Undifferentiated Uterine Sarcoma Research Articles

Undifferentiated Uterine Sarcoma Causing Non-puerperal Uterine Inversion: A case report

Undifferentiated Uterine Sarcoma Causing Non-puerperal Uterine Inversion: A case report

The Potential of Immunotherapy for SMARCA4-Deficient Undifferentiated Uterine Sarcoma (SDUS).

(1) Background: SMARCA4-deficient undifferentiated uterine sarcoma (SDUS) is a rare and aggressive cancer that urgently requires novel therapeutic strategies. Despite the proven efficacy of immunotherapy in various cancer types, its application in SDUS remains largely unexplored. This study aims to investigate the immune microenvironment of SDUS to evaluate the feasibility of utilizing immunotherapy. (2) Methods: Multiplex immunofluorescence (mIF) was employed to examine the immune microenvironment in two cases of SDUS in comparison to other subtypes of endometrial stromal sarcomas (ESSs). This research involved a comprehensive evaluation of immune cell infiltration, cellular interactions, and spatial organization within the tumor immune microenvironment (TiME). Statistical analysis was performed to assess differences in immune cell densities and interactions between SDUS and other ESSs. (3) Results: SDUS exhibited a significantly higher density of cytotoxic T lymphocytes (CTLs), T helper (Th) cells, B cells, and macrophages compared to other ESSs. Notable cellular interactions included Th-CTL and Th-B cell interactions, which were more prominent in SDUS. The spatial analysis revealed distinct immune niches characterized by lymphocyte aggregation and a vascular-rich environment, suggesting an active and engaged immune microenvironment in SDUS. (4) Conclusions: The results suggest that SDUS exhibits a highly immunogenic TiME, characterized by substantial lymphocyte infiltration and dynamic cellular interactions. These findings highlight the potential of immunotherapy as an effective treatment approach for SDUS. However, given the small number of samples evaluated, these conclusions should be drawn with caution. This study underscores the importance of additional investigation into immune-targeted therapies for this challenging cancer subtype, with a larger sample size to validate and expand upon these preliminary findings.

Exploring the Clinicopathological Diversity in Sarcomatous Transformations in the Uterus.

Introduction Uterine sarcomas are a rare group of mesenchymal tumors.They originate either from the uterine smooth muscle or from the endometrial stroma. The spectrum of malignant uterine sarcomatous transformations includes leiomyosarcoma, low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), undifferentiated uterine sarcoma, and carcinosarcoma. The purpose of this study is to determine the distribution of malignant uterine sarcomatous transformations, in relation to the patient's age, epidemiological aspects, and clinical features, and to analyze the different histological types of uterine sarcomas diagnosed at our institutionand thereby to quantify their frequency and determine the most common histopathological subtype occurring in the population. Materials and methods This was a retrospective descriptive study of 21 cases of malignant uterine sarcomatous transformations, diagnosed in Saveetha Medical College, Chennai, between January 2019 and December 2022. Data was collected from the archives of the department of pathologyand from the department of medical records in the hospital. The spectrum of uterine sarcomas was analyzed in relation to the patient's age, menopausal status, presenting symptoms, preoperative diagnosis, biopsy and frozen section reports wherever available, and histopathological reports with pathological staging. Results The most common age group in which uterine sarcoma was diagnosed was found to be 61-70 years. All 10 patients who were diagnosed with carcinosarcoma were aged 60 years, andall seven patients diagnosed with low-grade endometrial stromal sarcoma were less than 50 years of age. Most of the patients were postmenopausal females, except for one patient who was premenopausal. The most common histological variety found was carcinosarcoma, malignant mixed mullerian tumor (47.6%), followed by LG-ESS (33.3%), leiomyosarcoma (14.28%), and HG-ESS (4.7%). Conclusion Uterine sarcomas are anaggressive group of tumors having a very poor prognosis. Due to its rarity and histopathological diversity, there is a lack of consensus on the risk factors.

SMARCA4 / BRG1 -deficient Uterine Neoplasm With Hybrid Adenosarcoma and Carcinoma Features: Expanding the Molecular-morphologic Spectrum of SMARCA4 -driven Gynecologic Malignancies.

SMARCA4 gene encodes BRG1 , a member of the SWItch/sucrose non-fermentable protein family involved in epigenetic transcriptional regulation of important cellular processes. In the uterine corpus, SMARCA4 / BRG1 deficiency is associated with a novel class of undifferentiated uterine sarcomas, characterized by younger age onset, rhabdoid histology, focal phyllodiform architecture, high-risk pathologic findings, and dismal prognosis. Herein, we report a case of a 34-year-old Asian woman with a SMARCA4 / BRG1 -deficient uterine tumor fulfilling the clinicopathologic features of an undifferentiated uterine sarcoma. However, the tumor exhibited several unique features that have not been previously emphasized, including (1) conspicuous phyllodiform architecture recapitulating conventional adenosarcoma, (2) rhabdoid tumor cells forming cords and keratin-positive cohesive epithelial islands, and (3) cooccurrence with a spatially distinct and discrete endometrial complex atypical hyperplasia from the rest of the proliferation. By immunohistochemistry, the tumor cells were diffusely positive for synaptophysin, whereas BRG1 was lost. Pertinent molecular findings included frameshift mutations in the SMARCA4 gene, mutations in histone modification and chromatin remodeling genes, including KMT2C , ARID1B , KAT6A , and NCOR1 , and mutations in Wnt signaling involving APC and CTNNB1 . Copy number gain in MDM2 and CDK4 were also identified. The tumor mutation burden was intermediate (6.8/MB) and it was microsatellite stable. On balance, our case exhibited morphologic and molecular features that overlap with (1) an undifferentiated uterine sarcoma, (2) an adenosarcoma with sarcomatous overgrowth, and (3) a mixed adenosarcoma and undifferentiated endometrial carcinoma. These hybrid features further expand the molecular-morphologic spectrum of SMARCA4 / BRG1 -deficient uterine neoplasms.

Pan-TRK immunohistochemistry in gynaecological mesenchymal tumours: diagnostic implications and pitfalls.

NTRK-rearranged sarcomas of the female genital tract mainly occur in the uterus (more commonly cervix than corpus) and are characterized by a "fibrosarcoma-like" morphology and NTRK gene rearrangements. These neoplasms may exhibit histological overlap with other entities and can present diagnostic difficulties without molecular confirmation. Pan-TRK immunohistochemistry was developed to identify tumours harbouring NTRK rearrangements. The aim of this study was to characterize pan-TRK immunohistochemical expression in a large cohort of gynaecological mesenchymal neoplasms and investigate the utility of pan-TRK immunohistochemistry todistinguish NTRK-rearranged sarcoma from its mimics. A total of 473 gynaecological mesenchymal tumours (461 without known NTRK fusions and 12 NTRK-rearranged sarcomas) were selected. Pan-TRK immunohistochemistry (EPR17341, Abcam) was performed on whole tissue sections and tissue microarrays. Molecular interrogation of pan-TRK positive tumours was performed by RNA sequencing or fluorescence in situ hybridization (FISH). Of the 12 NTRK-rearranged sarcomas, 11 (92%) exhibited diffuse (≥70%) cytoplasmic pan-TRK staining with moderate/marked intensity, while the other wasnegative. Eleven (2.4%) additional tumours also exhibited pan-TRK immunohistochemical expression: three low-grade endometrial stromal sarcomas, seven high-grade endometrial stromal sarcomas, and an undifferentiated uterine sarcoma. Molecular confirmation of the absence of NTRK rearrangements was possible in nine of these tumours. Of these nine neoplasms, seven exhibited focal/multifocal (<70%) pan-TRK cytoplasmic staining with weak/moderate intensity. Even though pan-TRK immunohistochemical expression is not entirely sensitive or specific for NTRK-rearranged sarcomas, these neoplasms tend to exhibit diffuse staining of moderate/strong intensity, unlike its mimics. Pan-TRK should be performed in monomorphic uterine (corpus and cervix) spindle cell neoplasms that are negative for smooth muscle markers and hormone receptors and positive for CD34 and/ or S100. Ultimately, the diagnosis requires molecular confirmation.

A Retrospective Study Of 20 Cases Of Uterine Sarcoma In A Single Institute Over 10 Year Period

Objective: Uterine sarcomas are rare tumors arising from mesenchyme of uterus and th are diagnosed late because of confusing clinical and radiological presentation as urerine fibroids .In post hysterectomy pateints uterine sarcomas can present as pelvic or abdominal tumors causing confusion with tumors of bladder , bowel or other abdominal/pelvic malignancies. Histopathological examination and immuno histochemistry aids in diagnosis of uterine sarcoma and proper management of pateints. Hence 20 cases are studied in detail for better understanding of this rare entity. Methods: A retrospective study of 20 cases of uterine sarcoma was done. Details of patient are collected from departments of surgical oncology, medical oncology, pathology, radiology and outpatient records. Results: Uterine sarcomas are rare tumors and are usually diagnosed late. Most common types of uterine sarcoma are endometrial stromal sarcoma. leimyosarcoma, undifferentiated uterine sarcoma and adenosarcoma Abnormal uterine bleeding is the most common complaint and there are no specific complaints or radiological findings.Endometrial stromal sarcomas are known for their indolent course,in our study 6 pateints had hysterectomy in the past and years later presented as pelvic or abdominal masses causing diagnostic dilemma .Histopathology and immunohistochemistry aids in diagnosis and timely management of uterine sarcomas. Conclusion: In 20 cases of uterine sarcoma, patients presented with complaints of abnormal uterine bleeding, pain abdomen, mass per abdomen, hematuria and constipation, radiological findings revealed either fibroid uterus or degenerated fibroid or ovarian cyst or bladder tumor or bowel tumor or retroperitoneal tumor in none of the cases uterine sarcoma was in list of differential diagnosis. Diagnosis was made only after histopathological examination and immuno histochemistry. Cases of Uterine sarcomas diagnosed at early stage through proper suspicion for this rare tumor and confirmation with histopathology and immunohistochemistry have better survival and quality of life compared to cases which are mis managed. Hence study was done.

Diagnostic des sarcomes utérins et tumeurs mésenchymateuses utérines rares à potentiel de malignité. Référentiels du Groupe Sarcome Français et des Tumeurs Rares Gynécologiques

The landscape of uterine sarcomas is becoming more complex with the description of new entities associated with recurrent driver molecular alterations. Uterine sarcomas, in analogy with soft tissue sarcomas, are distinguished into complex genomic and simple genomic sarcomas. Leiomyosarcomas and undifferentiated uterine sarcomas belong to complex genomic sarcomas group. Low-grade and high-grade endometrial stromal sarcomas, other rare tumors associated with fusion transcripts (such as NTRK, PDGFB, ALK, RET ROS1) and SMARCA4-deficient uterine sarcoma are considered simple genomic sarcomas. The most common uterine sarcoma are first leiomyosarcoma and secondly endometrial stromal sarcomas. Three different histological subtypes of leiomyosarcoma (fusiform, myxoid, epithelioid) are identified, myxoid and epithelioid leiomyosarcoma being more aggressive than fusiform leiomyosarcoma. The distinction between low-grade and high-grade endometrial stromal sarcoma is primarily morphological and immunohistochemical and the detection of fusion transcripts can help the diagnosis. Uterine PEComa is a rare tumor, which is distinguished into borderline and malignant, according to a risk assessment algorithm. Embryonal rhabdomyosarcoma of the uterine cervix is more common in children but can also occur in adult women. Embryonal rhabdomyosarcoma of the uterine cervix is almost always DICER1 mutated, unlike that of the vagina which is wild-type DICER1, and adenosarcoma which can be DICER1 mutated but with less frequency. Among the emerging entities, sarcomas associated with fusion transcripts involving the NTRK, ALK, PDGFB genes benefit from targeted therapy. The integration of molecular data with histology and clinical data allows better identification of uterine sarcomas in order to better treat them.

High-Grade Endometrial Mesenchymal Sarcoma: Current Status and Future Trends

Endometrial Stromal Sarcoma (ESS) is a rare gynecological malignancy originating from endometrial stromal tissue. Representing only a tenth of uterine malignant tumors, ESS is categorized into Low-Grade (LGESS) and High-Grade (HGESS) based on nuclear division. Interestingly, prognostic studies have found no strong correlation between ESS prognosis and nuclear division activity. Undifferentiated Uterine Sarcoma (UUS) represents a spectrum of tumors with varied morphological, clinical, and prognostic features, and lacks a standardized naming convention. In 2014, the World Health Organization grouped ESS into LGESS, HGESS, and UUS based on clinical and pathological attributes. HGESS, despite its rarity, is notorious for its poor prognosis and low survival rate. Its early detection is complicated due to its asymptomatic presentation and ambiguous pathogenesis, leading to debates over treatment approaches. This article delves into the recent research developments concerning HGESS.

Next generation sequencing reveals a high prevalence of pathogenic mutations in homologous recombination DNA damage repair genes among patients with uterine sarcoma

ObjectiveInvestigate the incidence of homologous recombination DNA damage response (HR-DDR) genomic alterations among patients with uterine sarcoma. MethodsThe American Association for Cancer Research GENIE v13.0 database was accessed and patients with uterine leiomyosarcoma, adenosarcoma, undifferentiated uterine sarcoma, high-grade endometrial stromal sarcoma, low-grade endometrial stromal sarcoma, and endometrial stromal sarcoma not otherwise specified were identified. We determined the incidence of pathogenic alterations in the following genes involved in HR-DDR: ATM, ARID1A, ATRX, BAP1, BARD1, BLM, BRCA2, BRCA1, BRIP1, CHEK2, CHEK1, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, MRE11, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, WRN. Data from the OncoKB database, as provided by cBioPortal, was utilized to determine the presence of pathogenic genomic alterations. ResultsA total of 509 patients contributing with 525 samples were identified. Median patient age at sample collection was 56 years while the majority were White (80.7%). The most common histologic subtype was leiomyosarcoma (63.8%) followed by adenosarcoma (12.3%). The overall incidence of HR-DDR genomic alterations was 28.2%. The most commonly altered genes were ATRX (18.2%), BRCA2 (4%), and RAD51B (2.6%). The highest incidence of HR-DDR genomic alterations was observed among patients with leiomyosarcoma (35.4%), adenosarcoma (27%) and undifferentiated uterine sarcoma (30%), while those with low-grade endometrial stromal sarcoma had the lowest (2.9%) incidence. ConclusionsApproximately 1 in 3 patients with uterine sarcoma harbor a pathogenic alteration in HR-DDR genes. Incidence is high among patients with uterine leiomyosarcoma and adenosarcoma.

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

ObjectivesLow-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. MethodsWe 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. ResultsThe 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. ConclusionsPrognosis 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.

Complete Long-Term Response to Radioembolization of Hepatic Metastases from Undifferentiated Uterine Sarcoma

AbstractWe report a case of long-term complete response to selective intra-arterial radiation therapy in a 48-year-old female patient with metastatic liver disease from undifferentiated uterine sarcoma.

3D genomics identify alternate mechanisms of homologous recombination deficiency in uterine sarcoma.

e17624 Background: Uterine sarcomas are rare tumors with diverse morphologic appearances, genetic underpinnings, and clinical behavior. Molecular characterization of these tumors by next generation sequencing (NGS) has improved disease classification and prognostication, but its impact on therapeutic selection remains limited. Analysis of 3D genomics datasets has recently been shown to detect large complex structural variants (SV) and chromatin architecture in normal and diseased human tissues. We applied genome-wide chromosome conformation capture (Hi-C) techniques in a variety of uterine sarcomas to identify novel therapeutic targets. Methods: Formalin-fixed paraffin-embedded tissue from 48 primary or recurrent uterine sarcomas were subjected to Hi-C to identify chromosomal rearrangements. The cohort included leiomyosarcoma (LMS, n = 7), adenosarcoma (AS, n = 7), endometrial stromal sarcoma (n = 7; high grade (HGESS), n = 4; low grade (LGESS), n = 3), sarcoma not otherwise specified (n = 17; high grade (HGNOS), n = 10, low grade (LGNOS), n = 7), undifferentiated uterine sarcoma (UUS, n = 6) and heterologous sarcoma (n = 2). Tumors were previously subjected to targeted DNA (n = 10) and/or RNA (n = 26) NGS with no therapeutic targets identified and only BCOR internal tandem duplication detected in a HGESS. Results: Hi-C detected SV in 73% of uterine sarcomas (n = 35/48), including those previously negative by targeted RNA NGS (n = 25/26). Homologous recombination repair (HRR) gene alterations were detected by Hi-C in 42% of tumors (n = 20/48), including AS (n = 5/7), HGESS (n = 2/4), LGESS (n = 1/3), LMS (n = 2/7), UUS (n = 2/6), heterologous sarcoma (n = 1/2), HGNOS (n = 3/10) and LGNOS (n = 1/7). SV included gene (gene to gene, n = 3; gene to non-coding DNA, n = 8) and proximity (n = 13) fusions disrupting HRR genes ( ATM, BRIP1, CDK12, CHEK1, CHEK2, NBN, PARP3, RAD51B, RAD51C, RAD51D) with enrichment for RAD51B fusions (50%, n = 10/20). Among all tumors with HRR gene alterations detected by Hi-C, only one uterine sarcoma harbored a missense ATM mutation by targeted DNA NGS (n = 1/5). Conclusions: Molecular characterization of uterine sarcomas by Hi-C may uncover HRR gene alterations not currently detectable by targeted DNA and RNA NGS. Homologous recombination deficiency (HRD) is not limited to LMS and may frequently result from SV, particularly between HRR gene to non-coding DNA in a variety of uterine sarcomas. These alternate mechanisms for HRD may serve as a potential therapeutic biomarker for HRD-targeted therapy in uterine sarcoma.

Prognostic factors in undifferentiated uterine sarcoma: a subanalysis of the SARCUT study.

The aim of this study was to analyze the prognostic factors related to the recurrence rate and overall survival of patients with undifferentiated uterine sarcoma. An international multicenter study involving 43 international centers, the SARCUT study, collected 966 uterine sarcoma cases; among them 39 cases corresponded to undifferentiated uterine sarcoma and where included in the present subanalysis. The risk factors related to the oncological outcomes where analyzed. The median age of the patients was 63 (range 14-85) years. Seventeen (43.5%) patients presented FIGO stage I. The 5-year overall survival (OS) was 15.3% and 12-months disease-free survival (DFS) 41%. FIGO stage I was significantly associated with a better prognosis. In addition, patients who received adjuvant radiotherapy showed significant longer disease-free survival compared to those without adjuvant radiotherapy (20.5 vs. 4.0months, respectively; p = 0.04) and longer overall survival (34.7 vs. 18.2months, respectively; p = 0.05). Chemotherapy administration was associated with shorter DFS (HR 4.41, 95% CI 1.35-14.43, p = 0.014). Persistent disease after primary treatment (HR = 6.86, 95% CI 1.51-31.09, p = 0.012) and FIGO stage IV (HR 4.12, 95%CI 1.37-12.44, p = 0.011) showed significant worse prognosis for OS. FIGO stage seems to be the most important prognostic factor in patients with undifferentiated uterine sarcoma. Adjuvant radiotherapy seems to be significantly associated also to a better disease-free and overall survival. On the contrary, the role of chemotherapy administration remains unclear since was associated to a shorted DFS.

Pathological characteristics and immune microenvironment of SMARCA4-deficient undifferentiated uterine sarcoma

SMARCA4-deficient undifferentiated uterine sarcoma (SDUS) is a highly invasive single-gene malignant tumor caused by mutations in the SMARCA4 gene. SDUS has a poor prognosis, with no established treatment strategy at present. Further, there is a lack of relevant research on the role of the immune microenvironment in SDUS worldwide. Here, we report a case of SDUS that was diagnosed and analysed using morphological, immunohistochemical, and molecular detection techniques, along with the analysis of the immune microenvironment. By immunohistochemistry, the tumor cells showed retained INI-1 expression, focal CD10 expression, and loss of BRG1, CK-pan, synaptophysin, desmin, and ER expression. Further, some of the immune cells expressing CD3 and CD8 had infiltrated into the SDUS, but no PD-L1 expression was detected. The multiple immunofluorescent staining results showed that a proportion of the immune cells and SDUS cells expressed CD8/CD68/PD-1/PD-L1. Therefore, our report will help in the diagnostic awareness of SDUS.

Endometrial stromal neoplasia: An uncommon tumor at a tertiary health centre in coastal India

Introduction and Aim: Stromal malignancies of uterus are rare and accounts for 1-3% of all female genital tract malignancies. They are known to pose a diagnostic challenge to the clinicians and the pathologists. They show non-specific clinical features, gross appearance, varying histological and immunohistochemical features. This study highlights the important clinical, morphologic and immunohistochemical features of these tumors. Methodology: Histopathologically diagnosed cases of endometrial stromal neoplasia over a period of 5 years from 2013 to 2017 were retrieved. The cases were analysed based on age, tumor size and histological types. Immunohistochemistry (IHC) was done whenever feasible. Results: During the study period, we found 25 cases of endometrial stromal neoplasia. They were composed of four cases of endometrial stromal nodule (ESN), six cases of low grade endometrial stromal sarcoma (ESS) and three cases of ESS with smooth muscle differentiation. Twelve cases of carcinosarcomas and adenosarcomas and a single case of undifferentiated uterine sarcoma were seen. The mean age at presentation of Mixed epithelial stromal sarcoma (Carcinosarcoma) was 61 years while that of ESS and ESN was 46 and 47 years respectively. The mean size of ESN was 3.6cm (1.5-6cm), ESS was 4.5 cm (2-9.9 cm) and carcinosarcomas was 4.9 cm (2.5-16 cm). Conclusion: Endometrial stromal neoplasia should be diagnosed after proper evaluation of gross morphology, histological features and immunohistochemical findings in correlation with the clinical presentation. In addition, genetic profiling is useful as an ancillary test. The spectrum of endometrial stromal neoplasia is a beginner’s ordeal if not aware of.

Extrauterine Undifferentiated Uterine Sarcoma Arising from Bladder Endometriosis in a Postmenopausal Woman: A Case Report.

Endometriosis (EMS) is a rare condition in postmenopausal women. The incidence of transition from EMS to malignancy is as low as 1%, with endometrial stromal tumors (ESTs) occurring at an even lower incidence of 0.7%. Undifferentiated uterine sarcomas (UUSs) are a subtype of ESTs that account for 25% of all ESTs. Extrauterine UUSs are exceptionally rare, with only a few reported cases in the literature. We present the case of a woman who underwent surgery for deep infiltrating EMS and was later diagnosed with UUS, which originated from the bladder after surgical menopause.

Sarcoma of the Uterus. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/074, April 2021).

Purpose This is an official guideline, published and coordinated by the Germany Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG). Because of their rarity and heterogeneous histopathology, uterine sarcomas are challenging in terms of their clinical management and therefore require a multidisciplinary approach. To our knowledge, there are currently no binding evidence-based recommendations for the appropriate management of this heterogeneous group of tumors. Methods This S2k guideline was first published in 2015. The update published here is once again the result of the consensus of a representative interdisciplinary committee of experts who were commissioned by the Guidelines Committee of the DGGG to carry out a systematic search of the literature on uterine sarcomas. Members of the participating professional societies achieved a formal consensus after a structured consensus process. Recommendations 1.1 Epidemiology, classification, staging of uterine sarcomas. 1.2 Symptoms, general diagnostic workup, general pathology or genetic predisposition to uterine sarcomas. 2. Management of leiomyosarcomas. 3. Management of low-grade endometrial stromal sarcomas. 4. Management of high-grade endometrial stromal sarcoma and undifferentiated uterine sarcomas. 5. Management of adenosarcomas. 6.Rhabdomyosarcomas of the uterus in children and adolescents. 7. Follow-up of uterine sarcomas. 8. Management of morcellated uterine sarcomas. 9. Information provided to patients.

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

BackgroundUterine 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.MethodsThis 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.ResultsThe 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.ConclusionsIn 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.

Adult NTRK-rearranged spindle cell neoplasms of the viscera: with an emphasis on rare locations and heterologous elements

AbstractNTRK-rearranged mesenchymal neoplasms mostly affect the soft tissues of pediatric patients. Given the responsiveness to selective NTRK inhibitors, it remains critical to identify those ultra-rare cases occurring in the viscera of adults. In five females and two males aged 18–53 years, we characterized visceral mesenchymal tumors harboring TPM3-NTRK1 [uterine cervix (N = 2), pleura, prostate], LMNA-NTRK1 (lung), SQSTM1-NTRK3 (heart), and NTRK3 rearrangement with unknown fusion partner (colon/mesocolon) with RNA sequencing, FISH, RT-PCR, and immunohistochemistry. The tumors exhibited spindled to ovoid/epithelioid or pleomorphic cells, often arranged in fascicles, and were low-to-intermediate-grade and high-grade in three and four cases, respectively. Keloid-like stromal collagen and perivascular hyalinization was noted in five. Adenosarcoma-like appearances were observed in two, manifesting frond-like protrusions in one cervical tumor and phyllodes-like architecture in the prostatic tumor. Abrupt high-grade transformation into pleomorphic liposarcoma was found in another cervical tumor, while the pleural tumor contained intermixed rhabdomyoblasts. Pan-TRK immunostaining was positive in all cases. All cases expressed CD34, while five were S100-positive. CDKN2A homozygous deletion with concomitant p16 loss occurred in 4/7. Whole-exome sequencing identified TP53 mutation (c.672+2T>C, involving a splice site, with concomitant protein loss) in a cervical sarcoma, limited to its heterologous liposarcomatous component. At least moderate pan-TRK immunoreactivity was present in varying proportions of potential pathologic mimics, with BCOR-positive sarcoma (56%, 5/9), undifferentiated uterine sarcoma (50%, 3/6), and spindle cell/sclerosing rhabdomyosarcoma (33%, 2/6) being among the most frequent. This underscored the unsatisfactory specificity of pan-TRK immunohistochemistry and warranted molecular confirmation in the diagnosis of adult NTRK-rearranged visceral mesenchymal neoplasms. The current report highlights the ever-expanding clinicopathologic and genetic spectrum of this entity by describing the unprecedented cardiac and pleural locations and heterologous differentiation, as well as the second NTRK-rearranged “prostatic stromal sarcoma,” while substantiating CDKN2A deletion as a frequent occurrence.

Safety and feasibility of laterally extended endopelvic resection for sarcoma in the female genital tract: a prospective cohort study.

ObjectiveThis study aims to evaluate the safety and feasibility of laterally extended endopelvic resection (LEER) for sarcoma in the female genital tract.MethodsWe prospectively recruited gynecologic cancer patients with sarcoma arising from female genital tract who underwent LEER at Seoul National University Hospital from December 2016 to March 2021. Clinicopathologic characteristics, surgical outcomes including postoperative complications and pain control, and survival outcomes of the patients were investigated.ResultsA total of nine patients were registered for this study. The median age was 56 years. Carcinosarcoma (n=2, 22%), leiomyosarcoma (n=2, 22%), and undifferentiated uterine sarcoma (n=2, 22%) were common histology types. Complete resection was achieved in 88.9%. The most common location of pelvic sidewall tumors was infra-iliac acetabulum (66.7%). The pathologic outcome showed a median tumor size of 9.0 cm and internal iliac vessel resection with pelvic sidewall muscle was performed in all patients. The median estimated blood loss was 1,600 mL (range, 300–22,300), and the patients were postoperatively admitted to the intensive care unit for median 1 day (range, 0–8). Complete response was observed in 44.4% (4/9) in radiologic studies after LEER, and median progression-free survival, treatment-related survival, and overall survival were 3.3, 19.6, and 98.9 months, respectively.ConclusionLEER was feasible and safe in treating recurrent sarcoma presenting pelvic sidewall invasion with acceptable survival outcomes and manageable postoperative complications.