TSC2-mutant uterine sarcomas with JAZF1-SUZ12 fusions demonstrate hybrid features of endometrial stromal sarcoma and PEComa and are responsive to mTOR inhibition

The clinical and pathologic features of 34 uterine sarcomas were studied to determine the natural history of the disease. Sixteen patients had leiomyosarcoma, five mixed mesodermal sarcoma, ten endometrial stromal sarcoma, two carcinosarcoma and one endolymphatic stromal myosis. The patients were treated without an unique protocol. At 3 years the actuarial relapse-free survival was 53.6 %: 68.4 % in stage I-II patients and 22.2 % in stage III-IV patients. As regards the histologic subtype mixed mesodermal sarcomas had the best prognosis; endometrial stromal sarcomas the worst. The necessity of a uniform clinical and histologic classification as well as the importance of controlled clinical trials are pointed out.

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Isobolographic Analysis Demonstrates the Additive and Synergistic Effects of Gemcitabine Combined with Fucoidan in Uterine Sarcomas and Carcinosarcoma Cells

Cancers ◽

10.3390/cancers12010107 ◽

2019 ◽

Vol 12 (1) ◽

pp. 107 ◽

Cited By ~ 3

Author(s):

Marcin Bobiński ◽

Karolina Okła ◽

Jarogniew Łuszczki ◽

Wiesława Bednarek ◽

Anna Wawruszak ◽

...

Keyword(s):

Cell Cycle ◽

Synergistic Effect ◽

Cell Line ◽

Cell Lines ◽

Combined Treatment ◽

Endometrial Stromal Sarcoma ◽

Uterine Leiomyosarcoma ◽

Uterine Sarcomas ◽

Isobolographic Analysis ◽

Stromal Sarcoma

Background: Uterine sarcomas and carcinosarcoma are associated with unfavorable prognosis. The regimens that are used in chemotherapy are associated with high incidence of side effects and usually do not significantly increase patients’ survival rates. In this study we investigated the activity and interactions between gemcitabine and fucoidan, the natural compound known for its anti-tumor properties, in human sarcomas and carcinosarcoma cell models. Methods: SK-UT-1, SK-UT1-B (carcinosarcoma), MES-SA (leiomyosarcoma), and ESS-1 (endometrial stromal sarcoma) cell lines were used for the experiments. Cells were incubated in the presence of gemcitabine, fucoidan, and mixtures, after the incubation the MTT tests were performed. In order to assess the interactions between tested compounds isobolographic analysis was performed. Additional assessments of apoptosis and cell cycle were done. Results: Additive effect of combined treatment with gemcitabine and fucoidan was observed in ESS-1 and SK-UT-1 cell line. Although the supra-additive (synergistic) effect noticed in SK-UT-1B cell line. It was not possible to determine the interactions of fucoidan and gemcitabine in MES-SA cell line due to insufficient response to treatment. Addition of fucoidan to gemcitabine enhances its proapoptotic activity, what was observed especially in ESS-1 and SK-UT-1B cell lines. The arrest of cell cycle induced by mixture of gemcitabine and fucoidan, superior comparing gemcitabine alone was observed in SK-UT-1B. Conclusions: Obtained data showed that a combination of fucoidan and gemcitabine in uterine endometrial stromal sarcoma and carcinosarcoma cell lines has additive or even synergistic effect in decreasing cell viability. Furthermore, this drug combination induces apoptosis and arrest of cell cycle. The resistance of uterine leiomyosarcoma cell line, justifies searching for other drugs combinations to improve therapy efficacy.

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Uterine Sarcoma and Aromatase Inhibitors: Tom Baker Cancer Centre Experience and Review of the Literature

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e31825b7de8 ◽

2012 ◽

Vol 22 (6) ◽

pp. 1006-1012 ◽

Cited By ~ 23

Author(s):

Alon D. Altman ◽

Gregg S. Nelson ◽

Pamela Chu ◽

Jill Nation ◽

Prafull Ghatage

Keyword(s):

Partial Response ◽

Aromatase Inhibitors ◽

Retrospective Studies ◽

Response Rate ◽

Case Reports ◽

Endometrial Stromal Sarcoma ◽

Uterine Sarcoma ◽

Uterine Sarcomas ◽

Cancer Centre ◽

Stromal Sarcoma

ObjectivesUterine sarcomas are a rare group of mesenchymal tumors with a poor prognosis and aggressive biology. Standard treatment involves surgical staging. The role of further adjuvant treatment is unclear. The goals of this study were to determine the response rates to treatment of patients with uterine sarcomas and to review the currently available literature on the use of aromatase inhibitors (AIs).Materials and MethodsWe performed a retrospective analysis on all patients with uterine sarcoma treated with an AI between 2000 and 2010 at the Tom Baker Cancer Centre in Calgary, Alberta.ResultsFour patients with endometrial stromal sarcoma and 3 patients with leiomyosarcoma received treatment with an AI. A literature search resulted in 10 case reports and 4 retrospective studies of patients with endometrial stromal sarcoma and 1 case report and 2 retrospective studies of patients with leiomyosarcoma. On the basis of the available literature, combined with the current findings, the overall response rate of endometrial stromal sarcoma to AIs is 67% (complete response of 7% and partial response of 60%), and the partial response rate of leiomyosarcoma to AIs is 11%, with no reported complete responses.ConclusionsAromatase inhibitors are a well-tolerated class of medications that are effective in the treatment of endometrial stromal sarcomas. These medications may also have a role to help stabilize disease progression in the treatment of leiomyosarcoma. More large, prospective, multicentered trials will be needed to clarify this issue.

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Localized high grade endometrial stromal sarcoma and localized undifferentiated uterine sarcoma: a retrospective series of the French Sarcoma Group

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2018-000064 ◽

2019 ◽

Vol 29 (4) ◽

pp. 691-698 ◽

Cited By ~ 5

Author(s):

Marie Meurer ◽

A Floquet ◽

I Ray-Coquard ◽

F Bertucci ◽

M Auriche ◽

...

Keyword(s):

Overall Survival ◽

Adjuvant Chemotherapy ◽

Adjuvant Radiotherapy ◽

Disease Free Survival ◽

Endometrial Stromal Sarcoma ◽

High Grade ◽

Uterine Sarcomas ◽

Free Survival ◽

Stromal Sarcoma ◽

Disease Free

ObjectiveHigh grade endometrial stromal sarcoma and undifferentiated uterine sarcomas are associated with a very poor prognosis. Although large surgical resection is the standard of care, the optimal adjuvant strategy remains unclear.MethodsA retrospective analysis of patients with localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas (stages I–III) treated in 10 French Sarcoma Group centers was conducted.Results39 patients with localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas treated from 2008 to 2016 were included. 24/39 patients (61.5%) were stage I at diagnosis. 38/39 patients underwent surgical resection, with total hysterectomy and bilateral oophorectomy completed in 26/38 (68%). Surgeries were mostly resection complete (R0, 23/38, 60%) and microscopically incomplete resection (R1, 6/38, 16%). 22 patients (58%) underwent postoperative radiotherapy (including brachytherapy in 11 cases), and 11 (29%) underwent adjuvant chemotherapy. After a median follow-up of 33 months (range 2.6–112), 17/39 patients were alive and 21/39 (54%) had relapsed (9 local relapses and 16 metastases). The 3 year and 5 year overall survival rates were 49.8% and 31.1%, respectively, and 3 year and 5 year disease free survival rates were 42.7% and 16.0%, respectively. Median overall survival and disease free survival were 32.7 (95% CI 16.3–49.1) and 23 (4.4–41.6) months, respectively. Medians were, respectively, 46.7 months and 39.0 months among those who underwent adjuvant radiotherapy and 41.0 months and 10.3 months for those who underwent adjuvant chemotherapy. In multivariate analysis, adjuvant radiotherapy was an independent prognostic factor for overall survival (P=0.012) and disease free survival (P=0.036). Chemotherapy, International Federation of Gynecology and Obstetrics I–II stages, and Eastern Cooperative Oncology Group-performance status 0 correlated with improved overall survival (P=0.034, P=0.002, P=0.006), and absence of vascular invasion (P=0.014) was associated with better disease free survival.ConclusionsThe standard treatment of primary localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas is total hysterectomy and bilateral oophorectomy. The current study shows that adjuvant radiotherapy and adjuvant chemotherapy appear to improve overall survival. A prospective large study is warranted to validate this therapeutic management.

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Immunohistochemical panel to differentiate endometrial stromal sarcoma, uterine leiomyosarcoma and leiomyoma: something old and something new

Journal of Clinical Pathology ◽

10.1136/jclinpath-2015-202915 ◽

2015 ◽

Vol 68 (9) ◽

pp. 710-717 ◽

Cited By ~ 20

Author(s):

Helena Hwang ◽

Koji Matsuo ◽

Kara Duncan ◽

Elham Pakzamir ◽

Huyen Q Pham ◽

...

Keyword(s):

Predictive Value ◽

Smooth Muscle Actin ◽

Area Under The Curve ◽

Endometrial Stromal Sarcoma ◽

Low Grade ◽

Uterine Leiomyosarcoma ◽

Operating Characteristics ◽

Uterine Sarcomas ◽

Stromal Sarcoma ◽

Receiver Operating Characteristics Curve

AimsTo evaluate an immunohistochemical panel differentiating endometrial stromal sarcoma (ESS) from uterine leiomyosarcoma (ULMS) and leiomyoma (LM).Methods94 cases (28 ESS, 41 ULMS, 25 LM) were retrieved and arrayed. 10 immunomarkers (estrogen receptor (ER), progesterone receptor (PR), CD10, smooth muscle actin, desmin, h-caldesmon, transgelin, GEM, ASC1, stathmin1) were used. A predictive model was constructed and examined by receiver operating characteristics curve analysis to determine area under the curve (AUC).ResultsThe combination of ER+/PR+/CD10+/GEM−/h-caldesmon−/transgelin− can predict ESS versus ULMS with AUC predictive value of 0.872 (95% CI 0.784 to 0.961, p<0.0001). The combination of ER+/PR+/CD10+/h-caldesmon−/transgelin− can predict low grade (LG) ESS from ‘LG’ ULMS with AUC predictive value of 0.914 (95% CI 0.832 to 0.995, p<0.0001). Finally, ULMS and ESS, including the LGs, were more likely to be stathmin1+ than LM.ConclusionsDue to the different clinical course and management, adding novel antibodies (GEM, transgelin) to the well established immunohistochemistry panel seemed to be useful in distinguishing ESS from ULMS and LG ESS from ‘LG’ ULMS. Finally, stathmin1 expression could be of value in differentiating LM from uterine sarcomas.

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Endometrial stromal sarcoma in a 20-year-old woman

BMJ Case Reports ◽

10.1136/bcr-2018-228874 ◽

2019 ◽

Vol 12 (12) ◽

pp. e228874

Author(s):

Rubina Sohail ◽

Shahlla Kanwal ◽

Adnan Murtaza ◽

Bushra Haq

Keyword(s):

Adnexal Mass ◽

Stage Iv ◽

Endometrial Stromal Sarcoma ◽

Final Diagnosis ◽

Sexually Active ◽

Uterine Sarcomas ◽

Stromal Sarcoma ◽

Pelvic Wall ◽

The Right

Endometrial stromal sarcoma (ESS) is an uncommon and challenging condition comprising 10% of all uterine sarcomas and found in women 42–58 years of age. ESS is difficult to diagnose in young women as it masquerades as a leiomyoma. We report this tumour in a 20-year-old woman presenting with heavy and prolonged menses and urinary retention. She was not sexually active and did not give consent for pelvic examination. A preoperative diagnosis of a submucous leiomyoma with an adnexal mass was made. At laparotomy, the leiomyoma was found to be wedged between the cervix and the vagina, and was removed vaginally. A 5–6 cm retroperitoneal mass was adherent to the right pelvic wall, which was also removed. Histopathology of both specimens revealed ESS. The final diagnosis according to the International Federation of Gynaecology and Obstetrics classification was stage IV ESS. After oncology consult, she was referred for chemotherapy. She is now on follow-up.

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Laparoscopic management of endometrial stromal sarcoma in young: a case report

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20201820 ◽

2020 ◽

Vol 9 (5) ◽

pp. 2144

Author(s):

Shailesh Puntambekar ◽

Shetty Theertha Shankar ◽

Arjun Goel ◽

Shakti Panchal

Keyword(s):

Clinical Course ◽

Histopathological Examination ◽

Endometrial Stromal Sarcoma ◽

Initial Therapy ◽

Uterine Sarcoma ◽

Low Grade ◽

Lower Abdomen ◽

Uterine Sarcomas ◽

Stromal Sarcoma ◽

Locally Recurrent

Endometrial stromal sarcoma (ESS) is a case malignancy and accounts for 0.2% of all uterine malignancies and 10% of all uterine sarcomas. In the present case, an unmarried 27-year-old woman presented with complaints of on and off episodes of pain in the lower abdomen. On examination, a diffuse oval mass was felt occupying the hypogastrium, iliac and lumbar regions and extending up to the umbilicus. CT scan impression was given as? Complex retroperitoneal mass? solid cystic ovarian mass with grade I right hydro nephrosis. On laparoscopy, a huge mass measuring approximately 10×10 cm was noted arising from the uterus. Laparoscopic myomectomy was done and the specimen was retrieved in a bag and the tissue was sent for histopathological examination. The postoperative clinical course was uneventful. The patient was advised to undergo oocyte cryopreservation following which she was advised hysterectomy with bilateral salphingo-oophorectomy. Pelvic radiation was advised thereafter. ESS is a rare malignant tumor, which on histopathological examination reveals sheets of cells and endometrial stromal cell differentiation. Hysterectomy with bilateral salpingo-oophorectomy is optimum initial therapy. Radiotherapy is chosen when the tumour is inadequately excised or the pelvic disease is locally recurrent. Low grade ESS is a rare form of uterine sarcoma usually seen between 40-60 years of age with limited available data regarding the clinical course and management. Early diagnosis and management is associated with a favourable prognosis and outcome.

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A retrospective review of metastatic or recurrent uterine sarcomas treated with ifosfamide and doxorubicin (IMA)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.15053 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 15053-15053

Author(s):

N. Guler ◽

D. Hizli ◽

S. Sarici ◽

R. Ocalan ◽

M. Kose ◽

...

Keyword(s):

Survival Time ◽

Endometrial Stromal Sarcoma ◽

Progression Free Survival ◽

Median Number ◽

Uterine Sarcoma ◽

Uterine Sarcomas ◽

Free Survival ◽

Median Progression Free Survival ◽

Stromal Sarcoma ◽

Metastatic Sites

15053 Background: The prognosis of metastatic uterine sarcoma is poor with median survival reported between 4 to 26 months. We evaluated the efficacy and toxicity of ifosfamide (I) mesna (M) and doxorubicin (A) (IMA) chemotherapy regimen retrospectively in patients (pts) with metastatic, or recurrent uterine sarcomas. Methods: Eligible patients had measurable recurrent or metastatic disease, ECOG PS < 2, had adequate renal, hepatic and hematologic functions. The IMA regimen was ifosfamide 2500 mg/m2 days 1–3, mesna 2500 mg/m2 days 1–3, doxorubicin 60 mg/m2 day 1, repeated every 21 days. Patients were evaluated for response for each two cycles. Results: Thirty-five pts (17 leiomyosarcoma [LMS], 6 malignant mixed mesodermal tumor [MMMT], 5 endometrial stromal sarcoma, 4 carcinosarcoma, and 3 adenosarcoma) were enrolled in this study. The median age was 49 yrs (range, 18–72). Two pts were lost to follow up after the first cycle; one patient had ifosfamide encephalopathy on the third day of the first cycle. Thirty-two pts were assessable for response, toxicity, and survival. Nine pts had prior chemotherapy and 4 pts had radiotherapy. Most frequent metastatic sites were peritoneum, lung and liver. Median period of time from the diagnosis to starting IMA regimen was 14.5 months. A total of 132 cycles of chemotherapy were introduced and for each patient median number of chemotherapy cycles were 4 (range, 1–6). We observed CR in 2 pts; PR in 15 pts. Objective RR was % 48.6 (95% CI, 32% to 67%). Of 17 pts with LMS, 1 CR and 6 PRs were observed. The median progression-free survival time of the responders was 12.0 months. The median progression-free survival time of all patients was 7.0 months. NCI-CTC grade 3 or 4 leucopenia, neutropenia, thrombocytopenia, and anemia occurred in 40%, 55%, 12%, and 13%, respectively. There was no significant nausea/vomiting, nephrotoxicity. Febrile neutropenia was encountered in 6 pts. Dose modifications were required in 4 pts due to myelotoxicity. CNS toxicity was observed in one pts. Conclusions: IMA regimen has moderate anti-tumor activity (48.6%) with acceptable toxicity in pts with recurrent or metastatic uterine sarcomas. No significant financial relationships to disclose.

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Uterine sarcomas: Analysis of clinicopathologic factors and treatment outcomes—A single institution experience in long-term disease control.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15522 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15522-e15522

Author(s):

Mylene Sy Go ◽

Le Wang ◽

Michael Styler ◽

Stephanie King

Keyword(s):

Radiation Therapy ◽

Survival Analysis ◽

Lymph Node ◽

Adjuvant Chemotherapy ◽

Survival Benefit ◽

Endometrial Stromal Sarcoma ◽

Pelvic Lymphadenectomy ◽

External Beam Radiation ◽

Uterine Sarcomas ◽

Stromal Sarcoma

e15522 Background: Uterine sarcomas behave aggressively and are associated with poor prognosis. Carcinosarcomas was re-classified as more akin to endometrial adenocarcinomas. The objective was to analyze the survival outcomes of all uterine sarcomas treated with various combinations of chemotherapy, radiation, and lymph node dissections. Methods: 60 patients with proven uterine sarcomas were treated at Hahnemann Hospital from 2002-2011. Survival analyses in each treatment group were performed by Kaplan- Meier method Results: Among the 60 women examined, 51% were carcinosarcoma, 25% leiomyosarcoma, 20% endometrial stromal sarcoma, and 4% adenosarcoma. 27% presented with stage I disease, 20% stage II, 13% stage III, and 40% with metastatic disease at diagnosis. One third of the leiomyosarcomas and endometrial stromal sarcomas have advanced disease at diagnosis. Median survival of all patients was 26 months, 20 months for carcinosarcoma, 25 months for high grade endometrial stromal sarcoma, and a trend toward superior overall survival at 73 months for leiomyosarcoma. After surgery, 51% of patients mostly carcinosarcomas received carboplatin and paclitaxel as adjuvant chemotherapy and 66% of leiomyosarcomas received gemcitabine and docetaxel. However, the survival analysis showed no statistically significant benefit in disease progression free survival. On the other hand, 50% of patients were also treated with adjunctive pelvic external beam radiation and 21% received additional vaginal brachytherapy. Our results demonstrated a small but clear survival benefit after pelvic radiation therapy. Pelvic lymphadenectomy was performed in 55% of these patients and lymph node involvement was found in 30% of uterine sarcomas mostly carcinosarcomas. Survival analysis indicated that pelvic lymphadenectomy was associated with significant survival benefit. Conclusions: Size, stage, nodal involvement, and histology are independent prognostic factors. Complete cytoreduction followed by lymph node dissection, and radiation therapy offered a survival advantage than surgery alone. However, the role of adjuvant chemotherapy remains uncertain.

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Low-grade Endometrial Stromal Sarcoma with Unusual Metastasis to the Skull

Arquivos Brasileiros de Neurocirurgia Brazilian Neurosurgery ◽

10.1055/s-0037-1615257 ◽

2017 ◽

Vol 37 (01) ◽

pp. 42-46

Author(s):

Antonio Araújo Júnior ◽

Pedro Arlant ◽

Arnaldo Salvestrini Júnior ◽

Angelo Fernandez ◽

Marcos Docema ◽

...

Keyword(s):

Vaginal Bleeding ◽

Present Report ◽

Endometrial Stromal Sarcoma ◽

Metastatic Potential ◽

Low Grade ◽

Uterine Sarcomas ◽

Skull Metastasis ◽

Stromal Sarcoma ◽

One Year ◽

Abnormal Vaginal Bleeding

Background Endometrial stromal sarcomas (ESSs) are the second most common uterine sarcomas. Although ESSs are often indolent, they have metastatic potential. To the best of our knowledge, there are only three reports of brain metastasis, and the present report is the first to describe a late skull metastasis of an ESS. Case Report We describe the case of a 51-year-old woman who presented abnormal vaginal bleeding 14 years ago; she was diagnosed with an uterine mass and submitted to a hysterectomy. One year ago she presented ESS lung metastasis followed by a left parietal calvarial metastasis. The optimal treatment for metastatic ESS is controversial, but the use of progesterone and aromatase inhibitors is advisable.

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