Favorable Outcome of High-grade Endometrial Stromal Sarcoma in an Adolescent.

High-grade endometrial stromal sarcoma is a rare and aggressive soft tissue tumor characterized by YWHAE::NUTM2A/B translocations, diagnosis at a median of 50-60 years, and a poor prognosis (overall survival 30%-40%). We describe a 16-year-old patient with high-grade endometrial stromal sarcoma and regional nodal and pulmonary metastases who is a long-term survivor after grossly complete tumor resection, intensive chemotherapy, and pelvic radiotherapy. We discovered a previously undescribed YWHAE::NUTM2E translocation in the tumor. Our patient's favorable outcome suggests that intensive multimodality therapy with curative intent is appropriate for young patients with high-grade endometrial stromal sarcoma and highlights the importance of fertility preservation.

Prognostic factors, oncological treatment and outcomes of uterine sarcoma: 10 years' clinical experience from a tertiary care center in Pakistan.

BACKGROUND: Uterine sarcoma is an uncommon aggressive malignancy. Optimal management and prognostic factors have yet to be well recognized due to their rarity and various histological subtypes. This study aims to investigate these patients' prognostic factors, treatment modalities, and oncological outcomes. METHODS: A single-center retrospective cohort study was conducted on all patients diagnosed with uterine sarcoma and treated from January 2010 to December 2019 in a tertiary-care hospital in Pakistan. The data were analyzed using STATA software and stratified on the histological subtype. Survival rates were estimated using the Kaplan-Meier method. Crude and adjusted hazard ratios with 95% CI were estimated using univariate and multivariate analysis. RESULTS: Of the 40 patients, 16(40%) had uterine leiomyosarcoma (u-LMS), 10(25%) had high-grade endometrial stromal sarcoma (HGESS), 8(20%) had low-grade endometrial stromal sarcoma (LGESS) and 6(15%) had other histological subtypes. The median age of all patients was 49 (40-55.5). Thirty-seven (92.5%) patients underwent primary surgical resection, and 24 (60%) patients received adjuvant systemic chemotherapy. The survival plots showed the overall population's DFS of 64 months and the OS of 88 months (p-value = 0.001). The median DFS in all patients was 12 months, and the median OS was 14 months (p-value = 0.001). A small but significant DFS benefit was found in patients who received adjuvant systemic chemotherapy, 13.5 versus 11 months (p-value = 0.001). Multivariate Cox-regression analysis revealed that large tumor size and advanced FIGO stage were substantial factors associated with decreased survival. CONCLUSION: Uterine sarcomas are rare malignancies with poor prognosis. Multiple factors, including tumor size, mitotic count, stage of the disease, and myometrial invasion, impact survival outcomes. Adjuvant treatment may decrease the recurrence rate and improve DFS but do not affect OS.

Clinical characteristics and prognostic factors of endometrial stromal sarcoma and undifferentiated uterine sarcoma confirmed by central pathologic review: A multi-institutional retrospective study from the Japanese Clinical Oncology Group.

OBJECTIVES: Low-grade and high-grade endometrial stromal sarcomas (LGESS and HGESS) and undifferentiated uterine sarcomas (UUS) are rare tumors whose pathological classification and staging system have changed recently. These tumors are reported to contain fusion genes. We aimed to clarify the genetic background, clinical features, prognostic factors, and optimal therapy of these tumors using a new classification and staging system. METHODS: We analyzed the clinical features and prognostic information of 72 patients with LGESS, 25 with HGESS, and 16 with UUS using central pathological review. Estrogen and progesterone receptors (PgRs) were examined by immunohistochemistry. JAZF1-SUZ12 and YWHAE-NUTM2A/B gene fusions were tested using real-time polymerase chain reaction. RESULTS: The 5-year overall survival (OS) rates of LGESS, HGESS, and UUS were 94%, 53%, and 25%, respectively. In LGESS, stage IV, incomplete surgery, and absence of PgR were associated with poor OS. The presence of JAZF1-SUZ12 fusion gene was not associated with OS. In HGESS, the relationship between stage and prognosis was unclear. None of the 3 patients with YWHAE-NUTM2A/B fusion gene died during follow-up. Adjuvant chemotherapy was associated with a favorable OS. Incomplete resection of UUS was associated with poor OS; however, residual tumors frequently occurred. Although most patients underwent adjuvant chemotherapy, their prognosis was extremely poor even in stage I disease. CONCLUSIONS: Prognosis of LGESS is generally good; however, stage IV, incomplete surgery, and PgR-negative tumors are associated with poor prognosis. Adjuvant chemotherapy may be useful for HGESS. Prognosis of UUS is extremely poor, even with adjuvant chemotherapy.

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.

Prognostic factors in patients with uterine sarcoma: the SARCUT study.

OBJECTIVE: Uterine sarcomas are a rare and heterogeneous group of malignancies that include different histological sub-types. The aim of this study was to identify and evaluate the impact of the different prognostic factors on overall survival and disease-free survival of patients with uterine sarcoma. METHODS: This international multicenter retrospective study included 683 patients diagnosed with uterine sarcoma at 46 different institutions between January 2001 and December 2007. RESULTS: The 5-year overall survival for leiomyosarcoma, endometrial stromal sarcoma, undifferentiated sarcoma, and adenosarcoma was 65.3%, 78.3%, 52.4%, and 89.5%, respectively, and the 5-year disease-free survival was 54.3%, 68.1%, 40.3%, and 85.3%, respectively. The 10-year overall survival for leiomyosarcoma, endometrial stromal sarcoma, undifferentiated sarcoma and adenosarcoma was 52.6%, 64.8%, 52.4%, and 79.5%, respectively, and the 10-year disease-free survival was 44.7%, 53.3%, 40.3%, and 77.5%, respectively. The most significant factor associated with overall survival in all types of sarcoma except for adenosarcoma was the presence of residual disease after primary treatment. In adenosarcoma, disease stage at diagnosis was the most important factor (hazard ratio 17.7; 95% CI 2.86 to 109.93). CONCLUSION: Incomplete cytoreduction, tumor persistence, advanced stage, extra-uterine and tumor margin involvement, and the presence of necrosis were relevant prognostic factors significantly affecting overall survival in uterine sarcoma. The presence of lymph vascular space involvement and administration of adjuvant chemotherapy were significantly associated with a higher risk of relapse.

Primary low-grade extrauterine endometrial stromal sarcoma: analysis of 10 cases with a review of the literature.

BACKGROUND: This study aimed to analyze the clinical and pathological features of extrauterine endometrial stromal sarcoma (EESS) and explore an effective therapeutic regimen to reduce the recurrence rate in low-grade EESS patients. METHODS: Ten LG-EESS patients who were treated at the Chinese Academy of Medical Sciences Cancer Institute and Hospital from June 1999 to June 2019 were collected and analyzed. RESULTS: (1) Patient demographics are summarized in manuscript. Preoperative CA125 examination showed that 8 patients had a median level of 49.5 U/L (15.4-168.0 U/L). (2) All ten patients underwent tumor cytoreductive surgery. Five patients underwent optimal tumor resection and achieved an R0 resection. After the initial surgery, 7 patients who had multiple metastasis were treated with adjuvant chemotherapy, 2 patients with vaginal ESS were treated with chemotherapy and radiation therapy, and 6 patients with ER/PR positive received hormone therapy with or without chemotherapy. (2) Most EESS patients had multiple tumors. The omentum was the most commonly affected site, followed by the ovaries. (3) The median follow-up was 94 (range: 27-228) months, and recurrence was observed in 3 patients (n = 10, 30%) who underwent non-optimal surgery and no hormone therapy. The 5-year and 10-year DFS rates were both 70%, as shown in Fig. 2. OS was both 100% at 5 and 10 years. CONCLUSION: As a conclusion, EESS is a rare disease and LG-EESS has a good prognosis. Surgery remains the available treatment for patients. LG-EESS has a risk of late recurrence which requires a long-term follow-up. With a limited sample size, our study shows optimal tumor reductive surgery and adjuvant hormone therapy may significantly reduce the risk of recurrence.

Extrauterine endometrial stromal sarcoma: A systematic review and outcome analysis.

Endometrial stromal sarcoma (ESS) is the second most common uterine mesenchymal neoplasm. ESS can arise from extrauterine locations without any uterine involvement and is called extrauterine ESS (EESS). The epidemiological features of EESS are not well-known. Moreover, the factors affecting its outcome have not been systemically studied. The treatment of EESS closely follows that of uterine ESS, comprised of different combinations of surgical management, hormone therapy, chemotherapy, and radiation therapy. However, the effectiveness of different treatment protocols for EESS has not been studied. Here, we have performed a systematic review of all reported cases of EESS in the English literature. We further performed a meta-analysis of the outcome data and investigated how the patients' age, tumor site, tumor size, and management affect the overall and progression-free survival of the patients. We found that tumor site and mode of treatment significantly affected the overall survival and progression-free survival of the patients. Tumor size significantly affected overall survival but not progression-free survival, while the age at diagnosis did not affect patient outcome. As far as we know, ours is the first systematic study of this rare malignancy with an emphasis on outcome analysis.

Gynecological sarcomas: literature review of 2020.

PURPOSE OF REVIEW: This article, focus on recently published data of the last 18 months on the management of gynecologic sarcomas. RECENT FINDINGS: Different tools have been studied to identify the differences between benign from malignant uterine conjonctive tumor.Molecular biology impact more and more on the diagnosis of uterine sarcoma with new definitions of very specific groups. This will make it possible to better define the last group of endometrial sarcoma which has been defined as undifferentiated.In several articles, surgical approaches and fertility-sparing surgery were described including the role of surgery for recurrences.Some other articles have evaluated the potential benefice of adjuvant therapy for uterine sarcoma with early stages.Several new targeted therapies are in development. Notably deoxyribonucleic acid repair machinery in uterine leiomyosarcoma and also immune therapies, transforming growth factor beta pathway, mechanistic target of rapamycin inhibitor, anti angiogenics, etc. SUMMARY: This last year the potential interest for uterine sarcoma increased, demonstrated by the increasing number of publications in the literature compared to previous years. Despite this greater interest over time, the standard of care for uterine sarcoma does not change and we are always waiting for new innovative therapies able to change routine practice and survival of patients. Currently, the result of different clinical trials, which include new options as targeted molecular approach or immune checkpoint inhibitors are closed to be reported.

A retrospective study of endometrial stromal sarcoma: an institutional review.

This is a retrospective study conducted at Shaukat Khanum Memorial Cancer Hospital, Lahore, from January 1995 to April 2016, to determine the clinical presentations, pathological features, cancer free survival and rate of recurrence in patients with Endometrial Stromal Sarcoma (ESS). Data was collected from May to August 2017. A total of 31 patients with a mean age of 40.0±11.72 years were treated. Among them, 12 (38.7%) had stage I, 2 (6.4%) had stage II, 6 (19.3%) had stage III and 11 (35.5%) had stage IV ESS. All patients underwent surgical management as an initial treatment modality for ESS. Out of these 31 patients, 17 were under active surveillance, 4 had expired and 10 patients were lost to follow up. Eleven (65%) patients were disease free, recurrence was noted in 4 (23.5%) patients and 2 (12%) patients had persistent disease. Recurrence of disease was managed with surgical excision and multimodality treatment. Median duration of follow-up was 38.29 months. Endometrial stromal sarcoma (ESS) is a rare uterine tumour. Our patients were young and had lower rate of recurrence. Surgical management was the mainstay of treatment in patients with resectable disease while other options used included hormonal therapy, radio therapy or chemotherapy.

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

OBJECTIVE: High 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. METHODS: A 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. RESULTS: 39 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. CONCLUSIONS: The 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.

The clinical benefits of hormonal treatment for LG-ESS: a meta-analysis.

PURPOSE: To evaluate the clinical benefits of hormonal treatment for patients with low-grade endometrial stromal sarcoma (LG-ESS) by reviewing the published literature and performing a meta-analysis. METHODS: Correlational studies related to hormonal treatment for LG-ESS patients were collected by searching the PubMed, EMBASE, and Cochrane databases up to December 2018. Eligible studies were selected based on inclusion and exclusion criteria. The main inclusion criteria included: original studies with definite diagnoses of LG-ESS that evaluated the clinical benefits of hormonal treatment, studies with at least 10 cases, and studies published in English. Reviews, case reports, letters, comments or conference abstracts, studies without sufficient data and overlapping or republished studies were excluded. The study quality was evaluated, and pooled relative risks and 95% confidence intervals were calculated using Review Manager 5.3. RESULTS: A total of 10 retrospective studies were included. The NOS stars of the 10 studies ranged from 7 to 9 points, which was considered to be of high quality. Recurrence and death information was provided in 9 and 6 studies, respectively. The overall pooled RR for recurrence was 0.66 (95% CI 0.47-0.94), which indicated that hormonal treatment was effective at reducing the recurrence risk (P = 0.02). The overall pooled RR for death was 0.81 (95% CI 0.59-1.12), which showed that hormonal treatment had little effect in prolonging overall survival (P = 0.20). Stratified analysis showed that compared with the group without any adjuvant treatments, hormonal treatment alone significantly decreased the risk of recurrence (P = 0.02), while hormonal treatment had no significant effects on overall survival (P = 0.38). Another subgroup analysis indicated that for stage I-II patients, hormonal treatment could significantly decrease the risk of recurrence (P = 0.02) but could not influence overall survival (P = 0.87). However, for stage III-IV patients, hormonal treatment had little benefit both in reducing the recurrence risk and prolonging overall survival (P = 0.49/0.08). Egger's and Begg's test showed that the publication bias for the literature was satisfactorily controlled. CONCLUSION: Adjuvant hormonal treatment should be considered as a feasible adjuvant therapy for reducing the recurrence risk of patients with LG-ESS while bearing little benefit on overall survival.

Gynecological sarcomas: what's new in 2018, a brief review of published literature.

PURPOSE OF REVIEW: In this article, we focus on recent published data (2017) on the management of gynecologic sarcomas. RECENT FINDINGS: The most significant data published in 2017 develop definition of a new molecular subtype of high grade endometrial stromal sarcoma (ESS) using molecular technics added to histological analysis. The identification of a new translocation on presumed uterine leiomyosarcoma (LMS) points to refinement of nosological classification, with fragmentation of even rare tumors into distinct molecular entities: gynecologic sarcomas are now distinguished into distinct entities from a heterogeneous group of tumors. Other articles have discussed the real incidence of unsuspected sarcomas after fibroid mini-invasive surgery and evaluate the risk of relapse and dissemination after morcellation. Among several criteria, preoperative imagery could become a useful tool. For systemic treatment, no clinical trials changing practices were published, only one positive nonrandomized phase II with carboplatin and pegylated liposomal doxorubicin (PLD) in the treatment of uterine sarcomas after the conventional first line, especially in LMSs and ESSs. SUMMARY: Many articles were published on this confidential domain in oncology demonstrating interests on rare sarcomas. All specialties were represented in the literature, even though we are still waiting for urgent improvements in early diagnosis and therapeutic strategies to transform the poor prognostic of these tumors.

Management of uterine sarcomas and prognostic indicators: real world data from a single-institution.

BACKGROUND: Uterine sarcomas consist a heterogeneous group of mesenchymal gynecological malignancies with unclear therapeutic recommendations and unspecific but poor prognosis, since they usually metastasize and tend to recur very often, even in early stages. METHODS: We retrospectively analyzed all female patients with uterine sarcomas treated in our institution over the last 17 years. Clinico-pathological data, treatments and outcomes were recorded. Kaplan-Meier curves were plotted and time-to-event analyses were estimated using Cox regression. RESULTS: Data were retrieved from 61 women with a median age of 53 (range: 27-78) years, at diagnosis. Fifty-one patients were diagnosed with leiomyosarcoma (LMS), 3 with high grade endometrial stromal sarcoma (ESS), 5 with undifferentiated uterine sarcoma (UUS), 1 with Ewing sarcoma (ES) and 1 with Rhabdomyosarcoma (RS). 24 cases had stage I, 7 stage II, 14 stage III and 16 stage IV disease. Median disease-free survival (DFS) in adjuvant approach was 18.83 months, and median overall survival (OS) 31.07 months. High mitotic count (> 15 mitoses) was significantly associated with worse OS (P < 0.001) and worse DFS (P = 0.028). CONCLUSIONS: Mitotic count appears to be independent prognostic factor while further insights are needed to improve adjuvant and palliative treatment of uterine sarcomas.

Efficacy of Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery in the Treatment of Recurrent Uterine Sarcoma.

OBJECTIVE: Uterine sarcomas (USs) are characterized by poor response to systemic chemotherapy and high recurrence rates. This study evaluates whether the use of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) confers survival benefit in comparison with conventional treatment modalities in patients with recurrent US. METHODS/MATERIALS: A retrospective analysis of patients with recurrent US at a single institution for an 11-year study period was performed. All women with a pathologic diagnosis of leiomyosarcoma, adenosarcoma, endometrial stromal sarcoma, or undifferentiated US were identified. Overall and disease-free survival was estimated using Kaplan-Meier method. Comparisons between the study groups were performed with the log-rank test and Cox regression. RESULTS: A total of 26 patients were identified. Five patients received chemotherapy and/or radiotherapy without surgical intervention, 14 patients underwent surgery alone or a combination of surgery and adjuvant systemic chemotherapy, and 7 patients received cytoreductive surgery with HIPEC. There was no treatment-related mortality in any group, and only 1 patient had grade III-IV surgical complications. Median disease-free survival was 2.4 months for patients with nonsurgical treatments, 5.3 months for patients treated with conventional surgery, and 11.3 months for patients treated with HIPEC. Median overall survival was 35.9 months for patients treated with conventional surgery and 43.8 months for patients treated with HIPEC. CONCLUSIONS: Our study is the first to compare survival outcomes of HIPEC versus conventional therapies for recurrent US and is suggestive of treatment benefit. Further studies with more patients and longer follow-up to evaluate the role of HIPEC in management of this disease are warranted.

Low-grade and high-grade endometrial stromal sarcoma: A National Cancer Database study.

OBJECTIVE: To provide refined prognostic information from large cohorts of women with low-grade or high-grade endometrial stromal sarcoma (ESS). METHODS: We performed an observational retrospective cohort analysis of women diagnosed with low-grade or high-grade ESS from the 1998-2013 National Cancer Database. Kaplan-Meier and multivariable accelerated failure time survival analyses were performed to identify prognostic factors after multiple imputation of missing data. Recursive partitioning methods were used to rank prognostic factors in high-grade ESS. Matched cohort analyses were performed to hypothesis-test effects of adjuvant treatments. RESULTS: We identified 2414 and 1383 women with low-grade or high-grade ESS, respectively. Women with high-grade ESS had markedly decreased survival compared to women with low-grade ESS (five-year survival (95% CI): 32.6 (30.1-35.3%) versus 90.5% (89.3-91.8%), P<0.001). Among women with high-grade ESS, median survival (95% CI) was only 19.9 (17.1-22.1) months. Increased age and tumor size were associated with decreased survival in low-grade ESS. In high-grade ESS, additional negative prognostic factors were distant or nodal metastasis, omission of lymphadenectomy, and pathologically-positive surgical margins (all P<0.001). Use of adjuvant chemotherapy (time ratio (TR) (95% CI): 1.36 (1.17-1.58), P<0.001) and radiotherapy (TR (95% CI): 1.57 (1.32-1.87), P<0.001) were associated with increased survival for high-grade ESS. CONCLUSION: The contrasting excellent versus poor prognosis of low-grade versus high-grade ESS, respectively, was confirmed. The best treatment of high-grade ESS is early and complete surgical resection including lymphadenectomy. Adjuvant chemotherapy and radiotherapy may increase survival of women with high-grade ESS.

Endometrial Stromal Sarcoma Arising in Colorectal Endometriosis.

The malignant transformation of endometriosis is very uncommon. Whereas 75% of tumors arising from endometriosis arise in the ovary, location in extra-genital organs is rare and mesenchymal neoplasms are exceptional. A 47 year-old woman who underwent hysterectomy with bilateral salpingo-ooforectomy due to endometriosis 13 years before presented with abdominal pain. The magnetic resonance imaging (MRI) showed a 9.7×7.5 cm solid-cystic supravesical mass and a recto-vaginal tumor, as well as endometriotic nodules in the sigma, right parametrium and peritoneum that had significantly increased in size over a six months period. The patient underwent surgical resection of the masses. The histological study showed a low-grade endometrial stromal sarcoma (ESS) arising from endometriosis located at recotovaginal septum and affecting colonic wall and multiple peritoneal and pelvic implants. The patient received radiotherapy and aromatase inhibitors and is free of disease after a follow up of 2 years. Only 15 cases of ESS arising in endometriosis of the bowel have been reported. Tumor dissemination at diagnosis is unusual but does not imply a poor prognosis, as only one patient has died due to progression of the tumor. ESS should be included in the differential diagnosis of mesenchymal neoplasms in the intestine.

Anisakiasis mimics cancer recurrence: two cases of extragastrointestinal anisakiasis suspected to be recurrence of gynecological cancer on PET-CT and molecular biological investigation.

BACKGROUND: We report two cases of anisakiasis lesions that were initially suspected to be recurrence of gynecological cancer by positron emission tomography-computed tomography (PET-CT). Both cases were extragastrointestinal anisakiasis that is very rare. CASE PRESENTATION: The first case was a patient with endometrial cancer. At 19 months after surgery, a new low density area of 2 cm in diameter in liver segment 4 was found on follow-up CT. In PET-CT, the lesion had abnormal (18)fluoro-deoxyglucose (FDG) uptake with elevation in the delayed phase, with no other site showing FDG uptake. Partial liver resection was performed. A pathological examination revealed no evidence of malignancy, but showed necrotic granuloma with severe eosinophil infiltration and an irregular material with a lumen structure in the center. Parasitosis was suspected and consultation with the National Institute of Infectious Diseases (NIID) showed the larvae to be Anisakis simplex sensu stricto by genetic examination. The second case was a patient with low-grade endometrial stromal sarcoma (LG-ESS). At 8 months after surgery, swelling of the mediastinal lymph nodes was detected on CT and peripheral T-cell lymphoma was diagnosed by biopsy. A new peritoneal lesion with abnormal FDG uptake was detected on pre-treatment PET-CT and this lesion was increased in size on post-treatment PET-CT. Tumorectomy was performed based on suspected dissemination of LG-ESS recurrence. The findings in a pathological examination were similar to the first case and we again consulted the NIID. The larvae was identified as Anisakis pegreffi, which is a rare pathogen in humans. Having experienced these rare cases, we investigated the mechanisms of FDG uptake in parasitosis lesions by immunohistochemical staining using antibodies to glucose transporter type 1 (GLUT-1) and hexokinase type 2 (HK-2). While infiltrated eosinophils were negative, macrophages demonstrated positive for both antibodies. Therefore, mechanisms behind FDG uptake may involve macrophages, which is common among various granulomas. This is the first report to investigate parasitosis in such a way. CONCLUSION: These cases suggest that anisakiasis is a potential differential diagnosis for a lesion with FDG uptake in PET-CT, and that it is difficult to distinguish this disease from a recurrent tumor using PET-CT alone.

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.

Systemic therapy for endometrial stromal sarcomas: current treatment options.

Uterine endometrial stromal sarcomas including true low-grade endometrial stromal sarcoma (LG-ESS) and high-grade (HG-ESS) or undifferentiated endometrial sarcoma (UES) constitute a group of rare, aggressive malignancies. Most LG-ESSs express steroid receptors. Surgery is the principal primary therapy for endometrial stromal sarcomas and should be considered in all cases. These malignancies are relatively radio- and chemoresistant. Chemotherapy is used in recurrent and advanced HG-ESS and UES. Currently, the combination of gemcitabine and docetaxel is considered the most effective regimen, but at the expense of substantial toxicity. In steroid receptor positive advanced LG-ESS hormonal therapy, mainly with progestins, allows in some patients for a long-term survival. Aromatase inhibitors seem to be equally effective as first- and subsequent-line of treatment, and are well tolerated. The role of molecular-targeted therapies in endometrial stromal sarcomas remains to be established.