. The disease-free survival was significantly better for low-grade than that for high-grade ESS (P= 0.0001). By log-rank test the disease-free survival of high-grade ESS patients was related to stage (P= 0.0466) and mitotic count (P= 0.0014), but not to age. Cox model showed that mitotic count was the only independent prognostic variable for high-grade ESS (P= 0.006). In conclusion, low-grade and high-grade ESS have a completely different biological aggressiveness and clinical behavior.
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Endometrial stromal sarcoma: French Guidelines from the French Sarcoma Group and the Rare Malignant Gynecologic Tumors Group
2023, Bulletin du CancerLes sarcomes du stroma endométrial de bas grade représentent environ 15 % des sarcomes utérins. L’âge médian de survenue est de 50 ans. Ils sont de stade I dans 60 % des cas. Le diagnostic est histologique et une relecture en centre expert est indispensable (Réseau de référence en pathologie des sarcomes [RRePS]). Nous présentons dans cet article les référentiels français de prise en charge de ces sarcomes élaborés par le groupe sarcome français et le groupe des tumeurs malignes rares gynécologiques (TMRG). La chirurgie doit idéalement être réalisée en centre expert. L’hystérectomie totale est le traitement chirurgical recommandé, en évitant le morcellement. Le curage ganglionnaire ne doit être envisagé qu’en cas d’adénopathie macroscopiquement pathologique. Une épargne ovarienne avec salpingectomie peut être discutée chez les jeunes femmes non ménopausées dans les stades localisés. L’hormonothérapie adjuvante, par progestatifs ou par antiaromatases n’est pas un traitement standard ; elle peut être discutée en cas de stade I avec morcellement, et stade II pour une durée de deux à trois ans, et pour une durée prolongée en cas de stade III et IV ; néanmoins la durée de traitement reste encore indéterminée. Le tamoxifène est contre-indiqué. À la récidive, une chirurgie doit être envisagée si elle permet une cytoréduction complète sans morbidité inacceptable. L’hormonothérapie de complément, ou exclusive en cas de chirurgie impossible ou de forme métastatique, demeure le traitement médical de choix de ces récidives.
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.
Endometrial stromal tumors of the uterus: Epidemiology, pathological and biological features, treatment options and clinical outcomes
2023, Gynecologic OncologyEndometrial 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.
Adenocarcinoma of the uterine corpus and sarcomas of the uterus
2023, DiSaia and Creasman Clinical Gynecologic OncologyEndometrial cancer remains the only gynecologic malignancy with a rising incidence and mortality. Although diagnostic techniques have evolved modestly, the surgical management of endometrial cancer was transformed with incorporation of sentinel lymph node dissection paradigms. Furthermore, significant gains have been achieved in molecular characterization of endometrial cancer, with publication of The Cancer Genome Atlas (TCGA) endometrial and subsequent studies. Incorporation of molecular diagnostics has ushered in immunotherapy as an effective treatment strategy in select patients, with alternate targeted therapies emerging as promising options.
A giant metastatic low-grade endometrial sarcoma requiring surgical management
2022, International Journal of Surgery Case ReportsLow-grade endometrial stromal sarcomas are relatively rare tumors. We here report a case of a woman presenting with a giant metastatic low-grade endometrial stromal sarcoma with thromboembolic complications requiring urgent surgical management.
A 58-year-old obese female was admitted, with a voluminous abdominopelvic mass, due to complications related to its size and extent. The tumor derived from the uterus and invaded the ureters, bladder and rectum. It compressed the right iliac vessels causing both deep vein thrombosis and pulmonary embolism. She developed a painful irreducible umbilical. We proceeded with a debulking surgery (hysterectomy with bilateral salpingo-oophorectomy). Histological findings were consistent with a low-grade endometrial stromal sarcoma.
Low-grade endometrial stromal sarcomas are generally low-grade malignant neoplasms with an indolent clinical course. Surgery is the cornerstone of treatment. In low-income countries, malignancies are more often diagnosed at a late stage, which limits therapeutic options. Cytoreduction is recommended in advanced tumors with extrauterine manifestation, depending on symptoms and with palliative intent.
Low-grade endometrial stromal sarcomas are indolent uterine malignancies with metastatic potential. Even in advanced cases, cytoreduction must be considered.
Computer-aided diagnosis of low grade endometrial stromal sarcoma (LGESS)
2021, Computers in Biology and MedicineLow 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.
Mesenchymal and Miscellaneous Lesions of the Uterus
2020, Gynecologic Pathology, Second EditionThe spectrum of uterine lesions of mesenchymal and mixed mesenchymal-epithelial type has expanded in recent years, largely due to the cumulative experience reported in larger case series, as well as the identification of recurrent gene fusions and other molecular alterations. In routine practice, the approach to most mesenchymal neoplasms encountered of the uterus starts with a judicious morphologic approach, which in many cases suffices for the diagnosis. Smooth muscle tumors predominate, most of them being benign. Distinction of conventional and variant leiomyoma types from leiomyosarcoma is important but on occasion challenging, and some lesions remain in the category of unknown malignant potential. Endometrial stromal neoplasms follow in frequency; their distinction from other mesenchymal lesions may be difficult, and molecular testing is gaining momentum as a key ancillary tool in their diagnosis. These two major categories are covered in depth here, along with other mesenchymal lesions with significant occurrence in the uterus. An emphasis is given on the differential diagnosis of each entity. The chapter also covers neoplasms with mixed mesenchymal and epithelial components (except endometrial polyp, which is presented in Chapter 9); of these, the most important clinically is adenosarcoma. The chapter concludes with miscellaneous lesions of histopathologic diagnostic importance.