Myometrial Tumors Research Articles

A human-interpretable machine learning pipeline based on ultrasound to support leiomyosarcoma diagnosis

The preoperative evaluation of myometrial tumors is essential to avoid delayed treatment and to establish the appropriate surgical approach. Specifically, the differential diagnosis of leiomyosarcoma (LMS) is particularly challenging due to the overlapping of clinical, laboratory and ultrasound features between fibroids and LMS. In this work, we present a human-interpretable machine learning (ML) pipeline to support the preoperative differential diagnosis of LMS from leiomyomas, based on both clinical data and gynecological ultrasound assessment of 68 patients (8 with LMS diagnosis). The pipeline provides the following novel contributions: (i) end-users have been involved both in the definition of the ML tasks and in the evaluation of the overall approach; (ii) clinical specialists get a full understanding of both the decision-making mechanisms of the ML algorithms and the impact of the features on each automatic decision. Moreover, the proposed pipeline addresses some of the problems concerning both the imbalance of the two classes by analyzing and selecting the best combination of the synthetic oversampling strategy of the minority class and the classification algorithm among different choices, and the explainability of the features at global and local levels. The results show very high performance of the best strategy (AUC = 0.99, F1 = 0.87) and the strong and stable impact of two ultrasound-based features (i.e., tumor borders and consistency of the lesions). Furthermore, the SHAP algorithm was exploited to quantify the impact of the features at the local level and a specific module was developed to provide a template-based natural language (NL) translation of the explanations for enhancing their interpretability and fostering the use of ML in the clinical setting.

Overlap of Suspicious and Non-Suspicious Features in the Ultrasound Evaluations of Leiomyosarcoma: A Single-Center Experience.

Leiomyosarcoma (LMS) is a rare type of mesenchymal tumor. Suspecting LMS before surgery is crucial for proper patient management. Ultrasound is the primary method for assessing myometrial lesions. The overlapping of clinical, laboratory, as well as ultrasound features between fibroids and LMS makes differential diagnosis difficult. We report our single-center experience in ultrasound imaging assessment of LMS patients, highlighting that misleading findings such as shadowing and absent or minimal vascularization may also occur in LMS. To avoid mistakes, a comprehensive evaluation of potentially overlapping ultrasound features is necessary in preoperative ultrasound evaluations of all myometrial tumors.

Uterine leiomyosarcoma in a premenopausal woman. Clinical case

INTRODUCTION. Leiomyosarcoma (LMS) of the uterus is a rare soft‑tissue tumor of the female pelvis with <1% of uterine tumor. It usually arises from the uterine myometrium de novo or is very rarely transformed from a preexisting benign leiomyoma. These tumors are found mainly in females 40–60 years of age. Leiomyomas seen in the reproductive age group and a strong suspicion of LMS should be in mind in cases of fibroid with postmenopausal bleeding. CLINICAL CASE. A 39-year-old female came to the emergency room complaining of pelvic pain of 8 days duration, treated symptomatically with NSAIDs. It has the following background: hereditary family history, which is unimportant to the case. Gynecobstetric history: menarche 11 years old, regular cycles five to seven days, reports two months with uncontrolled cycle with heavy menstrual bleeding, start active sexual life 24 years old. Papanicolaou: last year reported normal; colposcopy last one and a half ago reported normal. DISCUSSION. Approximately 40-80% of women may develop leiomyomas, the most common benign gynecological disease, during their lifetime. Uterine sarcoma, on the other hand, is a rare disease with an incidence ranging from 1.55 to 1.95 per 100,000 women per year. According to the WHO, in 2011, a LMS is a specific type of rare sarcoma that accounts for over 60% of all cases of uterine sarcoma. It is essential to correctly evaluate myometrial tumors before surgery to ensure proper patient management and avoid delayed treatment. However, distinguishing an LMS from fibroids can be difficult due to similar clinical, laboratory, and ultrasound features. Ultrasound is a cost-effective, non-invasive, and widely accepted imaging method for evaluating the myometrium. The reporting of ultrasound characteristics of the myometrium and myometrial lesions was standardized by developing a consensus statement by the Morphological Uterus Sonographic Assessment group.

ASO Visual Abstract: Percutaneous Uterine Needle Biopsy with Microscopic and Array-CGH Analyses for Preoperative Sarcoma Diagnosis in Patients with Suspicious Myometrial Tumors on MRI: A Prospective Pilot Study (SARCGYN).

ASO Visual Abstract: Percutaneous Uterine Needle Biopsy with Microscopic and Array-CGH Analyses for Preoperative Sarcoma Diagnosis in Patients with Suspicious Myometrial Tumors on MRI: A Prospective Pilot Study (SARCGYN).

RF07 | PSUN350 Estradiol Effects on Polymorphonuclear Cell Production and Actions Contribute to Estrogen-mediated Lymphangioleiomyomatosis (LAM) Progression

Abstract Lymphangioleiomyomatosis (LAM) is a rare lung disease seen almost exclusively in female sexed individuals and characterized by slowly growing, metastatic smooth muscle cell-like adenomas that cause cyst formation in the lung parenchyma and irreversible loss of pulmonary function. Given the female specificity of disease manifestation, metastatic nature, and estrogen sensitivity of LAM cells, we previously proposed that LAM cells originate in the myometrium. Our subsequent reports showed that inactivation of TSC2 in the mouse uterus results in notable LAM features in the setting of primary myometrial tumors. Additionally, we established that estrogen is required to maintain LAM-like tumor progression in a uterine-specific Tsc2-knockout murine model. However, the observed estrogen sensitivity in vivo is more markedly pronounced than that of our estrogen receptor-positive TSC2-null cells when stimulated with estradiol in vitro, suggesting that estradiol may act elsewhere in vivo to promote LAM progression. Recent immunophenotyping of LAM-like TSC2-null uterine tumors revealed preferential increase in polymorphonuclear cell (PMNs) numbers of the tumor microenvironment; we also determined that PMNs are important regulators of tumor growth. Therefore, we hypothesize that, in addition to direct effects of estrogen on tumor cells, estrogen might also stimulate tumor growth by promoting PMN production in the bone marrow and actions in the tumor microenvironment. Here, we show that estrogen availability influences PMN mobilization in naïve and tumor-burdened mice. Using bone marrow cultures and CFC assay, we demonstrate that estradiol is a potent inducer of PMN production in chronic inflammatory conditions. Employing both pharmacologic agents and estrogen receptor (ER)-null bone marrow, we showed that ERα is necessary for promoting induction of PMN fate for myeloid progenitors. While we see that the migratory, invasive, and proliferative capacities of TSC2-null cell lines are not augmented when stimulated with E2 directly, experiments are underway to assess the extent to which estrogen promotes the pro-tumorigenic function of PMNs co-cultured with TSC2-null cell lines. Together these data provide insight into the robust effect of in vivo estrogen stimulation as estradiol may be a dual effector in LAM tumor progression and great target for anti-LAM therapeutic strategy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 1:05 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Percutaneous Uterine Needle Biopsy with Microscopic and Array-CGH Analyses for Preoperative Sarcoma Diagnosis in Patients with Suspicious Myometrial Tumors on MRI: A Prospective Pilot Study (SARCGYN).

Unlike for soft tissue sarcomas, percutaneous biopsy is not validated for uterine myometrial tumors, leading to leiomyosarcoma inadvertent morcellation and overtreatment in childbearing patients. This study aimed to evaluate preoperative percutaneous uterine needle biopsy (PUB) with microscopic examination (M-PUB) and array-comparative genomic hybridization (MCGH-PUB). This was a prospective single-center cohort study including all consecutive patients who were candidates for hysterectomy because of suspected uterine leiomyosarcoma on magnetic resonance imaging (MRI) who received PUB. Microscopic and array-CGH analyses with genomic index (GI) counts were performed to guide the therapeutic strategy. Smooth-muscle tumors with suspect features with a GI above 15 were deemed malignant, as were tumors without microscopic malignant features with a complex genomic profile (GI above 30 or malignant profile). Preoperative diagnoses based on M-PUB and MCGH-PUB were compared with the postsurgical pathological specimen or follow-up. From November 2016 to February 2022, 34 patients were included. Based on the surgical specimen (N = 23) or follow-up (N = 11), final diagnoses were 11 sarcomas and 23 non-sarcomas. The median follow-up was 12 months (IQR 6-37). The diagnostic accuracies of M-PUB and MCGH-PUB were 94% and 100%, respectively. The sensitivity, specificity, and negative predictive value of MCGH-PUB were 100%, 100%, and 100%, respectively. A high GI was significantly associated with malignancy (P < 0.001). Genomic analyses allowed malignancy upgrades for four tumors. There were no complications and no dissemination along the biopsy track. MCGH-PUB is safe and accurate for preoperatively diagnosing uterine sarcomas and should be used routinely after suspicious MRI to tailor surgery.

1485O Percutaneous uterine needle biopsy with microscopic and array-CGH analyses in patients with suspicious myometrial tumors on MRI: A prospective study

Preoperative diagnosis of uterine tumors is of utmost importance to avoid inadvertent morcellation of leiomyosarcoma (LMS) and unnecessary hysterectomy in childbearing patients. There are no pathognomonic criteria for malignancy on Magnetic Resonance Imaging (MRI). The diagnosis of malignancy includes microscopic and genomic analyses with array-Comparative Genomic Hybridization (CGH). To date, no study has evaluated preoperative percutaneous uterine needle biopsy (PUB) with microscopic examination (M-PUB) and array-CGH analyses (MCGH-PUB).

Ultrasound-Guided Trans-Uterine Cavity Core Needle Biopsy of Uterine Myometrial Tumors to Differentiate Sarcoma from a Benign Lesion—Description of the Method and Review of the Literature

Uterine sarcomas are rare, aggressive tumors with poor prognosis that can be further negatively affected by inadequate surgical approaches such as morcellation. There are no clinical and radiologic criteria for differentiating leiomyoma from malignant uterine tumors. However, some ultrasonography and magnetic resonance imaging findings may be informative. We present a technique of ultrasound-guided trans-uterine cavity (UG-TUC) core needle biopsy for uterine lesions. As the procedure is an in-organ biopsy, there is no risk of needle canal contamination. The technique also enables the biopsy of lesions inaccessible by the transvaginal tru-cut biopsy. The core needle of the automatic biopsy system is inserted via the cervical canal into the uterine cavity and is directed and activated at the myometrial lesion under ultrasound control. The standard local treatment of localized uterine sarcomas is en bloc total hysterectomy; for fibroids, there are multiple options including conservative management or tumorectomy and tumor morcellation using minimally invasive techniques. Fragmentation of the sarcoma significantly worsens oncologic outcomes and should therefore be avoided. The UG-TUC core needle biopsy of uterine lesions can complement imaging to obtain sufficient material for histologic and molecular analyses of suspected or undetermined lesions, thus facilitating treatment planning and decreasing the risk of unsuspected sarcomas.

Integrative Genomic and Transcriptomic Profiling Reveals a Differential Molecular Signature in Uterine Leiomyoma versus Leiomyosarcoma.

The absence of standardized molecular profiling to differentiate uterine leiomyosarcomas versus leiomyomas represents a current diagnostic challenge. In this study, we aimed to search for a differential molecular signature for these myometrial tumors based on artificial intelligence. For this purpose, differential exome and transcriptome-wide research was performed on histologically confirmed leiomyomas (n = 52) and leiomyosarcomas (n = 44) to elucidate differences between and within these two entities. We identified a significantly higher tumor mutation burden in leiomyosarcomas vs. leiomyomas in terms of somatic single-nucleotide variants (171,863 vs. 81,152), indels (9491 vs. 4098), and copy number variants (8390 vs. 5376). Further, we discovered alterations in specific copy number variant regions that affect the expression of some tumor suppressor genes. A transcriptomic analysis revealed 489 differentially expressed genes between these two conditions, as well as structural rearrangements targeting ATRX and RAD51B. These results allowed us to develop a machine learning approach based on 19 differentially expressed genes that differentiate both tumor types with high sensitivity and specificity. Our findings provide a novel molecular signature for the diagnosis of leiomyoma and leiomyosarcoma, which could be helpful to complement the current morphological and immunohistochemical diagnosis and may lay the foundation for the future evaluation of malignancy risk.

Comparison of the diagnostic accuracy of contrast-enhanced/DWI MRI and ultrasonography in the differentiation between benign and malignant myometrial tumors

BackgroundVarious modalities including ultrasonography and magnetic resonance imaging (MRI) have been developed as imaging technique for screening malignant myometrial tumors, but a few studies assessed the diagnostic value of these two techniques in differentiation of benign from malignant myometrial tumors that had been the main purpose of this study. Materials and methodsThis cross-sectional study was performed on 63 women underwent surgery for intrauterine masses that were initially assessed using MRI and ultrasound before surgery at a tertiary hospital in Tehran from 2016 to 2020. Their MRI was reviewed by a reputable radiologist in the field. The findings of histopathological assessment were considered as the gold diagnostic standard. ResultsThe sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MRI to detect sarcoma were revealed to be 94.6%, 92.3%, 94.6%, 92.3%, and 93.7% respectively. Ultrasonography had not preferable applicability to differentiate sarcoma from benign tumors with sensitivity, specificity, PPV, NPV and accuracy of 35.1%, 88.4%, 81.2%, 48.9%, and 57.1% respectively. The diagnostic performance of both modalities was not affected by baseline clinical conditions including pain, abnormal uterine bleeding and menopausal status. ConclusionMRI but not ultrasonography can effectively differentiate benign from malignant myometrial tumors.

Estradiol Augments the Production and Actions of Polymorphonuclear Cells to Promote Lymphangioleiomyomatosis (LAM) Progression

Affecting almost exclusively women, lymphangioleiomyomatosis (LAM) is a rare lung disease characterized by slowly growing, estrogen-sensitive metastatic smooth muscle cell-like adenomas that result in cystic lung changes and loss of pulmonary function. LAM tumors are caused by mutations in either TSC1 or TSC2 genes that induces defective inhibition of the mTORC1 pathway, leading to increased mTORC1 activity and augmented cell proliferation. We have previously reported that estrogen ablation in our uterine-specific Tsc2 knockout mouse, which grows tumors with characteristic LAM features and lung colonization potential, effects notable regression of tumors. Thus, estrogen is required for to maintain heightened mTORC1 activity and LAM-like tumor progression. Interestingly, the observed estrogen sensitivity in vivo is more markedly pronounced than that of our estrogen receptor-positive TSC2-null cells when stimulated with estradiol in vitro, suggesting that estradiol may act elsewhere—in mTORC1 independent manner—in vivo to promote LAM progression. Flow cytometry revealed large numbers of Ly-6Cint Ly-6Ghigh myeloid cells—polymorphonuclear cells or PMNs—in the blood and myometrial tumors of our uterine-specific Tsc2-null mice. Accordingly, we found that Tsc2-null tumors required PMNs for normal disease progression, as Gr-1 (Ly-6C/Ly-6G) depletion or inhibition of PMN recruitment reduced tumor growth. Therefore, we hypothesized that, in addition to direct effects of estrogen on tumor cells, estrogen might also stimulate tumor growth by promoting PMN production in the bone marrow and actions in the tumor microenvironment. Using bone marrow cultures, we found that estradiol is indeed a potent inducer of PMN production. This effect occurs equally in both male and female bone marrow. Employing both pharmacologic agents and bone marrow from ERα; knockout mice, we showed that ERα; is necessary for promoting a PMN fate for myeloid progenitors. Additionally, we have evidence implicating estrogen in the pro-tumorigenic function of PMNs co-cultured with TSC2-null cell lines. Overall, these data suggest that estradiol maybe facilitating crosstalk in LAM tumors, directly stimulating tumor cells while also promoting the production and actions of PMNs, which in turn promote tumor growth.

Using rADioMIcs and machine learning with ultrasonography for the differential diagnosis of myometRiAL tumors (the ADMIRAL pilot study). Radiomics and differential diagnosis of myometrial tumors

ObjectiveTo develop and evaluate the performance of a radiomics and machine learning model applied to ultrasound (US) images in predicting the risk of malignancy of a uterine mesenchymal lesion. MethodsSingle-center retrospective evaluation of consecutive patients who underwent surgery for a malignant uterine mesenchymal lesion (sarcoma) and a control group of patients operated on for a benign uterine mesenchymal lesion (myoma). Radiomics was applied to US preoperative images according to the International Biomarker Standardization Initiative guidelines to create, validate and test a classification model for the differential diagnosis of myometrial tumors. The TRACE4 radiomic platform was used thus obtaining a full-automatic radiomic workflow. Definitive histology was considered as gold standard. Accuracy, sensitivity, specificity, AUC and standard deviation of the created classification model were defined. ResultsA total of 70 women with uterine mesenchymal lesions were recruited (20 with histological diagnosis of sarcoma and 50 myomas). Three hundred and nineteen radiomics IBSI-compliant features were extracted and 308 radiomics features were found stable. Different machine learning classifiers were created and the best classification system showed Accuracy 0.85 ± 0.01, Sensitivity 0.80 ± 0.01, Specificity 0.87 ± 0.01, AUC 0.86 ± 0.03. ConclusionsRadiomics applied to US images shows a great potential in differential diagnosis of mesenchymal tumors, thus representing an interesting decision support tool for the gynecologist oncologist in an area often characterized by uncertainty.

MR imaging findings of unusual leiomyoma and malignant uterine myometrial tumors: what the radiologist should know.

Uterine sarcomas account for less than 1% of gynecological malignancies and 2-5% of all uterine malignancies. Such sarcomas mainly include leiomyosarcoma (LMS) and endometrial stromal sarcoma (ESS). Additionally, inflammatory myofibroblastic tumor (IMT) and endometrial carcinoma arising in adenomyosis can occur as uterine myometrial tumors. Their differentiation from leiomyoma (LM), particularly degenerated LM and the malignant tumors, is challenging, but preoperative diagnosis is very important for the patient's management. We demonstrate the useful and compulsory findings to differentiate between uterine myometrial malignant tumors and degenerated LM with an unusual appearance.

SUN-134 Estrogen Induces Granulocytic Myeloid Derived Suppressor Cell Production to Potentially Modulate Lymphangioleiomyomatosis (LAM) Tumor Progression

Affecting almost exclusively women, lymphangioleiomyomatosis (LAM) is a rare lung disease characterized by estrogen-sensitive metastatic smooth muscle cell-like adenomas that grow slowly, resulting in cystic lung change and loss of pulmonary function. LAM tumors are caused by mutations in tuberous sclerosis complex 1 or 2 genes (TSC1 or TSC2). Mutations in TSC1 or TSC2 genes results in deficient inhibitory regulation of the mammalian target of rapamycin complex 1 (mTORC1), which in turn leads to increased mTORC1 activity and cell proliferation. There is no consensus amongst LAM researchers regarding the origin of these estrogen receptor-positive smooth muscle like LAM cells; however, we previously reported inactivation of TSC2 in the mouse uterus results in notable LAM features in the setting of primary myometrial tumors. Approximately 50% of the TSC2-null mice had metastatic myometrial tumors present in the lung, suggesting that LAM tumor cells might in fact originate from the uterus, thus explaining the female sexual dimorphism, the estrogen sensitivity, and the metastatic nature of the LAM tumors.Interestingly, flow cytometry revealed large numbers of granulocytic myeloid derived suppressors cells (G-MDSCs) in the blood and myometrial tumors of uterine-specific Tsc2 null mice. MDSCs are known to accumulate in the setting of chronic inflammation caused by trauma, infection, and various cancers. This granulocytic subtype not only has the capacity to suppress anti-tumor immune cells of the tumor microenvironment, but also directly promotes tumor cell malignant neoplasicity. We found that Tsc2-null myometrial tumors required MDSCs for normal progression, as MDSC depletion or inhibition of MDSC recruitment reduced tumor growth. We have showed that these tumors expressed estrogen receptors and were exquisitely sensitive to estrogen, while other studies demonstrate that G-MDSCs are also positively influenced by estradiol. Therefore, we hypothesized that, in addition to direct effects of estrogen on tumor cells, estrogen also stimulates tumor growth by promoting MDSC production in the bone marrow. We have developed a technique to stimulate MDSC production from mouse bone marrow. Using this strategy, we found that estradiol is indeed a potent promotor of G-MDSC production. These effects occurred in both male and female bone marrow. Employing both pharmacologic agents and bone marrow from ERα; knockout mice, we showed that ERα; is necessary for promoting a G-MDSC fate for immature myeloid cells and precursors. Thus, estradiol may have duel effects in LAM, both directly promoting tumor growth and indirectly upregulating MDSC production, which in turn promotes tumor growth. We propose that these estrogen effects on MDSC production are not limited to LAM and may be important regulators of tumor growth in many tissues.

A Diagnostic Algorithm using Multi-parametric MRI to Differentiate Benign from Malignant Myometrial Tumors: Machine-Learning Method

This study aimed to develop a diagnostic algorithm for preoperative differentiating uterine sarcoma from leiomyoma through a supervised machine-learning method using multi-parametric MRI. A total of 65 participants with 105 myometrial tumors were included: 84 benign and 21 malignant lesions (belonged to 51 and 14 patients, respectively; based on their postoperative tissue diagnosis). Multi-parametric MRI including T1-, T2-, and diffusion-weighted (DW) sequences with ADC-map, contrast-enhanced images, as well as MR spectroscopy (MRS), was performed for each lesion. Thirteen singular MRI features were extracted from the mentioned sequences. Various combination sets of selective features were fed into a machine classifier (coarse decision-tree) to predict malignant or benign tumors. The accuracy metrics of either singular or combinational models were assessed. Eventually, two diagnostic algorithms, a simple decision-tree and a complex one were proposed using the most accurate models. Our final simple decision-tree obtained accuracy = 96.2%, sensitivity = 100% and specificity = 95%; while the complex tree yielded accuracy, sensitivity and specificity of 100%. To summarise, the complex diagnostic algorithm, compared to the simple one, can differentiate tumors with equal sensitivity, but a higher specificity and accuracy. However, it needs some further time-consuming modalities and difficult imaging calculations. Trading-off costs and benefits in appropriate situations must be determinative.

Neutrophil elastase from myeloid cells promotes TSC2-null tumor growth.

Chronic inflammation promotes progression of many cancers, with circulating myeloid-derived suppressor cell (MDSC) levels correlating with poor prognosis. Here we examine effects of MDSCs on lymphangioleiomyomatosis (LAM), a rare disease occurring almost exclusively in women whereby estrogen-sensitive metastatic TSC2-null tumors grow throughout the lungs, markedly reducing pulmonary function. The LAM cell origin remains unknown; however, previous work demonstrated that Tsc2 inactivation in the mouse uterus induced estrogen-dependent myometrial tumors with nearly all features of LAM. Half of these animals developed metastatic myometrial tumors in the lungs, suggesting that LAM cells might originate from the myometrium, possibly explaining its overwhelming female prevalence and estrogen-sensitivity. Here we report that MDSC levels, and in particular granulocytic myeloid cell levels, are elevated in the periphery and in tumors of uterine-specific Tsc2-null mice. Importantly, MDSC depletion or inhibition of their recruitment impairs myometrial tumor growth. RNA and protein analysis of Tsc2-null myometrial tumors and xenografts demonstrate high expression and activity of the serine protease neutrophil elastase (NE), with selective qPCR studies indicating a stromal origin of the NE. Notably, treatment with sivelestat, a known NE inhibitor already approved for human use in some countries, reduces tumor growth similar to MDSC depletion. Furthermore, NE promotes Tsc2-null tumor cell growth, migration, and invasion in vitro. Finally, NE-expressing myeloid cells are present throughout the lungs of LAM patients but not controls. These data suggest that NE derived from granulocytic myeloid cells might directly promote LAM tumor cell progression and could be a novel therapeutic target for LAM.

Ruptured myometrial tumors as a cause of spontaneous hemoperitoneum

Ruptured myometrial tumors as a cause of spontaneous hemoperitoneum

Порівняльна характеристика показників тривимірної енергетичної допплерографії тіла матки пацієнток з лейоміосаркомою, лейоміомою та здорових жінок у період менопаузи

Despite the data on the effectiveness of three-dimensional sonography in the improvement of the diagnostic capabilities for predicting the degree of proliferative activity of uterine tumorsalready obtained by other researchers in their previous studies, some aspects of the problem remain insufficiently studied, and the data obtained are contradictory. Thus, there are no quantitative characteristics of threshold values of blood flow indices (VI, FI, VFI) in simple uterine leiomyomas and sarcomas allowing predicting uterine sarcoma with sufficient accuracyat the stage of ultrasound. The objective: comparison of characteristics of uterine body three-dimensional power Doppler sonographyindices in female patients with leiomyosarcoma, leiomyoma, and in a group of healthy women for searching threshold differential diagnostic values of uterine body vascularization indices in patients with leiomyosarcoma. Materials and methods. 74 menopausal women aged 50 to 75 years were examined (Me=62.5). The main group consisted of 46 (62.16%) patients with myometrial tumors. Of these, the study included 10 (21.73%) women with uterine leiomyosarcoma and 36 (78.26%) with uterine leiomyoma. The comparison group consisted of 28 (37.84%) healthy menopausal women aged 50 to 75 years (Me=62.5). In case ofthree-dimensional (3D) reconstruction of the uterus using power mapping and options of VOCAL (Virtual Organ Computer–aided Analysis), an objective assessment of hemodynamics of the uterine body was carried out by calculating the vascularization index (VI) that characterizes the percentage of color voxels in the volume of the uterine body, index of flow intensity (FI) that shows median brightness of the color voxels depending on the flow velocity in a predetermined three-dimensional volume, and vascularization flowindex (VFI) that is a measure of organ perfusion and is the product of vascularization index and flow index divided by 100. Results. At pair comparison of the groups among themselves, VI and FI indicesof the uterine body in groups of women with leiomyoma and leiomyosarcoma differ at a statistically significant level (Mann-Whitney U-test, p &lt;0.05) from the comparison group, and when comparing groups with leiomyoma and leiomyosarcoma, differences between VI and VFI indices of the uterine body are statistically significant. According to the results of the study, in menopausal women, the differential diagnostic criteria of three-dimensional Doppler sonography for predicting the presence of uterine leiomyosarcoma are the following threshold critical values: 26.2% for VI index of the uterine body and 2.47 for VFI index of the uterine body. Conclusion. A method of three-dimensional power Doppler sonography increases the information content of the differential diagnosis of benign and malignant tumors of the myometrium. Prospects for further research involve the study of critical threshold values of three-dimensional indices of vascularization, allowing predicting the presence of uterine leiomyosarcoma in the group of women of reproductive age and the group of menopausal women in a larger sample. Key words: three-dimensional power Doppler sonography, hemodynamics of the uterine body, uterine leiomyoma, uterine leiomyosarcoma.

T2 hyperintense myometrial tumors: can MRI features differentiate leiomyomas from leiomyosarcomas?

To establish MRI features that help differentiate atypical leiomyomas and leiomyomas with degeneration that show hyperintensity on T2WI from leiomyosarcomas. This retrospective study evaluated 41 women who performed MRI before undergoing hysterectomy and had histologically proven atypical leiomyomas, leiomyomas with degeneration or leiomyosarcomas (21 leiomyomas; 20 leiomyosarcomas); only patients with T2 hyperintense myometrial tumors were included. The association between MRI features (contours; free pelvic fluid; intra-tumoral hemorrhagic areas, T2 heterogeneity; T2 dark areas; flow voids; restriction on diffusion-weighted images; signal intensity and heterogeneity after contrast administration; unenhanced areas, localization of unenhanced areas; necrosis; cystic areas) and the histology (leiomyoma vs. leiomyosarcoma) were calculated using Fisher's exact test. For those features that showed a significant association, a univariate linear regression was performed. Five MRI features demonstrated a significant correlation with malignant histology: irregular borders (p = 0.03); "T2 dark" areas (p = 0.02); presence of central necrosis (p = 0.01); presence of high signal on b1000 DWI (p < 0.001); ADC value lower than 0.82 × 10-3mm2/s; hyperenhancement of the tumor relative to the myometrium on post-contrast images (p = 0.02); and type 3 enhancing curve on DCE. Two of these features demonstrated a significant result predicting a malignant histology: lobulated contours and central necrosis [F(3;34) = 8,95; p < 0.001; R2 = 0.506]. The presence of lobulated borders, T2 dark areas, necrosis, hyperintensity relative to the myometrium after contrast administration, central necrosis, presence of high signal on b1000 DWI, ADC value lower than 0.82 × 10-3mm2/s and type 3 enhancing curve on DCE can help distinguish between leiomyoma and leiomyosarcoma. The association of lobulated borders and central necrosis can help predict a malignant histology.

The differential diagnoses of uterine leiomyomas and leiomyosarcomas using DNA and RNA sequencing

Although uterine leiomyomas and leiomyosarcomas are considered biologically unrelated tumors, they share morphologic and histologic characteristics that complicate their differential diagnosis. The long-term therapeutic option for leiomyoma is laparoscopic myomectomy with morcellation, particularly for patients who wish to preserve their fertility. However, because of the potential dissemination of undiagnosed or hidden leiomyosarcoma from morcellation, there is a need to develop a preoperative assessment of malignancy risk. Through an integrated comparative genomic and transcriptomic analysis, we aim to identify differential genetic targets in leiomyomas vs leiomyosarcomas using next-generation sequencing as the first step toward preoperative differential diagnosis. Targeted sequencing of DNA and RNA coding regions for solid tumor-associated genes was performed on formalin-fixed paraffin-embedded samples from 13 leiomyomas and 13 leiomyosarcoma cases. DNA sequencing was used to identify copy number variations, single-nucleotide variants, and small insertions/deletions. RNA sequencing was used to identify gene fusions, splice variants, and/or differential gene expression profiles. In leiomyosarcomas, tumor mutation burden was higher in terms of copy number variations, single nucleotide variants, small insertions/deletions, and gene fusions compared with leiomyomas. For copy number variations, 20 genes were affected by deletions in leiomyosarcomas, compared with 6 observed losses in leiomyomas. Gains (duplications) were identified in 19 genes in leiomyosarcomas, but only 3 genes in leiomyomas. The most common mutations (single-nucleotide variants and insertions/deletions) for leiomyosarcomas were identified in 105 genes of all analyzed leiomyosarcomas; 82 genes were affected in leiomyomas. Of note, 1 tumor previously diagnosed as leiomyosarcoma was established as inflammatory myofibroblastic tumor along this study with a novel ALK-TNS1 fusion. Finally, a differential transcriptomic profile was observed for 11 of 55 genes analyzed in leiomyosarcomas; 8.5% of initially diagnosed leiomyosarcomas showed high-confidence, novel gene fusions that were associated with these tumors. Through integrated comparative genomic and transcriptomic analyses, we identified novel differential genetic targets that potentially differentiate leiomyosarcomas and leiomyomas. This provides a new insight into the differential diagnosis of these myometrial tumors.