An Unusual Endometrial Stromal Neoplasm With JAZF1-BCORL1 Rearrangement.

Endometrial stromal tumors represent the second most common category of uterine mesenchymal tumors. Several different histologic variants and underlying genetic alterations have been recognized, one such being a group associated with BCORL1 rearrangements. They are usually high-grade endometrial stromal sarcomas, often associated with prominent myxoid background and aggressive behavior. Here, we report an unusual endometrial stromal neoplasm with JAZF1-BCORL1 rearrangement and briefly review the literature. The neoplasm formed a well-circumscribed uterine mass in a 50-yr-old woman and had an unusual morphologic appearance that did not warrant a high-grade categorization. It was characterized by a predominant population of epithelioid cells with clear to focally eosinophilic cytoplasm growing in interanastomosing cords and trabeculae set in a hyalinized stroma as well as nested and fascicular growths imparting focal resemblance to a uterine tumor resembling ovarian sex-cord tumor, PEComa, and a smooth muscle neoplasm. A minor storiform growth of spindle cells reminiscent of the fibroblastic variant of low-grade endometrial stromal sarcoma was also noted but conventional areas of low-grade endometrial stromal neoplasm were not identified. This case expands the spectrum of morphologic features seen in endometrial stromal tumors, especially when associated with a BCORL1 fusion and highlights the utility of immunohistochemical and molecular techniques in the diagnosis of these tumors, not all of which are high grade.

A Case of Uterine Tumor Resembling Ovarian Sex Cord Tumor With Prominent Myxoid Features.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor with low malignant potential that commonly occurs in middle age. Although more than 100 cases have been reported to date, myxoid morphology is not well documented. Here, we present a 75-yr-old woman with abnormal vaginal bleeding, with an 8-cm mass in the uterine corpus detected by irregular, high-intensity signaling on T2-weighted imaging. The uterine mass had a glistening mucinous appearance on gross examination. Microscopically, most of the tumor cells were floating in the myxoid stroma. The tumor cells formed clusters or nests with abundant cytoplasm, while some exhibited trabecular or rhabdoid appearances. Immunohistochemically, tumor cells were positive for pancytokeratin (AE1/AE3), α-smooth muscle actin, CD10, progesterone receptor, and some sex cord markers such as calretinin, inhibin, CD56, steroidogenic factor-1. Electron microscopy demonstrated epithelial and sex cord differentiation. This tumor was negative for JAZF1-JJAZ1 fusion gene that is frequently found in low-grade endometrial stromal sarcoma. Fusion genes related to UTROSCT, including NCOA2/3 , were not detected by reverse transcription polymerase chain reaction. The present case suggests that UTROSCT should be included in the differential diagnosis of myxoid uterine tumors.

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.

ZC3H7B-BCOR Fusion High-grade Endometrial Stromal Sarcoma With Morphologic Features of Low-grade Endometrial Stromal Sarcoma. A Case Report and Review of Literature.

High-grade endometrial stromal sarcomas with ZC3H7B-BCOR fusion are rare. They are predominantly located in the endomyometrium, with morphologic features characterized as haphazardly arranged fascicles of spindle cells with mild to moderate atypia, abundant myxoid matrix, high mitotic index, and tongue-like/pushing patterns of myometrial invasion. Furthermore, conventional or variant low-grade endometrial stromal sarcomas are often not present. Clinically, they present at a higher stage and are associated with worse prognosis compared with low-grade endometrial stromal sarcoma. Given the limited number of reported cases, we describe the case of a ZC3H7B-BCOR fusion high-grade endometrial stromal sarcoma initially diagnosed on the hysterectomy specimen as low-grade endometrial stromal sarcoma based on an endometrial stromal tumor showing tongue-like myometrial and lymphovascular invasion, minimal cytologic atypia, low-mitotic activity (0-1/10 high-power field), round/spindle cell component and immunohistochemical stain results (positive for CD10, estrogen receptor, progesterone receptor, and focally positive for cyclin D1). At the time of pathologic diagnosis, she was Stage Ia and managed conservatively. Subsequent molecular analysis revealed a ZC3H7B (exon 10)- BCOR (BCL-6 corepressor) (exon 7) gene fusion. On follow-up, she showed no evidence of disease at 37 months from the time of diagnosis. This case report expands the morphologic spectrum of ZC3H7B-BCOR fusion high-grade ESS, which includes an intramural location, morphologic and immunophenotypic features similar to LG-ESS, as well as the presence of round and spindle cell components. This case also underscores the value of molecular analysis in the proper classification of ESS.

Prognostic factors and survival of patients with uterine sarcoma: a German unicenter analysis.

PURPOSE: Uterine sarcoma (US) as a histologically heterogeneous group of tumors is rare and associated with poor prognosis. Prognostic factors based on systematic data collection need to be identified to optimize patients' treatment. METHODS: This unicenter, retrospective cohort study includes 57 patients treated at the University Hospital Freiburg, Germany between 1999 and 2017. Progression-free survival (PFS) and overall survival (OS) were calculated and visualized in Kaplan-Meier curves. Prognostic factors were identified using log-rank test and Cox regression. RESULTS: 44 Leiomyosarcoma (LMS), 7 low-grade endometrial stromal sarcoma (LG-ESS), 4 high-grade ESS and 2 undifferentiated US patients were identified. The median age at time of diagnosis was 51.0 years (range 18-83). The median follow-up time was 35 months. PFS for the total cohort was 14.0 (95%-Confidence-Interval (CI) 9.7-18.3) and OS 36.0 months (95%-CI 22.1-49.9). Tumor pathology was prognostically significant for OS with LG-ESS being the most favorable (mean OS 150.3 months). In the multivariate analysis, patients over 52 years showed a four times higher risk for tumor recurrence (hazard ratio (HR) 4.4; 95%-CI 1.5-12.9). Progesterone receptor negativity was associated with a two times higher risk for death (HR 2.8; 95%-CI 1.0-7.5). For LMS patients age ≥ 52 years (p = 0.04), clear surgical margins (p = 0.01), FIGO stage (p = 0.01) and no application of chemotherapy (p = 0.02) were statistically significant factors for OS. CONCLUSION: Tumor histology, age at time of diagnosis and progesterone receptor status were prognostic factors for US. Unfavorable OS in LMS patients was associated with advanced FIGO stage, suboptimal cytoreduction and application of chemotherapy.

JAZF1, YWHAE and BCOR gene translocation in primary extrauterine low-grade and high-grade endometrial stromal sarcomas.

AIMS: JAZF1 translocation is the most common genetic change in low-grade (LG) endometrial stromal sarcoma (ESS), and YWHAE and BCOR translocations are common in high-grade (HG) ESS. Primary extrauterine ESS is rare, and there are limited data on molecular alterations in these tumours. METHODS AND RESULTS: Cases of primary extrauterine ESS, comprising eight LG-ESS cases and five HG-ESS cases were collected. Haematoxylin and eosin and immunohistochemical staining were used to observe the histomorphology and analyse related protein expression. JAZF1, YWHAE and BCOR rearrangements were explored with fluorescence in-situ hybridisation (FISH). In LG-ESS, the tumour cells resembled normal proliferative-phase endometrial stromal cells; CD10, oestrogen receptor and progesterone receptor were expressed in all eight cases. In HG-ESS, the tumour cells had uniform HG round and/or spindle morphology, sometimes with an LG component; CD10 was fully expressed in one case and focally expressed in four cases; BCOR was expressed in all five cases, and cyclin D1 in four of five cases. FISH analysis showed JAZF1 translocation in one of eight LG-ESS cases (12.5%). YWHAE translocation occurred in four of five HG-ESS cases, with a positivity rate of 80%. BCOR translocation was absent in all five cases. CONCLUSIONS: In extrauterine LG-ESS, the rate of JAZF1 rearrangement was significantly lower than in uterine LG-ESS. This result limited the value of JAZF1 translocation for diagnosis. YWHAE rearrangement is a common genetic change in extrauterine HG-ESS. Further studies are required to confirm these findings, especially in LG-ESS.

Clinical characteristics and prognosis analysis of uterine sarcoma: a single-institution retrospective study.

BACKGROUND: Uterine sarcomas are rare and aggressive gynaecologic malignancies, characterized by a relatively high recurrence rate and poor prognosis. The aim of this study was to investigate the clinicopathological features and explore the prognostic factors of these malignancies. METHODS: This was a single-institution, retrospective study. We reviewed the medical records of 155 patients with pathologically confirmed uterine sarcomas including uterine leiomyosarcoma (ULMS), low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), undifferentiated uterine sarcoma (UUS) and adenosarcoma (AS) between 2006 and 2022. A total of 112 patients who underwent surgery between January 2006 and April 2019 were included in the survival analysis. The current study recorded the clinicopathological, treatment and outcome data to determine clinical characteristics and survival. RESULTS: The most common histopathological type was ULMS (63/155, 40.64%), followed by LG-ESS (56/155, 36.13%) and HG-ESS (16/155, 10.32%). The mean age at diagnosis of all patients was 49.27±48.50 years and 32.90% (51/155) of patients were postmenopausal. Fifteen patients underwent fast-frozen sectioning, 63(54.78%) were diagnosed with malignancy, 29(25.22%) were highly suspected of malignancy that needed further clarification and 23(14.84%) were diagnosed with benign disease. A total of 124(80%) patients underwent total hysterectomy (TH) and salpingo-oophorectomy. Multivariate analyses showed that histological type and tumour size were independent prognostic factors both for overall survival (OS) (p<0.001 and P=0.017, respectively) and progression-free survival (PFS) (p<0.001 and P=0.018, respectively). Tumour stage was only significantly associated with PFS (P=0.002). Elevated preoperative NLR, PLR and postmenopausal status were significantly correlated with shorter PFS and OS in univariate analysis, but no statistically significant difference was found in multivariate analysis. CONCLUSIONS: In patients with uterine sarcoma, in comparison to LMS and LG-ESS, UUS and HG-ESS tend to present as more aggressive tumour with poorer outcomes. Furthermore, larger tumour (>7.5 cm) were an important predictor of shorter PFS and OS.

Low-grade Endometrial Stromal Sarcoma With Sex Cord-like Differentiation and PHF1-JAZF1 Fusion With Deletions: A Diagnostic Pitfall of JAZF1 FISH.

The molecular knowledge of endometrial stromal neoplasms has been rapidly increasing and is considered complementary to morphologic and immunohistochemical findings for better categorization of these tumors. The most common molecular alteration observed in low-grade endometrial stromal sarcomas is the JAZF1-SUZ12 fusion, whereas, low-grade endometrial stromal sarcoma with sex cord-like differentiation have been shown more commonly to have fusions involving PHF1. Herein, we present a low-grade endometrial stromal sarcoma with sex cord-like differentiation with a fluorescence in situ hybridization showing the apparent loss of one copy of JAZF1 5' and 3' signals, rather than the expected "break-apart" pattern seen in the setting of a JAZF1 fusion. The case was then further evaluated by chromosome microarray and RNA fusion analysis. Overall, the molecular findings supported a PHF1-JAZF1 fusion with deletions right before and after the JAZF1 locus, impairing probe binding and resulting in the unusual "deletion" pattern observed in the JAZF1 fluorescence in situ hybridization, which would not intuitively suggest a fusion involving JAZF1. This case illustrates the importance of integration of morphological and molecular findings as well as the limitations of fluorescence in situ hybridization in detecting fusions, particularly in the setting of more complex chromosomal alterations even though the fusion partners are well-known.

Endometrial stromal tumors: Diagnostic updates and challenges.

Endometrial stromal tumors are rare uterine mesenchymal tumors of endometrial stromal origin. They are classified into endometrial stromal nodule, low-grade endometrial stromal sarcoma, high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma by the current (2020) WHO classification. Correct diagnosis of endometrial stromal tumors is critical for proper patient management. However, due to infrequent encounters, overlapping morphological features and immunohistochemical profiles, the differential diagnoses among endometrial stromal lesions and their morphologic mimics are often challenging. Partially with our own experience, here we review and summarize the tumor morphology, immunohistochemical phenotype, as well as molecular feature of endometrial stromal tumors and key differential diagnoses, emphasizing the newest developments and their utilization in daily practice.

Unusual morphologic features of low-grade endometrial stromal sarcoma: A case report.

BACKGROUND: Endometrial stromal tumours are uncommon tumours of the uterus. They mainly occur in perimenopausal women. Tumours with typical clinicopathological features do not usually pose diagnostic problems. However, rare clinicopathological features can occur, and clinicians without significant experience may have difficulty diagnosing these tumours and managing these patients. METHODS: Herein, we report a case of endometrial stromal sarcoma that occurred in a 25-year-old woman. The pathological features, immunophenotype, treatment and prognosis were discussed. RESULTS: The tumour revealed morphological heterogeneity, and there were similar proliferative-type endometrial stromal cells, an extensive amount of mature adipose tissue, and prominent rhabdomyoblastic and smooth muscle cells. Histopathological and immunohistochemical studies confirmed low-grade endometrial stromal sarcoma with smooth muscle, adipocytic and rhabdomyoblastic differentiation (approximately 60% were differentiated tissues). The final treatment of the tumour was total abdominal hysterectomy with bilateral salpingo-oophorectomy. There was no evidence of recurrence for 109 months postoperatively. CONCLUSIONS: We found that low-grade endometrial stromal tumours with extensive adipocytic and prominent rhabdomyoblastic differentiation are misdiagnosed because they are infrequent. They must be differentiated from rhabdomyosarcoma with accurate identification of adipocytes, and long-term follow-up is needed.

[Endometrial and other rare uterine sarcomas : Diagnostic aspects in the context of the 2020 WHO classification]. / Endometriale und weitere seltene uterine Sarkome : Diagnostische Aspekte im Kontext der WHO-Klassifikation 2020.

Uterine sarcomas are a heterogeneous group of rare malignancies. Mostly (40-50%), they are leiomyosarcomas, followed by endometrial stromal sarcomas (ESS), low-grade (LG) and high-grade (HG), as well as undifferentiated sarcoma of the uterus (UUS) and adenosarcomas (AS). Other, non-organ-specific tumours such as NTRK-rearranged spindle cell neoplasia, perivascular epithelioid cell tumour (PEComa) and inflammatory myofibroblastic tumour (IMT) are extremely difficult to differentiate.In the most recent WHO classification, endometrial stromal tumours are subdivided as follows: benign, expansively growing endometrial stromal nodule (ESN) with sharp demarcation, the histologically similar-looking LG-ESS with infiltrative growth, the highly malignant HG-ESS and, as a diagnosis of exclusion, the highly aggressive UUS lacking specific lines of differentiation. LG-ESS can be differentiated from HG-ESS in most cases histomorphologically and immunohistochemically, but molecular investigations are necessary in individual cases. HG-ESS can be divided into 4 subtypes (YWHAE/NUTM2 fusion low-grade component, YWHAE/NUTM2 fusion high-grade component, ZC3H7B-BCOR fusion or BCOR-ITD) on the basis of molecular findings. Prognostically unfavourable factors in AS are severe sarcomatous overgrowth, deep myometrial invasion, high-grade histology and lymphatic vessel invasion. Tumours with NTRK fusion are immunohistochemically positive for S100 and TRK. PEComas express cathepsin K and HMB45, as well as TFE3 when translocation is present. Almost every IMT shows an alteration in the ALK gene In the case of overlapping morphology and simultaneous therapeutic and prognostic relevance, it is becoming increasingly important to verify or confirm the suspected histomorphological diagnosis by immunohistochemical and possibly molecular investigations.

IFITM1, CD10, SMA, and h-caldesmon as a helpful combination in differential diagnosis between endometrial stromal tumor and cellular leiomyoma.

BACKGROUND: The differential diagnosis of endometrial stromal tumor (EST) and uterine cellular leiomyoma (CL) remains a challenge in clinical practice, especially low grade endometrial stromal sarcoma (ESS) and CL, suggesting the need for novel immunomarkers panels for differential diagnosis. Interferon-induced transmembrane protein 1 (IFITM1) is a novel immunomarker for endometrial stromal cells, h-caldesmon is an immunomarker for smooth muscle cells and has a higher specificity than smooth muscle actin (SMA). So this study aimed to evaluate whether IFITM1, cluster of differentiation 10(CD10), SMA, and h-caldesmon are useful biomarker combinations for the differential diagnosis of EST and CL. METHODS: Tissue microarrays were used to detect IFITM1, CD10, SMA, and h-caldesmon immunohistochemical staining in 30 EST and 33 CL cases. RESULTS: The expressions of IFITM1 and CD10 were high in EST (86.7 and 63.3%, respectively) but low in CL (18.2 and 21.2%), whereas those of h-caldesmon and SMA were high in CL (87.9 and 100%) and low in EST (6.9 and 40%). In diagnosing EST, IFITM1 shows better sensitivity and specificity (86.7 and 81.8%, respectively) than CD10 (63.3 and 78.8%). The specificity of h-caldesmon in diagnosing CL was significantly higher (93.1%) than that of SMA (60%). When all four antibodies were combined for the differential diagnosis, the area-under-the-curve (AUC) predictive value was 0.995. The best combination for diagnosing EST was IFITM1 (+) or CD10 (+) and h-caldesmon (-) (sensitivity 86.7%, specificity 93.9%). CONCLUSION: The best combination for diagnosing CL were h-caldesmon (+) and SMA (+) (sensitivity 87.9%, specificity 100%). IFITM1, CD10, SMA, and h-caldesmon are a good combination for the differential diagnosis of EST and CL.

Phase 2 study of anastrozole in patients with estrogen receptor/progesterone receptor positive recurrent low-grade endometrial stromal sarcomas: The PARAGON trial (ANZGOG 0903).

BACKGROUND: Aromatase inhibitors are standard of care for low-grade endometrial stromal sarcomas (LGESS), based on very high response rates reported in retrospective studies. We evaluated the activity of anastrozole in recurrent/metastatic LGESS patients enrolled in PARAGON, a basket trial of anastrozole in estrogen receptor (ER±)/progesterone receptor (PR+) gynecological cancers. METHOD: An investigator-initiated, single-arm, prospective open-label trial of anastrozole 1 mg/day in patients with ER ± PR + ve LGESS with measurable disease, treated until progressive disease or unacceptable toxicity. Primary endpoint was clinical benefit (complete/partial response + stable disease) rate (CBR) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life and toxicity. RESULTS: 15 eligible patients were enrolled. CBR at 3 months was 73% (95% CI: 48-89.1%); unchanged at 6 months. Best response was 26.7%, including complete response in one (6.7%; 95% CI 1.2-29.8%), partial response in three (20%, 95% CI 7.1-45.2%) and stable disease in seven (46.7%). Four patients ceased treatment by 3 months due to progression. Median PFS was not reached (25th percentile: 2.9 months (95% CI: 1.2-NR)). PFS was 73.3%, 73.3% and 66% at 6, 12, and 18 months, respectively. Six patients remained on treatment for an average of 44.2 months (range 34.5-63.6) up until data cut. Toxicity was as expected, with 3 patients stopping due to adverse effects. CONCLUSION: The 26.7% objective response rate with anastrozole is lower than reported in retrospective series, but the CBR was high and durable. The results underscore the importance of prospective trials in rare cancers.

APEX1/miR-24 axis: a promising therapeutic target in endometriosis.

PURPOSE: The present work aimed to explore the aberrant expression of APEX1 in endometrial stromal cells (ESC) and the underlying mechanisms. METHODS: The levels of APEX1 and miR-24 in endometriosis tissues were tested by qRT-PCR and Western blot. After cell transfection, cells were correspondingly classified into pcDNA3.1-NC, sh-NC, mimic NC, inhibitor NC, pcDNA3.1-APEX1, sh-APEX1, miR-24 mimic, miR-24 inhibitor, sh-NC + inhibitor NC, inhibitor-NC + sh-APEX1, sh-NC + miR-24 inhibitor, pcDNA3.1-NC + mimic NC, mimic NC + pcDNA3.1-APEX1 and pcDNA3.1-NC + miR-24 mimic group. Besides, cell proliferation, apoptosis in addition to apoptosis-related proteins Bax, Bcl-2 and cleaved-casase-3 were analyzed by BrdU assay, flow cytometry (FCM) and Western blot assays, respectively. Additionally, RIP assay was conducted to determine the interaction between pri-miR-24 and miR-24. RESULTS: APEX1 and miR-24 were highly expressed in endometriosis tissues. Overexpression of APEX1 and miR-24 potentiates ESC proliferation and inhibits apoptosis, while those effects could be reversed by APEX1 and miR-24 silencing. Meanwhile, APEX1 and miR-24 could elevate ESC apoptosis-related proteins Bax and cleaved-caspase-3 and decrease Bcl-2 expression. Importantly, APEX1 was positively correlated with miR-24 expression. CONCLUSION: APEX1 promotes ESC proliferation and inhibits apoptosis by upregulating miR-24 expression.

Does ovarian preservation have an effect on recurrence of early stage low-grade endometrial stromal sarcoma?

Surgical treatment of low-grade endometrial stromal sarcoma consists of hysterectomy. The role of oophorectomy is yet to be established. We aimed to examine the effect of preserving the ovaries on the pattern of recurrences in patients with stage I disease. Thirty-four patients with stage I low-grade endometrial stromal sarcoma were retrospectively analysed. Based on ovarian preservation the whole cohort was divided into two groups. Recurrence (liver, lung, groin and bone) was detected in 4 (11.8%) cases. No significant differences in overall survival or disease-free survival (DFS) were observed between the ovarian preservation and bilateral salpingo-oophorectomy (BSO) groups. Subset analysis revealed no significant difference in DFS between the ovarian preservation and BSO groups in the premenopausal arm. And also, the performance of pelvic (n = 2) or para-aortic lymphadenectomy (n = 6) or adjuvant hormonal therapy did not alter DFS significantly. The 5-year DFS rate for the group which received adjuvant radiotherapy was 62.5 and 94.4% for those which did not (p = .014). Preserving the ovaries had no adverse effect on the recurrence of stage I disease.IMPACT STATEMENTWhat is already known on this subject? Due to the rarity of the disease and the common postoperative diagnosis, only retrospective studies have been reported on low-grade endometrial stromal sarcoma. This disease is commonly diagnosed in premenopausal patients during the early stage. There is no consensus on preserving the ovaries, particularly in young patients, due to the tumour's hormonal characteristics and the risk of late recurrences.What do the results of this study add? Ovarian preservation had no effect on the recurrence of stage I low-grade endometrial stromal sarcoma. Lymphadenectomy and adjuvant hormonal treatment had no effect on DFS, and adjuvant radiotherapy decreased DFS in the current study.What are the implications of these findings for clinical practice and/or further research? Ovarian preservation should be considered, to prevent the negative effects of surgical menopause, particularly in young patients.

Practical roles for molecular diagnostic testing in ovarian adult granulosa cell tumour, Sertoli-Leydig cell tumour, microcystic stromal tumour and their mimics.

Within the last decade, molecular advances have provided insights into the genetics of several ovarian sex cord-stromal tumours that have otherwise been enigmatic. Chief among these advances are the identification of FOXL2, DICER1 and CTNNB1 mutations in adult granulosa cell tumours, Sertoli-Leydig cell tumours (SLCTs), and microcystic stromal tumours (MCSTs), respectively. As access to molecular diagnostic laboratories continues to become more widely available, the potential roles for tumour mutation testing in the pathological diagnosis of these tumours merit discussion. Furthermore, links to inherited cancer susceptibility syndromes may exist for some women with SLCT (DICER1 syndrome) and MCST [familial adenomatous polyposis (FAP)]. This review will address practical issues in deciding when and how to apply mutation testing in the diagnosis of these three sex cord-stromal tumours. The pathologist's role in recommending referral for formal risk assessment for DICER1 syndrome and FAP will also be discussed.

Uterine Endometrial Stromal Tumors With Limited Infiltration: First Report of a Case Series Indicating Potential for Malignant Behavior.

The distinction between a uterine endometrial stromal nodule (ESN) and low-grade endometrial stromal sarcoma (LGESS) is based on the nature of the interface between the lesion and the surrounding myometrium and the presence or absence of vascular invasion. Most LGESS exhibit widespread irregular myometrial invasion with or without vascular invasion, whereas ESNs are well-circumscribed without vascular invasion. Tavassoli and Norris proposed that minor marginal irregularity (up to 3 protrusions, each <3 mm beyond the main mass) is allowable in an ESN and these criteria have been incorporated into the World Health Organization Classification. There is a small group of neoplasms with marginal irregularity greater than that allowable in ESN but without the widespread myometrial infiltration typical of most LGESS. Such neoplasms have been categorized as endometrial stromal tumor with limited infiltration but there have been no studies which have provided follow-up in this group of neoplasms. We aimed to determine the clinical behavior of this uncommon group of neoplasms. From a series of 19 endometrial stromal tumors with limited infiltration, mainly from consultation practice, we obtained follow-up information in 16 cases by contacting referring pathologists and clinicians. The patient age ranged from 32 to 84 yr (median: 54 yr) and follow-up ranged from 16 to 187 mo (median: 52 mo). Two of 16 patients (12.5%) developed metastatic disease to the small intestine and peritoneum (1 case-metastasis at 23 mo) and bone and lung (1 case-humeral metastasis at 135 mo; lung and sacral metastases subsequently). No patient died from disease during the follow-up period. A small percentage of endometrial stromal tumors with limited infiltration exhibit malignant behavior with distant metastasis. Such neoplasms should be regarded as potentially malignant and the term LGESS with limited infiltration is an appropriate designation.

Vaginal Low-Grade Endometrial Stromal Sarcoma: An Extremely Rare Case Report and Review of the Literature.

Endometrial stromal sarcoma (ESS) is a malignant tumor of the uterus that has been described as the second most common malignant uterine mesenchymal tumor. Primary extrauterine ESS (EESS) is an extremely uncommon occurrence. We hereby report a new bona fide case of low-grade EESS in a 74-yr-old woman arising in the vagina, presenting as a polypoid mass associated with irregular vaginal bleeding. On examination, a 6×2×2 cm polypoid mass was found in the left vaginal wall. Consequently, the patient underwent partial vaginectomy and repair. No ESS or endometriotic lesion was found in the endometrium and bilateral adnexa. The diagnosis of ESS performed by typical pathologic and immunohistochemical evaluation was as follows: beta-catenin (+++), estrogen receptor (+++), progesterone receptor (++), vimentin (++), and uniformly negative for CD10, EMA, CD31, CD34, CD117,CD99, SMA, desmin, h-caldesmon, S-100, MelanA, and HMB45. She has remained disease free with no signs or symptoms of recurrent or advanced disease for 46 mo. Although CD10 is the most useful immunohistochemical marker for the diagnosis of this tumor, negative CD10 staining can be encountered with underfixation. Therefore, it is important to use a panel of immunostains that includes CD10, beta-catenin, and smooth muscle markers. The present study describes the clinical and pathologic features of low-grade EESS through a case report and literature review. To the best of our knowledge, this is the eighth report of EESS arising from the vagina.

Imaging in gynecological disease (19): clinical and ultrasound features of extragastrointestinal stromal tumors (eGIST).

OBJECTIVE: To describe the clinical and sonographic characteristics of extragastrointestinal stromal tumors (eGISTs). METHODS: This was a retrospective multicenter study. The data of patients with a histological diagnosis of eGIST who had undergone preoperative ultrasound examination were retrieved from the databases of nine large European gynecologic oncology centers. One investigator from each center reviewed stored images and ultrasound reports, and described the lesions using the terminology of the International Ovarian Tumor Analysis and Morphological Uterus Sonographic Assessment groups, following a predefined ultrasound evaluation form. Clinical, surgical and pathological information was also recorded. RESULTS: Thirty-five women with an eGIST were identified; in 17 cases, the findings were incidental, and 18 cases were symptomatic. Median age was 57 years (range, 21-85 years). Tumor marker CA 125 was available in 23 (65.7%) patients, with a median level of 23 U/mL (range, 7-403 U/mL). The vast majority of eGISTs were intraperitoneal lesions (n = 32 (91.4%)); the remaining lesions were retroperitoneal (n = 2 (5.7%)) or preperitoneal (n = 1 (2.9%)). The most common site of the tumor was the abdomen (n = 23 (65.7%)), and less frequently the pelvis (n = 12 (34.3%)). eGISTs were typically large (median largest diameter, 79 mm) solid (n = 31 (88.6%)) tumors, and were less frequently multilocular-solid tumors (n = 4 (11.4%)). The echogenicity of solid tumors was uniform in 8/31 (25.8%) cases, which were all hypoechogenic. Twenty-three solid eGISTs were non-uniform, either with mixed echogenicity (9/23 (39.1%)) or with cystic areas (14/23 (60.9%)). The tumor shape was mainly lobular (n = 19 (54.3%)) or irregular (n = 10 (28.6%)). Tumors were typically richly vascularized (color score of 3 or 4, n = 31 (88.6%)) with no shadowing (n = 31 (88.6%)). Based on pattern recognition, eGISTs were usually correctly classified as a malignant lesion in the ultrasound reports (n = 32 (91.4%)), and the specific diagnosis of eGIST was the most frequent differential diagnosis (n = 16 (45.7%)), followed by primary ovarian cancer (n = 5 (14.3%)), lymphoma (n = 2 (5.7%)) and pedunculated uterine fibroid (n = 2 (5.7%)). CONCLUSIONS: On ultrasound, eGISTs were usually solid, non-uniform pelvic or abdominal lobular tumors of mixed echogenicity, with or without cystic areas, with rich vascularization and no shadowing. The presence of a tumor with these features, without connection to the bowel wall, and not originating from the uterus or adnexa, is highly suspicious for eGIST. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Long-term impact of lymphadenectomies in patients with low-grade, early-stage uterine endometrial stroma sarcoma.

AIM: The aim of our study was to investigate the lymph node metastasis (LNM) rate and effect of lymph node dissection (LND) in patients with stage I, low-grade endometrial stromal sarcoma (LGESS). METHODS: Patients with stage I LGESS (n = 119) that underwent surgery from July 1969 to July 2017, following up over 48 years at the China National Cancer Center were retrospectively analyzed in this study. RESULTS: Surgical records and consulting data for patients with LGESS were analyzed to find that 47 patients received systematic pelvic LND. The number of patients with menopause in the LND(+) group were significantly lower than those in LND(-) group (2.1% vs 22.2%, P = 0.005), meanwhile, patients received bilateral salpingo-oophorectomy procedure in LND(+) group were significantly higher than LND(-) (97.9% vs 58.3%, P < 0.001). Neither progression-free survival nor overall survival was significantly improved in the LND(+) group even after propensity score matching although the progression-free survival has a stronger trend in LND(+) population. CONCLUSION: A systematic LND was not significantly associated with prognosis for patients with early-stage LGESS. There is no sufficient indication for a systematic LND for patients with early-stage LGESS. A systematic LND might be necessary if enlarged lymph nodes were detected by image graphology or observation during surgery.