Recurrent Low-grade Endometrial Stromal Sarcoma Research Articles

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

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. 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. 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. 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.

The value of surgery and the prognostic factors for patients with recurrent low-grade endometrial stromal sarcoma: a retrospective study of 38 patients.

As an indolent malignant tumor, the long-term management of low-grade endometrial stromal sarcoma (LGESS) patients required awareness, especially the management of recurrences. Unfortunately, few studies focused on the treatment of recurrent LGESS. Our study aimed to investigate the prognostic factors and the value of recurrent surgery on recurrent LGESS. This retrospective study consecutively recruited patients with pathologically diagnosed recurrent LGESS at our center from April 1, 2004 to April 1, 2020. After a median follow-up of 137.0 months (95% confidence interval=85.4-188.6), the 5-year cumulative survival rate of the cohort of 38 patients with recurrent LGESS was 71.1%. The median overall survival (OS) and post-recurrence survival (PRS) was 156 and 89.0 months. Survival analysis showed that patients with younger age, positive estrogen receptor (ER) and optimal abdominopelvic debulking in the first recurrent surgery had better prognosis (p<0.05). Multivariate analysis showed that optimal abdominopelvic debulking in the first recurrent surgery was the only independent prognostic factor for OS and PRS (OS=216.0/35.0 months, hazard ratio [HR]=5.319, p=0.034; PRS=not reached/4.0 months, HR=10.900, p=0.006). There was no significant difference in OS and PRS between patients recurred only once and those recurred at least twice (p>0.05). The prognosis of recurrent LGESS was favorable. Optimal debulking of no residual tumor in abdominal and pelvic cavity should be the first choice of treatment for recurrent patients, while preservation of ovary or fertility should not be recommended.

Outcomes after recurrence of low-grade endometrial stromal sarcoma (LGESS) (150)

Objectives: To evaluate clinical characteristics of patients with recurrent low-grade endometrial sarcoma (LGESS) and identify prognostic factors associated with improved outcomes. Methods: All patients with a diagnosis of recurrent LGESS treated for their first recurrence at our institution between 1980 and 2019 were retrospectively identified. All recurrent uterine pathologies were reviewed, and pertinent clinical data were abstracted from the medical record. Survival outcomes were estimated using Kaplan-Meier method and differences in survival were analyzed using Logrank tests. Results: Among 28 patients with recurrent LGESS, the median time to first recurrence after the initial diagnosis was 49.5 months (range: 5.1-265.5). The median age at the time of recurrence was 54 years (range: 26-83). The sites of first recurrence were abdomen/pelvis (20, 71%), lung only (7, 25%), lung/spine (1, 4%). Eighteen patients (65%) had multi-site recurrent disease. The median follow-up time was 75.9 months (range: 8.3-232.7). Twenty-two patients (79%) experienced subsequent recurrence(s) with median progression-free survival (PFS) of 34.3 months (95% CI: 14.5-54.2). Median overall survival (OS) after the first recurrence was 136.2 months (95% CI: 87.4-185.0). At the time of the first recurrence, 21 patients (75%) underwent secondary surgical cytoreduction (SSR), and seven (25%) received non-surgical management alone. Reasons for non-surgical management included bony involvement (n=2), diffuse metastatic disease (n=2), short disease-free interval (DFI) (n=1), local extent of disease (n=1), and patient declining resection (n=1). Of those who underwent SSR, complete gross resection (CGR) was obtained in 15 (71%). CGR was not associated with PFS or OS, as most subsequent recurrences were salvaged. Seventeen of 21 (81%) SSR patients received postoperative therapy. ER+ and PR+ recurrent tumors and single-site recurrent disease were factors associated with a significant improvement in PFS (p=0.005 and p=0.03, respectively), but these did not impact OS (p=0.5 and p=0.2, respectively). An initial DFI of >4 years was associated with improved PFS (p=0.06) but no improvement in OS (p=0.1). Conclusions: Patients with a first recurrence of LGESS are likely to recur again. Longer DFI, ER+/PR+ tumors and single-site disease are associated with greater time to subsequent recurrence. Outcomes are generally favorable with this rare tumor, and all multi-modality therapy options should be considered for salvage, including surgical resection. Objectives: To evaluate clinical characteristics of patients with recurrent low-grade endometrial sarcoma (LGESS) and identify prognostic factors associated with improved outcomes. Methods: All patients with a diagnosis of recurrent LGESS treated for their first recurrence at our institution between 1980 and 2019 were retrospectively identified. All recurrent uterine pathologies were reviewed, and pertinent clinical data were abstracted from the medical record. Survival outcomes were estimated using Kaplan-Meier method and differences in survival were analyzed using Logrank tests. Results: Among 28 patients with recurrent LGESS, the median time to first recurrence after the initial diagnosis was 49.5 months (range: 5.1-265.5). The median age at the time of recurrence was 54 years (range: 26-83). The sites of first recurrence were abdomen/pelvis (20, 71%), lung only (7, 25%), lung/spine (1, 4%). Eighteen patients (65%) had multi-site recurrent disease. The median follow-up time was 75.9 months (range: 8.3-232.7). Twenty-two patients (79%) experienced subsequent recurrence(s) with median progression-free survival (PFS) of 34.3 months (95% CI: 14.5-54.2). Median overall survival (OS) after the first recurrence was 136.2 months (95% CI: 87.4-185.0). At the time of the first recurrence, 21 patients (75%) underwent secondary surgical cytoreduction (SSR), and seven (25%) received non-surgical management alone. Reasons for non-surgical management included bony involvement (n=2), diffuse metastatic disease (n=2), short disease-free interval (DFI) (n=1), local extent of disease (n=1), and patient declining resection (n=1). Of those who underwent SSR, complete gross resection (CGR) was obtained in 15 (71%). CGR was not associated with PFS or OS, as most subsequent recurrences were salvaged. Seventeen of 21 (81%) SSR patients received postoperative therapy. ER+ and PR+ recurrent tumors and single-site recurrent disease were factors associated with a significant improvement in PFS (p=0.005 and p=0.03, respectively), but these did not impact OS (p=0.5 and p=0.2, respectively). An initial DFI of >4 years was associated with improved PFS (p=0.06) but no improvement in OS (p=0.1). Conclusions: Patients with a first recurrence of LGESS are likely to recur again. Longer DFI, ER+/PR+ tumors and single-site disease are associated with greater time to subsequent recurrence. Outcomes are generally favorable with this rare tumor, and all multi-modality therapy options should be considered for salvage, including surgical resection.

The prognosis of recurrent low-grade endometrial stromal sarcoma: a retrospective cohort study

BackgroundThe prognosis of recurrent low-grade endometrial stromal sarcoma (LGESS) is little known. This study was to investigate the survival outcomes of a cohort of patients with recurrent LGESS.MethodsPatients with primary LGESS diagnosed and treated for first recurrence confirmed by histology in the study center from February 2012 to June 2019 were retrospectively included. The progression-free interval (PFI) after the last treatment for first recurrence and overall survival (OS) since the diagnosis of first recurrence, which were followed up to June 1, 2020, were compared between groups of various therapy modalities.ResultsFifty-six patients were included, and 43 patients (76.8%) had definite follow-up outcomes. The 5-year PFI and OS rates were 30.0% (95% confidence interval [95% CI] 29.2–30.8) and 75.0% (68.0–82.0), respectively. In univariate analysis, only fertility-sparing treatment, ovarian preservation and surgical treatment had a significant impact on the PFI (hazard ratio [HR] 4.5, 3.1, and 0.2; 95% CI 1.5–13.1, 1.3–7.3, and 0.1–0.7; and p = 0.006, 0.009 and 0.006, respectively), but no factor was found to be associated with increased mortality risk. After adjusted with hormone treatment or chemotherapy, surgical treatment had significant effectiveness on OS (HR 0.3 and 0.3, 95% CI 0.1–1.0 and 0.1–1.0, p = 0.045 and 0.049, respectively). None of the patients with fertility-sparing treatment had successful conception, and all experienced repeated relapse.ConclusionFor patients with recurrent LGESS, fertility-sparing treatment or ovarian preservation should not be provided. Surgery is the treatment of choice, and hormone treatment and/or chemotherapy was effective for the survival benefits of surgical treatment.

Long-term multidisciplinary treatment including proton therapy for a recurrent low-grade endometrial stromal sarcoma and pathologically prominent epithelial differentiation: an autopsy case report

BackgroundLong-term follow-up reports of low-grade endometrial stromal sarcoma (LGESS) including its clinical course and pathological data are rare. We previously reported the case of a Japanese woman diagnosed with LGESS, who was treated with multidisciplinary therapy. She had been suffering from uterine cervical tumor diagnosed as cervical polyps, or fibroid in statu nascendi, since 24 years old. The patient had survived for 25 years with the disease. This report presents her progress and pathological change since the previous report.Case presentationAt age 45, the patient experienced a relapse of the remnant LGESS tumor between the right diaphragm and liver. Although chemotherapy was not effective, the tumor was eliminated by proton therapy. At age 46 years, the remnant tumors outside the irradiated field were resected. The disease was originally diagnosed as “neuroendocrine carcinoma (NEC)” using the surgical specimen. Therefore, cisplatin and irinotecan combination chemotherapy were administered to treat the remnant dissemination. After 4 cycles of chemotherapy, the liver metastases had enlarged and were resected surgically. Consequently, no remnant tumor was visible in the abdominal cavity at the end of the surgery. To determine the origin of NEC, we examined the previously resected specimens obtained from her ileum at age 40 years. A boundary between the LGESS and neuroendocrine tumor grade 2 (NET G2)-like lesion was found in the tumor, indicating that the origin of these tumors was LGESS. After less than 2 years of chemotherapy and undergoing surgery, a relapse of the tumor in the liver induced biliary duct obstruction with jaundice, which was treated with endoscopic retrograde biliary drainage. Although pazopanib prolonged her life for 10 months, she died from sepsis at age 49 years, which was caused by the infection that spread to the liver metastatic tumor via the stented biliary ducts. Autopsy revealed adenocarcinoma-like differentiation of the tumor.ConclusionThis LGESS patient has survived for a long time owing to multidisciplinary treatment including proton therapy. The LGESS tumor differentiated to NET G2-like tissue and then further to adenocarcinoma-like tissue during the long-term follow-up.

Recurrent Low-grade Endometrial Stromal Sarcoma Presenting as Isolated Pedunculated Vaginal Cuff Polyp.

Recurrent Low-grade Endometrial Stromal Sarcoma Presenting as Isolated Pedunculated Vaginal Cuff Polyp.

Letrozole as second-line hormonal treatment for recurrent low-grade endometrial stromal sarcoma: A case report and review of the literature.

Low-grade endometrial stromal sarcoma (LGESS) is a rare malignancy. The tumor is reportedly responsive to hormonal therapy, most commonly with medroxyprogesterone acetate (MPA), but the effectiveness of aromatase inhibitors for recurrent LGESS remains unclear. The present study reports a case of stage IC LGESS presenting with abnormal uterine bleeding, and also provides a review of the literature. Following a total abdominal hysterectomy and bilateral salpingo-oophorectomy, MPA therapy was initiated; treatment was successful, but discontinued 19 months later due to disruptive side effects. A further 2 months later, the patient presented with recurrent disease and received chemotherapy. MPA treatment was restarted with a partial response. A second recurrence, 4 years later, presented with lung and para-aortic lymph node metastases. The patient responded to treatment with the aromatase inhibitor letrozole. The patient has since exhibited stable disease and remained free of symptoms for 7 years. This case suggests that aromatase-inhibitor treatment may be effective for recurrent LGESS as a second-line treatment.

Long-Term Outcome of Aromatase Inhibitor Therapy With Letrozole in Patients With Advanced Low-Grade Endometrial Stromal Sarcoma.

There has been no consensus on the indications for the treatment of advanced low-grade endometrial stromal sarcoma (LGESS), and the possible effects of hormonal treatment including progestins and aromatase inhibitors have been reported. The aim of this study was to investigate the efficacy of aromatase inhibitor therapy with letrozole for patients with residual or recurrent LGESS. We retrospectively reviewed the clinical response of patients with advanced LGESS who had been treated with letrozole. We also analyzed the adverse effects after the administration of letrozole. The expression levels of estrogen receptor and aromatase in the tumors were immunohistochemically examined. In 5 patients who had been treated for unresectable LGESS lesions after initial or repeat surgical procedures, residual lesions in 3 patients and recurrence lesions in 2 patients were the indications for hormonal therapy with letrozole. The median duration of letrozole exposure at retrospective analysis was 53 (10-96) months. The clinical outcomes were classified as complete response in 2 patients, partial response in 1 patient, and stable disease in 2 patients. Myalgias, hot flashes, and arthralgias were not observed during the follow-up period in any patients. The median serum levels of estradiol were <5.0 (cutoff value, <0.5-11.8) pg/mL. The median age-matched bone mineral densities were 92% (79%-123%). The LGESS tissues in all 5 patients were positive for estrogen receptor and aromatase expression. Letrozole as well as progestins could be the first choice of treatment for patients with recurrent or residual LGESS, which is difficult to resect surgically because of its efficacy and minimal adverse effects.

Long-term treatment of residual or recurrent low-grade endometrial stromal sarcoma with aromatase inhibitors: A report of two cases and a review of the literature.

Endometrial stromal sarcoma (ESS) occurs rarely and accounts for only 0.2% of all uterine malignancies. ESS usually expresses estrogen and progesterone receptors, and is regarded as hormone-sensitive. Due to the rarity of these tumors, there are only few case series on the use of aromatase inhibitors in the treatment of low-grade ESS. The present study reports the cases of two patients with residual or recurrent low-grade ESS who experienced long-term disease-free survival following treatment with letrozole. The study also reviews the literature with regard to the data on aromatase inhibitors used in patients with low-grade ESS. In total, 30 patients with recurrent or residual low-grade ESS who were treated with aromatase inhibitors were identified, including the present cases. Among the 30 patients, the overall response rate of advanced low-grade ESS to aromatase inhibitors was 77.4% (complete response, 25.8%; partial response, 51.6%) and the disease control rate was 90.3%. The response rate of first-line treatment was similar to that of second-line therapy or higher (84.6 vs. 72.2%; P=0.453). Duration of aromatase inhibitor treatment ranged from 1.5 to 168 months (median, 26.5 months). The aromatase inhibitors showed minimal adverse effects. In conclusion, aromatase inhibitors, particularly third-generation drugs, are a well-tolerated class of medications that are effective in the treatment of advanced low-grade ESS, with a favorable toxicity profile.

Recurrent low-grade endometrial stromal sarcoma with intracaval and intracardiac tumor thrombus: diagnosis, treatment, and surgical management

Low-grade endometrial stromal sarcoma (LG-ESS) accounts for approximately 1 % of malignant tumors in the uterine corpus, grows slowly, and frequently expresses ER and PR. The 5-year survival of patients with primary LG-ESS was shown to be over 90 %. However, approximately 50 % of cases will recur, with recurrence commonly occurring more than 10 years later. Lymph-vascular space invasion is frequently observed, and several cases of LG-ESS with extension into the major vessels have been reported previously. We herein present a case of a 65-year-old Japanese woman diagnosed with recurrent LG-ESS 16 years after receiving primary treatment. Recurrent tumors were located in the left ovary and also in the para-aortic region below the left renal vein, extending into the inferior vena cava and the right atrium through the left renal vein and left lumbar segmental veins. We judged primary total resection of all tumors to be impossible and described the surgical procedure, risks associated with removing intracaval and intracardiac tumor thrombus, and hormone therapy in this case conference.

Long-term medroxyprogesterone acetate therapy for low-grade endometrial stromal sarcoma

Low-grade endometrial stromal sarcoma (ESS) is a rare tumor. Endocrine treatment is frequently necessary, but treatment details have not been established. Thirteen consecutive patients with low-grade ESS were examined clinicopathologically. All patients underwent surgery, and six were treated with a uniform regimen of medroxyprogesterone acetate (MPA) against residual or recurrent disease. Of the 13 patients, 9 were in stage I, whereas the others were in advanced stages. The median follow-up period was 117 months (range 43-170 months). Six patients, including three with residual peritoneal dissemination and three with recurrent tumors, were treated with MPA. Six months after the initiation of treatment, 3 patients demonstrated a partial response, and 3 patients demonstrated stable disease. The median dosing period was 64 months (range 28-92 months). Five of the patients, including 2 patients who are alive with no evidence of disease and 3 patients who are alive with disease, continue with MPA therapy. The clinicopathological characteristics of the low-grade ESS in this study are consistent with those reported in previous studies. MPA therapy with residual or recurrent disease achieved excellent disease control over a period of 5 years. These results indicate that MPA therapy might be considered as a therapeutic option for residual or recurrent low-grade ESS and perhaps chosen as a first-line therapy.

Aromatase inhibitor anastrozole as a second-line hormonal treatment to a recurrent low-grade endometrial stromal sarcoma: a case report

Low-grade endometrial stromal sarcoma (ESS) is a rare neoplasm and is generally an indolent tumor with estrogen and progesterone receptors. Objective responses by hormonal treatment with progestin or aromatase inhibitor have been reported, however, long-term management of this disease could be difficult if it becomes refractory to one of these hormonal therapies. A 34-year-old woman was diagnosed with stage I low-grade ESS at the time of hysterectomy for presumed uterine fibroma. Five years later, she recurred with multiple tumors in the lower abdomen. After an optimal surgery, she was free from progression for 6years with progestin treatment (medroxyprogesterone acetate: MPA, 200-600mg daily). Thereafter, she recurred twice during the MPA treatment and received debulking surgery each time. MPA was discontinued at age of 53, because another recurrent tumor grew up to 13cm in diameter. Aromatase inhibitor anastrozole was then given at a daily dose of 1mg with partial response (the tumor size decreased to 7cm in diameter) for a duration of 9months. After complete resection of the recurrent tumor, she remains progression-free for 16months. Anastrozole was effective to recurrent low-grade ESS even after being refractory to progestin therapy. Aromatase inhibitor treatment may be a useful option as a second-line hormonal treatment to low-grade ESS.

The efficacy of hormonal treatment for residual or recurrent low-grade endometrial stromal sarcoma. A retrospective study

Objective Low-grade endometrial stromal sarcoma (EES) is a rare tumour with a high recurrence rate but a very good prognosis. Responses to hormonal treatment of these recurrences have been published in case reports. The aim of this study was to determine the objective response rate and response duration of hormonal treatment for recurrent or residual low-grade ESS in a consecutive series of patients. Study design Thirteen consecutive patients with residual or recurrent disease were retrieved from the files. Eleven patients with measurable disease were treated with hormones and form the basis of this study. The following data were collected: age, date of primary diagnosis, type of primary treatment, the presence and localization of residual or recurrent disease, type of treatment, response, duration of response and survival. Results After hormonal treatment 9 (82%) patients showed an objective response (4 complete response; 5 partial response), one showed stable disease (26+ months) and one progressive disease. Response duration was from 4+ to 252+ months (median 48+ months). Conclusion Hormonal treatment for measurable residual or recurrent low-grade ESS has a high response rate and should be considered as the treatment of choice for patients in which recurrent disease cannot easily be resected.

The efficacy of hormonal treatment for residual or recurrent low-grade endometrial stromal sarcoma. A retrospective study

The efficacy of hormonal treatment for residual or recurrent low-grade endometrial stromal sarcoma. A retrospective study

Treatment of Endometrial Stromal Sarcoma With a Gonadotropin-Releasing Hormone Analogue

Endometrial stromal sarcoma can present management difficulties due to its lack of response to conventional chemotherapy and radiotherapy. Various hormonal therapies have been shown to reduce tumor volume in both primary and recurrent disease. A woman who underwent myomectomy was discovered to have a low-grade endometrial stromal sarcoma. Treatment with the gonadotropin-releasing hormone (GnRH) analogue triptorelin before surgery had produced reduction in uterine size. The woman developed tumor recurrence six months after definitive surgical treatment. The tumor enlarged rapidly during a 2-month period, with development of a right-sided hydronephrosis. Repeat administration of triptorelin was accompanied by resolution of the hydronephrosis and reduction in tumor volume. Biopsy results confirmed recurrent low-grade endometrial stromal sarcoma with moderate estrogen and progesterone receptor positivity. Control of progression of a recurrent endometrial stromal sarcoma was achieved with the GnRH analogue triptorelin. This is the first report in the English-language literature during a 30-year period of single-agent GnRH analogue being an effective treatment intervention in this context.

Low-Grade Endometrial Stromal Sarcoma Recurring After 9 Years

A 61-year-old Japanese woman had recurrent low-grade endometrial stromal sarcoma (ESS) after primary treatment 9 years earlier. Initial and recurrent tumors showed the same configuration that the polycystic part showed in the solid tumor ultrasonographically. The central part of both the initial and recurrent tumors showed typical histologic findings, but bizarre cells were detected in the peripheral layer of the recurrent tumor. They resembled glandular cells, Comet cells of high-grade ESS, fibroblasts, decidual cells, and predecidual endometrial stromal cells at the middle to late secretory phases. The change and differentiation of low-grade ESS by therapy and environment seem to be the same as the differentiation in mesenchymal stem cells. We speculate that recurrence and prognosis of low-grade ESS are related by extrauterine development but not by mitotic activity or DNA content.

Low-Grade Endometrial Stromal Sarcoma Recurring After 9 Years

A 61-year-old Japanese woman had recurrent low-grade endometrial stromal sarcoma (ESS) after primary treatment 9 years earlier. Initial and recurrent tumors showed the same configuration that the polycystic part showed in the solid tumor ultrasonographically. The central part of both the initial and recurrent tumors showed typical histologic findings, but bizarre cells were detected in the peripheral layer of the recurrent tumor. They resembled glandular cells, Comet cells of high-grade ESS, fibroblasts, decidual cells, and predecidual endometrial stromal cells at the middle to late secretory phases. The change and differentiation of low-grade ESS by therapy and environment seem to be the same as the differentiation in mesenchymal stem cells. We speculate that recurrence and prognosis of low-grade ESS are related by extrauterine development but not by mitotic activity or DNA content.

Intracaval Extension of a Recurrent Low-Grade Endometrial Stromal Sarcoma

We report the case of a patient undergoing successful removal of an intracaval extension of a recurrent low-grade endometrial stromal sarcoma sixteen years after complete surgical resection. Low-grade endometrial stromal sarcoma is rare uterine neoplasm with a excellent 5-year survival but with high incidence of relapse after a very long time. The tumour has a tendency for lymphatic and venous extension. Intracaval extension is an exceptional indication to perform caval surgery in the treatment of malignant neoplasm.

Recurrent endometrial stromal sarcoma resembling intravenous leiomyomatosis

A case of recurrent low-grade endometrial stromal sarcoma (endolymphatic stromal myosis) presenting as an intracardiac neoplasm is reported. Pronounced leiomyomatous differentiation was noted in the recurrence. This together with the gross pathology closely resembled intravenous leiomyomatosis.