Endometrial stromal tumors of the uterus: Epidemiology, pathological and biological features, treatment options and clinical outcomes.

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.

Treatment of low-grade endometrial stromal sarcoma in a nulligravid woman.

A 32 year-old nulligravid woman with a uterine mass underwent exploratory laparotomy with myomectomy. Final pathology revealed a low-grade endometrial stromal sarcoma (ESS) with positive margins. She subsequently underwent definitive robotic hysterectomy and bilateral salpingectomy with ovarian preservation. She was diagnosed with a stage IB low-grade ESS. She is currently undergoing observation. Discussion of classification, surgical options, and adjuvant therapy is presented.

Clinicopathological characteristics and treatment strategies for patients with low-grade endometrial stromal sarcoma.

To investigate and evaluate the clinicopathological characteristics and treatment strategies for patients with low-grade endometrial stromal sarcoma (LG-ESS).The medical records of LG-ESS patients who were treated at 2 cancer referral centers from January 2005 to December 2015 were retrospectively reviewed.Twenty patients with LG-ESS met the inclusion criteria and were included in this analysis. Hysterectomy with bilateral salpingo-oophorectomy was the mainstay of surgery. Lymphadenectomy was performed in 12 (60%) cases, and no positive nodes were identified. CD10 was the most commonly used immunohistochemistry marker, followed by smooth muscle actin (SMA), estrogen receptor (ER), desmin, progesterone receptor (PR), and S-100; the positivity rates of these markers were 88.2%, 66.7%, 75.0%, 16.7%, 88.9%, and 0, respectively. Postoperative chemotherapy, radiotherapy, and hormonal treatment were provided alone or in combination in 10 (50%) patients, 4 (20%) patients, and 1 (5%) patient, respectively. One patient developed lung metastasis at initial diagnosis, and 2 (10%) patients had recurrence with distant metastasis. They all underwent complete or incomplete resection followed by hormonal treatment. The overall survival time of these patients was 66, 89, and 109 months at last contact, respectively. The 5-year and 10-year disease-free survival rates for the entire cohort were 90% and 72%, respectively. No patients died of the disease.CD10/SMA/ER/PR in combination with desmin/S-100 might improve the diagnostic accuracy. Surgical resection is the foremost treatment for LG-ESS patients with recurrence or distant metastasis. Hormonal treatment may be beneficial for unresectable or residual tumors.

Silencing nc886, a Non-Coding RNA, Induces Apoptosis of Human Endometrial Cancer Cells-1A In Vitro.

BACKGROUND The role that nc886, a non-coding microRNA, plays in human endometrial cancer is unknown. The present study aimed to describe the functional role of nc886 in human endometrial cancer-1A (HEC-1A) cell line, which may provide another target for human endometrial cancer treatment. MATERIAL AND METHODS The expression levels of nv886 in normal human endometrial tissue and the early phase and late phase of human endometrial cancer tissues were determined and compared by fluorescence in situ hybridization (FISH). Small interference RNA (siRNA) was used to inhibit nc886, and cell proliferation was evaluated with the MTT test. mRNA levels of PKR, NF-κB, vascular endothelial growth factor (VEGF), and caspase-3 were determined against glyceraldehyde 3-phosphate dehydrogenase (GAPDH between the HEC-1A control group and the silenced group (nc886 silenced with siRNA) by real-time reverse transcription polymerase chain reaction (RT-PCR). The protein levels of PKR (total and phosphorylated form), NF-κB, VEGF, and caspase-3 were determined against GAPDH by Western blotting, and cell apoptosis was determined by flow cytometry. RESULTS Our results indicated that a higher level of nc886 was expressed in the late phase of human endometrial cancer tissue, less than in the early phase but still higher than in normal human endometrial tissue. After nc886 was silenced, protein levels of p-PKR (phosphorylated PKR) and caspase-3 were increased, whereas NF-κB and VEGF were decreased. CONCLUSIONS The rate of apoptosis in the silenced group was increased and the rate of cell proliferation was slower in comparison to the control.

Outcome and prognosis in uterine sarcoma and malignant mixed Mullerian tumor.

PURPOSE: There is low evidence regarding the optimal treatment in patients with uterine sarcomas and malignant mixed Mullerian tumors (MMMTs). This study provides an overview of experience at our center with patients diagnosed with uterine sarcoma and MMMT, in relation to the clinical management and outcome. METHODS: The medical records for 143 patients with low-grade endometrial stromal sarcoma (ESS), leiomyosarcoma (LMS), and high-grade (undifferentiated) endometrial sarcoma (UES) and MMMT were reviewed. All available clinical and pathological data were collected and analyzed. Putative prognostic factors were entered into a multivariate analysis using a Cox proportional hazards ratio model, and survival data were calculated. RESULTS: The 5-year overall survival rates were significantly different between patients with ESS, LMS, and UES and MMMT (86 vs. 40 vs. 57 vs. 45 %; P < 0.001). The multivariate analysis showed that the patients' age, higher FIGO stage (III-IV), a history of smoking, prior pelvic radiation, diabetes, and residual tumor after surgery were associated with a poorer overall survival. Histological subtypes of LMS (HR 4.68; 95 % CI 1.35-16.17), UES (HR 1.21; 95 % CI 0.26-5.77) and MMMT (HR 1.63; 95 % CI 0.42-6.43) were also associated with a poorer overall survival than ESS (P = 0.008). Adjuvant therapies showed no associations with overall survival. CONCLUSIONS: Adjuvant therapy has so far not shown any overall survival benefit, and the focus is therefore on primary surgery. In future studies, the entities should be investigated separately in relation to prognostic factors and effective therapeutic management.

Endometrial stromal sarcoma: clinicopathological and immunophenotypic study of 16 cases.

PURPOSE: Endometrial stromal sarcomas (ESSs) are rare tumors and are divided into two groups: low-grade endometrial stromal sarcoma (ESS-LG) and undifferentiated endometrial sarcoma (UES). The purpose of this study was to compare the clinicopathological features and immunophenotypes of ESS-LG and UES. METHODS: The authors evaluated 16 patients diagnosed with ESS at the Hyogo Cancer Center, reviewed their files and data, and performed an immunohistochemical study for oncogenic proteins (EGFR, PDGFR-α, and PDGFR-ß) and cell cycle regulators (cyclin D1, cyclin E, p16(INK4a), p21(cip1), p27(kip1), and p53) to compare ESS-LG and UES using the World Health Organization (WHO) classification. RESULTS: Four cases (25 %) were classified as ESS-LGs and 12 (75 %) as UES. Patients with UES had a significantly worse overall survival than did those with ESS-LG (p = 0.0445). Although no ESS-LGs showed expression of p16(INK4a), 10 of 12 (83 %) UESs showed expression of p16(INK4a). UESs showed a trend toward higher expression of cyclin D1, p21(cip1), and p53 compared with ESS-LGs. CONCLUSIONS: Our data emphasize the clinical importance of the WHO classification of ESS. It is of utmost importance to establish a proper classification to increase the consistency of data that may be useful for improving clinical and therapeutic management of patients with ESS.

Outcome and prognostic factors in endometrial stromal tumors: a Rare Cancer Network study.

PURPOSE: To provide further understanding regarding outcome and prognostic factors of endometrial stromal tumors (EST). METHODS AND MATERIALS: A retrospective analysis was performed on the records of 59 women diagnosed with EST and treated with curative intent between 1983 and 2007 in the framework of the Rare Cancer Network. RESULTS: Endometrial stromal sarcomas (ESS) were found in 44% and undifferentiated ESS (UES) in 49% of the cases. In 7% the grading was unclear. Of the total number of patients, 33 had Stage I, 4 Stage II, 20 Stage III, and 1 presented with Stage IVB disease. Adjuvant chemotherapy was administered to 12 patients, all with UES. External-beam radiotherapy (RT) was administered postoperatively to 48 women. The median follow-up was 41.4 months. The 5-year overall survival (OS) rate was 96.2% and 64.8% for ESS and UES, respectively, with a corresponding 5-year disease-free survival (DFS) rate of 49.4% and 43.4%, respectively. On multivariate analysis, adjuvant RT was an independent prognostic factor for OS (p = 0.007) and DFS (p = 0.013). Locoregional control, DFS, and OS were significantly associated with age (≤60 vs. >60 years), grade (ESS vs. UES), and International Federation of Gynecology and Obstetrics stage (I-II vs. III-IV). Positive lymph node staging had an impact on OS (p < 0.001). CONCLUSION: The prognosis of ESS differed from that of UES. Endometrial stromal sarcomas had an excellent 5-year OS, whereas the OS in UES was rather low. However, half of ESS patients had a relapse. For this reason, adjuvant treatment such as RT should be considered even in low-grade tumors. Multicenter randomized studies are still warranted to establish clear guidelines.

[Postoperative radiotherapy of uterine sarcoma: a multicentric retrospective study]. / Radiothérapie postopératoire dans les sarcomes utérins: étude rétrospective multicentrique.

PURPOSE: Surgery is the treatment of choice for localized uterine sarcomas. We conducted a retrospective study to define prognostic factors. PATIENTS AND METHODS: We studied 111 cases of patients treated by adjuvant radiotherapy for uterine sarcoma in seven French centers. The median decline was 31 months. We conducted a univariate analysis to identify factors correlated with local recurrence. The statistically significant factors were studied in multivariate analysis by Cox model. RESULTS: The median dose of external beam radiotherapy was 45 Gy. Forty-three percent of patients had vaginal vault brachytherapy and 21 % chemotherapy. Only 6.3 % of patients had complications of acute grade III and 8.1 % of long-term sequelae of radiotherapy. The survival rate at 5 years was 74.6 %. They noted 12.6 % of isolated locoregional recurrences, against 29.7 % for distant recurrences, 80 % were pulmonary. Factors correlated with the risk of locoregional relapse were menopausal status (P = 0.045) and surgical margins suspicious or not healthy (P = 0.0095). The chemotherapy did not improve overall survival or disease free survival but the numbers were low. CONCLUSION: The postoperative radiotherapy provides good local control in this disease. Brachytherapy is sometimes done, but it does not improve local control. Chemotherapy is not a standard localized stage but the rate of metastatic recurrence calls for the development of strategies involving systemic treatment with radiotherapy.

A rare case of low-grade endometrial stromal sarcoma with myxoid differentiation and atypical bizarre cells.

Endometrial stromal sarcoma (ESS) is a rare mesenchymal tumor with characteristic histological appearances, consisting of diffuse infiltrate of small uniform endometrial stromal cells with a multinodular arrangement and distinct vascular pattern. Less common variants of ESS include "mixed endometrial stromal and smooth muscle tumors", "endometrial stromal tumors resembling ovarian sex cord tumors" and "endometrial stromal neoplasms with endometrial glands", and "aggressive endometriosis". Rarely do endometrial stromal tumors have a prominent fibrous or myxoid appearance which causes confusion and possible misdiagnosis as myxoid leiomyosarcoma. In this report we present a very unusual subtype of ESS in a 32-year-old woman. The tumor revealed atypical pleomorphic bizarre cells which were stained positive only with vimentin and CD10 in an abundant myxoid matrix. A low-proliferative rate was established with MIB-1 staining. To our knowledge such appearance has not been previously reported.

Tumores estromales yeyunales y hemorragia digestiva oculta. Empleo de técnicas mínimamente invasivas en tres casos clínicos / Stromal tumors of the jejunum and obscure gastrointestinal bleeding. Use of minimally invasive techniques in three cases

Se considera hemorragia digestiva oculta cuando las técnicas habituales endoscópicas (esofagogastroscopia y colonoscopia) no encuentran el origen de la hemorragia. Esta hemorragia supone el 5% de todas las hemorragias digestivas. El 27% de las hemorragias ocultas son por lesiones de intestino delgado; los tumores estromales (GIST) son una causa frecuente, fundamentalmente en pacientes de mediana edad. Presentamos 3 casos que reflejan la dificultad en el diagnóstico de este cuadro clínico y destacamos el empleo de técnicas poco invasivas, como la tomografía computarizada y la cirugía laparoscópica, en el complicado manejo de estos enfermos. Creemos que la incorporación de estas técnicas podría evitar otros procedimientos más agresivos y permiten aplicar el tratamiento definitivo quirúrgico de forma temprana con las ventajas de la cirugía laparoscópica (AU)

Gastrointestinal bleeding is considered to be obscure when routine endoscopic techniques (esophagogastroscopy and colonoscopy) fail to identify the origin of the hemorrhage. These hemorrhages represent 5% of all gastrointestinal bleeding. Twenty-seven percent of these hemorrhages are due to small bowel disease and gastrointestinal stromal tumors (GIST) are a frequent cause, especially in middle-aged patients. We present three cases that illustrate the difficulty of diagnosing this clinical entity. We emphasize the use of minimally invasive techniques such as computed tomography and laparoscopic surgery in the complicated management of these patients. We believe that the use of these techniques could avoid the need for other more aggressive procedures and allow the application of early definitive surgical treatment with the advantages of laparoscopic surgery (AU)

Gynecologic cancers: factors affecting survival after pulmonary metastasectomy.

BACKGROUND: Little information is available regarding long-term survival after pulmonary metastasectomy for gynecologic malignancies. METHODS: All patients who underwent pulmonary resection for gynecologic malignancies at our institution between January 1985 and June 2001 were reviewed. Factors affecting long-term survival were analyzed. RESULTS: There were 103 patients, 70 of whom had metastatic disease limited to the lungs. Median age of these 70 patients was 59.4 years (range, 31 to 80 years). The primary tumor originated in the uterine corpus in 37 patients, endometrium in 23, cervix in 7, ovaries in 2, and vagina in 1. Histopathology was leiomyosarcoma in 29 patients, adenocarcinoma in 23, other sarcoma in 11, squamous cell carcinoma in 5, and choriocarcinoma and endolymphatic stromal myosis in 1 each. The median time interval between the first gynecologic procedure and pulmonary resection was 24 months (range, 0 to 237 months). A wedge excision was performed in 44 patients, lobectomy in 14, bilobectomy in 2, pneumonectomy in 1, and a combination in 9. Five patients (7%) had an incomplete resection. Eighteen patients (25.7%) developed at least one complication and 1 died (operative mortality, 1.4%). At last follow-up, 35 had died, and the median follow-up among those who were still alive was 36 months (range, 6 months to 13 years). Five-year and 10-year survival was 46.8% (95% confidence interval, 34.2% to 63.0%) and 34.3% (95% confidence interval, 19.7% to 52.5%), respectively. Factors that adversely affected survival include a disease-free interval between the first gynecologic procedure and pulmonary resection of less than 24 months (p = 0.004) and a primary site located in the cervix (p < 0.001). CONCLUSIONS: Pulmonary resection for metastatic gynecologic cancer in selected patients is safe and effective. Both a short disease-free interval between the primary gynecologic procedure and pulmonary metastasectomy, and a primary cervical tumor had an adverse effect on survival.