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BACKGROUND: Uterine sarcoma is a rare and heterogeneous gynecological malignancy characterized by aggressive progression and poor prognosis. The current study aimed to investigate the relationship between clinicopathological characteristics and the prognosis of uterine sarcoma in Chinese patients. METHODS: In this single-center retrospective study, we reviewed the medical records of 75 patients with histologically verified uterine sarcoma treated at the First Affiliated Hospital of Xi'an Jiaotong University between 2011 and 2020. Information on clinical characteristics, treatments, pathology and survival was collected. Progression-free survival (PFS) and overall survival (OS) were visualized in Kaplan-Meier curves. Prognostic factors were identified using the log-rank test for univariate analysis and Cox-proportional hazards regression models for multivariate analysis. RESULTS: The histopathological types included 36 endometrial stromal sarcomas (ESS,48%), 33 leiomyosarcomas (LMS,44%) and 6 adenosarcomas (8%). The mean age at diagnosis was 50.2 ± 10.7 years. Stage I and low-grade accounted for the majority. There were 26 recurrences and 25 deaths at the last follow-up. The mean PFS and OS were 89.41 (95% CI: 76.07-102.75) and 94.03 (95% CI: 81.67-106.38) months, respectively. Univariate analysis showed that > 50 years, post-menopause, advanced stage, ≥ 1/2 myometrial invasion, lymphovascular space invasion and high grade were associated with shorter survival (P < 0.05). Color Doppler flow imaging positive signals were associated with shorter PFS in the LMS group (P = 0.046). The ESS group had longer PFS than that of the LMS group (99.56 vs. 76.05 months, P = 0.043). The multivariate analysis showed that post-menopause and advanced stage were independent risk factors of both PFS and OS in the total cohort and LMS group. In the ESS group, diagnosis age > 50 years and high-grade were independent risk factors of PFS, while high-grade and lymphovascular space invasion were independent risk factors of OS. CONCLUSION: In Chinese patients with uterine sarcoma, post-menopause and advanced stage were associated with a significantly poorer prognosis. The prognosis of ESS was better than that of LMS. Color Doppler flow imaging positive signals of the tumor helped to identify LMS, which needs to be further tested in a larger sample in the future.
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Neoplasias Uterinas , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Uterinas/patologia , Neoplasias Uterinas/mortalidade , China/epidemiologia , Adulto , Prognóstico , Sarcoma do Estroma Endometrial/patologia , Sarcoma do Estroma Endometrial/mortalidade , Sarcoma/patologia , Sarcoma/mortalidade , Leiomiossarcoma/patologia , Leiomiossarcoma/mortalidade , Idoso , Adenossarcoma/patologia , Adenossarcoma/mortalidade , Adenossarcoma/terapia , Intervalo Livre de ProgressãoRESUMO
Leiomyosarcoma is one of the rarest types of gynecological cancer. It is a relatively rare condition that affects young women. The most frequent symptom of this disease is vaginal bleeding. The primary treatment for localized disease is still surgical intervention. It is widely recognized that leiomyosarcoma has a poor prognosis, with reduced survival rates and a high likelihood of early recurrence. This report presents a case of uterine leiomyosarcoma in a 22-year-old female patient. Following a total hysterectomy and bilateral salpingo-oophorectomy, the diagnosis of leiomyosarcoma was confirmed through a histopathological examination of the surgical specimen.
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Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the USs. Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), 3 adenosarcomas, 2 carcinosarcomas, and 1 uterine tumor resembling an ovarian sex-cord tumor (UTROSCT). ESS (including high-grade ESS and low-grade ESS) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A - PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uDEGs were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named MMN-MIL showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion: USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.
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Background: There are conflicting data regarding the detection rate of high-risk uterine sarcoma (HRUS) by endometrial biopsy. In addition, there are no studies in the literature on its impact on the chosen surgical approach and survival. Methods: This study includes 415 patients with HRUS. Of these, 178 (42.9%) patients had undergone endometrial biopsy. We analyzed the detection rate of endometrial biopsy and its impact on surgical approach and survival data. Results: Correct specific histologic diagnosis was achieved in only 30.0% of LMS and 33.3% of HGESS/UUS. Other uterine sarcoma, unspecified malignant mesenchymal tumor, carcinosarcoma or carcinoma were found in 45% of LMS and 78.2% of HGESS/UUS. As a result of the histologic findings, the rate of inadequate surgery was reduced by up to 19.9%. As tumor morcellation was performed significantly less often with biopsy (32.5% with vs. 55.4% without biopsy, p < 0.001), the locoregional recurrence-free interval remained unaffected between the two groups (p = 0.81). This is obviously an advantage of biopsy, although it does not affect the local recurrence rate in morcellated patients. Conclusions: Indicated endometrial biopsy is an important step in the diagnosis of HRUS, despite its low detection rate. It helps to avoid inappropriate surgical procedures but does not affect OS.
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OBJECTIVE: To develop a diagnostic model for predicting occult uterine sarcoma in patients with presumed uterine fibroids. MATERIALS AND METHODS: We retrospectively reviewed 41631 patients with presumed uterine fibroids who presented for HIFU treatment in 13 hospitals between November 2008 and October 2023. Of these patients, 27 with occult uterine sarcoma and 54 with uterine fibroids were enrolled. Univariate analysis and multivariate logistics regression analysis were used to determine the independent risk factors for the diagnosis of occult uterine sarcoma. A prediction model was constructed based on the coefficients of the risk factors. RESULTS: The multivariate analysis revealed abnormal vaginal bleeding, ill-defined boundary of tumor, hyperintensity on T2WI, and central unenhanced areas as independent risk factors. A scoring system was created to assess for occult uterine sarcoma risk. The score for abnormal vaginal bleeding was 56. The score for ill-defined lesion boundary was 90. The scores for lesions with hypointensity, isointensity signal/heterogeneous signal intensity, and hyperintensity on T2WI were 0, 42, and 93, respectively. The scores for lesions without enhancement on the mass margin, uniform enhancement of tumor, and no enhancement in the center of tumor were 0, 20, and 100, respectively. Patients with a higher total score implied a higher likelihood of a diagnosis of occult uterine sarcoma than that of patients with a lower score. The established model showed good predictive efficacy. CONCLUSIONS: Our results demonstrated that the diagnostic prediction model can be used to evaluate the risk of uterine sarcoma in patients with presumed uterine fibroids.
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Ablação por Ultrassom Focalizado de Alta Intensidade , Leiomioma , Sarcoma , Neoplasias Uterinas , Humanos , Feminino , Leiomioma/diagnóstico por imagem , Leiomioma/terapia , Sarcoma/diagnóstico por imagem , Sarcoma/terapia , Pessoa de Meia-Idade , Adulto , Neoplasias Uterinas/terapia , Medição de Risco , Estudos Retrospectivos , Ablação por Ultrassom Focalizado de Alta Intensidade/métodosRESUMO
OPINION STATEMENT: The cornerstone of treatment for uterine sarcoma, regardless of histologic type, remains en bloc surgical resection with total hysterectomy. In the case of incidental diagnosis during another procedure, such as myomectomy, where a hysterectomy was not performed initially, completion hysterectomy or cervical remnant removal is recommended. The completion of additional surgical procedures, including bilateral salpingo-oophorectomy and lymphadenectomy, remains nuanced. Bilateral salpingo-oophorectomy remains controversial in the setting of most subtypes of uterine sarcoma, except in the case of hormone-receptor positivity, such as in low grade endometrial stromal sarcoma, where it is indicated as part of definitive surgical treatment. In the absence of apparent nodal involvement, we do not recommend performing universal lymphadenectomy for patients with sarcoma. We recommend systemic therapy for patients with extra-uterine or advanced stage disease, high-grade histology, and recurrence. The most active chemotherapy regimens for advanced, high-grade disease remain doxorubicin or gemcitabine and docetaxol combination therapy. A notable exception is low grade endometrial stromal sarcoma, where we recommend anti-hormonal therapy in the front-line setting. Radiation therapy is reserved for selected cases where it can aid in palliating symptoms.
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Sarcoma , Neoplasias Uterinas , Humanos , Feminino , Neoplasias Uterinas/terapia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/patologia , Sarcoma/terapia , Sarcoma/diagnóstico , Terapia Combinada/métodos , Estadiamento de Neoplasias , Gerenciamento Clínico , Gradação de Tumores , Resultado do Tratamento , HisterectomiaRESUMO
BACKGROUND: Uterine sarcoma (US) is a highly malignant cancer with poor prognosis and high mortality in women. In this study, we evaluated the expression of human fibroblast growth factor 23 (FGF23) in different US subtypes and the relationship between survival and clinicopathological characteristics. METHODS: We conducted a comparative analysis of FGF23 gene expression in different pathological types of US. Utilizing a cohort from The Cancer Genome Atlas of 57 patients, a 50-patient microarray dataset (GSE119043) from the Gene Expression Omnibus and a Suining cohort of 44 patients, we analyzed gene expression profiles and corresponding clinicopathological information. Immunohistochemistry was used to examine the expression level of FGF23 in four US subtypes. Survival analysis was used to assess the relationship between FGF23 expression and prognosis in US patients. RESULTS: Compared with uterine normal smooth muscle and uterine leiomyoma, FGF23 expression was significantly upregulated in US and was differentially expressed in four US subtypes. Uterine carcinosarcoma exhibited the highest expression of FGF23 among the subtypes. Survival analysis revealed no correlation between FGF23 expression and either overall survival or progression-free survival in US (P > 0.05). Similar results were obtained from the validation cohorts. Univariate and multivariate analyses showed no significant correlation between FGF23 expression and the US prognosis. Tumor stage, CA125, and tumor recurrence were independent prognostic factors for survival of US patients. CONCLUSION: FGF23 was highly expressed in US and was promising as a novel potential biomarker for the diagnosis and prognosis of US.
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Neoplasias Pélvicas , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Feminino , Fator de Crescimento de Fibroblastos 23 , Prognóstico , Recidiva Local de Neoplasia/genéticaRESUMO
Secreted frizzled-related proteins (SFRPs) are involved in the development of various types of cancer and function by suppressing the Wnt signaling pathway. To elucidate the clinical implications of SFRPs in uterine sarcoma, SFRP expression levels and their effects on uterine leiomyosarcoma cells were examined. Immunostaining for SFRP4 was performed on uterine smooth muscle, uterine fibroid and uterine leiomyosarcoma tissues. Additionally, the effects of SFRP4 administration on cell viability, migration and adhesion were evaluated in uterine leiomyosarcoma SKN cells using the WST-1 assay (Roche Diagnostics) and the CytoSelect™ 24-well Cell Migration Assay Kit and the CytoSelect™ 48-well Cell Adhesion Assay Kit. The expression levels of SFRP4 in uterine leiomyosarcoma tissues were lower than those in normal smooth muscle and uterine fibroid tissues. In addition, SFRP4 suppressed the viability and migration, and increased the adhesion ability of uterine leiomyosarcoma cells compared with in the control group. In conclusion, SFRP4 may suppress the viability and migration, and enhance the adhesion of sarcoma cells. These results suggested that SFRP4 could be considered as a novel therapeutic target for uterine sarcoma.
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Intravascular leiomyoma (IVL) is usually defined as a histologically benign leiomyoma that originates in a uterine fibroid or the intrauterine vein wall and grows and expands intravenously. We report a case in which pelvic IVL was detected early and discuss the early diagnosis of and best treatment for this tumor.
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Metabolic reprogramming is considered as a hallmark of cancer and is clinically exploited as a novel target for therapy. The E2F transcription factor-1 (E2F1) regulates various cellular processes, including proliferative and metabolic pathways, and acts, depending on the cellular and molecular context, as an oncogene or tumor suppressor. The latter is evident by the observation that E2f1-knockout mice develop spontaneous tumors, including uterine sarcomas. This dual role warrants a detailed investigation of how E2F1 loss impacts metabolic pathways related to cancer progression. Our data indicate that E2F1 binds to the promoter of several glutamine metabolism-related genes. Interestingly, the expression of genes in the glutamine metabolic pathway were increased in mouse embryonic fibroblasts (MEFs) lacking E2F1. In addition, we confirm that E2f1-/- MEFs are more efficient in metabolizing glutamine and producing glutamine-derived precursors for proliferation. Mechanistically, we observe a co-occupancy of E2F1 and MYC on glutamine metabolic promoters, increased MYC binding after E2F1 depletion and that silencing of MYC decreased the expression of glutamine-related genes in E2f1-/- MEFs. Analyses of transcriptomic profiles in 29 different human cancers identified uterine sarcoma that showed a negative correlation between E2F1 and glutamine metabolic genes. CRISPR/Cas9 knockout of E2F1 in the uterine sarcoma cell line SK-UT-1 confirmed elevated glutamine metabolic gene expression, increased proliferation and increased MYC binding to glutamine-related promoters upon E2F1 loss. Together, our data suggest a crucial role of E2F1 in energy metabolism and metabolic adaptation in uterine sarcoma cells.
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Fator de Transcrição E2F1 , Fibroblastos , Regulação Neoplásica da Expressão Gênica , Glutamina , Neoplasias Uterinas , Animais , Fator de Transcrição E2F1/metabolismo , Fator de Transcrição E2F1/genética , Glutamina/metabolismo , Camundongos , Feminino , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologia , Fibroblastos/metabolismo , Humanos , Sarcoma/genética , Sarcoma/metabolismo , Sarcoma/patologia , Camundongos Knockout , Linhagem Celular Tumoral , Proliferação de Células , Regiões Promotoras GenéticasRESUMO
Objective: Endometrial stromal tumors are rare and complex mesenchymal tumors that often present with clinical symptoms similar to uterine leiomyomas. Due to their atypical nature, they are prone to be misdiagnosed or overlooked by healthcare professionals. This study presents a case report of an incidentally discovered endometrial stromal sarcoma with venous metastasis, which was initially misdiagnosed as a uterine leiomyoma. In addition, this study reviews previously documented cases of similar tumors. Case report: During a routine medical examination in 2016, a 50-year-old woman was diagnosed with uterine fibroids. In June 2020, she began experiencing moderate, irregular vaginal bleeding. Nevertheless, a histopathological examination indicated an endometrial stromal sarcoma with a striking amalgamation of both low-grade and high-grade features. Molecular analysis identified a rare MED12 gene mutation. The patient underwent total hysterectomy, bilateral salpingectomy, and resection of the metastatic lesions. Postoperative management included radiotherapy, chemotherapy, and hormone therapy. After completion of chemotherapy, the patient was followed up for 27 months with no evidence of tumor recurrence. Conclusion: This case report highlights the importance of pathological, immunohistochemical, and molecular aspects of this rare tumor involving the inferior vena cava and showing the presence of atypical gene mutations. The successful treatment outcome further emphasizes the importance of advances in diagnostic modalities for managing rare tumors like this.
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INTRODUCTION: In the context of female genital tract malignancy, uterine sarcoma is considered the rarest form of the disease. Despite the inert nature of low-grade endometrial sarcoma, they must be meticulously diagnosed on time, with an exact grading of the severity and staging of the disease, which further guides the treatment modality and prognosis. CASE SUMMARY: A married Asian female without any significant past medical and surgical history complained of abdominal distension and discomfort, which was progressive in nature, for which a radiological assessment was made that showed features suggestive of endometrial sarcoma. Total abdominal hysterectomy with sapingoopherectomy was done without any perioperative complications. Histology further confirmed the diagnosis. Post-operatively, the patient had an unremarkable hospital stay and was discharged home. DISCUSSION: Endometrial stromal sarcoma is one of the rare malignant entities presenting usually in late adult females, but sometimes it can present at an earlier age as well. Abdominal masses in females, although usually overlooked as benign, can sometimes be associated with a malignant picture. Low-grade endometrial sarcomas have been seen to masquerade other minor benign cases, such as leiomyoma. Despite the rarity of such malignant conditions, diagnosis and management are rather straightforward, and post-operative patient prognosis has been found to be rewarding. CONCLUSION: Among the uterine sarcoma cases, endometrial sarcoma comes under the malignant disease of the least occurrence. Compared to other malignant conditions, these patients present with minor symptoms like discomfort, which may go unchecked. The major factor that should be noted is the on-time diagnosis and appropriate choice of treatment modality. Overall, despite a minute prevalence and difficult diagnosis, the prognosis of the patient is rather good.
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BACKGROUND: This systematic review and meta-analysis aimed to determine the potential value of neutrophil to lymphocyte ratio (NLR) as an assessment tool in the clinical distinction between uterine sarcoma and uterine leiomyoma. METHODS: We comprehensively searched Web of Science, Scopus, and PubMed for relevant papers published before March 19, 2023. The standardized mean difference (SMD) was provided, along with a 95% confidence interval (CI). The random-effects model was employed to derive pooled effects due to the high levels of heterogeneity. The Newcastle-Ottawa scale was used for the quality assessment. Our study was registered in PROSPERO (CRD42023478331). RESULTS: Overall, seven articles were included in the analysis. A random-effect model revealed that patients with uterine sarcoma had higher NLR levels compared to those with uterine myoma (SMD = 0.60, 95% CI = 0.22-0.98; p = 0.002). In the subgroup analysis according to sample size, we found that patients with uterine sarcoma had elevated levels of NLR compared to those with uterine myoma in either large studies (SMD = 0.58, 95% CI = 0.04-1.13; P < 0.001) or small studies (SMD = 0.64, 95% CI = 0.33-0.96; P = 0.32). In the sensitivity analysis, we found that the final result was not significantly changed when single studies were removed, suggesting that the finding of this meta-analysis was stable. The pooled sensitivity of NLR was 0.68 (95% CI = 0.61-0.73), and the pooled specificity was 0.64 (95% CI = 0.59-0.69). CONCLUSION: NLR might be utilized as an assessment tool in clinics to help clinicians differentiate between patients with uterine sarcoma and those with myoma.
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Leiomioma , Mioma , Neoplasias Pélvicas , Sarcoma , Neoplasias de Tecidos Moles , Neoplasias Uterinas , Feminino , Humanos , Neutrófilos , Linfócitos , Sarcoma/diagnóstico , Neoplasias Uterinas/diagnóstico , Leiomioma/diagnósticoRESUMO
OBJECTIVE: To evaluate the added value of diffusion-weighted imaging (DWI)-based quantitative parameters to distinguish uterine sarcomas from atypical leiomyomas on preoperative magnetic resonance imaging (MRI). MATERIALS AND METHODS: A total of 138 patients (age, 43.7 ± 10.3 years) with uterine sarcoma (n = 44) and atypical leiomyoma (n = 94) were retrospectively collected from four institutions. The cohort was randomly divided into training (84/138, 60.0%) and validation (54/138, 40.0%) sets. Two independent readers evaluated six qualitative MRI features and two DWI-based quantitative parameters for each index tumor. Multivariable logistic regression was used to identify the relevant qualitative MRI features. Diagnostic classifiers based on qualitative MRI features alone and in combination with DWI-based quantitative parameters were developed using a logistic regression algorithm. The diagnostic performance of the classifiers was evaluated using a cross-table analysis and calculation of the area under the receiver operating characteristic curve (AUC). RESULTS: Mean apparent diffusion coefficient value of uterine sarcoma was lower than that of atypical leiomyoma (mean ± standard deviation, 0.94 ± 0.30 10-3 mm²/s vs. 1.23 ± 0.25 10-3 mm²/s; P < 0.001), and the relative contrast ratio was higher in the uterine sarcoma (8.16 ± 2.94 vs. 4.19 ± 2.66; P < 0.001). Selected qualitative MRI features included ill-defined margin (adjusted odds ratio [aOR], 17.9; 95% confidence interval [CI], 1.41-503, P = 0.040), intratumoral hemorrhage (aOR, 27.3; 95% CI, 3.74-596, P = 0.006), and absence of T2 dark area (aOR, 83.5; 95% CI, 12.4-1916, P < 0.001). The classifier that combined qualitative MRI features and DWI-based quantitative parameters showed significantly better performance than without DWI-based parameters in the validation set (AUC, 0.92 vs. 0.78; P < 0.001). CONCLUSION: The addition of DWI-based quantitative parameters to qualitative MRI features improved the diagnostic performance of the logistic regression classifier in differentiating uterine sarcomas from atypical leiomyomas on preoperative MRI.
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Leiomioma , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Adulto , Pessoa de Meia-Idade , Modelos Logísticos , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Leiomioma/diagnóstico por imagem , Leiomioma/cirurgia , Sarcoma/diagnóstico por imagem , Sarcoma/cirurgiaRESUMO
â¢Metastatic disease to the small bowel may present with intussusception.â¢Clinical decision making for malignant bowel obstruction is difficult and individual specific.â¢Malignant bowel obstruction due to metastatic year has an average life expectancy of less than 200 days.
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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.
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RNA Helicases DEAD-box , Neoplasias do Endométrio , Neoplasias dos Genitais Femininos , Leiomiossarcoma , Rabdomiossarcoma Embrionário , Ribonuclease III , Sarcoma do Estroma Endometrial , Neoplasias de Tecidos Moles , Neoplasias do Colo do Útero , Neoplasias Uterinas , Adulto , Criança , Feminino , Humanos , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/genética , Leiomiossarcoma/terapia , Rabdomiossarcoma Embrionário/diagnóstico , Rabdomiossarcoma Embrionário/genética , Rabdomiossarcoma Embrionário/terapia , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/genética , Sarcoma do Estroma Endometrial/terapia , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Neoplasias Uterinas/terapia , Receptores Proteína Tirosina Quinases , DNA Helicases , Proteínas Nucleares , Fatores de TranscriçãoRESUMO
COL1A1::PDGFB fusion uterine sarcoma is a rare uterine mesenchymal tumor with some clinicopathological features that overlap with those of soft tissue dermatofibrosarcoma protuberans. However, the varied clinicopathologic and genetic characteristics have not been fully revealed, which may be a potential pitfall for diagnosis. Here, we present a case of COL1A1::PDGFB fusion-positive uterine sarcoma in a 49-years-old female. Histologically, the tumor from the initial marginal excision predominantly exhibited high-grade fibrosarcomatous and myxofibrosarcoma-like appearances, while a low-grade focal area displaying storiform growth was identified in the residual tumor after subsequently extended resection. Immunohistochemically, the high-grade components mainly exhibited focal positivity for CD34 and mutated-type p53 immunoreactivity, whereas the low-grade component showed diffuse positivity for CD34 and wild-type p53 staining. The COL1A1::PDGFB fusion was confirmed by fluorescence in situ hybridization and next-generation sequencing. In addition, the TERT-124 C > T mutation was further identified in this lesion's fibrosarcomatous and classic storiform components. To the best of our knowledge, this is the first described case of COL1A1::PDGFB fusion uterine sarcoma with a TERT promoter mutation, which might be a novel genetic finding associated with tumorigenesis of this rare tumor.
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Dermatofibrossarcoma , Fibrossarcoma , Neoplasias Pélvicas , Neoplasias Cutâneas , Neoplasias de Tecidos Moles , Telomerase , Neoplasias Uterinas , Feminino , Humanos , Pessoa de Meia-Idade , Dermatofibrossarcoma/genética , Fibrossarcoma/genética , Hibridização in Situ Fluorescente , Mutação , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas c-sis/genética , Neoplasias Cutâneas/genética , Telomerase/genética , Proteína Supressora de Tumor p53/genética , Neoplasias Uterinas/genética , Neoplasias Uterinas/cirurgiaRESUMO
OBJECTIVE: Uterine sarcomas are rare tumors with a poor prognosis. Their diagnosis is often incidental, following surgery. Our goal was to examine the early management strategies for uterine sarcomas, and to assess the impact of guideline adherence and expert center referral on both the management approaches and the clinical outcomes in patients with uterine sarcomas. METHODS: We retrospectively analyzed medical records from patients with uterine sarcoma referred to the Institut Curie and registered in the database of the French NETSARC network. RESULTS: In total, 100 patients, with a median age of 54 years, were included in the analyses. On MRI scans (n = 36), all patients had at least two signs suggestive of malignancy, and 77.8 % had four or more signs. No preoperative biopsy was performed in 65.6 % of cases. Only 14.1 % of patients underwent initial surgery at an expert center. Surgery performed outside the network was significantly associated with morcellation (32.9 % vs. 0 %; p = 0.036), fewer negative margins (R0 margins 52.4 % vs. 100 %; p = 0.006), and poor adherence to surgical guidelines (28.3 vs. 72.7 %; p = 0.013). Multivariate analysis showed that non-adherence to surgical recommendations was not significantly associated with relapse-free survival (HR = 0.54; 95 % CI [0.21-1.38]), but was an independent predictor of poor overall survival (HR = 0.12; 95 % CI [0.03-0.52]; p = 0.005). CONCLUSION: Despite a high frequency of suspicious clinical and radiological signs, a large proportion of women undergoing sarcoma surgery are treated outside of expert networks. We provide guidelines, integrating the clinical context and radiological signs to encourage early referral to reference centers for sarcoma.
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Neoplasias Pélvicas , Sarcoma , Neoplasias de Tecidos Moles , Neoplasias Uterinas , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fidelidade a Diretrizes , Sarcoma/diagnóstico por imagem , Sarcoma/cirurgia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Encaminhamento e ConsultaRESUMO
PURPOSE: Uterine sarcomas are a rare group of uterine malignancies. Due to the low incidence and changes in uterine sarcoma classification, risk factors are not well characterized. Our objective was to evaluate risk factors for uterine sarcoma and compare risk factors between uterine sarcoma, malignant mixed Mullerian tumors (MMMTs), and type I endometrial carcinomas. METHODS: This nested case-control study utilized linked data from population-based medical birth and cancer registries in Denmark, Finland, Norway, and Sweden. Up to 10 controls were matched on country and birth year for each uterine cancer case. Using multivariable adjusted multinomial logistic regression, estimates of the associations between pregnancy-related factors and risk of uterine sarcoma, MMMTs, and type I endometrial carcinomas were determined. RESULTS: Having a very-low-birth-weight infant (< 1500 vs. 2500-3999 g: OR [95% CI] 2.83 [1.61-4.96]) was associated with an increased risk of uterine sarcoma. Whereas, having a more recent pregnancy was associated with reduced risks of MMMT (< 10 vs. ≥ 30 years: 0.66 [0.20-2.23]) and type 1 endometrial carcinomas (0.35 [0.30-0.41]) but not uterine sarcomas (1.33 [0.90-1.98], p-heterogeneity < 0.01). CONCLUSION: Our study provides evidence that risk factors for uterine sarcoma and MMMT, previously grouped with uterine sarcomas, vary substantially. Additionally, MMMT and type I endometrial carcinomas are more similar than uterine sarcoma in that pregnancy complications like gestational hypertension and preeclampsia were associated with reduced risks of both but not uterine sarcoma, suggesting different etiologies.
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Sarcoma , Neoplasias Uterinas , Humanos , Feminino , Estudos de Casos e Controles , Gravidez , Neoplasias Uterinas/epidemiologia , Fatores de Risco , Adulto , Pessoa de Meia-Idade , Sarcoma/epidemiologia , Sistema de Registros , Países Escandinavos e Nórdicos/epidemiologia , Suécia/epidemiologia , Idoso , Finlândia/epidemiologia , Noruega/epidemiologia , Dinamarca/epidemiologiaRESUMO
NTRK-rearranged uterine sarcoma is a recently described entity that represents a subset of uterine sarcomas with distinct clinicopathological features. From a molecular point of view, this tumour is defined by NTRK gene rearrangement, resulting in overexpression or constitutive activation of Trk receptors. The presence of NTRK fusion is indicative of treatment response with a selective small-molecule inhibitor of the Trk kinases. Here, we report a case of an NTRK-rearranged sarcoma of the uterine cervix in a 43-year-old patient, measuring 80 mm in its largest dimension, with a novel NUMA1-NTRK1 fusion, not previously reported in NTRK-rearranged uterine sarcomas or other NTRK-rearranged tumours. The fusion, involving NUMA1 exon 14 (NM_006185.4) and NTRK1 exon 11 (NM_002529.4), was identified by next-generation sequencing (NGS) studies (FusionPlex Pan Solid Tumor v2 panel). Although the presence of NTRK fusion has been reported in a variety of neoplasms, a fusion involving NUMA1 (nuclear mitotic apparatus protein 1) and a tyrosine kinase partner has previously been reported in human neoplasms only in a handful of cases. The resulting fusion protein comprises the oligomerization domain of NUMA1, which is predicted to cause constant activation of the tyrosine kinase domain of NTRK1. The recognition and accurate diagnosis of these tumours are important due to the availability of potential targeted therapeutic options.